MASARYK UNIVERSITY IN BRNO
FACULTY OF MEDICINE
UNIVERSITY TEXTBOOK OF ORAL MUCOSAL DISEASES
(SELECTED CHAPTERS)
MUDr. Lydie Izakovičová Hollá, PhD.
Doc. MUDr. Antonín Fassmann, CSc.
BRNO 2003
Authors:
MUDr. Lydie Izakovičová Hollá, PhD., Institute of Pathological Physiology, Faculty of Medicine,
Brno
Doc. MUDr. Antonín Fassmann, CSc., Department of Stomatology, Faculty of Medicine, Brno
Reviewer: MUDr. Věra Sazmová
Lydie IZAKOVIČOVÁ HOLLÁ, Antonín FASSMANN, Masaryk University Brno 2003
ISBN
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C O N T E N T S:
Preface..………………………………….………………………………………………………….6
The list of acronyms………………….…………………………………………………………......7
1 NOTES ON THE MORPHOLOGY OF THE ORAL
MUCOSA………..………………….........8
2 PATHOLOGICAL PROCESSES IN THE ORAL
MUCOSA……………..........................……10
2.1 Principles of patient examination………..……………………………………………….…..11
2.1.1 Patient history…….…………………………………………………………………..…………….11
2.1.2 Objective findings and procedures during the examination of the oral cavity…………….……….11
2.1.2.1 Histopathological changes………………………………………………………………12
2.1.2.2 Morphology of mucosal manifestations…………………………………………….13
2.1.2.3 Localization and duration of symptoms……………………………………….………….15
2.1.2.4 Description of the examination………………………………………….………….….15
2.1.3 Additional laboratory tests………………………………………………………..……………16
2.1.4 Specialist examination and consultation ……………………………………………….…………19
2.2 Causes of oral mucosal diseases………………………………………………………………..19
2.2.1 External causes..…………………………………………………………………….…………..19
2.2.2 Internal causes………………………………………………………………………….……….21
3 COMMON ANATOMICAL ABNORMALITIES……………………………....……………….23
3.1 Linea alba………………………………………………………………………………… …….23
3.2 Oral pigmentation………………………………………………………………………………..24
3.3
Leukoedema…………………………………………………………………………………..…..24
4 LIP PATHOLOGIES……….……….........………………………………………………………..24
4.1 Congenital abnormalities…………………………………………………………………..……24
4.1.1 Fordyce’s disease………………………………………………………………………...…….…..24
4.1.2 Cleft lip and lip fissures …………………………………………………………………………….24
4.1.3 Double lip……………………………………………………………………………..…………….25
4.2 Inflammations of the lips (cheilitis)………………………………………………………….25
4.2.1 Overview of cheilitis……………………………………………………………………………….25
4.3 Painful mouth corners (the inflammation of mouth corners, angular stomatitis)……………….26
5 TONGUE
PATHOLOGIES…………………………….………………….......…………………..27
5.1 Congenital abnormalities………………………………………………………………….….27
5.1.1 Ankyloglossia……………………………………………………………………..…...…………….27
5.1.2 Geographic tongue (lingua geographica, glossitis migrans)…………………………….……….27
5.1.3 Fissured tongue…………………………………………………………….………………………28
5.1.4 Melkerson-Rosenthal syndrome………………………………………………………………..28
5.1.5 Median rhomboid glossitis (glossitis rhombica mediana)……………………………….………….28
5.2. Macroglossia ………………………………………………………………………………..29
5.2.1 Congenital abnormalities………………………………………………………………..………….29
5.2.2 Acquired abnormalities……………………………………………………………………………...29
5.3. Tongue coating……………………………………………………………………………...30
5.3.1 Physiological coating……………………………………………………………………………...30
5.3.2 Pathologically enlarged tongue coating…………………………………………………………...30
5.3.3 Pathologically reduced tongue coating…………………………………………………………...31
5.4. Inflammations of the tongue (glossitis)………………………………………………………..31
5.4.1 Overview of glossitis………………………………………………………………………..31
5.4.2 Luetic interstitial glossitis (glossitis interstitialis luetica)……………………………………...32
5.4.3 Glossitis associated with deficiency conditions …………………………………………………..32
5.5.
Glossodynia
(stomatodynia)………………………....………………….......……………….….34
6 DISORDERS OF SALIVA SECRETION……………………………………………………...35
6.1 Functions of saliva…………………………………………….……………………….35
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6.2 Saliva secretion……...…………………………………………….………………………36
6.3 Disorders of saliva secretion……………………………………….……………………….36
6.3.1 Ptyalism (sialorrhoea)…………………………………………………………………………....36
6.3.2 Reduced saliva secretion (hyposialia)………………………………………………………..36
6.3.2.1 Xerostomia………………………………………………………………………………….37
7 HALITOSIS (FOETOR EX ORE, BAD BREATH)……………………………………………..38
8 MUCOSAL LESIONS IN THE ORAL CAVITY WITH CHARACTERISTIC FINDINGS....39
8.1 Pigmentation – differential diagnostic remarks………………..………………………………39
8.1.1 Addison’s disease……………………………………………………………………..…………...39
8.1.2 Bronchogenic lung carcinoma (and some other forms of malignant tumours)………………….39
8.1.3 Peutz-Jeghers syndrome………………………………………………………………………...39
8.1.4 Acanthosis nigricans………………………………………………………..………………………40
8.1.5 Hemochromatosis……………………………………………………………………………………40
8.1.6 Porphyria…………………………………………………………………………….…………..40
8.1.7 Pigmented naevi……………………………………………………………………………………40
8.1.8 Precancerous circumscribed melanosis (Melanosis circumscripta praeblastomatosa Dubreuilh)…40
8.1.9 Malignant melanoma…………………………………………………………………………….41
8.1.10 Exogenic pigmentation……………………..……………………………………………………….41
8.2 White patch symptom - differential diagnostic remarks……...………………………..…...42
8.2.1 Leukoplakia…………………………………………………………………….……..……………42
8.2.2 Candidiasis (moniliasis, soor, thrush)…………………………………………..……………..43
8.2.2.1 Median rhomboid glossitis (glossitis rhombica mediana, Brocq-Pautrier glossitis)……...44
8.2.2.2 Black hairy tongue (lingua villosa nigra)…………..............…………………..………....44
8.2.3 Lichen ruber planus………………………………………………………………………………...45
8.2.3.1 Lichenoid reactions of the oral mucosa………………..........……………………………..46
8.2.3.2 Drug-induced mucosal lichenoid reactions…………......………………………………..46
8.2.4 White sponge naevus (naevus spongiosus albus, Cannon’s disease).......................….……………46
8.2.5 Smoker’s leukokeratosis (stomatitis fumantium)…..……………………………………………..47
8.2.6 Darier’s disease (hereditary follicular dyskeratosis)…...........................................…………...47
8.2.7 Psoriasis (psoriasis vulgaris)…..................................................................................……………47
8.2.8 Lupus erythematosus…................................................................................…...........……………48
8.2.8.1 Discoid lupus erythematosus (DLE)...........................................................….…………48
8.2.8.2 Systemic lupus erythematosus (SLE)....................................................…………………48
8.2.9 Fordyce’s disease………………………………………………………………………………….49
8.2.10 Erythroplakia…………………………………………………………………………………….49
8.3 Erosions in the oral cavity - differential diagnostic remarks………………………………….49
8.3.1 Viral diseases……………………………………………………………………….………...49
8.3.1.1 Diseases caused by herpes simplex virus…………………………………….………….49
8.3.1.2 Herpes zoster (shingles)………………………………………………………………..52
8.3.1.3 Varicella…….......................……………………………………………….…………..53
8.3.1.4 Herpangina…………………………………………………………………………………53
8.3.1.5 Vesicular stomatitis with exanthema on the hands and feet (Hand, foot and mouth disease)...54
8.3.1.6 Infectious mononucleosis………………………………………….……….…………..54
8.3.1.7 Cytomegalovirus disease…………………………..………………………………….…54
8.3.1.8 Morbilli (measles) …………………………………………………………………….…55
8.3.2 Recurrent aphthae ………………………………………………………………….…………55
8.3.2.1 Erythema multiforme (Erythema exsudativum multiforme Hebrae)………..………58
8.3.2.2 Behçet's syndrome………………………………………………………………..………..59
8.3.2.3 Touraine’s aphtosis………………………………………………………………………. ...59
8.3.3 Toxic-allergic exanthema…………………………………………………………….…………59
8.3.4 A group of blistering diseases…………………………………………………………………..60
8.3.4.1 Pemphigus …..……………………....…………………………………………………….60
8.3.4.2 Pemphigoid group......……………….………………………….……………….………...61
8.3.4.3 Dermatitis herpetiformis (Duhring-Brocq disease)….........…………….…………..……..62
8.3.4.4 Epidermolysis bullosa acquisita………………………………………………..……….…63
8.4. Ulcers in the oral cavity – differential diagnostic remarks ………………………………..…..64
8.4.1 Diseases primarily affecting the gingiva ……………………….……………………….………64
8.4.1.1 Ulcerative gingivostomatitis (gingivostomatitis ulcerosa)……………………..………….64
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8.4.1.2 Leukemia and lymphoma……………………………………………………….….………..65
8.4.1.3 Agranulocytosis………………………………………………………………….………65
8.4.2 Diseases that do not afffect the gingiva primarily……………………………………..……….66
8.4.2.1 Traumatic ulcer (decubitus ulcer)….....…………………………………………..……...66
8.4.2.2 Suction injury to the palatine mucosa………………………………………...………….67
8.4.2.3 Cheek bite stomatitis (morsicatio buccalis)……........................................................…...67
8.4.2.4 Cotton-roll stomatitis………..............................………………………………………….67
8.4.2.5 Recurrent aphthae (stomatitis aphtosa)……...……………………………………………...67
8.4.2.6 Ulcers of toxic-allergic origin.........……………………………………………………….67
8.4.2.7 Electrogalvanic stomatitis....………………………………………………………...……...67
8.4.2.8 Stomatitis caused by thermal factors……..………………………………………………67
8.4.2.9 Stomatitis caused by chemical factors (chemical burning)…………..……….………….68
8.4.3 Ulcers associated with specific infammations ...........................................................................68
8.4.3.1 Syphilis (lues, French disease)………………………………………………….………..68
8.4.3.2 Tuberculosis…………………………………………………………………….………....70
9 SYMPTOMS OF SYSTEMIC DISEASES IN THE ORAL CAVITY
………………………….71
9.1 Mucosal changes in the oral cavity in patients with HIV-infection/AIDS………………………71
9.1.1 Viral infections…………………………………………………………………………..………….71
9.1.2 Bacterial infections…….....……….……………………………………………………….………..73
9.1.3 Fungal infections.............…………………………………………………………………………..74
9.1.4 Neoplasms……………………………………………………………………………...75
9.1.5 Diseases of the mucosa of nonspecific etiology in HIV-positive patients ………………….……..75
9.1.5.1 Cystic lymphoid hyperplasia associated with AIDS…......…………........……………………...75
9.1.6. Guidelines for the treatment of HIV-positive patients ……….....……………………………….75
9.2 Mucosal changes in the oral cavity associated with diseases of the hematopoietic system …..76
9.2.1 White blood cell diseases……………………………………………………………………..76
9.2.1.1 Leukemia and lymphoma………………………………………………………………...76
9.2.1.1.1 Medicines….....……………………………………………………….…………..76
9.2.1.2 Plasmocytoma………………………………………………………………………………76
9.2.1.3 Agranulocytosis……………………………………………………………..……………..76
9.2.2 Red blood cell diseases…………………………………………………………….…………...77
9.2.2.1. Anemia…………………………………………………………………………………….77
9.2.2.2 Polyglobulia……………………………………………………………….……………….77
9.2.3 Hemorrhagic diseases (bleeding diathesis)……………………………………….………….77
9.2.3.1 Coagulopathy (disorders of plasmatic factors)…………………………………………...77
9.2.3.2 Disorders of thrombocytes………………………………………………………………..78
9.2.3.3 Disorders of the vessel wall (vasculopathy)……………………………………………..78
9.3 Diseases of the heart and blood circulation …………………………………………….……..78
9.4 Respiratory diseases……………...................…………………………………………………..78
9.5 Renal
diseases……….........…………………………………………………………………..…79
9.6 Gastrointestinal
diseases…........……………………...…………………………………………79
10 PRECANCEROSES…………………………………………………………………………….79
10.1 Leukoplakia…………………………………………………………………………………...80
10.2 Erythroplakia………………………………………………………………………………...80
10.3 Senile keratoma (keratoma senile)………………………………………………………….80
10.4 Cutaneous horn (cornu cutaneum)…………………………………………………………80
10.5 Other facultative precanceroses…………………….......………………………………….81
10.5.1 Sideropenic dysphagia (Plummer-Vinson syndrome)…......…………………………………..81
10.5.2 Discoid lupus erythematosus (DLE)………...…………………………………….…………...81
10.5.3 Xeroderma pigmentosum……………………………………………………….……………...81
10.5.4 Epidermolysis bullosa……………………………………………………………………….....81
10.5.5 Lues………………………………………………………………………………….………....81
10.5.6 Lichen ruber planus………………………………………………………………….………...81
10.5.7 Sjögren's syndrome…………..………………………………………………….………………81
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10.6 Paraneoplastic syndromes…………………………………………………………………….81
Literature………………………………………………………………………………………………82
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UNIVERSITY TEXTBOOK OF ORAL MUCOSAL DISEASES
The diseases of the oral mucosa represent a very varied group of diseases of different etiology and
seriousness. The conditions of the orofacial region cannot be taken out from the context of other
medical fields as they are closely connected with internal and dermatovenerological diseases. On the
basis of symptoms in the oral cavity, the dentist can be the first physician to diagnose a general
disease that can be very serious.
Although this textbook is primarily intended for students of dental medicine, it can also be useful for
the students of general medicine whom it can help in clinical and field practice. It is adapted to the
curriculum of current courses, which also determines its extent.
Authors
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THE LIST OF ACRONYMS
ACTH
ACV
AIDS
APC
ARC
ATB
B-MALT
C3a (C5a)
CHX
CMV
Dif. dg.
DLE
EBA
EBNA
EBV
EGF
ELISA
GIT
HIV
HLA
HSV
HTLV
ICAN
IF
Ig
IL
KFR
MSH
PCR
PGE2
PNC
PTT
RA
RIA
RTG
Sine
SLE
SRS
TB
TGF
TNF-
Th
TPHA
TPIT
TTC
UV
VCA
VZV
ZK
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Adrenocorticotropic hormone
Acyclovir
Acquired immunodeficiency syndrome
Antigen-presenting cell
AIDS-related complex
Antibiotics
Mucosa-associated lymphoid tissue (MALT) lymphoma
Complement components
Chlorhexidine
Cytomegalovirus
Differential diagnosis
Discoid lupus erythematosus
Epidermolysis bullosa acquisita
Epstein-Barr virus nuclear antigen
Epstein-Barr virus
Epithelial growth factor
Enzyme-linked immunosorbent assay
Gastrointestinal tract
Human immunodeficiency virus
Human leucocyte antigen
Herpes simplex virus
Human T leukemia virus
Intracellular adhesion molecule antigen
Immunofluorescence
Immunoglobulin
Interleukin
Complement fixation reaction
Melanocyte-stimulating hormone
Polymerase chain reaction
Prostaglandin E2
Penicillin
Partial thromboplastine time
Rheumatoid arthritis
Radioimmunoassay
X-ray
None (without therapy)
Systemic lupus erythematosus
Slow reacting substance
Tuberculosis
Transforming growth factor
Tumour necrosis factor alpha
Therapy
Treponema pallidum hemagglutination test
Treponema pallidum immobilization test
Tetracycline
Ultraviolet
EB viral capsid antigen (virus cellular antigen)
Varicella-zoster virus
Tartar
1 NOTES ON THE MORPHOLOGY OF THE ORAL MUCOSA
The thorough knowledge of both macroscopic and microscopic structures of tissues at
physiological conditions is necessary for being able to assess pathological changes in the oral mucosa.
The structures of individual segments of the oral mucosa compared mutually or with the skin are
shown in Fig. 1.
Fig. 1: A schematic view of the microscopic structure of the skin and oral mucosa (taken from Oral
mucosal diseases (Onemocnění ústní sliznice) by Škach et al., 1982)
Česky
Epidermis
Corium
Tela subcutanea
Epitel
Lamina propria
Submucosa
Kůže
Kůže rtu
Kůže tvrdého patra
Kůže dásně
Kůže jazyka
Kůže tváře
Vestibuli oris
Kůže spodiny ústní dutiny
Str. corneum
Pojivová tkáň mukosy
Žlázky
Str. lucidum
Svalstvo
Pojivová tkáň submukosy
Anglicky
Epidermis
Corium
Subcutaneous tissue
Epithelium
Lamina propria
Submucosa
Skin
The skin of the lip
The skin of the hard palate
The skin of the gingiva
The skin of the tongue
The buccal skin
Oral vestibule (vestibuli oris)
The skin of the base of the oral cavity
Stratum corneum
The connective tissue of the mucosa
Glands
Stratum lucidum
Muscles
The connective tissue of the mucosa
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Str. granulosum
Kost
Str. spinosum
Tuková tkáň
Stratum granulosum (granular layer)
Bone
Stratum spinosum (spinous layer)
Fat tissue
Major differences between the mucosa and the skin:
1) Colour – pink colour in the areas with the keratinization of the epithelium (it is caused by the
thinner layer of the stratum corneum, and a greater degree of blood supply). The red colour of the
mucosa in the areas with incomplete cornification is more intense.
2) Moisture – depends on the secretion of saliva.
3) Skin appendages are missing.
From a topography point of view, the oral mucosa can be divided into several regions that
correspond with the anatomy of jaws and attached muscles. The following types of the mucosa are
recognized: buccal mucosa, labial mucosa, alveolar mucosa, palatine mucosa including the uvula and
frontal palatine arches, the mucosa of the oral base and the tongue. The oral mucosa consists of
stratified squamous-cell epithelium whose properties differ, depending on the function, i.e. according
to the load to which it is exposed (they differ in the presence or absence of the cornified layer on the
surface of the mucous epithelium):
a) The ortho-keratinizing epithelium can be found on the hard palate, alveolar mucosa and attached
gingiva; it has four layers - stratum basale, stratum spinosum, stratum granulosum and stratum
corneum. Layers resemble the epidermis of the skin but are substantially thinner and the stratum
lucidum is absent (Fig. 2).
b) The para-keratinizing epithelium covers the other segments of the oral mucosa (vestibular
mucosa, buccal mucosa, soft palatine mucosa, sublingual region). It has two layers - stratum
basale and stratum spinosum.
The lip red has a specific role, being located on the border between the skin and mucosa. Clinically, it
resembles the oral mucosa. Histologically, it resembles the epidermis with keratinization without the
presence of most skin appendages (hair follicles, skin glands) and without the presence of the orifices
of salivary gland ducts.
Fig. 2: The illustration of the keratinizing epithelium (taken from Oral Medicine, Tyldesley WR, 1981)
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Česky
Anglicky
Stratum corneum
Stratum corneum
Keratinizované buňky
Keratinized cells
Stratum granulosum
Stratum granulosum
Keratohyalinní granule
Keratohyalin granules
Stratum spinosum
Stratum spinosum
Desmosom
Desmosome
Bazální buňka
Basal cells
Jádro
Nucleus
Hemidesmosom
Hemidesmosome
Among epithelial cells (keratinocytes) in the basal layers of the mucous epithelium, there are other
kinds of cells such as melanocytes (that form and accumulate the pigment melanin), Langerhans and
dendritic cells (antigen-presenting cells) that are involved in immune reactions. The epithelium on the
dorsum of the tongue forms duplicatures, i.e. papillae. The following kinds of papillae are recognized:
filiform papillae, fungiform papillae, circumvallate papillae, foliate papillae. Filiform and fungiform
papillae form the basis of the physiological coating of the tongue; foliate papillae are predominantly
located along the side of the tongue whereas circumvallate papillae are located on the border between
the body of the tongue and the root of the tongue, accommodating taste receptors.
Fig. 3: The scheme of the basal complex of the oral epithelium: Connection of basal cells and
connective tissue by means of hemidesmosomes (taken from Oral medicine, Tyldesley WR, 1981)
Česky
Anglicky
Bazální buňka
Basal cell
Hemidesmosom
Hemidesmosome
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Buněčná membrána
Cell membrane
Lamina lucida
Lamina lucida
Lamina densa
Lamina densa
Bazální membrána
Basement membrane
Kotvící vlákno
Anchoring fibre
Pojivová tkáň
Connective tissue
Kolagenní vlákno
Collagen fibre
The cells of the stratum basale are attached to the basement membrane which they form
themselves (Fig. 3). This fibrous membrane is located between the epithelium and lamina propria
mucosae. It is folded variously – depending on the height of lamina propria papillae and the depth of
epithelial spikes. The density of interdigitation (the interlocking of epithelial and fibrous parts)
determines the mechanical resistance of the mucous membrane. The lamina propria mucosae consists
of thin collagen tissue penetrated with elastic fibres, cellular elements (fibroblasts, fibrocytes,
histiocytes, heparinocytes), blood and lymphatic vessels and nerve endings, being gradually turned
into the submucous tissue (except for the dorsum of the tongue where it is firmly attached to lingual
aponeurosis (aponeurosis linguae) or the periostal ligament (the alveolar process, hard palate). The
submucous tissue contains tiny salivary glands (serous, mucinous or mixed) practically in the whole
oral mucosa, which permanently produce small amount of saliva, thereby keeping the oral mucosa wet
and lubricated.
Generally, the oral mucosa can be divided into the following three groups, depending on the
function of individual segments:
1) Specialized mucosa: the dorsum of the tongue
2) "Functional” mucosa – masticatory: palate, attached gingiva
3) "Non-functional” mucosa – lining: other parts of the oral cavity
2 PATHOLOGICAL PROCESSES IN THE ORAL MUCOSA
The oral mucosa reacts to harmful effects by different manifestations. When establishing the
diagnosis of a disease of the oral mucosa, one has to take into account the general variability of
pathological processes, the individual response of a particular individual and - last but not least - the
specific features of the oral environment which characterize a particular disease but can also lead to
diagnostic uncertainty (morphea maceration in wet conditions, a finding of the covering of a blister
only very rarely due to mastication, etc.). In order to establish the exact diagnosis, it is necessary to
take into account not only the distribution of lesions and their clinical appearance but also medical
records in the patient history and the results of additional tests (histology, serology …)
2.1 PRINCIPLES OF PATIENT EXAMINATION
The patient examination includes:
1) Patient history
2) Objective finding
3) Additional tests
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4) Specialist examination and consultation
2.1.1 Patient history
The patient history is an essential part of every examination. The procedure is identical with that
used in other medical fields and includes the family and personal history and questioning regarding
current diseases. As for present diseases, the following pieces of information are collected: when the
disease occurred and how long it has lasted, how it is associated with external and internal factors,
what is the intensity of local and general symptoms. The talk usually starts with the following
questions: when did the disease occur, how long has it lasted, and did it occur for the first time or
repeatedly. Recurrences are typical of recurrent aphthae whereas seasonal character is characteristic
for erythema multiforme (however, one has to take into account that this can be the first attack of the
disease). Subsequently, possible links are investigated – the patient often recalls some facts after a
targeted question (consequences after a dental treatment – cotton-wool stomatitis, allergic reaction
after the use of a new product - cosmetic products, toothpaste, etc.). Information on the speed of the
development of symptoms is also important - the treatment of acute symptoms must be initiated
quickly whereas in the case of chronic problems, additional tests should be performed. The subjective
information concerning pain - spontaneous pain or pain induced by a stimulus - is also very important
since it is usually typical of acute conditions. A typical feature of some diseases is that they do not
hurt (syphilis, carcinoma) although the inflammatory modification is possible (for example secondary
infection). Bleeding is another symptom that may occur when the integrity of the mucous surface is
affected. However, it is often seen when vessels have been afflicted. It is also a sign of serious
changes in the blood count (leukemia, agranulocytosis, thrombocytopenia or thrombocytopathy) or it
occurs during the use of some medications (anticoagulants, antiaggregants, etc.). Mouth odour (foetor
ex ore) is another frequently examined symptom that accompanies the diseases of the oral mucosa. It
can be a non-specific symptom of poor hygiene (the etiological cause or patient’s efforts to avoid
pain). A typical sweetish odour is usually associated with necrotic mucosal decomposition (for
example ulcerative gingivostomatitis, necrosis associated with leukemia). The disorders of salivation
– hyposalivation or hypersalivation - are usually accompanying symptoms of oral mucosal diseases.
Xerostomia is usually associated with fever, being typical of the Sjögren's, Mikulicz or Felty's
syndromes. They may occur at dehydration of different origins, atherosclerosis, after the use of some
medication or X-ray therapy. Hypersalivation usually occurs at acute inflammations of the oral
mucosa (herpetic gingivostomatitis, epidemic stomatitis) or heavy metal poisoning.
General symptoms, which forego the symptoms in the oral cavity, may be part of the clinical
picture of the disease (for example prodromes during herpetic gingivostomatitis). Other time, they
present an individual disease that lowers the body immunity body and has an indirect effect on the
finding on the oral mucosa (herpes simplex after getting chilled). General symptoms, which are
parallel to local symptoms, can indicate a potentially serious general disease (necrosis associated with
acute leukemia) or a metabolic disorder (candidiasis in diabetic patients).
2.1.2 Objective findings and procedures during the examination of the oral cavity
Easy access is the main advantage. Visual inspection should always include palpation in order to
identify the unevenness of the surface, the consistency and size of formations, the mobility and
relationship to the surrounding tissues, and pain. The examination should proceed at perfect lighting.
Attention is paid to the face as a whole, the oral cavity, tonsils, nasopharynx, and submaxillary and
13
submadibular regions and cervical region. The examination of the oral cavity starts systematically
with the lips and mouth corners, followed by the vestibular region, dental arches including the
marginal periodontium, the dorsum and base of the tongue, the base of the oral cavity, buccal mucosa,
hard and soft palates and palatine arches with the uvula and the outlets of large salivary glands. All
changes in the mucosa are examined, paying attention to the colour, thickness, and moisture of the
mucosa, the presence of mucosa-associated efflorescences, the localization and extent of any
affliction. The colour of the mucosa shows race and individual variations. Normally, the mucosa has a
light pink colour; enhanced paleness occurs in patients with anemia whereas the white colour of the
mucosa is typical of hyperkeratosis and leukoedema, reddened mucosa is characteristic of
inflammations. Sometimes, physiological or pathological pigmentations can be found (see Chapter
Pigmentation – differential diagnostic remarks). The thickness of the mucosa: hyperplasia sometimes
occurs (augmentation) – usually during chronic tissue irritation, tumour growth or hormonal
disorders. In other cases, atrophy (reduction) of the mucosa is found, being usually associated with
deficiency conditions (Fe and vitamin B deficiency), estrogen deficiency or some autoimmune
conditions. The physiological atrophy of the mucosa often occurs at older age. Moisture may vary due
to pathophysiological conditions; the healthy mucosa is always wet. Reduced moisture or complete
dryness usually occur at Sjögren's and Mikulicz syndromes, at dehydration or after the use of some
medicines, for example atropine.
2.1.2.1 Histopathological changes
The microscopic picture of mucosal diseases in the oral cavity is diagnostic in itself only in some
cases. In most cases, it can only help to classify a particular pathological symptom in a certain group
of afflictions. Exact diagnosis is often established by using additional diagnostic methods. The
schematic view of basic histopathological changes is in Fig. 4:
Fig. 4: The schematic view of basic histopathological changes (taken from Dermatovenerologie
(Dermatovenerology), Záruba et al., 1992)
Česky
Anglicky
Spongióza
Spongiosis
14
Hyperkeratóza
Hyperkeratosis
Parakeratóza
Parakeratosis
Akantóza a papilomatóza
Acanthosis and papillomatosis
Hyperkeratosis: The sole enlargement of the corneal layer (the stratum corneum). Other layers of the
epithelium can be narrowed, normal or enlarged. Hyperkeratosis can be a result of different processes.
It is clinically manifested as a white patch.
Parakeratosis: Defective cornification characterized by persistent nuclei in the stratum corneum, with
the thickening of this layer as in the case of hyperkeratosis. It is clinically manifested as a white patch.
Dyskeratosis: Abnormal cornification being manifested by the premature keratinization of individual
epidermal cells, with characteristic corneal granules and bodies being formed in their plasma. It is a
premalignant change in the epithelium with changes in cell polarity, the presence of mitotic figures
and changes in nuclei.
Acanthosis: The thickening of the Malpighian layer of the epidermis (the stratum spinosum) due to
the cell growth. It is usually accompanied with the extension and enlargement of intrapapillary spikes.
It may occur with or without hyperkeratosis.
Spongiosis: This term is used to describe the intercellular edema with dilated intercellular spaces in
the epithelium, with the prominence of intercellular bridges in the stratum spinosum
Hydropic (vacuolar) degeneration: Due to the intracellular edema and cell degeneration in the
stratum germinativum, the cell nuclei are replaced with empty space. The whole cells gradually
degenerate. The border of the epithelium and connective tissue is difficult to distinguish.
Acantholysis: It is a process, which manifests itself by the dissolution of desmosomes. Intraepithelial
spaces are formed between epithelial cells, leading to the formation of intraepithelial blisters (typical
of pemphigus).
Epithelial atrophy: It is manifested by the loss of different layers of the epithelium (particularly the
stratum spinosum) and can result from very different processes (inflammations, trophic disorders).
2.1.2.2 Morphology of mucosal manifestations
All diseases of the oral mucosa manifest themselves morphologically by visible lesions that can be
divided into primary and secondary efflorescences:
Primary efflorescences (Fig. 5):
 Macule (spot): The circumscribed redness in the niveau of the mucosa, having a different shape
and size. It can be either sporadic or multiple, with individual spots merging together. Erythema
located on the larger area of the mucosa is called enanthema (scarlet fever, drug-induced
allergies).
 Papule (bud): A small, circumscribed bulge, varying in size and shape, protruding above the
surrounding mucosa. Papular eruptions are usually multiple, the colour of papules on the oral
mucosa is usually whitish or white-grey. Lichen ruber planus is a typical manifestation with the
eruption of papules in the mouth.
 Tuber (bulge): A large-sized papule, for example lipoma.
15


Vesicle (blister): A small (up to 5 mm), circumscribed, elevated lesion filled in its centre with
fluid that distinguishes it from the papule. The large blister sized from 5 mm to several cm is
called bulla. The contents of the blister is usually clear, the thickness of the blister‘s covering
depends on a location (subepithelial blisters have a thicker covering than intraepithelial blisters).
It occurs in the oral cavity during viral infections such as herpetic infections, blistering diseases
such as pemphigus or pemphigoid (intraepithelial), exsudative erythema multiforme, or Duhring’s
dermatitis herpetiformis (subepithelial).
Pustule: A vesicular lesion that is - unlike the vesicle - filled with pus (the pus causes yellowish
colouration). It occurs during varicella infection.
Fig. 5: Primary efflorescences (taken from Dermatovenerologie (Dermatovenerology), Záruba et al.,
1992)
Česky
Anglicky
Macula - skvrna
Macule - spot
Papula - pupen
Papule - bud
Tuberculum - hrbol
Tuber - bulge
Pustula - neštovička
Pustule - pustule
Vezikula subepidermální
Subepidermal vesicle
Vezikula intraepidermální
Intraepidermal vesicle
Secondary efflorescences (Fig. 6):
 Crack (crevice): – It is formed by the rupture of the mucosa, it mostly occurs in mouth corners,
on the lip or on the tongue. A deep, bleeding crevice is called a fissure.
16







Erosion: A mucosal defect with the loss of superficial layers of the epithelium (this does not
include the stratum germinativum). It is the most common mucosal efflorescence. It can be
painful and heals without scars. It usually occurs after mechanical injury or may result from the
loss of the blister‘s covering in a bullous disease. Sometimes, it is covered by a pseudomembrane
on the mucosa or by a crust on the skin.
Squama (scale): It is a flattened plate of the superficially cornified layer that separates from the
mucosa during hyperkeratosis; it can only be present on the lip red.
Crust (scab): Dry exudate on the skin (it can also occur on the lip red). It does not occur on the
mucosa.
Eschar: It is formed during skin necrosis caused by chemical or thermal burning or after freezing
or as a result of trophic disorders. Initially, the necrotic tissue is whitish, then grey or black. It is
separated by circumscribed inflammation, leaves an ulcer behind that heals by a scar.
Ulcus (ulcer): Unlike erosion, it is a deeper loss of tissue – the base of the ulcer consists of
connective tissue and fibrin with the infiltration of polymorphonuclear leukocytes. It always heals
with a scar. The edges of the ulcer can be distinct or jagged, elevated or depressed, hard or soft. It
is usually rounded although linear ulcerated areas may also occur as a result of mechanical or
chemical injury. Like erosions, ulcers can also be the final picture of blistering diseases. Pain
depends on etiology (painless ulcers are associated with carcinoma, syphilis!).
Tumour: It is a solid mass of tissue including the mucosa, and can have a different size. It is a
typical symptom of tumours, or tumour-like lesions, for example pyogenic granuloma.
Aphtha: It is a specific efflorescence in the oral cavity. The primary morphea is a blister; the
removal of the blister‘s covering results in an erosion whose base is covered by fibrin. A red halo
is formed around the erosion.
Fig. 6: Secondary efflorescences
Česky
Anglicky
Squama - šupina
Squama - scale
Crusta - strup
Crust - scab
Eschara - přískvar
Eschar - eschar
17
Rhagas - puklina
Crevice - crack
Fissura - trhlina
Fissure - fissure
Erosio, excoriatio - oděrka
Erosion, excoriation - abrasion
Ulcus - vřed
Ulcus - ulcer
2.1.2.3 Localization and duration of symptoms
Not only symptoms found in a particular individual but also the localization of lesions can help to
establish the diagnosis. For example, the eruption of vesicles in the rear part of the oral cavity and
oropharynx indicates herpangina whereas the affliction of the gingiva and mucosa in the front part of
the oral cavity can be a typical symptom of herpetic stomatitis. The presence of vesicles and bullae on
the labial mucosa indicates erythema multiforme, which is associated with symptoms on other mucous
membranes. The shape and arrangement of efflorescences can be valuable diagnostically (linear,
herpetiform, follicular, multiform). The time of the onset (or recurrence) of clinical symptoms can
help in diagnosis (aphthous stomatitis).
2.1.2.4 Description of the examination
The examination begins at the lips where the symptoms of various conditions can be present either
on the cutaneous part of the lips (common skin diseases) or on the vestibular part of the lips (mucosal
diseases). The lip red is a transitional part where changes typically occur for example during at fever
(dry lips, the formation of crevices). The normal labial mucosa is red. The pale colour is usually
associated with poor circulation or anemia whereas the blue-red colour (cyanosis) is typical of a
number of congenital cardiac abnormalities, intoxications and cardiac insufficiency. Blisters and
crusts (during infections – particularly herpetic infections) or hyperkeratosis (lichen ruber planus) are
very common symptoms found on the lips. The examination of mouth corners is important as it often
reveals painful mouth corners such as cracks, macerated skin and crusts. The gingiva is also
examined. The healthy gingiva has a light pink colour. It can be red in the case of inflammations, or
pale in the case of anemia. Epithelial desquamation - the scaling of the superficial epithelium - can
also be present, with patches of exposed connective tissue that bleed easily (a typical sign of
desquamative gingivitis, pemphigus). The bleeding gingiva is one of the most common problems in
patients with acute or chronic inflammations of the gingiva; severe bleeding can occur at gingival
inflammation associated with serious general diseases. Pain is another serious symptom associated
with acute inflammations (ulcerative gingivitis). In the case of chronic inflammations, pain is usually
induced (during teeth cleaning, eating, etc.). The condition of periodontal pockets must be examined
thoroughly in order to distinguish true and false pockets (gingival hyperplasia may hide serious
general diseases such as hemoblastosis or tumours). After the examination of the gingiva, the tongue
will be examined, focussing on the tongue‘s size, the condition of the tongue‘s edges and tip. The
surface of the mucosa of the tongue‘s dorsum depends on the condition of papillae, the tongue‘s
coating, colour and moisture. Erosions, inflammations of the outlets of salivary glands or leukoplakia
(hyperkeratosis) are often found on the base of the oral cavity whereas the vestibular and buccal
mucosa often show inflammatory symptoms, lichen planus and leukoplakia (hyperkeratosis).
Herpetic, allergic or hyperkeratotic changes can be found on the palatine mucosa.
2.1.3 Additional laboratory tests
18
They are used to diagnose oral diseases, verify and refine the clinical diagnosis of diseases whose
etiology is not clear from the clinical picture, and determine the sensitivity of a particular infectious
agent to certain medicines (antibiotics, antimycotics, etc.)
Hematological examination
It is needed in patients with symptoms of acute infectious stomatitis (caused for example by the
herpes virus) that is severe or prolonged, ulcerative gingivostomatitis, or some other diseases, in order
to exclude any possible serious general disease. Routine tests such as erythrocyte sedimentation and
complete white and red blood cell counts are performed. When indicated (angular cheilitis, glossitis),
the complete red blood cell count is combined with the determination of plasma iron values and ironbinding capacity. The basic coagulation test (thrombocyte count, Quick test, aPTT= activated partial
thromboplastin time) is carried out in cases where coagulation cascade disorders are suspected.
Immunological examination
The complete immunological examination is performed in patients with oral mucosal diseases such
as chronic forms of oral candidiasis and recurrent infections caused by herpes viruses, or recurrent
aphthae. This examination should always be performed in patients before the general administration
of medicines that affect the immune system (immunosuppressants, immunostimulants).
Biopsy
This is a key procedure in terms of differential diagnosis performed in patients with chronic and
recurrent conditions of unknown origin where histopathological or immunofluorescence tests of
excised samples help distinguish similar symptoms (for example chronic hyperplastic candidiasis
from leukoplakia). Diagnostic excision is also performed when the abnormal intraoral manifestation
of a disease that does not normally affect the oral mucosa (for example primary TB ulcer) is
suspected. The bioptic examination of the mucosa is also necessary to confirm the diagnosis of
"hairy” leukoplakia and all blistering diseases.
The physician must know at which circumstances it is possible to collect the material contraindications include acute viral diseases of the oral mucosa, ulcerative gingivostomatitis,
bleeding disorders, suspected hemangioma or malignant melanoma. The extent of the excision and the
site of biopsy is of key importance. Efforts during the diagnostic excision should always be made to
collect a sample from the entire pathological formation. When the affliction is large, a typical part
should be collected together with the adjacent healthy tissue. The procedure is usually performed at
local anesthesia; the collection of a sample should be performed very gently, without causing the
unnecessary bruising of the surrounding tissue. The most common excision uses an auxiliary stitch
where the forceps will not bruise the collected tissue. The mucosa is not disinfected prior to the
excision, the patient has to be properly instructed about the nature of the procedure and possible
complications which may occur due to the presence of the sutured wound in the mouth.
Excised tissue is usually placed in a 10% solution of formaldehyde. The sample of tissue together
with the cut-off, shortened stitch is placed on filter paper or cork; to facilitate orientation during
examination. A properly filled-in dispatch note must be attached to the specimen. Staining is usually
performed using hematoxylin and eosin, or special staining is performed in some case. In order to
distinguish blistering afflictions and confirm the diagnosis of lichen, it is sometimes necessary to
perform the examination of non-fixed tissue by using the direct immunofluorescence method to prove
19
the presence of autoantibodies bound to the target tissue (an assay for circulating antibodies using the
indirect immunofluorescence method is also performed).
Microbiological examination
It is used to determine the causative agent of a particular infectious disease either directly or
indirectly. It also serves for the determination of the sensitivity to ATBs. In field practice, it is
recommended that the respective transfer and the use of media be agreed upon with the laboratory that
will perform the examination. The direct determination of the infectious agent (microscopically, by
cultivation) is not usually possible (for example due to secondary changes in symptoms). Indirect
(serological) methods are therefore used to prove the presence or absence of specific antibodies or
microbial antigens.
1) Virological examination
The isolation of viruses and detection of viral antigens
For successful isolation, it is necessary to meet the following requirements:
a) The collection of the specimen must be performed as soon as possible after the onset of the
disease (within 2-3 days).
b) The specimen is collected from the site with the largest assumed release of the virus.
c) The specimen must be stored and transported at a suitable temperature (+4º C)
d) The dispatch note must be filled in correctly and the respective test tube with the specimen must
be labelled properly. It must contain the patient‘s name and surname, birth identification number,
health insurer, diagnosis, the date of sample collection, the onset of the disease, and the name of
the physician who performed sample collection.
The isolation of the virus is performed in living cells, usually cell cultures grown in vitro (other living
species such as laboratory mice, chicken embryos can also be used, but it is quite expensive). The
viral antigen is visualized using the labelled, (preferably) monoclonal antibody that binds to it.
Depending on the method of labelling, antibodies can be detected either by fluorescence or by the
enzyme-linked immunosorbent assay (ELISA). For exact diagnosis, molecular biological methods are
currently used, for example in-situ hybridization or polymerase chain reaction (PCR) methods. The
principle of the PCR method is that the selected piece of DNA is amplified across several orders of
magnitude. The product obtained can be analysed for the presence of specific sequences of bases (for
example for the presence of typical viral segments).
Indirect evidence of viral infections
It is based on the determination of specific antibodies in the patient’s serum. In order to be able to
interpret the results, one must know the principle and the dynamics of the formation of these
antibodies. It is useful to monitor antibodies IgM and IgG out of five existing classes of
immunoglobulin antibodies. IgM antibodies are produced first. Their production will only last for a
limited period of time and stop in a few weeks. The presence of IgG antibodies reaches the maximum
level several weeks after infection (they may be lifelong for some infections – it is therefore possible
to see whether an individual has had a particular infection in his/her life). Specific antibodies can be
monitored using various methods. The complement-fixation reaction (CFR) is a relatively less
sensitive method, compared to the methods mentioned below. Its main disadvantage is that 2 samples
must be collected from a patient in 2-3 weeks in order to follow the dynamics of changes. The
20
immunofluorescence method is a more advanced and accurate method. It is based on the principle that
some dyes emit light after being exposed to UV radiation. Detection can be direct when the
fluorescent substance is bound directly to the specific antibody and used for the direct evidence of the
antigen. Indirect immunofluorescence means that the antibody is bound to the antiviral antibody of
animal origin that is applied on the immune serum. Enzymatic methods such as ELISA (which is one
of the best known methods) are based on the formation of the antigen-antibody complex where the
antibody is labelled with an enzyme. The result of the reaction is proportional to the enzyme activity
of this complex, which is measured by following the decay of the enzyme. In the case of
radioimmunoassay (RIA), the antigen-antibody complex is determined using the radiolabelled
antibody.
2) Bacteriological examination
Methods for the cultivation of bacteria are usually used to identify the infectious agent and
determine its sensitivity to antimicrobial therapy.
Aerobic and anaerobic cultivation
The biological specimen is collected to determine both aerobic and anaerobic species. The main
prerequisite for successful cultivation is that the specimen is protected from air. It is therefore
recommended that the sample should be collected in the morning on an empty stomach by means of a
smear from the afflicted site on the mucosa using a sterile cotton swab, which is then placed on the
bottom of the test tube containing a semi-solid transport medium (on rare occasions, it is transported
in a test tube containing CO2). Cultivation then proceeds on bacteriological media selected depending
on a particular (assumed) infectious agent (blood agar, End medium, Fortner medium for aerobes,
etc.). It should be pointed out that anaerobic cultivation is usually much longer than the cultivation of
aerobic bacteria. The identification of some causative agents such as gonorrhoea (N. gonorrhoea),
tuberculosis (M. tuberculosis) and other infections, requires the use of special media.
Microscopic examination
For example, dark field examination using a screen is used to diagnose the first stage of syphilis
where serum reactions are still negative.
Serological examination
It is important when syphilis is suspected; specific serum reactions are used to diagnose the
second and third stage:
BWR (evidence of nonspecific lipid antibodies) – precipitation reaction with a cardiolipid antigen.
The positive finding is expressed by the number of crosses according to the density of flakes. The
reaction is detectable in Week 3-4 of the first stage.
TPHA (Treponema pallidum hemagglutination test – evidence of specific protein antibodies).
Agglutination reaction with the antigen from dead treponemes. The positive finding is expressed by
the number of crosses according to a degree of agglutination. The reaction is detectable from Week 4
of the first stage.
TPIT (Treponema pallidum immobilization test – Nelson test). Evidence of highly specific protein
antibodies. The immobilization of living treponemes (Nichols strain). The positive finding is
expressed by the percentage of immobilized treponemes by immobilizins present in the patient‘s
21
serum (80-100 %). Reaction is detectable in the end of the first stage (Weeks 5 - 7). The special
preparation of the patient is necessary.
3) Mycological examination
It is used to verify the clinical diagnosis and determine the sensitivity of yeast (typical species) to
antimycotic therapy. Smears are performed at the above-mentioned precautions. Cultivation is usually
performed using the Sabouraud agar with the addition of antibiotics to suppress bacterial
contamination.
2.1.4 Specialist examination and consultation
Specialist examination and consultation is indicated:
a) when other than a dental basic disease is suspected, in order to confirm the diagnosis and
proposed or approved therapy,
b) in the case of diagnostic doubts – even if the attending physician has good knowledge and adheres
to good practices of patient examination, the oral mucosa may exhibit symptoms whose cause is
too difficult to determine or classify. The specialist consultation component includes the
examination by more experienced dentist or specialist.
The following clinical tests are usually necessary: dermatological (SLE, pemphigus),
ophthalmological (Sjögren’s syndrome, Behçet’s disease), neurological (glossodynia, neuralgia),
allergological (drug-induced exanthema, Quincke’s edema), hematological (anemia, hemoblastosis),
otorhinolaryngological and rheumatological (required in the case of the Sjögren’s syndrome), or
general internal examination. The report for the consulting physician should contain the detailed
description of present therapeutic procedures and used medication (the possibility of artificial change
in the clinical finding after use) with a brief patient history.
2.2 CAUSES OF ORAL MUCOSAL DISEASES
Any disease (oral mucosal diseases or any other disease in general) has its causes and results in
reactions in the body of an affected individual. Such reactions depend on the genetic predispositions
and the individual‘s current state of health. The causes of oral mucosal diseases are very varied – they
differ in quality, quantity and the duration of action and may combine or amplify. Causes can be local
or general, and external or internal.
2.2.1 External causes
External causes include the following factors: physical (mechanical, thermal, radiation and
electrogalvanic), chemical, allergic and infectious (bacterial, viral, fungal).
Physical effects
a) Mechanical – such as injuries to the mucosa (the sharp edges of carious teeth, dental tartar,
defective prosthesis) that can be acute or chronic
b) Thermal – the effect of heat (burns – caused by hot food or dental treatment) or cold, caused by
the patient alone or the attending physician;
22
c) Radiation – ultraviolet rays, X-ray radiation overdose (but also after therapeutic doses),
penetrating radiation during accidents of atomic emitters;
d) Electric current – it can damage tissue in the oral cavity either at an accident or due to the
galvanic irritation in the oral cavity. The presence of different metals in the form of metal fillings
or prostheses can initiate electric irritation with metals serving as electrodes and the saliva serving
as an electrolyte. All substances that can be used as electrodes in a galvanic cell are ranked
according to their potential. When the two metals lying one beside the other in the table (silver,
platinum, gold) coincide, the risk of hazardous voltage between them will be smaller as compared
to the metals that are more far apart in the table (gold versus zinc or tin). The function of the
galvanic cell depends on a difference between potentials of both metals. This produces currents of
different intensity, depending on the resistance of particular tissues (Ohm’s law). The
manifestation of galvanism result from the direct effect of a current (the tolerated intensity
causing no damage is 10 microampere, tolerable voltage is approximately 80-100 mV) or from
electrolysis where the ionization of tissue liquids causes the decomposition of organic substances.
This results in electrogalvanic stomatitis which may have different symptoms - general symptoms
(GIT symptoms, headache, joint pain) and local symptoms in the oral cavity. Patients usually
report subjective problems such as tingling, burning or metallic taste. Objective findings reveal
various changes ranging from erythema, erosion or ulcer to hyperplastic changes. Symptoms
usually occur at the site of contact between both metals at the edge of the tongue or the buccal
mucosa.
Chemical effects
They occur due to accidents (drinking, spilling) or carelessness of the attending physician. This
includes chemical burning by acids, bases, or salts of heavy metals. This group also includes the
effects of some locally (arsenic) or generally applied medicines.
Allergic effects
Over the last few years, the number of people with allergic reactions to different substances with
which they come into contact during their lives has increased. Reactions of the oral mucosa to such
substances can be divided into the two groups - drug-induced stomatitis and stomatitis caused by
contact allergy (stomatitis venenata):
1) Drug-induced stomatitis (stomatitis medicamentosa)
It develops after some delay (approximately 48 hours) after the application of a drug
(sulphonamides, procaine, Brufen) and can be manifested anywhere on the oral mucosa. In the
foreground, there is acute inflammation with swollen mucosa which can be catarrhal or blistering,
with the development of erosions or ulcerations. Changes disappear spontaneously when the medicine
is discontinued.
Reaction can also proceed as anaphylactoid reaction with skin symptoms resembling urticaria. The
face, oral cavity and larynx show the symptoms of the Quincke’s edema with swollen lips,
macroglossia and inspiratory stridor (laryngeal edema). Anaesthetics and antibiotics play a major role
in dental medicine. In the case of penicillin, sensitization occurs after local application in up to 10%
of people – as compared to 0.1% of people after oral application. This is why the application of
penicillin in the oral cavity is contraindicated.
2) Stomatitis venenata (at contact allergies)
23
Contact allergies are relatively common on the lips and the oral mucosa after the direct contact of
the mucosa with a particular substance. They can be induced by some foodstuffs (nuts, fruit) or
materials used in dental treatment (monomers or resin prostheses, essential oils). They can also occur
after the use of oral hygienic products (toothpaste, mouthwash or some medicines, for example
propolis). Clinical and histological examinations reveal the edema of the mucosa with intraepithelial
blisters and distinct leukocyte infiltration.
The effects of drugs
Apart from allergic effects of drugs, toxic effects and adverse pharmacological effects should also
be mentioned here (see Chapter 8.3.3). They usually manifest themselves at higher doses but can also
occur at normal doses. Typical symptoms include biological complications induced by antibiotics.
Dysmicrobia is a disorder of microbiological balance caused by the suppression of normal microflora,
which facilitates the development of superinfection – when sensitive microflora (on mucous
membranes, skin or in the intestine) is suppressed, pathogenic flora which is insensitive to particular
ATBs and suppressed at normal conditions will overgrow (for example the overgrowth of yeast after
ATB therapy).
Infectious effects
Some pathogenic microorganisms can cause local infection in very rare cases (for example
Mycobacterium tuberculosis cause primary TB in the oral cavity only very rarely), others are involved
in local diseases of the oral mucosa in combination with a general disease. General infections such as
bacillary infections (typhoid, diphtheria, pertussis), coccal infections (scarlet fever), viral infections
(herpetic gingivostomatitis, morbilli, varicella, infectious mononucleosis, AIDS etc.), also have their
symptoms in the mouth.
2.2.2 Internal causes
Predispositions for the development of a disease can be associated with internal factors such as
age, gender, race, and congenital individual differences (genetic factors). The combination of these
factors defines the constitution of the organism.
Age
A number of oral mucosal diseases manifest themselves more frequently in patients from certain
age groups. For example, herpetic gingivostomatitis typically occurs in children whereas ulcerative
gingivostomatitis is common in adolescents, which may help establish a correct diagnosis. Generally,
there are some stages in human life which can be considered a risk factor for the development of a
mucosal disease in the oral cavity because of immunological and hormonal changes in the body. In
newborns and infants, the passively acquired immunity induced by the entry of maternal IgG type
antibodies through the placenta decreases sharply during the first weeks after birth. After several
weeks, the production of immunoglobulins starts to increase and cell defence is being built. At this
age, moniliasis often occurs. Puberty is the next critical period of life, being characterized by
significant hormonal changes where the occurrence of ulcerative gingivostomatitis (with a peak
between 16-21 years of age), infectious mononucleosis or erythema multiforme reaches the maximum.
At old age, physiological reserves are decreased and pathological processes accumulate. Generally,
immunity lowers and the “immunological control” decreases, resulting in the manifestation of
24
autoimmune processes (pemphigus, Sjögren’s syndrome) and tumour growth. Hormone dysfunction,
particularly in women, is associated with the atrophy of the skin and mucous membranes, vasomotor
disorders and emotional instability. Deficiency conditions and endocrine disorders (diabetes mellitus)
may occur, further contributing to the development of mucosal diseases (soor, stomatodynia). The
loss of natural teeth and dental treatment using prosthetic replacement extend general causes with
irritant effects (stomatitis protetica, painful mouth corners).
Disorders of metabolism and glands of internal secretion
Metabolism consists of complex biochemical reactions to supply energy to the cells and build up
the living substance. Metabolic disorders may involve all of its components and basic substances such
as sugars, fats, proteins, vitamins, minerals, enzymes and hormones. Metabolic changes are in a close
relationship with nutrition disorders, food intake, food composition, digestion in the gastrointestinal
tract and utilization in tissues. Metabolism is also affected by the glands of internal secretion whose
disorders may cause similar symptoms. Sexual hormones also have a direct effect on the
morphological structure of mucous membranes and can cause changes in the oral cavity at
physiological (puberty, pregnancy) or pathological conditions, usually interacting with nervous and
immune systems.
Immune disorders
Defence against foreign substances (particularly microbial antigens) is a prerequisite for the
existence of every individual. The first contact of the organism with a foreign protein leaves
permanent information in the body so that the agent will be recognized and inactivated upon a
repeated contact. Specific antibodies are produced at levels that reach a maximum in 2 - 3 weeks, then
their levels decrease. This is the primary immune response. At every other contact with the respective
antigen, antibodies are produced faster and in a large amount. This is the secondary immune response.
However, the result of the immune reaction is not always positive and may lead to the development of
diseases (at pathological reactions). In the case of mucosal diseases, pathological reactions such as
immune hypersensitivity (allergy), autoimmune damage to tissues and immunodeficiency conditions
may occur.
Immune hypersensitivity (allergy, hypersensitivity)
The pathogenesis of allergies is identical with defensive immunity mechanisms. This includes
humoral hypersensitivity (anaphylactic type, cytotoxic type and immunocomplex hypersensitivity)
and cellular hypersensitivity.
Type 1 – Anaphylaxis: it is a reaction between the antigen and IgE antibody. Mast cells and basophils
show degranulation followed by the release of vasoactive substances such as histamine, SRS. IgG
antibodies are also involved in the reaction with the antigen - this binding is activated by the
complement whose anaphylactogenic components C3a and C5a are histamine liberators. Anaphylactic
shock is an example (in dental medicine, particularly after the application of anaesthetics, antibiotics
or other substances).
Type 2 – Cytotoxic type: the binding of antibodies to the surface of cell antigen will result in the
activation of the complement, affecting the cell membrane and cytolysis. Examples include
autoimmune hemolytic anemia and drug-induced purpura.
Type 3 – Immunocomplex hypersensitivity: the binding of the antigen to the antibody to form
pathological immunocomplexes that activate the complement. The result of the reaction depends on
25
the ratio between the antigen and antibodies. If the antibody is in excess, the Arthus-type reaction will
occur at the site of antigen‘s entry - necrosis. When the antigen is in excess, circulating
immunocomplexes (CIC) penetrate the vessel wall to give rise to vasculitis (for example systemic
lupus erythematosus).
Type 4 – Cellular: this reaction is sometimes called the tuberculin-type reaction (according to the
occurrence in TB–Mantoux). Its onset is delayed, the antigen binds to the antigen-presenting cells
(APC) and sensitizes T-lymphocytes that proliferate and differentiate in subpopulations of regulatory
(suppressor and auxiliary) and executive cells (cytotoxic T-ly) that are able to kill the target cells. The
regulatory subpopulation of auxiliary T-lymphocytes produces lymphokines that can also damage
tissues (contact eczema is an example of this kind of reaction).
Autoimmune diseases
At normal conditions, the immune system is able to distinguish between “own” and “foreign”. It
has a high capacity and can react practically against all molecules and/or cells. Although the ability to
react against self-antigens exists in all people, the most common result of this reaction is tolerance or
anergy, which indicates the involvement of mechanisms capable of preventing or suppressing
autoimmune response. In addition, autoreactive T and B lymphocytes as well as autoantibodies can be
found relatively frequently in people who do not suffer from any autoimmune disease. This indicates
that immunological reactivity in itself is not sufficient for the development of the disease
(autoimmune diseases are those where the autoimmune response causes tissue damage). Mechanisms
assumed to be involved in the prevention/suppression of autoimmune response include the
inactivation or deletion of autoreactive T and B cells (the forbidden-clone theory), the active
suppression of cells or cytokins, idiotype/anti-idiotype interactions and immunosuppressive adrenal
hormones, glucocorticoids. When suppression mechanisms are not sufficient, reactivity against selfantigens may occur and lead to the development of autoimmune diseases, which can be either organspecific (diabetes, thyroiditis) or systemic (organ non-specific) such as systemic lupus erythematosus
(SLE) and rheumatoid arthritis (RA) that can affect multiple organs. Primary autoantibodies (for
example hemolytic anemia), immunocomplexes (SLE), cellular immunity (for example multiple
sclerosis) or the combination of antibody-mediated and cell-mediated immunity (for example RA)
may play a role in the pathogenesis of autoimmune diseases. It is assumed that there are several key
cofactors that contribute to the development of autoimmune diseases: genetics (for example HLA
association), gender and age. The properties of respective antigens, particularly the way how they are
presented to the immune system, are also important. Some infections, for example the EB virus or
mycoplasma, may induce the production of antibodies in otherwise normal individuals. Some
medicines such as procainamide (used in the treatment of some cardiac arrhythmias) or toxic
substances such as mercury (II) chloride and polyvinylchloride can induce autoimmune pathology. A
number of autoimmune diseases such as pemphigus, pemphigoid, Sjögren’s syndrome, SLE etc. may
occur in the oral cavity.
Immunodeficiency conditions
Any component of specific and non-specific immunity can be absent, present at a lowered level or
malfunctioning. Immunodeficiencies have common manifestations such as impaired defence against
infection and being prone to infections with a severe course, minimally reacting to common antiinfectious therapy. When antibody defence mechanisms are impaired, pyogenic infections are
26
predominant whereas when cellular immunity is impaired, viral, fungal or parasitic infections will
occur.
Specific immune deficiency conditions can be divided into primary and secondary. Primary
conditions include the DiGeorge syndrome or congenital pediatric agammaglobulinemia (Bruton).
From a stomatological point of view, one should mention chronic mucocutaneous candidiasis which is
a disorder of cellular immunity combined with a disorder of non-specific immunity. Secondary
disorders of immunity are associated with some diseases (AIDS, malignant lymphoma), or may occur
after intensive immunosuppressive, cytostatic therapy or radiotherapy. Both antibody (humoral)
immunity and cellular immunity are affected.
3 COMMON ANATOMICAL ABNORMALITIES
3.1 Linea alba
Linea alba is a typical linear elevation of the buccal mucosa that runs at the level of the occlusal
line from the mouth corner to third molars. Clinically, it is a bilateral linear elevation of a normal or
slightly white colour with normal consistence upon palpation. It occurs more frequently in obese
individuals in whom the oral mucosa can be slightly compressed and adapted to the shape of the
occlusal line of teeth.
Th: The removal of mechanical irritation
3.2 Oral pigmentation
Melanin is a pigment produced by melanocytes. It occurs in the skin and oral mucosa. The degree
of skin pigmentation does not need to be identical with that of the pigmentation of the oral mucosa.
The increased accumulation of melanin in the oral mucosa can be a symptom of a number of diseases
although the areas of darker colouration of the oral mucosa can normally be found in black people or
in people with the darker skin. Clinically asymptomatic black or dark coloured patches with a
different size and extent (melanoplakia) can be found in the oral cavity of healthy people, mainly on
the gingiva, buccal mucosa, palate or less frequently on the tongue, oral base or lips. Pigmentations
are usually noticeable in the regions exposed to pressure or friction, and usually become more distinct
with age.
Th.: It is not necessary in patients with melanoplakia, therapy of other diseases depends on etiology.
Dif dg: It is necessary to distinguish the Addison’s disease, pigmented naevus, melanoma, the
deposits of heavy metals, lentigo maligna, drug-induced pigmentation, Peutz-Jeghers syndrome and
Recklinghausen's disease.
3.3 Leukoedema
It is a non-pathological anatomical variation of the oral mucosa caused by the increased thickness
of the epithelium and intracellular edema of the Malpighian layer. It occurs bilaterally and affects the
buccal mucosa in most cases or the lips and the tongue in rare cases. Clinically, it presents as an
opalescent or white-grey tinge with slight shrinking which disappears when the buccal mucosa is
stretched. Leukoedema has normal consistence upon palpation and should not be confused with
leukoplakia or lichen.
Th.: Sine
27
4 LIP PATHOLOGIES
4.1. CONGENITAL ABNORMALITIES
4.1.1 Fordyce’s disease
It is a developmental abnormality characterized by the occurrence of heterotopic sebacious glands
in the mucosa of the oral cavity. Clinical finding shows multiple small, slightly elevated, white-yellow
dots that are well circumscribed (rarely accumulated and forming plaques). They often occur on the
mucous surface of the upper lip, in commissures and on the buccal mucosa bilaterally and
symmetrically attached to molars. It is a relatively frequent finding and occurs in both genders. They
are asymptomatic. With an increasing age, they can become more noticeable but should not cause
major concern.
Th.: Sine
Dif. dg.: Lichen planus, candidiasis, leukoplakia
4.1.2 Cleft lip and lip fissures
They are developmental abnormalities that usually affect the upper lip, usually in combination with
cleft jaw and palate. They are caused by the incomplete adhesion of jaw and nasal processes in the
upper jaw during the embryonic development. The cleft can be unilateral or bilateral, complete or
incomplete.
Th.: Complex treatment according to the seriousness of a particular abnormality
Congenital abnormalities include congenital fistula and lip pits (recesses and paramedian sinuses)
which may secrete mucus.
4.1.3 Double lip
This abnormality can be either congenital or acquired as a result of injury. There is a mucous
duplicature on the upper or lower lip which can protrude particularly at smiling or speaking.
Th.: Surgical correction
4.2 INFLAMMATIONS OF THE LIPS (CHEILITIS)
When evaluating inflammatory changes on the lips, one should take into account the specific
configuration of the lips in comparison with other sections of oral mucosa. The diseased process may
affect the skin of the lips, lip red or oral mucous membrane. Inflammation can affect either one or all
three parts of the lip; each part has its own morphology. It is necessary to take into account that
individual infectious agents can attack only certain site selectively (predilection). For example,
impetigo can only be found on the skin part, similar to folliculitis and furuncles that depend on the
presence of hair follicles whereas aphthae affect typically the mucous parts.
4.2.1 Overview of cheilitis
Causes:
Objective finding :
 Physical - Mechanical :
erythema, excoriation, crevice, erosion, ulcer, crust
- Thermal:
erythema, vesicula, eschar
- Radiation: - phototoxicity :
cheilitis actinica
28
- photoallergy:
cheilitis venenata
- radioactivity:
erythema, ulcer
 Chemical - chemical burns (acids, lyes): eschar (lye – grey colour, acids – specific colouration
depending on a particular type of acid – for example, nitric
acid - yellowish burns, sulfuric acid – burns can be black, hydrochloric acid - white burns)
- dyes:
cheilitis exfoliativa (upper layers of the epithelium are peeled
off)
 Infection - coccal:
furuncles, phlegmon, impetigo, erysipelas, painful
mouth corners
- viral :
herpes labialis
- bacterial:
ulcer, gangrene, noma (when the body is weakened)
- specific – TB:
macrocheilia, ulcer
- syphilis:
primary – erosion, ulcer
secondary – erosion, plaques muqueuses (mucous papule)+
opalines (opaline plaques), condyloma
tertiary – gumma (rare)
- fungal:
painful mouth corners (with other factors)
 Allergies: - plant and animal antigens,
eczema, Quincke’s edema
proteins in foodstuffs,
chemicals

Unclassified units: erythema multiforme – blisters, erosions, crusts
pemphigus - blisters, erosions, crusts
granulomatous cheilitis (cheilitis granulomatosa) at the MelkersonRosenthal syndrome – lip edema
- at salivary gland heterotopia: cheilitis glandularis simplex (Puent)
cheilitis glandularis aposthematosa (Volkmann)
cheilitis glandularis suppurativa (Baelz)
4.3. PAINFUL MOUTH CORNERS (ANGULI INFECTIOSI, ANGULAR STOMATITIS (STOMATITIS
ANGULARIS), PERLÈCHE)
This is a relatively common disease usually caused by combined mycotic and bacterial infections.
The typical underlying factors for the settlement of the infection are macroscopically undetectable
skin and mucosal defects in this region which can be infected by conditionally pathogenic
microorganisms. Anatomically, the region can be divided into 3 zones:
a) Skin zone (external) that covers the normal skin with all skin appendages.
b) Transitional zone (central) covered by the multi-layer, squamous, less cornifying epithelium of
the lip red. Apocrine sweat glands and hair follicles are missing out of skin appendages.
Sebacious glands are present in a smaller amount.
c) Mucous zone (internal), which is covered by the non-cornifying epithelium of the oral mucosa
with the outlets of tiny salivary glands.
Predisposing conditions for the formation of painful mouth corners depend on a particular age
category.
29
Clinical picture: The typical course is characterized by distinctly reddened and painful patches in
commissures with a central crevice in the skin or transitional zone. Sometimes, there can be a minor
whitish margin in the surroundings of reddened patches. The disease is usually bilateral and its course
depends on many factors.
Painful mouth corners in children can be associated with rare congenital skin fistulas which can be
infected secondarily. Otherwise, there are a number of other predisposing factors (different habits,
bad habits such as cheek and lip biting lip licking, inserting foreign objects into the mouth and biting
these objects). Microtrauma of the mouth corners can get easily infected, causing secondary
traumatization and infection (usually streptococcal impetigo). Impetigo contagiosa streptogenes is a
very contagious disease caused by beta-hemolytic streptococci and usually affects children in groups
of children. It has a seasonal occurrence, with a maximum in summer and autumn. Primarily, it is
characterized by the eruption of tiny blisters whose covering will soon rupture, causing erosions
covered by honey-coloured, yellow crusts. Regional lymph nodes are usually swollen. Impetigo may
spread (per continuitatem) further on the facial skin.
At adolescent age, the conscious or unconscious mechanical traumatization of mouth corners
occurs quite often, with the development of angular cheilitis. Atopic eczema is a significant
predisposition, with Staphyloccocus aureus occurring on the skin relatively frequently (in up to 90%
as compared to 10% in healthy population). It may cause impetigo contagiosa staphylogenes. The
primary symptom of this condition is a blister that quickly turns opalescent with pus and after its
covering has been removed, dirty green crusts are formed. After healing, pigmentation may persist for
some time. Local therapy and the prevention of underlying factors are difficult due to some
negativistic attitudes typical of this period.
In adults, painful mouth corners occur relatively often since the number of local and general
predisposing factors increases. The elasticity of the skin decreases with a decrease in subcutaneous
connective tissue and fat tissue, the height of the occlusion decreases due to the abrasion of hard
dental tissues, or at the loss of supporting zones. General factors such as diabetes mellitus, the
Sjögren’s syndrome, malignant tumours and a number of other diseases are important. Angular
candidiasis (most frequently C. albicans) affects the mucosa of mouth corners either separately or in
combination with a more extensive affliction of the oral cavity. Crevices and red patches with a vague
minor whitish margin are typical.
The following methods are important: bacteriological and mycological examinations, hematological
and biochemical examinations (glycaemia) in the case of resistant symptoms, sialometric examination
and assessment of the quality of dental prosthesis.
Th.: To try to eliminate the causes (the reconstruction of the height of occlusion - rebasing, new
dental prosthesis, the replacement of supporting zones). Therapy differs depending on etiology.
Antimycotics can be applied locally (nystatin, azole-derived antimycotics), antibiotics. In adult
patients, combined products containing anti-inflammatory corticosteroids can also be used
(application must be careful and short-time!)
Dif.dg.: Herpes simplex (labialis) infection in the region of the mouth corner is unilateral, prodroms
(paresthesia) occur before the eruption, the surrounding area is usually edematous and red, and can be
painful. Syphilitic primary efflorescence is a unilateral, painless erosion or crevice whose base is
hardened. It is painless lymphadenitis. It is also important to distinguish squamous-cell carcinoma
(rarely being other than that) of the lip that is painless, does not respond to therapy, usually has a
30
larger extent (if the affection does not respond to therapy within 1-2 weeks, surgical excision should
be performed at a specialized clinic!).
5 TONGUE PATHOLOGIES
5.1 CONGENITAL ABNORMALITIES
Many congenital malformations of the tongue are quite rare, for example aglossia (the absence of
the tongue), microglossia (congenitally small tongue), tongue tie (lingua accreta), cleft tongue (lingua
bifida), or double tongue (diglossia vera).
5.1.1 Ankyloglossia (lingua accreta, tongue tie)
Ankyloglossia is a relatively rare developmental abnormality in which the frenulum of the tongue
is short or attached close to the tip of the tongue. In these cases, the frenulum is usually strong and
fibrotic. Tongue mobility and function are affected which results in difficulties swallowing and
talking.
Th.: Surgery
5.1.2 Geographic tongue (lingua geographica, glossitis migrans)
It is considered to be a developmental abnormality. It may occur at every age in approximately 210% of population. Familial occurrence is common; it usually occurs together with plicated tongue
(lingua plicata). Clinical signs include vast red patches on the mucosa of the dorsum of the tongue.
Some patients experience enhanced sensitivity of the tongue when eating some foods (citrus, spices).
It is associated with the formation of vast red patches that change quickly, spreading centripetally into
the surrounding physiological coating of the tongue. Their formation is associated with the complete
loss of all 3-4 keratin hairs of filiform papillae. This erythema is preceded by excessive keratinization
(macroscopically, it looks like the focal whitish thickening of the mucosa) and the significant
desquamation of squamous-cell epithelium of hair-like prominences covered with bacterial colonies.
Spongy papillae are maintained and visible in the red patches. Such red foci can be circumscribed
with white margins along their perimeter where the above-mentioned process is proceeding, thereby
spreading the depapillated patches into the surroundings. In several hours or days, the filiform
papillae will restore quickly and red patches will disappear completely. Tendency to recurrence is
great. Besides familial occurrence, there are also infectious, psychogenic and neurohumoral factors.
Th.: Therapy is not possible, it is necessary to instruct the patient about the nature of the disease.
Dif. dg: It is important to distinguish the geographic tongue from the onset of atrophic glossitis. Major
differences are:
Geographic tongue..............................................................Smoothed tongue
 Smoothed patches are changing quickly
 Smoothed patches are changing very slowly
 Spontaneous reversibility of changes
 They do not disappear spontaneously
 The same intensity of changes
 Changes usually progress to the picture of
the smoothed tongue
 The surface area of the unaffected part of the tongue is normal  Papillae are also changed on other
parts, fissures, erosions or petechia may be present
 The transition of papillae has usually circumscribed, often rolled margins
 The transition of
papillae into smoothed areas is not sharp
31
 Most common in children and young individuals
 Common in adults and elderly
 General examination is usually negative
 Anemia, metabolic disorders or the use of
medicines are usually found during general examination
5.1.3 Fissured tongue (l. plicata, l. gyrata, l. scrotalis, l. cerebriformis, l. fissurata)
This condition belongs to a class of developmental disorders of nonspecific origin. It is an
abnormality in the formation of the dorsum of the tongue, sometimes associated with the general
enlargement of the tongue (macroglossia) characterized by the presence of symmetrical notches and
elevations determined by muscle fascicles (resembling cerebral convolutions). Changes are usually
asymptomatic and mostly stationary, and may sometimes progress with age. Some individuals
experience the enhanced sensitivity and burning of the tongue of different intensity, particularly at a
meal (often after the intake of alcohol).
Th: Therapy is not possible, it is important to instruct patients properly about the harmlessness of
changes (the possibility of cancerophobia)
Dif.dg: It may sometimes occur together with other diseases such as lues, TB, lichen ruber planus.
Facial nerve paralysis combined with granulomatous cheilitis constitutes the Melkerson-Rosenthal
syndrome.
5.1.4 Melkerson-Rosenthal syndrome
Its etiopathogenesis is still unclear. Besides a congenital disposition, a functional disorder of the
autonomous nervous system, inflammatory and allergic reactions to different microbial agents seem to
play a role. It usually occurs in younger individuals of both genders. A typical triad of symptoms is
found:
a) The fissured tongue with macroglossia
b) Facial nerve paralysis (usually the paralysis of a peripheral nerve, however, it can also be central
with unilateral tinnitus, vertigo, migraine headaches)
c) Recurrent oedema of lips (asymmetrical edema of both lips will transform into macrocheilitis in a
few days because of granulomatous inflammation. It usually spreads into the surroundings –
cheeks, eyelids, face including the forehead, auricles and neck. In the oral cavity, it affects the
buccal mucosa and spreads over to the tongue and the mucosa of the hard palate, hypertrophic
gingitivis is also present.
Organ symptoms such as dysphagia, aphonia, asthma attacks, megacolon, and the like are rare.
Remissions are rare.
Th: No causal therapy, Kenalog injections are applied, surgical therapy.
5.1.5 Median rhomboid glossitis (glossitis rhombica mediana)
It is characterized by the oval (or rhomboid) patch with a noticeably glossy, red surface (filiform
papillae are completely missing), localized in the rear part of the tongue dorsum (before circumvallate
papillae) in the central line. It is a congenital (the remainder of tuberculum impar), clinically nonsignificant condition which is currently classified as Candida-associated lesion (due to its coincidence
with yeast infection) (see Chapter 8.2.2.1).
Th: Sine
5.2 MACROGLOSSIA
32
Macroglossia means that the tongue is larger than normal. There are considerable individual
deviations –reliable diagnosis is possible when the difference in the size of the tongue is noticeable
and causes difficulties in a patient. The causes of macroglossia are very varied and can be congenital
or acquired.
5.2.1 Congenital abnormalities
Congenital macroglossia occurs due to the enlargement of the muscle component (macroglosia
muscularis) or it can present diffuse lymphangioma or hemangioma (macroglossia lymphangiomatosa
et hemangiomatosa). Partial macroglosia may be induced by struma lingualis or cysta ductus
thyreoglossus. Macroglossia can also occur in a number of other diseases – for example at cretinism
(congenital hypothyroidism – due to the massive accumulation of mucopolysaccharides in the muscles
of the tongue – the tongue may protrude out of the mouth) or Down syndrome.
5.2.2 Acquired abnormalities
Myxedema
Hypothyroidism is associated with the accumulation of mucous substances in the corium of the
skin and in the submucosa of mucous membranes. The skin is dry, pale, waxy solid and cold.
Noticeable swelling occurs particularly in the face in the area of the nose, lips and suborbital regions.
Mucopolysaccharides are accumulated similarly as in the case of cretinism and also into the muscles
of the tongue, which causes its enlargement.
Acromegaly
Acromegaly is caused by the overproduction of the growth hormone (somatotropin) after the
natural growth has finished. It is caused by eosinophilic adenoma of the pituitary gland which occurs
in women more frequently than in men (in the second or third decade of life - it can occur after
pregnancy or menopause). It is characterized by changes in the configuration of acral parts – facial
dysmorphic changes (rough contours, the enlargement of terminal parts). The enlargement of the
tongue is usually associated with the finding of fissured tongue (lingua plicata).
Amyloidosis
In primary amyloidosis (AL), amyloid can be deposited in the tongue (which is very rare), in its
muscles or vessel walls. Sometimes, prominent, tumour-like deposits can be formed at focal
deposition (not only in the oral cavity but also in the skin, eyes, and urinary bladder). The mucous
membrane of the dorsum of the tongue is smoothed, practically without papillae, the tongue has a
distinct yellow-grey colour. Patients with amyloidosis also show symptoms in the oral cavity.
Glycogenoses
Glycogenoses are disorders in the degradation or synthesis of glycogen caused by inherited
enzyme deficiency which results in the increased accumulation of glycogen in tissues. Depending on
the type and localization of the enzyme defect, different types of this disease can be recognized. For
example, the Pompe’s disease (Type II - maltase: 1,4-glucosidase is missing) is characterized by the
accumulation of glycogen in tongue muscles.
Syphilitic gumma
33
Gumma in Stage III syphilis localized in the tongue may cause its enlargement. The tongue is
enlarged irregularly and is usually lobed (lingua lobata), with cauliflower-like hyperplasia. The
mucosa of the dorsum of the tongue is smoothed, without papillae (the finding resembles deficiency
glossitis) but the furrowing of the tongue is absent!
Tumours
Tumours characterized by the enlargement of the tongue are not very common. They particularly
include lymphangioma (capillary, cavernous or cystic), sometimes with the multiple occurrence –
lymphangiomatosis. Hemangioma may also occur, being manifested as a blue spot shining through the
mucous surface (it is filled with erythrocytes), which is a differential diagnostic sign, as compared to
lymphangioma. The focal enlargement of the part of the tongue can also be caused by neurofibroma (a
tumour originating from Schwann cells) - as part of the Recklinghausen’s disease (neurofibromatosis)
in this locality.
5.3 TONGUE COATING
The tongue coating consists of the prominences of epithelial parts of filiform papillae that rise
above the niveau of the tongue mucosa. Other parts of the coating (scaled epithelial cells, cellular
detritus, saliva, bacterial flora and food residues) are its side components. The intensity of the tongue
coating is therefore determined by the condition of filiform papillae - their density, length and the
degree of keratinization. A number of processes participate in the formation of the tongue coating.
Factors such as temperature, food consistency, the intensity of chewing and tongue motor function
(particularly its decrease due to paralysis, unconsciousness, etc.) are important.
5.3.1 Physiological coating
This can only be found in healthy individuals. However, its intensity varies (increases or
decreases) even in healthy individuals, throughout the day and depending on the kind of a diet. The
most intensive coating can be found in the morning where scaled epithelial cells and microbes
accumulated through the night are present. In some conditions, the coating is pathological - either
pathologically enlarged or pathologically reduced.
5.3.2 Pathologically enlarged tongue coating
It results from the hypertrophy and extension of filiform papillae and the enhanced keratinization
of their epithelial prominences. Acute coating is formed quickly, usually in 24 hours after the onset of
a disease. It is usually one of the symptoms of severe acute diseases – severe infections (pneumonia,
meningitis, sepsis, scarlet fever) or diseases associated with shock (acute abdominal episodes, coma
conditions, serious myocardial infarctions). At these conditions, the self-cleaning function of the
tongue is stagnant, the body is dehydrated and a fever is present. The tongue is dry, with a very
intensive, brown-coloured coating - individual papillae look as if they were stuck together (forming a
crust). This is also called fuligo linguae. There are also other forms of the acute enlarged coating. For
example, the fresh, whitish coating can be found at herpetic gingivostomatitis or allergic conditions.
The tongue is wet (unlike fuligo).
Pathologically enlarged coating of the tongue that appears chronically is most frequently
associated with chronic conditions of the digestive tract. It is often called dyspeptic coating. However,
it can only be present at a certain stage of a gastrointestinal disease, in a period of the exacerbation of
the respective disease (dyspepsia, gastric ulcer, gastritis, etc.). The coating is not noticeable and its
34
intensity does not reach the intensity of acute coating. Hairy tongue (lingua villosa nigra) is a specific
type of chronically enlarged coating of the tongue.
Lingua villosa nigra
This condition is called “hairy tongue". It is the hyperplasia and hyperkeratosis of filiform
papillae which are arranged in such a way that their endings point towards the apex of the tongue.
Hypertrophy is the most significant around the median sulcus in the distal and medium third of the
dorsum of the tongue. Colouration (caused by chromogenic bacteria) is usually brown-black. Due to
coincidence with yeast infection, this condition of the tongue belongs to the class of Candidaassociated lesions (see Chapter 8.2.2.2).
5.3.3 Pathologically reduced tongue coating
There are a number of stages from the nearly normal coating through the coating in which filiform
papillae are void of their cornifying prominences to the coating with atrophic papillae. The tongue
coating can be absent either on the whole area of the tongue or only on some parts of the tongue. The
reduced coating is often associated with deficiency syndromes - vitamin B complex and iron
deficiencies, deficiencies associated with cachexia (due to liver cirrhosis, tumours). The reduced
coating of the tongue may occur at some drug-induced intoxication (for example gold or barbiturate
intoxication, etc.). The Möller-Hunter glossitis is most typical in pernicious anemia – see Chapter
5.4.3.
In summary, the tongue coating plays an important role in establishing the diagnosis. However, the
appearance of the tongue coating changes in different stages of a disease and respective changes are
not typical of any disease (for example, the raspberry tongue, which was described as a typical sign of
scarlet fever in the past, can also occur in other exanthematic diseases, for example measles). It is
only an indicator of the general condition of a patient at a particular moment. The dry, coated, brown
tongue is a sign of the poor state of health, indicating an acute risk for the patient (for example, it is
typical of shock conditions). If the disease deteriorates, the tongue coating will become crusty. When
the patient improves, the tongue coating will usually separate and the tongue will be smooth without
coating. Over the next 2-4 weeks, filiform papillae will regenerate and the mucous membrane will
become wet, which indicates recovery. The tongue without a coating (smoothed) indicates a metabolic
disorder or circulation deficiency (i.e. processes where oxygen supply in tissues is not sufficient). As
mentioned above, transitions may occur between both types at different phases of the disease.
5.4. INFLAMMATIONS OF THE TONGUE (GLOSSITIS)
The surface of the tongue can be divided into two parts according to the composition of the
mucous membrane. Changes in the base of the tongue are part of more diffuse changes in the lining
mucosa. The mucosa of the dorsum of the tongue is usually afflicted separately and the picture of
inflammation depends on its specific arrangement. Many changes on the tongue can be symptoms of a
large number of general diseases (atrophic glossitis can be due to anemia, avitaminosis, or toxic
effects). It is also necessary to evaluate the dynamics of changes (“migratory” changes in migratory
glossitis). In the case of the inflammations of the mucosa of the tongue, one has to distinguish
35
superficial inflammations (exsudative) that only affect the mucosa, and deep inflammations
(interstitial) that proceed in depth.
5.4.1 Overview of glossitis
Causes:
 Physical - Mechanical:
Objective finding
erythema, crevices, erosion, necrosis, ulcer (traumatic
glossitis)
- Thermal:
erythema, vesicula (erosion), necrosis, ulcer
- Electrogalvanic:
electrogalvanic glossitis
 Chemical - Chemical burning (acids, lyes): eschar (lyes – grey colour, acids – colour depends on
the kind of acid)
- Dyes, antiseptics:
lingua villosa nigra
- Other (smoking):
leukoplakia
 Infection - Coccal: streptococci
raspberry tongue (scarlet fever)
staphylococci
glossitis profunda, abscess of the tongue
- Viral :
glossitis at gingivostomatitis herpetica, herpes zoster
- Bacterial:
abscess, phlegmon, noma (when the body is weakened)
- Specific – TB:
ulcer – primary, secondary, tuberculoma
- syphilis:
primary – erosions, ulcer
secondary – erosions, plaques muqueuses (mucous
papule)+ opalines (opaline plaques), lisses
tertiary – gummata, lingua lobata
 Allergies:
- antigens originating from plants and animals, the Quincke’s edema, glossitis
venenata
Proteins from foodstuffs,
Chemicals, haptens:
 Non-classified units : Recurrent aphthae – blisters, erosions
Lichen ruber planus – white area
Erythema exsudative multiforme
5.4.2 Luetic interstitial glossitis (glossitis interstitialis luetica)
It is a typical symptom on the tongue in Stage III syphilis. It has two forms - superficial and deep where glossitis interstitialis luetica superficialis is manifested by the formation of prominent
infiltrates with leukoplastic changes in the squamous epithelium and with the formation of atrophic
patches, resulting in the “paving stone” pattern (usually having a whitish colour resembling porcelaine
– the glazed tongue). Deep inflammation (glossitis interstitialis luetica profunda) affects the whole
tongue which will become solid, enlarged (lingua lobata) and has limited mobility. It shows scarring.
Leukoplakia is formed on the mucosa. It is a precancerous condition which may result in squamouscell carcinoma of the tongue.
5.4.3 Glossitis associated with deficiency conditions
Any pathological change of the tongue is called glossitis, although this term specifically means the
inflammatory disease of the tongue, according to the terminology used in pathology. The more exact
term is glossopathy (or the tongue at deficiency). It describes the changes of the tongue caused by
36
nutrient, energy or vitamin deficiency. From an etiological point of view, this group of diseases is
very varied. Morphologically, the surface of the tongue is usually atrophic, smooth (sometimes glossy
- the papillae are missing). The tongue is often flaccid, reduced, with decreased tissue turgor, cervices
or ulcerations are sometimes present. The colour of the tongue depends on etiology – the colour is
light red in anemic patients, dark red in patients with liver cirrhosis, or violet at cachexia. Patients
usually report pain, burning sensation or itching of the tongue. Deficiency glossitis can occur in a
number of diseases with a negative metabolic balance - inflammatory diseases or tumours of the
gastrointestinal tract, malabsorption, impaired liver function (including alcohol abuse), uremia,
chronic cardiac insufficiency and many other conditions.
Th.: Different, depending on etiology
An overview of symptoms of vitamin A and B deficiency and iron (Fe) deficiency
Vitamin:
A
Participation in metabolism:
affects the synthesis of dehydrogenase enzyme
Objective finding:
hyperkeratinization of the epithelium
(+ retina)
B1 (aneurin)
carbohydrate cleavage
dry lips, lip scaling, red and swollen
tongue
B2 (riboflavin) a component of the Warburg oxygenase
exfoliative cheilitis, angular stomatitis
glossitis (purple), stomatitis
B3 (PP, niacin) a component of dehydrogenase
stomatitis, glossitis (reddening, swelling)
B6 (pyridoxine) a component of transaminases, carboxylases, decarboxylases
the effect
on vitamin B2 and PP deficiencies
B12 (cyanocobalamin) (Castle’s external factor)
Hunter glossitis (pernicious anaemia)
Fe
a component of haemoglobin, cytochromoxidase,
angular stomatitis, glossitis
myoglobin…
(the Plummer-Vinson syndrome)
Hunter’s glossitis (Möller-Hunter glossitis)
It is part of a characteristic picture of pernicious anemia (Addison’s anemia, Biermer’s anemia,
pernicious anemia), which is caused by Castle’s internal factor deficiency at irreversible atrophic
gastritis. The disease is usually manifested around the age of 50.
Clinical picture: General symptoms are due to the anemic syndrome characterized by paleness,
tiredness, weakness and dyspnoea on exertion that is accompanied with tachycardia and systolic
murmur. Myocardial hypoxia results in myocardial steatosis characterized by yellow stripes (tiger’s
heart). Clinically, the symptoms on the tongue are manifested by tongue’s paresthesias and burning
sensation, or impaired taste sensation. Three stages of the disease are recognized. The first, acute
stage is characterized by crevices, erosions and macular efflorescences on the tongue. In the second,
subchronic stage, the atrophy of filiform papillae is present. In the third chronic stage, atrophic
mucosa is observed. Similar changes also occur at megaloblastic anaemia of other etiology (for
example the total and partial resections of the stomach, malabsorption syndrome, Crohn’s disease,
extensive diverticulosis of the intestine or the resections of the terminal ileum where the absorption of
vitamin B12 takes place. Furthermore, it also occurs at absolute vegetarianism and during pregnancy
at folic acid deficiency. Atrophic glossitis can also be induced by some drugs, for example cytostatics.
37
People suffering with the relatively common neuroanemic syndrome show not only anemic but
also neurological symptoms such as tendon hyporeflexia, reduced muscle strength and uncertain gait.
In some cases, mental performance in these patients is also markedly lowered and disorders in
consciousness may also occur. Histologically, demyelinization in the posterior and lateral ligaments
or in spinal ganglia and peripheral nerves can be found.
Th.: Vitamin B12 is used, therapy is controlled by a specialist in internal medicine
Sideropenic anemia
It is caused by iron deficiency. It is typical hypochromic anemia. In most cases, it presents as
“loss” anemia after chronic bleeding (menorrhagia in women, bleeding from the GI tract or other
organs in both genders). Other etiological factors include the reduced intake of iron in a diet or
impaired iron absorption, or combination of both.
Clinical picture: Anemic symptoms (dyspnoea, tiredness, weakness, fainting, sensitivity to cold,
inability to concentrate, irritability, lowered performance, gastrointestinal symptoms, loss of appetite).
Atrophic glossitis occurs in the oral cavity with the disappearance of papillae. Subjective
manifestations include burning sensation or pain of the tongue (particularly after irritating meals).
Crevices and mucosal atrophy in the oral cavity or painful mouth corners may occur. Changes can
also be found on the mucosa of the esophagus which may be manifested as dysphagia. Symptoms that
occur on the mucous membrane in the upper part of the digestive tract during hypochromic anemia are
described as the Plummer-Vinson syndrome.
Plummer-Vinson syndrome (Patterson-Kelly syndrome)
It is characterized by the combination of hypochromic anaemia, dysphagia (at stenosing
esophagitis of the upper part of the esophagus), koilonychia (fragile spoon nails), changes in the oral
cavity and achlorhydria. Lesions in the oral cavity are identical with those found in patients with
sideropenic anemia with characteristic atrophic and furrowed mucosa of the tongue or the oral cavity
and pharynx and crevices or erosions of the mouth corners. Xerostomia is also present. On the basis
of these changes, leukoplakia and squamous-cell carcinoma often develop. This syndrome is therefore
considered as precancerosis. It affects particularly middle-age women.
Th.: Modification in a diet (a high content of iron). Iron can be administered orally (for example
Ferrum sulphuricum drg) or parenterally.
5.5. GLOSSODYNIA (STOMATODYNIA)
Glossodynia (or stomatodynia) is unpleasant sensation in the oral cavity whose objective reason is
not usually found at local examination. The burning sensation of the tongue is the most common
symptom (the term glossodynia was derived from it). Stomatodynia is a broader term than glossodynia
and is used in some situations where respective symptoms are localized at multiple sites in the oral
cavity. The symptoms can be associated with many different internal and external factors - hormone
changes, atherosclerosis, psychogenic effects, neuroanemic syndrome without mucosal changes, etc.
In a broader sense, stomatodynia includes conditions where objective changes can be found for
subjectively unpleasant sensations in the oral cavity, for example stomatodynia due to deficiency
conditions – the Plummer-Vinson syndrome, Sjögren’s syndrome, etc. In a more specific sense,
stomatodynia includes conditions where no pathological changes are found in the oral cavity and the
38
general examination is negative. This group includes stomatodynia resulting from psychogenic
effects, hormone disorders during menopause or at atherosclerosis. It occurs most frequently in
middle-aged women and older women at the age of 45-70 years (stomatodynia under the age of 30 is
rare). The origin of stomatodynia seems to be associated with the coincidence of several factors – the
body’s constitutional disposition (abundant sensitive innervation), regional disposition (neuropathic
or psychoneuropathic constitution), acute disposition (for example menopause in women) and a
triggering mechanism (this may include all pain or unpleasant sensations including dental treatment).
Clinical picture: The patient reports unpleasant sensation in the oral cavity such as paresthesia
(tingling, burning, itching, pain, dryness, bad taste). The objective finding on the mucous membranes
in the oral cavity does not correspond with the described symptoms, or is negative. The tongue is
affected in approximately 80% of cases, followed by mucous membranes of the palate. Other sites are
affected less often. Problems may migrate and their intensity may vary.
The detailed patient’s history may help establish the diagnosis (possible general disease), together
with the thorough examination of the entire oral cavity (the examination of teeth, prosthetic
replacement, galvanic currents, microbiology), general (consultation with specialists including
clinical, psychiatric or neurological examination) and laboratory tests (blood count, biochemical
parameters, the levels of iron in plasma), X-ray of the cervical spine and jaw joints. For example, nontypical forms of glossopharyngeal neuralgia may manifest themselves only by pain of the tongue.
Th: Glossodynia (or stomatodynia) should be considered a symptom rather than a disease because it is
common to a number of pathological conditions. Since it is a symptom which can be induced by
multiple factors, it is necessary to focus on the elimination of the cause (for example galvanic
irritation) or the treatment of the basic internal disease (such as pernicious anemia). If the cause
cannot be found, the effect of vitamins, anabolics, physical therapy, sedatives and psychotherapy is
tested.
GINGIVITIS
It is described in the text book of periodontology.
STOMATITIS
It is the inflammation of the mucosa in the oral cavity. It is discussed in some subchapters in
Chapter 8 (Mucosal lesions in the oral cavity with characteristic findings)
6 DISORDERS OF SALIVA SECRETION
6.1 FUNCTIONS OF THE SALIVA
Reduced saliva secretion is the most common disorder of saliva secretion whereas increased saliva
secretion occurs less often. In order to gain deep insight into the consequences of insufficient
salivation, let us make a brief overview of the functions of saliva:
a) Lubrication – saliva helps soften the food in the mouth so it is easier to break down the food into
small pieces, chew and swallow them. It also makes speaking easier, washes oral tissues and
protects the teeth against damage;
b) Digestion and taste – saliva contains digestive enzymes (amylase and lipase) that initiate the
cleavage of starches contained in food. It enables us to feel the taste of a meal and other
substances.
39
c) The repair of soft tissues – Epidermal growth factor (EGF) and transforming growth factor (TGF)
found in the saliva support the growth and differentiation of tissue and wound healing.
d) Maintaining the healthy equilibrium of the oral microflora – saliva contains different
antibacterial, antiviral and antimycotic factors which maintain the microbial equilibrium and
inhibit the bacterial colonization of teeth and soft tissues by modifying the adherence of
microorganisms.
e) Buffer capacity – Saliva has the capacity to decrease the acidic pH and maintain the pH at an
adequate level, which lowers the risk of caries. Saliva also protects the upper part of the
gastrointestinal tract by buffering the acid reflux and regurgitation from the esophagus.
f) Remineralization – Saliva protects the teeth and supports the remineralization of the dental
enamel because it contains essential minerals, increasing the uptake of minerals into the
demineralized enamel.
g) Immunity and defence – small proteins, IgA, defensins, cytokines, growth factors, hormones,
mucins and other saliva components can play a role in the body’s natural immunity and defence.
Non-specific defence reactions are associated with the presence of a large number of antibodies
and enzymes in saliva (lysozyme – cationic protein that cleaves the components of bacterial cell
walls, lactoferrin – glycoprotein that binds free ferric ions which are necessary for the growth of
bacteria). Saliva also contains naturally occurring substances with antiviral effects (leukocyte
protease inhibitor, lactoperoxidase, etc.). The complement system also contributes to immunity
with its major cytolytic activity and participates in phagocytosis (opsonization) and inflammatory
reaction. The cellular component of non-specific immunity is represented by phagocytosis
mediated by the cells of the oral mucosa (polymorphonuclear leukocytes, macrophages and
Langerhans cells which are also antigen-presenting cells in the oral mucosa - important for
specific immune response). The main specific defensive mechanism of the oral mucosa is
represented by the production of sIgA (the IgA dimer). Its molecules are connected via a linking
chain. In addition, it bears a secretion component consisting of glycoprotein, which serves as
transmembrane receptor of polymeric immunoglobulin IgA (and also IgM) and enables sIgA to be
transported through the epithelial cell (transcytosis) and thus protected against proteolysis.
6.2 SALIVA SECRETION
Saliva is secreted by three pairs of large salivary glands and a great number of small mucosal
glands. The permanent moisture of the oral mucosa is maintained by small glands that release saliva
permanently. In contrast, large salivary glands secrete saliva upon a stimulus. Stimuli for saliva
secretion usually come from the oral cavity where there are mechanoreceptors and chemoreceptors.
Saliva secretion at physiological conditions depends on a degree of the activity of vegetative nervous
system whereas this activity largely depends on a degree of masticatory action. Saliva secretion from
the parotic gland is serous whereas sublingual and submandibular glands produce mixed saliva. As
mentioned above, salivary glands are innervated by the autonomic nervous system. Parasympathetic
fibres entering the submandibular and sublingual glands come out of the intermediate nerve, they run
together with the facial nerve and reach the glands through the chorda tympani and the lingual nerve.
Parasympathetic fibres for the parotid gland come from the glossopharyngeal nerve and enter the
gland via the auriculotemporal nerve. Sympathetic fibres enter the glands together with vessels. The
salivary nucleus is the salivary centre in the medulla oblongata with the control centre in the
hypothalamus. The stimulation of the parasympathetic nervous system increases the production of
40
saliva, whereas anticholinergic drugs decrease saliva secretion. The stimulation of the sympathetic
nervous system induces the secretion of dense saliva.
6.3. DISORDERS OF SALIVA SECRETION
Disorders of saliva secretion, particularly those that concern the quality of saliva are manifested
in a number of diseases of oral mucosa.
6.3.1 Ptyalism (sialorrhoea)
It is an increase in saliva secretion which may also occur at physiological conditions on the basis
of conditioned reflexes (pleasant in most cases – stimulating the taste, smell, sight, hearing - the
Pavlov’s reflex). The increased secretion of saliva is observed during pregnancy due to hormone and
neurovegetative changes occurring in this period.
Infections are among the major pathological causes. Many cases of acute stomatitis are associated
with reflex hypersalivation, being sometimes accompanied with pain and difficulties swallowing. It
disappears spontaneously with the healing of mucosal affliction, and requires no therapy. Sialorrhoea
can also be a symptom of injuries to the mouth and salivary glands or their outlets. Hypersalivation
can also be caused by intoxication with the salts of some heavy metals (mercury, arsenic, lead) or
central nervous system diseases (hemiplegia, bulbar paralysis). Some drugs (pilokarpine, prostigmin,
iodides, etc.) can also enhance saliva secretion.
Th: Therapy is not necessary in some cases – symptoms disappear spontaneously after the elimination
of infection. Otherwise, causal therapy is used according to etiology. Symptoms are treated by the
administration of atropine.
6.3.2 Reduced saliva secretion (hyposialia)
Saliva secretion decreases in many pathological conditions. The lack of saliva is typical of the
congenital aplasia of salivary glands. Reduced saliva production occurs in individuals with deficiency
conditions (severe anemia, avitaminosis) or metabolic disorders (diabetes mellitus, hypothyroidism,
liver cirrhosis, etc.), affecting not only saliva production but also the release of HCl, with the
symptoms of hypoacidity (anacidity). Hyposialia can also be present in advanced atherosclerosis; it
was reported to occur due to a decrease in secretion stimuli or the involution of salivary glands.
Unconditioned secretion is usually affected to a larger extent. A major decrease in saliva secretion is
observed at radiation-induced mucositis associated with the disappearance of small mucosal glands in
patients with tumours who underwent radiotherapy in the region of the head and neck. Hyposialia also
occurs at infections of the oral mucosa, primarily only at acute erythematous candidiasis associated
with dysmicrobia of the gastrointestinal tract, and in patients in whom the mucosal disease coincides
with drug-induced hyposialia (psychopharmaceuticals, parasympatholytics, non-selective
antihistamines, etc.). It is also observed in patients with a high fever at acute general diseases (not
only a decrease in the reflexive production of saliva but also dehydration play a major role). It is
relatively common in HIV-positive individuals (the question is whether it is due to the primary
affiction of salivary glands or due to drug-induced hyposialia).
The production of saliva can decrease in a different range. Due to large interindividual variability,
hyposialia is usually suspected when subjective problems have appeared. The objective finding of the
lack of saliva is usually made when changes in saliva production are significant - the Škach’s test:
41
The examined person will spit the saliva accumulated in his/her mouth for a period of 15 minutes into
a calibrated cylinder. Saliva must not be swallowed or aspirated by the patient. The saliva collected in
this procedure is called the rest saliva. The patient will then chew a paraffin tablet and spit the
accumulated saliva into a container for another 15 minutes (stimulated saliva). Both values are
measured and combined. The lower limit of normal range is 8-10 ml of saliva for two times 15
minutes. The values below 8 ml are pathological.
6.3.2.1 Xerostomia
Hyposalivation results in the constant feeling of dry mouth (xerostomia) and many other problems
such as difficulty chewing and swallowing (particularly dry pieces of food), increased sensitivity to
spiced foods, bad taste, burning or pain, pain of salivary glands, or difficulty speaking. At mild
hyposalivation, the oral mucosa seems to be clinically normal, at serious hyposalivation, it shows
objective changes (dry mucosa combined with atrophy, erythema, crevices; the tongue is usually
smoothed, dried, and matt and glossy as wax). It may also affect the lacrimal glands causing the
corresponding eye symptoms of dry keratoconjunctivitis.
Etiology: There are many factors (acute and chronic) that may cause xerostomia:
a) Congenital hypoplasia or aplasia of salivary glands
b) Inflammations of salivary glands – particularly epidemic parotitis, TB, sarcoidosis,
actinomycosis
c) Tumours - primary tumours of salivary glands or secondary infiltrations in the case of other
tumours
d) Outlet obstruction – lithiasis, tumours, inflammatory changes
e) Salivary gland atrophy – senile, post-radiation changes
f) Autoimmune diseases – Sjögren’s syndrome, Mikulicz syndrome
g) Medication – anticholinergic agents, opiates, ergotamine and a number of other medicines
h) Other factors – dehydration, vitamin deficiency, diabetes mellitus, hypothyroidism, anemia,
advanced atherosclerosis, emotional disorders (depression), etc.
Th: The elimination of cause, otherwise symptomatic therapy. The production of saliva can be
stimulated using some medicines such as pilocarpine (alkaloid with a parasympatomimetic efect): Rp.
Sol. Pilocarpini chlorati 2% aquosae ml 25,0. M.D.S. 3x4 drops daily). The effect differs among
individuals, therapy may induce adverse cardiovascular effects (discontinuation!). The reflexive
stimulation of saliva production can be used by sucking sugar-free candies, chewing gums, or by
frequent drinking liquids (free of caffeine, alcohol and sugar). If therapy fails, substitution with
artificial saliva is necessary.
Sjögren’s (sicca) syndrome.
It is a chronic autoimmune disease whose pathogenesis is probably associated with HTLV-1
viruses and affects lacrimal, salivary and other exocrine glands, causing a decrease in the production
of respective glands. The disease usually occurs in women at the age of 40-50 years and is
characterized by xerostomia and dry keratoconjunctivitis. New, clinical, serological and genetic
criteria were applied to distinguish two forms of the disease: primary and secondary. The Sjögren’s
syndrome can be a primary disease, when it is not accompanied with a disease of the connective tissue
(collagenoses), or a secondary disease, when it coexists with other diseases of connective tissue such
as rheumatoid arthritis, SLE, polyomyositis, or with primary biliary cirrhosis, thyroiditis or vasculitis.
Apart from eye symptoms such as keratoconjunctivitis sicca, and joint symptoms (progressive
42
polyarthritis is common), there are also symptoms in the oral cavity, including insufficient salivation
causing difficulties swallowing solid meals and speaking. Major symptoms of xerostomia manifest
themselves on the tongue where they can cause the atrophy of filiform and fungiform papillae
resulting in the smoothed tongue. The oral mucosa can be red and dry. Lips are also affected, being
crusty and dry with the desquamation of superficial layers of the epithelium. Angular cheilitis and
increased cariosity of teeth are present. Parotic glands in some patients are enlarged. The prognosis is
uncertain. The Sjögren’s syndrome is (together with helicobacterial gastritis and Hashimoto’s
thyroiditis) reported to be a precancerosis of B-MALT lymphoma.
Dg: The biopsy of the lower lip is used to identify a mononuclear infiltrate with periductal
distribution in patients with primary SS and perivascular location in the case of secondary SS.
Sialometry is used to measure the production of saliva (the Škach’s test). Similarly, the decreased
secretion of the lacrimal glands can be determined by the Schirmer’s test, or by using specific
staining. Saliva production can also be examined using scintigraphy and immunological evidence of
different species of autoantibodies. Sialography is used to examine the condition of the parenchyma,
outlets and function of the salivary gland.
Th: Symptomatic therapy, every piece of food should be received with liquid (particularly when the
food is dry), maintaining perfect oral hygiene (preventing new dental caries), the stimulation or
substitution of saliva production (see above – Xerostomia), the protection of the cornea using
artificial tears. When the Sjögren’s syndrome is part of a systemic disease, it is treated within
complex therapy.
Dif. dg: Similar symptoms in the oral cavity can occur at chronic interstitial sialoadenitis which
affects the submandibular salivary gland, resulting in the sclerotization of the parenchyma with major
lymphocytic infiltration (it is often confused with neoplasia – the Küttner’s tumour).
7 HALITOSIS (FOETOR EX ORE, BAD BREATH)
Halitosis or foetor ex ore is a term used to describe very intensive odour coming out of the oral
cavity. It is a symptom to which a number of local, intraoral causes as well as extraoral factors
contribute due to pathological changes in the nasopharynx, nasal cavities, lungs, or due to odour from
eaten food.
A) Local causes:
 Mouth: - improper hygiene, dental plaques, gangrenous teeth, periodontal sockets
- the retention of food residues in carious teeth, or under the prosthesis
- mucosal diseases: ulcerative gingivostomatitis, post-extraction decay of the coagulum,
ulcerating tumours, etc.
 Nose: chronic rhinitis and sinusitis (particularly ozaena), tumours
 Nasopharynx: angina, pharyngitis (particularly chronic atrophic forms)
 Esophagus: diverticles, strictures, decayed tumours
 Lungs: bronchiectasis, pulmonary abscesses
B)



General diseases:
Diabetes mellitus (acetone odour)
Uremia (ammonia)
Lead intoxication (sweet metallic)
43
After some foods and beverages (onion, garlic, alcohol), the odour originates from the metabolic
products absorbed from particular foodstuffs in the GI tract and subsequently excreted from the blood
circulation in the lungs.
Th: Causal therapy to identify and eliminate a particular cause. Compliance with the proper hygiene
of the oral cavity, perfect dental treatment, adequate therapy in the case of diseases. The local use of
deodorants and antiseptic products (hydrogen peroxide, chlorhexidine in commercially available
products).
8
MUCOSAL LESIONS IN THE ORAL CAVITY WITH CHARACTERISTIC FINDINGS
8.1 PIGMENTATION – DIFFERENTIAL DIAGNOSTIC REMARKS
Hyperpigmentations of the oral mucosa are usually found during dental examination by chance.
They are not usually associated with subjective problems. They differ in etiology, appearance,
localization and prognosis. Generally increased pigmentation (melanoplakia) due to the enhanced
production of melanin in the skin and mucosa can be found in some races (Arabs, Romani).
Physiological pigmentation also presents as freckles (ephelides) that may occur not only on the facial
skin but also on the lip red. They are never found in the oral cavity! Enhanced pigmentation of the
facial skin is often seen in pregnant women – chloasma gravidarum.
Pigmentation in the oral cavity is among pathological changes associated with many diseases:
8.1.1 Addison’s disease
Primary adrenal hypofunction caused by the destruction of the adrenal cortex is characterized by
general symptoms (hypotension, disorders in metabolism of electrolytes), diffuse hyperpigmentation
of the skin (or hyperpigmentations in the genital area, human nipples (areola mammae)) and focal
grey-black pigmentations (graphite spots) on the mucosa of the oral cavity, particularly on the buccal
mucosa in the area of molar teeth and along the tongue. The increased production of ACTH and MSH
(or their common precursor propiomelanocortin, to be specific) is responsible for the increased
hyperpigmentation of the skin and oral mucosa, particularly in the area of mechanical irritation. No
hyperpigmentations occur at secondary adrenal insufficiency (hypothalamic and pituitary diseases).
8.1.2 Bronchogenic lung carcinoma (and some other forms of malignant tumours)
Some malignant tumours can be associated with melanotic changes on the palate that originate
from the same mechanism due to the ectopic production of the common precursor of ACTH and
MSH.
8.1.3 Peutz-Jeghers syndrome (Peutz-Tourain-Jeghers-Klostermann syndrome)
Autosomal dominant inherited phacomatosis (a tumour syndrome accompanied with skin
symptoms) that affects both genders at the same rate. It is hamartomatous polyposis of the digestive
tract (usually affecting the large intestine), being accompanied with mucocutaneous, predominantly
oral focal hyperpigmentations. These melanotic (dark brown), well circumscribed spots are usually
located around body orifices such as the eyelids in the face, nasal openings, the mouth, sometimes on
the lip red, buccal mucosa, labial mucosa, tongue mucosa or palatine mucosa. Polyps in the digestive
tract can cause acute abdominal episodes or bleeding into the GIT. Due to the increased rate of
carcinoma not only in the GIT but also in the uterus, ovaries, breast and testicles, this syndrome is
ranked among precanceroses and skin (and mucosal) paraneoplasias.
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8.1.4 Acanthosis nigricans
It is papillomatous-verrucous, focal, melanin-pigmented disease of the skin or mucosa that can
occur in two variants: benign and malignant. Benign variants can be classified as follows:
1) A genetic type manifesting itself in childhood or early adulthood, rarely affecting the oral cavity
(in 10-15%)
2) Acanthosis nigricans as part of syndromes (Prader-Willi, Bloom) which also occurs in childhood
and does not affect the oral mucosa, and
3) Pseudoacanthosis – it often occurs in obese individuals who have a darker discolouration of the
skin. It is only manifested on the skin.
Malignant acanthosis nigricans has a character of a paraneoplastic process and can be observed in
more than 50% malignancies of the stomach and large intestine. From a diagnostic point of view, it is
important to point out that it may occur one year before the manifestation of the tumour. Facial
symptoms are usually symmetric, affecting the lips, tongue (macroglossia) and buccal mucosa. The
lesion is not well circumscribed, usually consisting of patches with a rough surface. Similar lesions
can also occur on other mucous membranes (for example on the conjunctiva, rectal mucosa).
8.1.5 Hemochromatosis
It is a rare, autosomal recessive disease with excess resorption and deposition of iron in the body.
It particularly occurs in middle-aged men. The clinical picture shows both skin and mucosal
hyperpigmentations of a dark bronze-red to brown discolouration caused by the accumulation of
hemosiderin and hemofuscin. Furthermore, hepatomegaly, liver cirrhosis (which progresses to
hepatoma in one fourth of patients) and diabetes mellitus ("bronze diabetes“) are present.
8.1.6 Porphyria
This group of diseases includes disorders of porphyrin metabolism that cause the overproduction
of porphyrins and their precursors. Each variant of this disease is characterized by deficiency in a
specific enzyme that is needed in heme biosynthesis. Depending on the site (tissue) of the abnormal
synthesis of porphyrins, porphyria can be classified into 3 major groups (with multiple subgroups):
erythropoetic, hepatic and mixed. Among typical findings are skin photosensitivity with increased
skin fragility, the formation of erythema, vesicles or bullae, erosions, hyperpigmentations and
hypertrichosis. The mucosa of the oral cavity is rarely involved, lesions are a cinnabar colour,
occurring on the lips, in commissures, on the vestibular mucosa and the gingiva.
8.1.7 Pigmented naevi
Pigmented naevi on the lips and oral mucosa, particularly on the palatine mucosa, are quite
uncommon. They also occur in younger age groups (in children). However, they prevail in individuals
at the age of 30-40 years. They do not vary in a long-time perspective and can differ by colour (blue,
brown, black, amelanotic forms are also common).
8.1.8 Precancerous circumscribed melanosis (Melanosis circumscripta praeblastomatosa
Dubreuilh)
Dubreuilh’s circumscribed melanosis rarely occurs on the lips and oral mucosa and always
transforms into a malignant melanoma. It is typically manifested by a dark, central, melanotic spot
(usually on the palate and the lower alveolus), with small satellite lesions that can differ in colour,
being partially indistinctly circumscribed, and quickly changing their appearance.
45
Dg. It can only be verified by histological examination as in the case of malignant melanoma.
Th: Surgical
8.1.9 Malignant melanoma
It occurs in the oral cavity very rarely (1% of all malignant tumours in this area). It usually occurs
on the palate or in the alveolar process of the upper jaw, in all age categories, with a higher incidence
rate in men. It originates from a pre-existing pigmented lesion that becomes malignant or develops "de
novo”. A typical feature is that it develops suddenly and quickly (weeks-months), progresses into the
surroundings, shows solid consistency and often presents exulcerations of the existing melanocytar
lesion.
Dg.: The pathologist will decide on the nature of the lesion on the basis of morphological signs from a
biopsy (the signs of malignancy include multiple mitosis, enhanced proliferation activity and
circumscribed inflammatory reaction).
Th.: Surgical; excision must have a broad “safety margin” in the healthy tissue for preventive reasons.
8.1.10 Exogenic pigmentation
It is caused by heavy metals or their salts that enter the body orally, parenterally, by injury or via
blood or lymph.
Lead
Chronic lead poisoning is very characteristic. Lead binds to red blood cells (basophilic stippling
of erythrocytes, determined by lead (II) phosphate on their surface) and accumulates in all organs and
particularly in bones. In the oral cavity, insoluble lead (II) sulphide forms a grey or blue-black margin
on the gingiva which cannot be removed mechanically. Other symptoms include metallic taste in the
mouth and increased salivation.
Bismuth
In the past, bismuth compounds were used in the treatment of syphilis. The finding in the oral
cavity was manifested by the characteristic grey-blue discolouration of the marginal gingiva,
resembling mercury poisoning. Bismuth intoxication is very rare today.
Mercury
Mercury poisoning (mercurialism) occurred during the treatment of syphilis in the past.
Nowadays, it can be caused the inhalation of mercury vapours. One characteristic finding in the oral
cavity is the presence of stomatitis with increased salivation and a grey-blue discolouration of the
gingiva. Metallic taste can also occur.
Gold
Gold accumulates in tissues upon the long-time application of injections containing colloidal gold
solutions that are used in the treatment of rheumatoid arthritis. It causes a typical blue-violet
discolouration of the gingival mucosa (chrysocyanosis).
Silver
It is received via a meal or as a component of amalgams or prosthetic metal alloys (Koldan,
Aurix) during therapeutic use. It may result in argyrosis – a distinct grey discolouration of the skin
and gingiva. Hyperpigmentations have a bluish colour even at the posttraumatic tattoo of the oral
46
mucosa. The metal can be detected in soft tissues by X-ray. It should be pointed out that except for
amalgam tattoos that are unambiguous, it is necessary to perform a histopathological examination of
dark pigmentations of the lips and oral mucosa, particularly when they are located on the palate or on
the upper alveolar process.
8.2 WHITE PATCH SYMPTOM - DIFFERENTIAL DIAGNOSTIC REMARKS
The most noticeable clinical symptom of diseases in this group is the presence of whitish patches
on the mucosa of the oral cavity. The origin of these white patches is not identical - they can be the
colonies of microorganisms (usually yeast), or the thickened epithelium with an enlarged, cornified
layer or they can be due to a congenital disease. Since the nature of such manifestations is very
different, the classification of individual subunits, which differ both etiologically and
pathophysiologically, to one group can only be done for the purpose of differential diagnosis and for
the fact that they look clinically almost the same and cannot be distinguished without more detailed
examination.
The group of diseases characterized by whitish patches on the mucosa of the oral cavity includes
leukoplakia, localized soor, lichen ruber planus, naevus spongiosus albus and less common diseases
such as some drug-induced exanthema of lichenoid type, lupus erythematosus and psoriasis.
8.2.1 Leukoplakia
According to the macroscopic picture, leukoplakia as a clinical term to include a number of
different conditions whose common sign is a “white patch” (leukos = bílý). Currently, leukoplakia
means white spots or patches of different appearance that cannot be characterized as some of the
above-mentioned diseases. The definitive diagnosis of oral leukoplakia can be established after the
evaluation of a macroscopic finding, potential etiological factors and histological examination. In
general, leukoplakia is the keratinization of mucous membranes that are normally covered with the
non-keratinizing squamous epithelium. White patches can occur anywhere on the mucosa. The buccal
mucosa is a predilection site. Generally, the following types of leukoplakia can be recognized:
homogenic – white lesions with the smooth folded or cracked surface; non-homogenous that can be
verrucous, nodular, ulcerating or erythroplakia. “Hairy leukoplakia" is a specific unit as it occurs
mainly in HIV-positive individuals and usually affects the edge of the tongue. The etiology of
leukoplakia is very varied. Etiological factors include various irritating factors inducing chronic
inflammation or contributing to the development of carcinoma into which leukoplakia may be
transformed. Factors can be mechanical (dental caries, unsuitable prosthesis, injuries due to cheek
biting, etc.), chemical, electrogalvanic or actinic factors. Tobacco use is also one of the factors - the
effect of side products of smoking. The highest incidence rate is among men at the age of 40-60 years.
Malignant transformation of leukoplakia varies in a range of 3-6%. The development of malignancy
depends on a combination of factors - local irritation combined with general factors and the
predisposition of an individual. Verrucous and erosive leukoplakia have a higher risk of
transformation into carcinoma (up to 30% of erosive leukoplakia may transform into carcinoma).
Th: The method of therapy of leukoplakia depends on the clinical and histological picture. In the case
of plain hyperkeratosis, it is usually sufficient to eliminate irritating factors and stop smoking (some
47
will disappear over time). However, it is necessary to perform a regular follow-up (every 6 months) of
leukoplakic lesions, or recommend a surgery when the finding is still present. In the case of nonhomogeneous forms, a radical surgical approach is necessary since the risk of malignant
transformation for these forms is high - particularly when the histological finding shows epithelial
dysplasias in a diagnostic tissue excision.
8.2.2 Candidiasis (moniliasis, soor, thrush)
It is an inflammatory (fungal) condition. The predilection site is the oral mucosa from which it
may spread to the mucous membrane of the pharynx, esophagus or airways.
Etiology: The disease is caused by yeast (usually yeast of the Candida genus such as C. albicans, C.
glabrata, C. tropicalis) which is a saprophyte of the oral cavity at normal conditions (in 40-50% of
healthy individuals in our population). Yeast can overgrow in predisposed individuals with lowered
local or general immunity. A number of predisposing factors (physiological - gravidity,
pathophysiological - trauma, chemical injury to the mucosa, severe infections, endocrine disorders diabetes mellitus, malabsorption, blood diseases - leukemia, agranulocytosis, aplastic anemia,
medicines from certain groups - immunosuppressants, corticoids, cytostatics and broad-spectrum
antibiotics that also inhibit the growth of other microorganisms). Some properties of yeast play an
important role in the pathogenesis, for example yeast’s ability to adhere to the surface of the oral
mucosa (as well as to the surface of plastics) or grow in the epithelial covering of the oral mucosa.
This results in transformation from the saprophytic into the parasitic mode of existence. Many local
and general factors are involved in this process. Their number is increasing, which increases the
number of predisposed individuals (and those who are at risk).
Clinical picture is very varied. There are many clinical forms that may not always have the
characteristic appearance of a disease belonging to a group of diseases of the oral mucosa called “the
white patch syndrome”.
Acute pseudomembranous candidiasis is the most common, typical form of oral candidiasis. It
develops abruptly, being manifested by the formation of whitish, partially removable coatings pseudomembranes (resembling precipitated milk) that are produced by yeast colonies. They do not
have a typical predilection site in the oral cavity. Their occurrence on the gingiva is not typical. The
growth of pseudohyphae into the superficial layers of the mucosal epithelium results in the strong
adhesion of coatings to the mucosa. After they are peeled off, the mucosa will bleed and erosions will
develop on the mucosa. The mucosa of the oral cavity in the surroundings of coatings has a distinct
red discolouration. Subjective difficulties are varied including a burning sensation, increased
sensitivity or pain of the affected mucosa, impaired taste sensation. Painful swallowing indicates the
progression of fungal infection into the swallowing routes. If the inflammation does not heal
spontaneously (or after therapy), it may progress to the chronic stage or to the dissemination or
generalization of the process.
Acute erythematous candidiasis usually develops due to dysmicrobia in the oral cavity or GIT, as a
result of therapy using broad-spectrum antibiotics. Clinically, it presents as diffuse reddening of the
mucosa (without pseudomembranes) associated with burning sensation, pain and dryness in the oral
48
cavity. Mycotic angular stomatitis (anguli infectiosi) can be present. It disappears quickly at adequate
therapy (with the simultaneous modification of microflora in the digestive tract).
Chronic pseudomembranous candidiasis is another form of yeast-induced inflammation. It is a
severe disease of the oral mucosa with a risk of the dissemination and generalization of the process. It
particularly affects immunodeficient and cancer patients. It is usually vast and spreads into the
oropharynx and other parts of the swallowing and respiratory routes. Subjectively, there are only
difficulties swallowing. It does not usually heal spontaneously; the success of therapy depends on the
patient's general condition and the efficacy of antifungal therapy.
Chronic hyperplastic candidiasis is a less common form of oral candidiasis. It is always a long-time
disease (months - years) and can occur within chronic mucocutaneous candidiasis, particularly in
individuals with congenital immunological abnormalities. It occurs in childhood and is usually
associated with some polyendocrinopathies, for example with the simultaneous hypofunction of the
adrenal cortex and parathyroid gland, or myasthenia. Subjective problems are minimal, or can be
absent in some cases, which is in contrast to the major extent of the disease (white patches that cannot
be removed, usually occurring on the buccal mucosa and tongue with calm surroundings, without
reddening). Therapy is difficult since the disease is refractory to treatment.
Chronic erythematous, atrofic candidiasis - It usually occurs as prosthetic stomatitis in individuals
with removable dental prosthesis. The mucosa of the prosthetic bed is usually diseased, showing
massive hypertrophy or papillomatous hypertrophic mucosa. This form tends to recur - probably, it is
constant reinfection where the prosthesis serves as a reservoir of yeast. The optimum solution is to
make a new dental prosthesis and prevent the development of oral candidiasis through the proper care
of the prosthesis. The mucosa on the dorsum of the tongue is another common site of chronic atrophic
candidiasis. It has a distinct red discolouration, without a coating, sometimes showing papillomatous
hypertrophy with calm surroundings.
Angular candidiasis affects the mucosa of mouth corners alone or in combination with a more
extensive affliction of the oral cavity. Its typical symptoms include crevices and red patches with an
indistinct, white margin of the labial mucosa, usually bilaterally. Deep defects such as fissures are not
usually formed, being accompanied with bleeding or purulent exsudate and crusts. Bacteriological
tests usually reveal Staphylococcus aureus. Patients also show the decreased height of occlusion in the
defective dentition with unsatisfactory dental prostheses. The maceration of mouth corners with saliva
causes symptoms to aggravate further. In children, secondary streptococcal infection (impetigus) may
occur and spread into the surrounding facial skin.
In countries with a higher incidence rate of HIV-positive individuals and patients with AIDS
symptoms in the oral cavity, the clinical spectrum of oral candidiasis becomes broader. Oral
candidiasis is a typical symptom of AIDS in the oral cavity, characterized by the formation of whitish
margins and pseudomembranes on the gingiva. Symptoms of yeast infection are combined with other
infectious and non-infectious pathological manifestations. Causative agents can include Cryptococcus
neoformans, Histoplasma capsulatum, Blastomyces dermatidis, Rhyzopus oryzae and R. arrhizus.
Manifestations of oral candidiasis also include other, less common diseases of the lingual mucosa that
are - together with prosthetic stomatitis - referred to as “Candida-associated lesions”.
8.2.2.1 Median rhomboid glossitis (Glossitis rhombica mediana, Brocq-Pautrier glossitis)
It is a red, smoothed patch of oval, rectangular or rhomboid shape on the mucosa in the central
third of the tongue dorsum (before circumvallate papillae). Its surface is noticeably smooth, glossy
49
and red. The physiological coating consisting of filiform and spongiform papillae is absent in this
zone. The mucosa can be more sensitive or painful on touch during eating a meal or speaking. The
disease occurs in adulthood, its origin is not yet known (the yeast of the genus Candida in
combination with other etiological factors – mechanical irritation?, congenital abnormalities?). It can
result in cancerophobia. However, the smear test mostly reveals yeast.
Therapy is difficult – to stop smoking and eliminate mechanical irritation, the administration of
antimycotics (local or general).
Dg.: By using differential diagnosis, it is necessary to distinguish the mechanical irritation of the
tongue dorsum, geographic tongue (lingua geografica), acute erythematous candidiasis, herpetic
glossitis (glossitis herpetica) and hemangioma.
8.2.2.2 Black hairy tongue (lingua villosa nigra)
It is caused by dysmicrobia in the GIT or in the oral cavity, with subsequent overgrowth of yeast.
This condition is quite common in patients after the prolonged use of antiseptics, in smokers or at
poor hygiene. In occurs in adulthood and is rare in children. A massive yellow or brown-black coating
is formed within a few days on the central third of the tongue due to hypertrophy, hyperkeratosis and
hyperpigmentation of filiform papillae. Subjective problems are usually absent.
Th: Therapy is based on the application of local antimycotics in combination with the mechanical
removal of the coating using a scraping spoon, toothbrush (wiping using a swab - the procedure can
be unpleasant and painful). Nicotinamide can be applied generally (if nicotinamide deficiency is
assumed because its biosynthesis by microorganisms in the GIT was disturbed), patients are advised
to quit smoking.
Dif. dg: Malignant acanthosis nigricans
Examination: The diagnosis of candidiasis with or without a membrane is based on the clinical
appearance, mycological examination (microscopy, cultivation), histopathological proof of yeast,
serological and immunological examinations. Medical records in the patient’s history are also
important (general diseases, therapy-using ATBs, immunosuppressant).
Therapy: Antimycotic therapy (local and general) of oral candidiasis should be combined with the
elimination or treatment of predisposing diseases, if possible. The attending physician should take
into account the severity of clinical symptoms, the state of patient’s health and sensitivity of yeast to
antimycotic treatment. Local therapy is always sufficient at angular candidiasis and in most cases of
acute candidiasis. In the case of chronic forms, local therapy combined with complete antimycotic
therapy is recommended (optimum therapeutic results are obtained with third-generation azole
antimycotics, triazoles). In the case of atrophic candidiasis, it is recommended that a new prosthesis
(or laboratory rebasing) is made; proper hygienic care of the prosthesis is also necessary (mechanical
cleaning after every meal, cleaning with soap and a tooth brush under running water in the evening
and placing the prosthesis in an alkaline solution of bicarbonate, borax-glycerine or hexetidine
overnight). Supporting measures include the proper hygiene of the oral cavity, the treatment of dental
caries, proper periodontal treatment and the extraction of destructed teeth and roots (the elimination
of sources of yeast). It is also important to treat predisposing general diseases, if possible. Therapy is
discontinued when clinical symptoms disappear or the mycological test shows a negative finding. In
patients with general diseases that predispose them to oral candidiasis, long-time prophylaxis
(systemic or local) is recommended.
50
Dif. dg: Mucosal diseases with keratinization disorders such as hyperkeratosis or parakeratosis
associated with the occurrence of "white patches”.
8.2.3 Lichen ruber planus
It belongs to a group of chronic diseases that affect the skin and mucosa of the oral cavity and that
are associated with a disorder of epithelial keratinization (hyperkeratosis) which causes a white
discolouration of the mucosa. Changes in the mucosa are usually the only symptoms of this disease
(in 25% of cases). 50% of patients with skin diseases also show oral mucosal symptoms. The disease
affects all races, with a higher incidence rate in women as compared to men. The largest population of
patients (approximately 70%) is in the age category of 30-60 years. Etiopathogenesis is not yet clear
although the most recent findings indicate the involvement of immunological mechanisms. This is
corroborated by the presence of lichen in many autoimmune conditions as well as by the presence of
cytotoxic lymphocytes, Langerhans cells and the expression of HLA Class II antigens (DR) and
intracellular adhesion antigen (ICAN-I) in keratinocytes or squamous epithelial cells that are absent
on the surface at normal conditions.
Clinically: The basic skin manifestation (morphoea) found on the mucosa is a flat, whitish, opalescent
glossy papule. Papules can occur either sporadically or in groups, forming whitish, oval patches on
the mucosa (lichen annularis). When present on the buccal mucosa, they form white, porcelain-like
patches arranged in a network or garland-like formations. On the lip red, radial white stripes run out
from the focally arranged patches. Lesions in the oral cavity can be combined with the disease of the
genital mucosa (the vulvo-vaginal-gingival syndrome). Papules on the skin are usually small, flat and
polygonal. Initially, they have a red colour, which turns into a typical violet discolouration in older
lesions. Predilection sites include the skin above the flexors of the forearm and wrist, sacral region,
the back and lateral sides of the neck, or the distal third of the shanks. Besides the most common
reticular form, the disease can also occur in other forms: papular, erosive (ulcerative), atrophic
(uncommon), placoid and bullous. The disease can be asymptomatic. However, it is usually chronic
with remissions and exacerbations. It can also be asymptomatic. On the skin, it is usually manifested
by itching of a different intensity whereas burning sensation and irritation upon the contact with a
meal are typical in the oral cavity. Erosive and bullous forms can be painful. The diagnosis of lichen
with typical symptoms in the mouth is relatively easy. In practice, it is usually confused with
leukoplakia (particularly in situations where lesions form continual whitish patches).
Histology: Microscopic examination reveals hyperkeratosis and acanthosis (i.e. the well-developed
stratum corneum and stratum granulosum at sites where they do not normally occur) with a chronic
inflammatory infiltrate in the corium (or submucosa). The direct immunohistological examination is
more valuable from a diagnostic point of view, showing fibrin deposits on the basement membrane
and the presence of colloid Civatte bodies.
Th.: Causal therapy does not exist, symptomatic treatment (usually local) provides relief – the
application of corticoids in the orabase (for example Dexaltin), or corticoid injections around the foci.
In the case of asymptomatic lesions, therapy is not necessary.
Dif. dg.: The finding of sporadic lichen papules at the edges of patches (diagnosis using
immunohistology is reliable) is a differential diagnostic sign. Similar manifestations can be observed
in the case of lichenoid reaction at allergic reactions, "graft-versus-host” reaction and upon the
contact of the mucosa with formaldehyde-releasing materials. Prognosis quod vitam (survival) is
51
relatively favourable (cancer develops in approximately 2% of patients, usually with a more serious
affliction - erosive forms), prognosis quoad sanationem (healing) is unfavourable.
8.2.3.1 Lichenoid reactions of the oral cavity
They are the most common manifestations of intolerance to dental metallic or non-metallic
materials, with whitish lesions typically found on the buccal mucosa or less frequently observed in
other regions (labial, lingual mucosa), at the site of contact with an allergy-inducing material (but not
when the mouth is opened during examination!). The edges are not distinct, the surroundings of the
altered mucosa are usually intensely red, the mucosa can be sensitive (not painful). Clinically, the
disease has similar symptoms like idiopathic lichen ruber planus, or drug-induced lichenoid reactions
in the oral mucosa.
8.2.3.2 Drug-induced mucosal lichenoid reactions
These reactions occur most frequently during therapy with antihypertensives, nonsteroidal antiinflammatory agents and antidiabetic medication (Grinspan‘s syndrome = diabetes mellitus, lichen
planus and essential hypertension). They occur in HIV-positive individuals treated with zidovudine
and ketoconazole.
8.2.4 White sponge naevus (naevus spongiosus albus, Cannon‘s disease)
It is a rare, autosomal dominant hereditary disease with which the child is born or which will first
manifest itself in childhood. It progresses to early adulthood. Later it is stable.
Clinical: The oral mucosa is affected by white or white-grey efflorescences with multiple furrows and
a “spongy" surface. Lesions are usually symmetric, occurring most frequently on the buccal mucosa
but they can also occur anywhere in the oral cavity. Some patients also show similar symptoms on the
vaginal or rectal mucosa. Histological examination reveals hyperplasia of the mucosa with local
hydropic degeneration of the epithelium.
Th.: It is not necessary. The familial occurrence with the progression of mucosal changes in childhood
together with histological examination can help in the differential diagnosis of diseases with the white
patch symptom.
8.2.5 Smokers’ leukokeratosis (stomatitis fumantium, leukokeratosis nicotinica palati)
Some smokers with long-time tobacco abuse (particularly cigarette smoking) show the chronic,
toxic-mechanical irritation of the palatine mucosa. This causes the major keratinization of the mucous
epithelium and the dilation of orifices of salivary ducts in both the hard and soft palates. Major
inflammatory changes may result in the formation of tiny prominences - papules compressed in the
centre, with a red orifice of the salivary duct. Histopathological examination only shows
hyperkeratosis (it is not a precancerosis) without dysplastic changes. However, it may coincide with
smokers’ leukoplakia.
Th: Diagnostic excision is not necessary, a long-time follow-up is recommended due to the potential
risk of leukoplakia or squamous cell epithelial carcinoma.
8.2.6 Darier’s disease (hereditary follicular dyskeratosis)
It is a rare disease with autosomal dominant inheritance. It occurs more frequently in men than in
women. Symptoms manifest themselves in childhood or adolescence. The disease predominantly
affects the skin and nails; the mucosa (oral, rectal and genital) can also be affected.
52
Clinical: Multiple, brown-red papules on the skin that usually combine to form large areas. The oral
mucosa is affected in 20-40% of patients. The extent and severity of the disease of the mucosa in the
oral cavity depends on the activity of the disease in the skin. Typical lesions present in the mouth as
small white papules, which may combine to form vast areas and can be hypertrophic.
Th: Vitamin A and retinoic acid derivatives are used in therapy.
8.2.7 Psoriasis (psoriasis vulgaris)
Psoriasis is a relatively common chronic disease mostly affecting the skin - it occurs on the mucosa
of the oral cavity only very rarely. If the disease occurs on the oral mucosa, it is always associated
with another coexisting serious skin condition. This facilitates the diagnosis to some extent. Although
the pathogenesis of psoriasis has not yet been fully explained, it is assumed that it is associated with
disorders of the normal development of the epidermis, which result in epidermal hyperproliferation,
altered maturation of skin cells, vascular and inflammatory changes. Psoriasis is genetically
determined, being associated with polygenic inheritance. Triggering factors include infections,
mechanical or chemical damage to the skin, stress, smoking and many other factors.
Clinical picture: Skin lesions are usually localized in the region of extensors above the joints (mainly
elbows and knees), the lumbar region, scalp and nails. The skin is thickened, dry, scaly, silvery white.
According to the morphology of skin lesions, several types of psoriasis can be distinguished (annular,
circinate, guttate, nummular and pustular). The clinical picture of psoriasis on the mucosa of the oral
cavity is rare and variable. The lip red usually shows whitish, dry patches that peel off, resulting in the
phenomenon of dot bleeding. The buccal mucosa shows whitish, round patches but scaling is absent
due to maceration. The tongue shows smoothed patches lined with whitish hyperkeratic filiform
papillae. Ring-shaped plaques on the edges and the base of the tongue may resemble annular form of
psoriasis on the skin. Changes in the oral mucosa do not cause any subjective problems. Interestingly,
the clinical and histological pictures of psoriasis and the geographic tongue are similar. Some authors
describe the geographic tongue as the manifestation of psoriasis on the oral mucosa.
Th. Therapy of mucosal symptoms of psoriasis is not necessary because they disappear spontaneously
and more quickly than changes on the skin treated within complete therapy prescribed by a
dermatologist (psoralens + PUVA, steroids, methotrexate, cyclosporin, retinoids).
8.2.8 Lupus erythematosus (LE)
It is a chronic inflammatory autoimmune disease with a variable spectrum of clinical forms, with
mucocutaneous lesions occurring either alone or in combination with the systemic manifestation of
the disease. The etiopathogenesis of the disease has not yet been fully explained. The disease is
probably associated with a failure in regulatory mechanisms constituting autotolerance.
8.2.8.1 Discoid lupus erythematosus (DLE) is a more common, chronic form of the disease. It
progresses slowly, with symptoms in the orofacial region, scalp, auricles and other parts of the skin.
Skin symptoms are noticeable particularly on uncovered parts of the body. They present as livid
papules and spots with noticeable follicular hyperkeratosis. In the centre of plaques, there are strongly
adherent scales. When they are peeled off, keratic pegs will appear on the bottom side, reaching up to
the orifice of the follicles - the “wallpaper nail” phenomenon. Plaques are sharply separated from the
surrounding healthy tissue, with skin atrophy and teleangiectasias in a more advanced phase of the
disease (the clown’s face). “Erythema centrifugum” is a characteristic finding with typical
localization above the root of the nose where it forms a well-known butterfly-like pattern,
53
characterized by itching and burning. Symptoms on the mucosa of the oral cavity at DLE only occur
in 15-25% of cases, usually together with skin lesions. There are rare cases where only oral symptoms
are present. Lupus erythematosus presents on the mucosa of the oral cavity as discoid atrophic
plaques that are red in the centre. Lesions are well circumscribed, slightly elevated above the
surrounding mucosa. They are circumscribed distinctly and have whitish edges. Teleangiectasias,
erosions and ulcerations may occur in the centre of enanthema. The disease mainly affects the buccal
mucosa, lower lip, palate, gingiva and tongue. Unlike lichen with an uninterrupted, whitish drawing,
lesions have whitish edges with a characteristic crosshatched pattern.
Laboratory test: A range of antibodies can be detected in serum (antibodies against DNA, histons,
nonhiston proteins bound to RNA and antibodies against nuclear membrane antigens).
Immunofluorescence methods are used to detect subepidermally deposited immunoglobulins.
Th.: Oral lesions are treated using local steroids in the orabase. Systemic steroids and antimalarial
agents are administered.
8.2.8.2 Systemic lupus erythematosus (SLE). It is a typical example of a multisystemic autoimmune
disease that affects internal organs. Skin symptoms may or may not be present. It can present as an
acute, rapidly progressing or chronic, initially latent disease that tends to recur. It affects a number of
internal organs and systems such as the cardiovascular system, the gastrointestinal system, lungs,
kidneys, joints and the nervous system. The disease is usually accompanied with general symptoms
such as a fever, weight loss and lymphadenopathy. From a diagnostic point of view, the presence of
butterfly-shaped exanthema in the face, renal symptoms (glomerulonephritis) and the finding of the
antinuclear factor are important. The mucosa in the oral cavity is affected in 30-45% of cases. Clinical
examination reveals painful erosions or ulcers, circumscribed with a red or white zone. Petechia,
hemorrhagia and xerostomia are common. Hyperkeratotic lesions occur rarely and are difficult to
distinguish in differential diagnosis from other conditions with the “white patch” symptom,
particularly in subacute stages where general symptoms may not be expressed sufficiently. The palate,
lips and buccal mucosa are mostly affected.
Laboratory evidence: See DLE.
Th: Depending on the severity of the disease: systemic steroids, antimalarial drugs, immunosuppressants or plasmapheresis.
8.2.9 Fordyce’s disease
See chapter Developmental abnormalities – it presents no problems for differential diagnosis.
8.2.10 Erythroplakia
It belongs to a group of diseases with a whitish discolouration of the skin although it presents on
the skin as flame-red spots. This clinical term is only descriptive and is used to describe a red patch,
which cannot be characterized as the manifestation of any other known nosological unit. The lesion
has a velvet-like appearance; it is smooth or knotty with a distinct margin. Sometimes, it can be
penetrated with white patches of leukoplakia. Histological findings show distinct epithelial dysplasias
with a high risk of transformation into carcinoma.
Th: Radical surgical therapy.
Dif. dg.: From a differential diagnosis point of view, it is sometimes difficult to distinguish
erythroplakia from chronic erythematous candidiasis where the erythematous region of the affected
mucosa is usually located on the palatine mucosa or on the mucosa of the tongue dorsum, in one plane
54
with the surrounding mucosa. Erythroplakia is not common at these sites. It is also difficult to
distinguish erythroplakia from atrophic lichen ruber planus – nearly 1% of cases of oral lichen is
associated with the simultaneous presence of erythroplakia – biopsy!).
55
Fig. 7. Differential diagnosis of diseases with the white patch symptom as the major clinical symptom
(taken from Onemocnění ústní sliznice (Oral mucosal diseases), Škach et al., 1975)
Česky:
Soor lokalizovaný
Psoriáza
Lékové exantémy lichenoidního typu
Bílý naevus
LEUKOPLAKIA
Lichen ruber planus
Leptotrichosis
m. Darier
Chron. erytematodes
English:
Localized soor
Psoriasis
Drug-induced lichenoid-type exanthema
White naevus
LEUKOPLAKIA
Lichen ruber planus
Leptotrichosis
Darier’s disease
Chron. erythematosus
8.3 EROSIONS IN THE ORAL CAVITY - DIFFERENTIAL DIAGNOSTIC REMARKS
Diseases with a clinical picture of erosions as a predominant symptom in the oral cavity can be
divided into the following groups:
1) Viral diseases – mostly from the group of herpesviruses
2) Aphthae
3) Toxic-allergic exanthema
4) A group of blistering diseases
Herpetic gingivostomatitis, herpes simplex and recurrent aphthae are the most common diseases in
this group.
8.3.1. Viral diseases
8.3.1.1 Diseases caused by herpes simplex virus
Infection caused by herpes simplex virus is so common in man that one can speak about a
complete population immunity rate. Primary infection usually occurs at the age of 1-5 years. There are
two types of the virus - Type 1 (HSV-1) and Type 2 (HSV-2). The virus is transmitted by a direct
contact with the infected person. Type 1 is usually transmitted by oral secretion whereas Type 2 is
transmitted by genital secretion. The areas afflicted by both types of viruses will gradually combine.
After infection with HSV-1 and HSV-2 (whether clinically noticeable or not), specific neutralizing
and complement fixing antibodies will be produced in about 1 week in the body. However, the virus
will survive in the latent state in the ganglia of sensitive nerves and may cause recurrences in the skin
and mucous membranes via the retrograde intra-axonal transport.
Gingivostomatitis herpetica
Herpetic stomatitis is the most common clinical manifestation of primary infection caused by HSV
(particularly Type 1) particularly in children at the age of 1-5 years. Another wave occurs in
56
adolescence and adulthood up to the age of 35 years. It is transmitted by a direct contact or via the airborne route; the incubation period is approximately 7 days.
Clinical picture: The disease begins with the prodromal stage with non-characteristic general
symptoms resembling flu (fever, headache, cervical pain, backache, loss of appetite and fatigue). In 23 days, general symptoms will disappear and the generalized intraoral disease will develop, with the
typical eruption of multiple, tiny, intraepithelial blisters on the red oral mucosa. Predilection sites
include the gingiva (which becomes diffusely red and edematous), the tongue dorsum and the mucosa
of the hard palate. Changes in the palatine gingiva are very important – major inflammatory
hyperplasia of interdental papillae can be found behind the upper incisors. Changes in the palatine
mucosa in the region of molars can be found in children with temporary teeth. Blisters will quickly
merge together and break to form very painful erosions and ulcerations. The tongue has an enlarged,
whitish coating - sometimes with a diagnostically valuable finding of herpes blisters or erosions on
the tip and along the sides of the tongue. Hypersalivation is common and the mouth odour (foetor ex
ore) is not too distinct. The perioral affliction of the lip red and the facial skin is not a constant
finding. Food intake, swallowing and sometimes pronunciation are impaired. Submandibular and
superficial cervical lymph nodes are painful and swollen. The disease will usually disappear
spontaneously in 7-10 days; erosions will heal completely (ad integrum). Due to poor oral hygiene
(i.e. oral hygiene lowered because of pain), plaque-induced gingitivis may persist. Early
complications are not usually present, only patients with atopy may show the dissemination of
infection, with a clinical picture of eczema herpeticatum Kaposi. Neurological complications
(meningoencephalitis) or process generalization in immunodeficient individuals can be dangerous.
Recurrences occur in 30% of patients.
Th: Symptomatic therapy – a diet of suitable consistency (pulpy, non-irritating), the sufficient intake
of liquids. Before a meal, an anaesthetic can be applied on the mucosa, the oral cavity can be washed
using herbal solutions, or 0.25% solution of ZnSO4 with virostatic and antiseptic effects (Zn2+ inhibits
viral DNA-polymerase through the mechanisms that has not yet been fully elucidated) or 0.12%
aqueous solution of chlorhexidine. Antiseptics can only be used at prescribed concentrations and for a
required period of time (otherwise, there is a risk of undesirable dysmicrobia in the oral cavity). The
frequency of washing is varied (2-10x daily). The use of virostatics is not necessary. Virostatics are
only used in patients with a general serious disease. Antibiotics are not indicated. The performance of
any surgical procedure in the mouth is contraindicated.
Dif. dg.: The following symptoms are very important for a diagnosis: acute diffuse inflammation of
the gingiva, usually with fibrin deposits with the typical affliction of the palatine gingiva behind the
upper median incisors, the intense whitish coating of the tongue with the eruption of tiny erosions
along the tongue’s sides and on the tongue’s tip, the swelling of lymph nodes and the alteration of
general condition in the prodromal stage (unlike ulcerative gingivostomatitis). It is necessary to
distinguish the first attack of erythema multiforme in the form of the Stevens-Johnson syndrome (the
lip red always shows symptoms such as bleeding crevices and hemorrhagic crusts, with the nasal
apertures, conjunctivae, genitals and skin being also affected, general symptoms are less expressed).
Acute gingivostomatitis occurs rarely during infectious mononucleosis (the following signs can occur:
pseudomembranous angina, hepatomegaly, typical changes in the blood count, serological evidence of
EBV). Enteroviral stomatitis does not affect the gingiva.
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Stomatitis herpetica (recidivans)
It is a collective term used to describe a recurrent disease of the oral mucosa after the formation of
specific protective mechanisms - it is not primary infection. It develops due to the reactivation of
latent HSV infection that is not a common clinical manifestation as herpes simplex (labialis) and the
causes of reactivation are not usually established. Local prodromal symptoms (burning, pain) may not
always precede the eruption of blisters; headache may occur in some cases. The disease usually
affects the keratinizing sections of the mucosa of the oral cavity (the gingiva, hard palate, tongue
dorsum). However, blisters are not usually detected since they turn very quickly into erosions that are
very painful and tend to merge together. The lip red can also be affected. The surrounding mucosa is
red, edematous; regional lymph nodes are not affected. Spontaneous healing takes 5-10 days,
complications usually occur in predisposed individuals (cancer patients, immunodeficient patients) in
whom the caudal propagation of the mucosal disease (pain during swallowing!), process
dissemination and generalization are possible. The skin and mucous membranes of the genitals can
also be affected. Recurrences of the disease occur at different rates.
Th: Local symptomatic therapy is identical with that of herpetic gingivostomatitis. Acyclovir
(Zovirax, Herpesin) can be used in immunodeficient patients; immunomodulation (transfer-factor,
gamma-globulin – after immunological examination!) can be used to prevent recurrences
Dif. dg: Unlike herpetic gingivostomatitis, this condition does not show general alteration and a twophase progression; it may recur under the same clinical picture. It is difficult to distinguish between
the herpetiform type of recurrent aphthae (they tend to merge together and do not affect the
keratinizing region of the oral mucosa!). When any autoaggressive disease from the group of
pemphigus and pemphigoid is suspected, bioptic immunofluorescence examination should be carried
out.
Herpes simplex (labialis)
It is the most common clinical form of HSV-infection in the orofacial region, with the virus
persisting in the trigeminal ganglion (the Gasserian ganglion). It affects the lips repeatedly; the
frequency of recurrence is very variable. Many external and internal factors are involved in the
reactivation of latent infection: UV-B radiation, trauma, fatigue, mental and physical stress, other
viral infections or menstruation.
Clinical picture: In the majority of patients, the eruption of labial herpes is preceded by short-lasting
paresthesia at the site of the later manifestation of the disease. The eruption of a blister will soon
appear on the lip red (usually on one of the lips). Intraepithelial blisters are formed, merge together
and dry out to form tiny crusts, or break to form erosions. The affected part of the lip is red,
edematous and painful. Painful crevices can be formed in the region of mouth corners, causing
difficulties opening the mouth. The general alteration of the condition is absent. The affliction tends
to heal spontaneously. Particularly in children, the secondary impetiginization of herpetic symptoms
(the autoinoculation of streptococcal or staphylococcal infection) may occur. The condition may
deteriorate when the affected site is traumatized during dental examination.
Th: It should be initiated as soon as possible – preferably in the prodromal stage! – by the local
application of virostatic agents.
Dif. dg.: It is not difficult to distinguish this disease from other diseases. Recurrent aphthae on the
keratinizing lip red are not formed, pyoderma (folliculitis, furuncle) affects primarily the skin part of
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the lips; the progression of the disease and the clinical picture will be confused with the disease
caused by HSV virus.
Eczema herpeticatum Kaposi (pustulosis varioliformis)
This serious form of primary infection caused by HSV can occur in atopic individuals (usually in
infants) who show the generalized eruption of skin blisters. Skin blisters will turn into pustules and
subsequently into erosions or crusts. This is associated with the alteration of the general condition
accompanied with a fever, fatigue or the affliction of internal organs (meningoencephalitis,
pneumonia). Oral symptoms occur in 10-15% of patients who develop painful erosions in the mouth
that are more severe than those associated with herpetic stomatitis.
Th: The general application of virostatic agents – acyclovir (ACV), symptomatic therapy, or gammaglobulin. Antibiotics can be administered for prophylaxis.
Dif. dg: Erythema multiforme which usually occurs in different age categories and has polymorphic
skin symptoms.
8.3.1.2 Herpes zoster (shingles)
Herpes zoster virus is identical with the varicella virus. When the virus is spread via blood, it may
induce viral infection on the mucosa of the oral cavity that resembles varicella infection, affecting the
skin of the head and body. The secondary attack of the cerebrospinal ganglia of cephalic peripheral
nerves is the starting point for a neurodermal viral disease. The disease manifests itself in a weakened
individual. Symptoms include facial neuralgia with sensation disorders. Warning! The manifestation
of zoster infection can be a paraneoplastic syndrome and may indicate malignancy.
Herpes zoster n. trigemini (zoster facialis)
It is the reactivation of endogenic viral infection with the persistence of varicella-zoster virus
(VZV) in the trigeminal ganglion (the Gasserian ganglion); the mucosa of the oral cavity can be
affected, with zoster symptoms in the cephalic region sensitively innervated with the 2nd or 3rd
branch of the trigeminal nerve. The disease is manifested in regions with sensitive innervation by
spinal nerves rather than in the region of the head and neck.
Clinical picture: Mild prodromes (fatigue, loss of appetite) are followed by neuralgic pain in the
region of the affected nerve. In most patients, the oral mucosa is affected together with skin regions of
the respective dermatome. The affliction in the region of the 2nd branch (maxillary nerve, n.
maxillaris) causes herpetic efflorescence on the facial skin in the cheek region – facial (including the
upper lip and the nasal wing) and in the temporal region – on the vestibular mucosa (buccal, labial
mucosa in the region of the upper lip and lower alveolus) and on the hard palatine mucosa (the region
of palatine nerves (nn. palati)). The affliction of the 3rd branch (the mandibular nerve, n.
mandibularis) results in the eruption of blisters on the facial skin in the mental region, including the
lower lip, in the perimandibular and preauricular regions. The intraoral manifestation occurs on the
mucosa of the frontal two thirds of the tongue (in the course of the lingual nerve, n. lingualis), the
base of the mouth, the lower lip and the alveolar process. Pain of different severity (or sensation
disorders – hypesthesia, paresthesia) occurs before the eruption of blisters. The skin shows dark red,
maculopapular exanthema (enanthema on the mucosa), followed by the eruption of blisters that are
usually covered with crusts, when on the skin, or turn into erosions, when on the mucosa. The
59
affliction is usually unilateral and does not overreach the central line! Healing takes 2-3 weeks. After
healing, postherpetic pain refractory to therapy may persist.
Th: The general application of virostatic agents (ACV at sufficient dosage!). Additional analgesic
therapy with local symptomatic therapy.
Dif. dg: Stomatitis herpetica – is often recurrent, mucosal symptoms do not respect the innervation of
individual sections of the oral cavity and overreach the central line, pain is less intense. Sometimes, it
is difficult to distinguish acute pain of odontogenic origin from essential trigeminal neuralgia (the
patient history together with the complete examination of the oral cavity including X-ray and ORL
examination will help establish a correct diagnosis).
Herpes zoster n. facialis (zoster oticus)
It occurs due to the reactivation of latent VZV infection persisting in the geniculate ganglion
(ggl. geniculi) of the intermediate nerve (n. intermedius). Clinical symptoms are very variable,
affecting skin and mucous regions of the head, which are sensitively innervated by the facial nerve.
The Ramsay-Hunt syndrome is a term used to describe conditions when other cephalic nerves are
afflicted at the same time.
It occurs relatively rarely, sometimes it is preceded by prodromal symptoms such as otalgia with
propagation into the regions of the neck, shoulder or chest, disorders of sensation in the area of the
auricle and the external auditory canal. Intraoral symptoms are usually more extensive than skin
symptoms, being localized in the two frontal thirds of the tongue (via chorda tympani) and on the soft
palate. Mucosal symptoms such as blisters or erosions are very painful and make a food intake,
swallowing and speech difficult. The condition is often accompanied with facial plegia that causes
additional problems such as motor disorders of mimic muscles and lagophthalmos. Symptoms
disappear spontaneously in 14-28 days; the affliction of the facial nerve with motor disorders of facial
muscles usually persists.
Th: Therapy does not differ from that of herpes zooster n. trigemini.
8.3.1.3 Varicella (chicken-pox)
It is a very contagious disease caused by varicella-zoster virus that also causes shingles. It affects
predominantly children, with almost 100% manifestation in sensitive individuals, and is transmitted
via the air-borne route or by a direct contact. The clinical progression of the disease is usually mild (it
can be more serious in adults), with symptoms such as fever, the eruption of blister-type exanthema
on the skin or enanthema on mucous membranes, after the incubation period of 3 weeks. Since the
eruption comes in waves, the picture is typically polymorphic, symptoms on mucous membranes
usually precede the eruption of skin manifestations (morphoea) and usually prevail on the palate (hard
and soft), lips and gingiva.
Dif. dg.: The localization of skin manifestations (morphoea) may also occur on the hairy part of the
head which is important for diagnosis. In the case of intraoral efflorescences, it is necessary to
distinguish all diseases with erosions on the basis of differential diagnosis (small epidemics usually
occur among children – it is necessary to monitor the epidemiological situation).
Th: Symptomatic therapy
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8.3.1.4 Herpangina
It is caused by Coxsackie A virus, Coxsackie B virus or ECHO virus. It usually affects children or
young people in the form of small seasonal epidemics (summer) and disappears in 14 days. The
transmission of infection is possible by a direct contact or via the air-borne route. It usually presents
as acute stomatitis with pharyngitis, usually with indistinct clinical problems (sore throat, headache,
vomiting, diarrhoea, fever). Oral symptoms include tiny blisters or erosions (usually well
circumscribed, rarely merging together) that are formed on the mucosa of the soft palate, tonsils and
pharyngeal mucosa. Difficulty swallowing is the major subjective problem.
Th: Symptomatic local therapy to relieve subjective problems – non-irritating food, the sufficient
intake of liquids, washing the oral cavity with antiseptic solutions.
Dif. dg.: Hand, foot and mouth disease has also skin symptoms. Herpetic gingivostomatitis usually
has a more serious progression, with the more extensive affliction, affecting the gingiva and hard
palate. In herpes zoster, the affliction is strictly unilateral (other skin and mucosal symptoms, pain and
sometimes neurological symptoms may also occur) and its incidence rate varies, depending on a
particular category. The eruption of petechiae on the soft palate in young individuals with tonsilitis
that disappears quickly may indicate infectious mononucleosis.
8.3.1.5 Vesicular stomatitis with exanthema on hands and feet (Hand, foot and mouth disease)
It is caused by enteroviruses, usually by Coxsackie A virus, Coxsackie B virus or ECHO-virus. Its
etiopathogenesis and clinical manifestation are similar to those of herpangina. It differs from
herpangina by the presence of maculopapular and vesicular exanthema that affects the hands and feet
(sometimes the skin on other parts of the body). The disease can affect all parts of the oral mucosa
and pharynx, except for the gingiva.
Th a dif. dg: It is identical with the treatment of herpangina.
8.3.1.6 Infectious mononucleosis (monocytic angina, Pfeiffer’s disease)
It is caused by EBV (Epstein-Barr virus) or cytomegalovirus (CMV), with prevalence in younger
people (adolescents). Infection is transmitted by saliva from an infected individuals or clinically
healthy carriers. After the incubation period, the disease presents initially as unspecific general
symptoms (fever, loss of appetite, tiredness), followed by gingivostomatitis with ulcerations
(however, some forms cannot be distinguished from the herpetic form), with petechiae on the soft
palate (Holzer’s sign) that may disappear quickly, or by temporary facial edema (Bass symptom). This
results in pseudomembranous angina with coatings that may spread from tonsils into the
surroundings. In some cases, only acute pharyngitis will develop, being accompanied with painful
swallowing and the edema of the pharynx and larynx, and inspiratory stridor. Submandibular and
painless cervical lymphadenopathy is always diagnosed. Some individuals also show enlarged lymph
nodes in other parts of the body; hepatosplenomegalia is sometimes present. Neurological
complications such as meningitis, meningoencephalitis, polyradiculoneuritis or organ-specific
complications (hepatopathy, pancreatitis, nephritis) can also occur. The disease shows a prolonged
progression and tends to chronicity in some patients.
Dg: Blood count examination shows lymphocytosis with the finding of atypical lymphoid cells; the
high count of monocytes is a typical finding (up to 50%), together with the positive Paul-Bunnel test
and laboratory signs of hepatopathy. Virological examination is performed to detect antibodies
against viral antigens VCA, EBNA, sometimes IgG and IgM antibodies against CMV-infection.
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Th: General therapy is provided by infectologists, bed rest is important as well as liver diet +
hepatoprotective products, gradual recovery. When acute gingivostomatitis occurs, local symptomatic
therapy is recommended (anesthetics, antiseptic washes…)
Dif. dg: Streptococcal angina (angina lacunaris) will resolve during ATB therapy in 2-3 days;
enlarged lymph nodes are painful. Herpetic gingivostomatitis has a typical “two-phase” progression
(general symptoms disappear with the development of the intraoral disease) and pseudomembraneous
angina is absent. Herpangina is not accompanied with lymphadenopathy, the affliction is usually mild.
Particularly in children, it is necessary to distinguish initial acute hemoblastosis from the symptoms of
acute pharyngitis or tonsilitis with great general alteration (blood count!).
8.3.1.7 Cytomegalovirus disease
It is caused by cytomegalovirus (CMV), usually upon the reactivation of endogenic latent infection
in the presence of immune dysfunction (it is not primary infection).
Clinical picture: The red mucosa shows either single or multiple defects that can be painful on the
surface, such as erosions or ulcerations that are usually vaguely circumscribed and differ in diameter.
They usually occur on the soft palate (including the uvula), the hard palate, gingiva, vestibular and
lingual mucosa. They persist for several weeks and heal spontaneously in most cases, sometimes
forming scars. The disease may recur and be more extensive, affecting the oesophagus and the distal
parts of the GIT.
Dg: Since neither the morphological picture or localization are specific, clinical diagnosis must be
verified by histological examination (to prove halonated epithelial cells resembling peacock’s eyes).
Virological examination can be performed (evidence of DNA is preferred to the determination of a
titre of specific antibodies).
Th: Antiviral therapy is possible. However, it is not usually necessary due to spontaneous healing.
Local symptomatic therapy is recommended to relieve subjective problems and speed up the healing
of mucosal defects.
Dif. dg: For therapeutic reasons, targeted tests (histopathological, virological, bacteriological,
mycological, etc.) should be used to distinguish other mucosal defects such as erosions or ulcerations.
8.3.1.8 Morbilli (measles)
It is caused by the morbilla virus that belongs to a group of paramyxoviruses. It mainly affects
children under 6 years of age.
Clinical picture: A slowly increasing body temperature with catarrhal symptoms (coryza, dry cough,
conjunctivis). The temperature will drop in 2 days. Symptoms will deteriorate and progress into
maculopapular, merging exanthema that develops across the forehead, the region behind the ears, to
the neck and the face, trunk and limbs. Enanthema is detected in the oral cavity. It manifests itself
before exanthema. The buccal mucosa in the region of molars shows red round patches with small
necroses known as Koplik's spots. Red spots can also occur on the palate and labial mucosa.
Th: Prevention is important – vaccination, symptomatic therapy when symptoms occur.
8.3.2 Recurrent aphthae
Recurrent aphthae (stomatitis aphtosa, habitual aphthae, benign aphthae, English term: recurrent
aphthous stomatitis) are a typical symptom of the most common stomatitis which affects up to 25% of
the current population without any major link to age or gender.
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Etiopathogenesis: There are a number of hypotheses that have not been confirmed. The cause of the
disease is still unknown. Based on current knowledge, it is assumed that the following predisposing
factors rather than etiological factors are important:
 Inheritance – the role of genetic factors is supported by the familial occurrence of the disease with
a rate of 50% in first-degree relatives. There is some correlation between the occurrence of
aphthae and the presence of some HLA molecules.
 Age – The disease mostly occurs in childhood and adolescence, the first manifestation of the
disease after the age of 35 is rare, it does not occur in old toothless patients.
 Immunopathological conditions - It is currently assumed that the development of this disease is
associated with immune system dysregulation. It follows from immunological studies that the
destruction of oral mucosal epithelial cells during recurrent aphthae appears to be the terminal
phase of the immunopathological mechanism whose pathway is known but its causes still remain
unknown. The immune system is probably activated by the production of activating cytokines (for
example TNF-, IL-1, IL-6), which involves not only keratinocytes of the oral mucosa but also
Langerhans cells, dendritic cells and lymphocytes. Chemotactic stimulation ensures the transfer of
immunocompetent cells into the respective sites where lytic enzymes are released, causing
necrosis. The reason that some epithelial cells are determined for destruction by means of local
defence reaction is not known.
 Infectious effects – the autoimmune cross-reaction theory based on the similarity of oral
streptococcal antigens with mucous structures has been rejected. However, it is generally assumed
that some conditionally pathogenic oral microorganisms that contaminate existing mucosal
defects have a secondary effect and may deteriorate the progression of the disease.
 Endocrine effects – It is assumed that hormone imbalance during the menstrual cycle may play a
major role (exacerbation of aphthae during the menstrual cycle), unambiguous results are not
available.
 Mental effects – recurrences of aphthae may appear via the neuroendocrine route
 Local factors - aphthae often develop on the oral mucosa that was previously injured (cheek
biting, injury caused by food or tools). Traumatic etiology is supported by the following findings:
the most common occurrence of aphthae at sites with frequent injuries to the oral mucosa and the
absence of aphthae in toothless patients or at sites with continual keratinization (gingiva, hard
palate)
 General conditions (including GIT diseases and hypovitaminoses) – when lesions resembling
recurrent aphthae are found in patients with general diseases, it is better to use the term
“aphthous-like ulcers” (when sideropenic anemia, neutropenia, coeliac disease, etc. are
confirmed).
Division: Aphthae can be classified into a group of diseases associated with the loss of tissue such as
erosion-ulceration. Depending on the progression, they can be transient (the mucosal defect heals
spontaneously approximately in 3 weeks) or persistent (healing takes more than 3 weeks). The disease
occurs in three basic clinical forms:
1) minor aphthosis – it is the most common form of the disease (around 80% of all cases). It is
prolonged, showing familial occurrence with prevalence in women.
2) major aphthosis (syn. periadenitis mucosae necrotisans recurrents) – a less common form
(approximately 10-15% of all cases). The appearance is not typical, it is usually a single, larger
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and deeper defect (exceeding 1 cm, reaching up to the submucosa), with major inflammatory
changes in the surroundings. It mostly occurs on the edges of the tongue, or on the buccal or labial
mucosa. Healing takes long (months), and may result in scars.
3) herpetiform type – less common (up to 10%). Clinical finding is similar to that of herpetic
gingivostomatitis. However, the affliction of the gingiva and general symptoms are absent.
Recurrences are rare, multi-year remissions are common.
The primary mucous morphoea (aphtha) is a common finding. Macroscopically, it presents as oval or
round erosion with the base covered with a yellow-grey fibrin coating, with a distinct red margin in its
surroundings. It develops from a blister that is not observed on the mucosa (the fine epithelial
covering is practically torn off immediately after formation). Its size ranges from several mm up to
several centimetres. Larger defects show the collateral edema of adjacent soft tissues with regional
lymphadenitis. The alteration of the general state is not a typical finding. When the aphtha is
developing, hyperesthesia may occur, being associated with intense pain in the ulcer stage (probably
caused by the irritation of nerve endings by released inflammatory mediators - IL-1, PGE2). Aphthae
are mostly formed sporadically in different time intervals (sometimes with a pause of several years),
or they can be multiple (several unhealed afflictions are still present).
Differential diagnosis: The localization of the disease will help in diagnosis (particularly to
distinguish it from herpetic infections). Aphthae usually develop on the non-keratinizing sections of
the oral mucosa, particularly on labial and buccal mucosa in the vestibulum, the edges of the tongue,
the oral base, soft palatine mucosa and palatine arches. The affliction of the gingiva, hard palatine
mucosa or lip red is rare – as these are predilection sites for herpetic efflorescence. Recurrent aphthae
are usually sharp, well circumscribed, with an inflammatory margin (unlike herpetic efflorescences
that are grouped and have irregular margins).
 In most patients, it is not difficult to distinguish minor aphthosis from other mucosal diseases,
on the basis of typical symptoms, localization and the typical progression of the disease with
relapses and remissions.
 Major aphthosis can be clinically confused with other diseases characterized by the
development of deeper defects in the oral cavity. For further dif. dg. remarks, see chapter
Differential diagnosis of stomatitis with the major finding of ulcers.
 Herpetiform aphthae are the most difficult form of recurrent aphthae to diagnose. It is
particularly suitable to distinguish them from the following conditions:
- Viral stomatitis
- Autoaggressive conditions such as pemphigus and pemphigoid
- Secondary stage of syphilis
- Toxic-allergic reactions
Th.: No specific therapy is currently available. The correct diagnosis and adequate therapy of this
disease (not any other disease that looks similar) is important. Symptomatic therapy prevails as it
resolves subjective problems in a patient, accelerates the healing of mucosal defects and prevents the
manifestation of new symptoms, or possibly prolongs the period of remission.
Local therapy: It is performed in patients in a period of acute eruption in order to alleviate
subjective difficulties and accelerate the healing of developed efflorescences. Local therapy can be
applied in each patient with recurrent aphthae of all forms. Substances such as superficial
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anaesthetics, antiseptics, antibiotics, antiinflammatory drugs and bioadhesives, or their combinations,
are used.
Local anesthetics: Superficial application uses ester anesthetics (the procaine group – 1%
tetracaine, 20% benzocaine), or amide-type anesthetics (2-10% lidocaine) in the form of sprays, gels
or solutions. Polidokanol can also be used; it is a substance with anesthetic and sclerotizing effects
(Solcoseryl dental adhesive paste). Prior to prescribing local anesthetics, patients must be informed
about their potential toxicity (only the prescribed dose should be applied, particularly before a meal)
and potential mechanical or thermal damage to the nonsensitive mucosa.
Antiseptics: chlorhexidine, hexetidine, triclosan, benzydamine. They are usually used for a short
period of time (5-10 days) in the form of solutions or gels (for example Corsodyl containing 0.1-0.2%
of chlorhexidine) 3x daily in order to prevent the development of new lesions (in the case patient noncompliance, there is a risk of undesirable effects: tooth discolouration, dysgeusia, toxic damage to the
mucosa). It is necessary to consider the interaction with lauryl sulfate (a component of most
toothpastes) and apply the antiseptic 30-60 minutes after the cleaning of teeth. Hexetidine (Stopangin)
blocks the formation of thiamine diphosphate (the coenzyme that is essential for life processes in
microorganisms) by competitive inhibition. By interfering with glycolytic processes, it inhibits the
fermentation of food residues in the oral cavity. It is used in the form of solution or spray 3x daily.
Nonsteroidal antiinflammatory drugs: particularly benzydamine and formulations containing
salicylic acid. Benzydamine has antiinflammatory, analgesic, anesthetic and antimicrobial effects. For
application into the oral cavity, it is used in a 0.15% concentration 4-6x daily at a dose of 10-15 ml for
30s for a period of 7 days (for example Tantum verde). It is used relatively frequently and is also
suitable for the prophylaxis and treatment of mucositis in the oral mucosa in patients undergoing
anticancer therapy (radiotherapy, chemotherapy). Adverse effects are not usually severe even if it is
used for several weeks. Salicylic acid: its mechanism of action is based on the blockade of
cyclooxygenase – the enzyme that participates in the synthesis of prostaglandins and other derivatives
of arachidonic acid. It can be applied locally using gel formulations. It is less effective than
benzydamine.
Corticosteroids: their use is limited to therapy of developed defects (one has to take into account
both general and local contraindications – viral, bacterial and fungal stomatitis). It is applied on the
dry mucosa in the form of gel (for example Lidex, Dexaltin Oral Paste) 2-4x daily. The depot
formulation of corticosteroids can be applied into soft tissues in the surroundings of the lesion (for
example, 5-20 mg of triamcinolon per dose) in some cases (major aphthosis). This therapy is
restricted to specialized clinics due to possible local and general adverse effects.
Bioadhesives and mucoprotective agents: cellulose hydrogels and polyacrylates (for example
Orabase, Iso-Dent) are applied to cover a lesion with a film and relieve pain. They can also be used to
cover a range of active substances enabling them to remain on the mucosa longer. The mucoprotective
agent sucralfate is able to adhere to damaged mucosa, accelerates the regeneration of the epithelium,
improves microcirculation and has a local stimulating effect on the mucosa of the GIT. It is used in
therapy of erosive lesions in the esophagus, stomach, or duodenum and in therapy of recurrent
aphthae in extensive eruptions that repeat frequently (Ulcogant suspension).
Among other medicinal products that can be used in specialized clinics as non-standard treatment
are the preparations containing cyclosporin, interferon-alpha or prostaglandin E2.
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General therapy: It is only used in some patients with major aphthosis, the herpetiform type of
RA or recurrences of a. minor with multiple aphthae. The main goal of therapy is to prevent
recurrences and mitigate the serious progression of the disease. Generally applied substances include
vitamins (Pyridoxin 3x1 tbl + folic acid 2x1 tbl for 6 weeks; treatment can be repeated),
antihistamines, vasodilating agents, corticoids, immunosuppressants and immunostimulants. Since
most drugs intended for general application (which is usually long-term) are restricted to specialized
clinics, their list is not provided here.
8.3.2.1 Erythema multiforme (erythema exsudativum multiforme Hebrae)
According to current concepts, this term is only descriptive, as it does not specify the origin and
nature of the disease. The allergic component plays a role in the etiology of the disease, being
presented as the eruption of papules and pustules on the skin and the mucosa of the oral cavity. It is a
phenomenon usually associated with the use of some drugs (Acylpyrin, barbiturates, PNC,
tetracycline, sulfonamides), or locally applied cosmetic products (toothpaste, mouth wash, lipstick…).
It prevails in young people. Initially, it can proceed as recurrent aphthae. Seasonal occurrence is
typical, with peaks in spring and autumn. It usually starts with brick red, well-circumscribed spots that
will later develop into circularly arranged blisters. Itching exanthema is usually noticeably symmetric.
Blisters can be large. After their rupture, they are covered with a thick hemorrhagic crust. Extensive,
mucosal, flat erosions covered with a fibrin coating, hemorrhagic crusts on the lip red and
polymorphic skin symptoms develop suddenly anywhere in the oral cavity, causing serious subjective
difficulties and general alteration (particularly idiopathic forms can be fatal). They tend to recur. In
the case of deeper lesions, there is a risk of secondary infection. Hypersalivation, mouth odour and the
enlarged coating of the tongue are typical symptoms. Except for the altered peripheral blood count
(leukocytosis and lymphopenia), changes in other internal and immunological laboratory parameters
are minimal.
Histology: Non-specific, degenerative changes with subepithelial blisters, without the signs of
acantholysis unlike pemphigus.
Th: Therapy is based on the use of antiinflammatory drugs (NSAIDs) combined with antibiotic
irrigation. At serious progression, corticoids are administered for a short period of time, preferably at
patient hospitalization.
Stevens-Johnson syndrome
The Stevens-Johnson syndrome as a variant of this disease often shows unfavourable clinical
progression. It is a serious bullous form of the disease with the major affliction on the lip red, and
additional symptoms on the conjunctiva, urethra, perianal region and genitals.
8.3.2.2. Behçet's syndrome
Some authors classify the Behçet’s syndrome (aphthosis maligna) as recurrent aphthae. Unlike
"classic” aphthae, this is a serious systemic disease of unknown etiology. It develops on the basis of
vasculitis. Besides ulcerations in the oral cavity, it shows a number of other extraoral symptoms.
Similar to many other diseases, major (recurrent ulcerations in the oral cavity) and minor criteria
(recurrent genital ulcerations, skin and eye lesions and the development of a pustule (pathergy) at the
site of puncture) were suggested for the diagnosis of this syndrome. Some authors classify three types
of this disease according to the clinical picture: mucocutaneous type (the disease affects the mouth,
66
genitals, conjunctiva and the skin), arthritic type and neuroocular type (the disease affects the eyes
and/or the nervous system and shows mucocutaneous or arthritic symptoms).
Th.: Combined (corticoids, cytostatics).
8.3.2.3 Touraine's aphthosis
Touraine's aphthosis belongs to a group of chronic aphthoses. Apart from aphthae on the mucosa
of the oral cavity, it shows similar changes in the stomach, intestines, genitals and respiratory tract. In
addition, symptoms can also occur in the eyes and the CNS. This is a generalized disease affecting
multiple organs, therapy is only symptomatic.
8.3.3 Toxic-allergic exanthema
To establish the diagnosis of drug-induced stomatitis can be very difficult since the mechanism of
the origin of these diseases involves allergic or toxic factors. The clinical picture of drug-induced
stomatitis with allergic etiopathogenesis is very polymorphic (and may resemble stomatitis of other
etiologies, for example erythema multiforme or herpetic gingivostomatitis). The inflammation
progresses relatively severely with a significant exsudative component. It usually affects larger areas
of the oral mucosa at different sites (the gingiva is affected very rarely). The coating of the tongue is
typically enlarged, wet and whitish. However, its colour can be altered by previous therapy (for
example, yellow to brown discolouration after the use of ATBs). The thorough and targeted medical
history of a patient will help establish the diagnosis. The picture of drug-induced stomatitis of toxic
origin is different – the inflammatory component is less significant whereas tiny erosions and
hemorrhagia are more distinct and symptoms are more localized. The physiological coating of the
tongue is reduced or absent, with hyperkeratotic changes on the mucosa on the residual areas of the
coating on the tongue dorsum. The presence of skin manifestations may help in the diagnosis of druginduced exanthema. Toxic reactions can be caused either by very high doses of a drug or by reduced
tolerance to the drug, or the accumulation of a drug during long-term administration. Mixed toxicallergic manifestations present the symptoms of both groups described above. As a result, the clinical
picture combines both inflammatory and non-inflammatory symptoms. The smoothed lingual mucosa
with the present inflammation can be observed whereas hyperkeratic changes are absent. Small
erosions in some localizations are typically found. They arise due to the decomposition of the walls of
small capillaries in the respective region (arteriolitis). When larger vessels are afflicted, extensive
necrosis will develop.
Dif.dg: It is necessary to distinguish enanthema associated with infectious diseases, which can closely
resemble drug-induced stomatitis (general examination will help since infectious diseases usually
show alterations of the general condition).
8.3.4 A group of blistering diseases
Another group characterized by the finding of erosions in the oral cavity includes blister diseases
and can be divided into three major subgroups:
1) Pemphigus group
2) Pemphigoid group
3) Dermatitis herpetiformis
8.3.4.1 Pemphigus
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This chronic autoimmune blistering disease affects the skin and mucosa. On the basis of clinical,
histopathological and immunological criteria, four basic forms of the disease can be distinguished:
pemphigus vulgaris, p. vegetans, p. foliaceus and p. erythematosus (the Senear-Usher syndrome).
Pemfigus vulgaris
It is the most common form of the disease from this group. It is associated with the production of
antibodies against keratinocytes' membrane antigens and the intercellular substance that disrupt the
intercellular links, thereby disturbing acantholysis and the development of intraepithelial blisters. It
occurs in individuals at the age of 50-60 years, with the same incidence rate in both genders.
Practically, it can occur at any age. In most patients (approximately 90 %), it affects the mucosa of the
oral cavity where it also starts in more than 50 % of patients! Symptoms can be limited only to the
oral mucosa for several months and years. Apart from the mucosa of the oral cavity, mucous
membranes of genitals and conjunctiva can also be diseased.
Clinical picture: The disease develops on any part of the healthy, non-inflamed skin or mucosa as
blisters with the clear contents. The contents of a blister become gradually opalescent, yellowish or
hemorrhagic. Blisters differ in size and usually merge together. After their rupture, painful erosions
are formed and can spread into the surroundings. Eruptions come in attacks and the process may
become generalized after a differently long period of time. The generalized form involving organs is a
serious disease with a high risk of death. It often occurs as one of the complications of
immunosuppressive therapy. Erosions rather than blisters are found on the mucosa; they are epithelial
defects that remain after the blister has been torn off. The mucosa is cloudy with edema, showing no
signs of inflammation (major dif. dg. sign – inflammatory manifestations are less acute). Erosions
may develop anywhere in the oral cavity. They usually occur on the mucosa of the soft palate, buccal
mucosa and lower lip. Yellowish crusts can be observed on the lip red, arising from drying the
exudate on the surface of erosions. One typical sign of pemphigus is that the blister increases by
spreading intraepidermally into the periphery - by exerting pressure and traction on the normal skin
with a finger, the surperficial part of the epidermis will separate and shift (the direct Nikolsky’s sign).
By pressing the finger on the surface of a fresh blister, its contents will be pushed through into the
surrounding epidermis and the blister becomes larger (the indirect Nikolsky’s sign). The healing of
erosions is very slow, epithelized sites can be slightly atrophic, with the formation of pigmentations
(hyperpigmentation).
Dg.: Histological examination reveals an intraepithelial acantholytic blister. Immunofluorescent
examination (IF) shows the presence of IgG antibodies and C3 component of the complement in
intercellular spaces, or circulating antibodies in serum. Acantholytic cells can be confirmed in the
smear from the base of the blister (the Tzank test).
Th.: Corticosteroids systematically administered at high doses or combined with other
immunosuppressants. General therapy and active prevention in patients is restrained to specialized
dermatovenerological clinics. Therapy requires frequent clinical and laboratory follow-up. Locally:
corticosteroids in the orabase or in solutions intended for irrigation, combined with local ATBs.
Dif. dg.: Bullous pemphigoid, erythema exsudativum multiforme, bullous drug-induced eruptions, the
oral cavity with erosive lichen ruber planus, persistent aphthae, the Behçet’s disease, benign familial
chronic pemphigus (the Hailey-Hailey disease that is a hereditary form, with the same histological
character but it is chronic and much less aggressive).
68
Pemphigus vegetans
It is a variant of pemphigus vulgaris, with the development of soft, wet, dark red pustular
vegetations, with sporadic blisters typically occurring on their periphery. It is the more distinct
proliferation of the base of some excoriations. They mainly occur in the region of mouth corners.
Their secondary infection by C. albicans is common.
Dg., dif.dg. a th. The same as in the case of p. vulgaris.
Pemphigus foliaceus
It is a superficial, less serious form with a prolonged progression. It occurs rarely. It is
characterized by the subcorneal localization of acantholytic blisters. Due to the superficial location,
intact blisters can be observed only rarely. Eroded areas covered with crusts are usually present. In
most cases, lesions are located in the scalp, cheeks, body and seborrhoeic regions. The disease affects
the mucosa of the oral cavity very rarely (small, superficial erosions).
Pemphigus erythematosus
This is another rare superficial variant of pemphigus with a mild progression and usually a good
prognosis. The disease is characterized by erythematous eruption - similar to lupus erythematosus,
with which it can coexist (or with myasthenia gravis or thymoma). The oral mucosa is rarely affected
by superficial erosions.
Paraneoplastic pemphigus
It is a rare, recently described autoimmune form of pemphigus, with skin and mucous lesions,
occurring in patients with cancer (lymphoma and leukemia). The clinical picture is characterized by:
a) polymorphic skin lesions, usually resembling papulosquamous eruptions, b) painful erosions
refractory to therapy (usually affecting the lower lip), c) persistent erosions of the conjunctiva.
8.3.4.2 Pemphigoid group
Benign mucous pemphigoid (cicatricial pemphigoid)
This chronic autoimmune blistering disease predominantly affects the mucosa and causes the
atrophy of the epithelium. It usually occurs in middle-aged individuals and seniors.
Etiopathogenesis: Genetic predisposition is assumed, with the involvement of the HLA complex
genes (a higher frequency of HLA-B12 antigen). Immunological and histological tests show the
presence of IgG and IgA antibodies against the basement membrane and complement C3 component
deposits.
Clinical picture: The disease mainly affects the oral mucosa and conjunctiva, and also the mucosa of
the nasopharynx, esophagus and the anal region. Skin lesions only occur in 20-40 % patients. The
manifestations in the oral cavity predominantly involve the gingiva as desquamative gingitivis.
However, other parts of the mucosa can also be affected. Intact blisters can be found only rarely
whereas erosive changes are present, with secondary scarring! When the disease is in the eye, it can
affect the cornea and subsequently cause blindness. Lesions on the mucous membranes of the GIT
often result in the development of strictures.
Dg: Histological examination reveals subepithelial blisters, without degenerative changes in the
epithelium. The immunohistochemical test shows the presence of IgG, IgA, IgM and complement C3
component in the basement membrane.
69
Th: Systemic corticosteroids, or their combination with other immunosuppressants. Mild forms can be
treated locally using topic steroids.
Dif. dg.: Pemphigus, erosive lichen planus, recurrent aphthae, the Behçet’s disease
Bullous pemphigoid (old-age pemphigus)
It is the most common disease from the group of blistering diseases that affect persons over 60
years of age.
Etiopathogenesis: It is an autoimmune disease with the presence of circulating antibodies against
antigens in the stratum lucidum of the basement membrane. The complement cascade is activated and
subepidermal blisters are formed.
Clinical picture: Blisters are usually formed on vaguely demarcated, grouped erythematous spots,
rather than on the normal skin. After blister disruption, erosions will develop and tend to spread into
the periphery. The mucosa of the oral cavity is affected only rarely, usually secondarily after the
eruption of skin lesions. The progression of the disease is prolonged, with spontaneous remissions and
a favourable prognosis. The Nikolsky’s sign is negative, the Tzanck test is also negative.
Th: Systemic corticosteroids
Dif. dg: Pemphigus vulgaris, dermatitis herpetiformis Duhring, erythema exsudativum multiforme
8.3.4.3 Dermatitis herpetiformis (Duhring-Brocq disease)
It is chronic dermatosis associated with gluten-sensitive enteropathy that can be asymptomatic.
Associations with HLA antigens (HLA-B8, DR3 and DR7 – in up to 90 % of patients) is confirmed. It
can occur at any age (including children). It is most common at the age of 20-50 years, with
prevalence in men.
Etiopathogenesis: Defective immune response to gluten antigens (Ag of gluten); gliadin is probably
the most important of the whole range of antigens. Chronic inflammatory reaction develops in the
small intestine, being accompanied with the production of IgA antibodies against gliadin. This
activates the complement cascade via an alternative pathway, the production of chemotactic factors,
and the migration of leukocytes to the papillae of the corium. After the decomposition of cells and the
release of enzymes, the epidermis is separated from the corium to form a subepidermal blister.
Clinical picture: Symmetric papulovesicular eruption on the skin - usually above the extensors of the
limbs and in the sacral region. Because it is itchy, excoriation or crusts can be found due to intense
scratching. The mucosa of the oral cavity is affected in 10-20 % of cases, usually secondarily after
primary manifestations on the skin. Although the maculopapule is a typical skin manifestation in the
oral cavity, vesicles and erosions resembling aphthous ulcers can also be present. The palate, tongue
and buccal mucosa are affected more frequently than the gingiva, lips or tonsils. Clinically manifested
enteropathy occurs in 10-20 % of patients.
Dg.: Histological proof of the subepidermal blister, the presence of IgA antibodies against smooth
muscle reticulin confirmed by direct immunofluorescence.
Th: Gluten-free diet, sulfones and sulfapyridines
8.3.4.4 Epidermolysis bullosa acquisita (EBA)
It is a rare autoimmune blistering disease characterized by the formation of subepidermal blisters
in persons over the age of 50. Both inflammatory and non-inflammatory mechanisms play a role in the
pathogenesis, including immune mechanisms.
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Clinical picture: Its symptoms are very varied, particularly in the beginning of the disease - they may
resemble any other blistering disease. The classic picture gradually develops showing extreme skin
fragility, trauma-induced blisters and erosions that heal with scars. The disease usually manifests
itself on the dorsum of the arms and extensor areas of the limbs. In one third of patients, erosions also
develop on the oral mucosa or rarely in the larynx and esophagus, with subsequent scars.
Dg.: It is very difficult to recognize pemphigoid – both diseases are characterized by the formation of
subepidermal blisters and the deposits of IgG and the complement C3 component in the area of the
basement membrane. Indirect IF test can distinguish both diseases – in the case of EBA, circulating
immunocomplexes are bound to the sublamina densa whereas in the case of pemphigoid they bind to
the lamina lucida of the basement membrane.
Th: Difficult, the combination of corticosteroids and cytostatics (one typical sign of the disease is that
it is refractory to therapy).
Fig. 8. Differential diagnosis of the disease with erosion as the basic skin manifestation (taken
from Onemocnění ústní sliznice (Oral mucosal diseases), Škach et al., 1975).
Česky:
Mechanické a chemické vlivy
Hemoblastosy
Multiformní erytém
Alergickotoxické reakce
Pemphigus
Lichen ruber planus (erosivní forma)
EROSIO
Recidivující afty (stomatitis aphtosa)
Gingivostomatitis herpetica (stomatitis epidemica)
Herpes simplex
Zoster
Herpangina
Varicella
English:
Mechanical and chemical factors
Hemoblastosis
Erythema multiforme
Allergic-toxic reactions
Pemphigus
Lichen ruber planus (erosive form)
EROSION
Recurrent aphthae (aphthous stomatitis)
Gingivostomatitis herpetica (stomatitis epidemica)
Herpes simplex
Zoster
Herpangina
Varicella
Fig. 9:. Differential diagnosis of the disease with a vesicle as the basic skin manifestation (taken from
z Onemocnění ústní sliznice (Oral mucosal diseases), Škach et al., 1975).
71
Česky:
Fyzikálně chemické vlivy
Multiformní erytém
Pemphigus
Benigní pemphigus (desvamativní gingivitis)
Lichen ruber planus (vesikulosní forma)
VESICULA
Afty v počáteční fázi (vzácně)
Alergické reakce
Herpex simplex
Zoster
Herpangina
Stomatitis epidemica
Varicella
English:
Physicochemical factors
Erythema multiforme
Pemphigus
Benign pemphigus (desquamative gingitivis)
Lichen ruber planus (vesicular form)
VESICULA, VESICLE
Aphthae in the initial stage (rarely)
Allergic reactions
Herpex simplex
Zoster
Herpangina
Stomatitis epidemica
Varicella
Fig. 10:. Differential diagnosis of the disease with a bulla as the basic skin manifestation (taken from
z Onemocnění ústní sliznice (Oral mucosal diseases), Škach et al., 1975).
Česky:
Fyzikální a chemické vlivy
Lékové alergie
Benigní slizniční pemphigus
Pemphigus
BULLA
Lichen ruber planus (bulosní forma)
Multiformní erytém (bulosní forma)
Epidermolysis bullosa
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English:
Physical and chemical factors
Drug-induced allergies
Benign mucosal pemphigus
Pemphigus
BULLA
Lichen ruber planus (bullous form)
Erythema multiforme (bullous form)
Bullous epidermolysis
8.4 ULCERS IN THE ORAL CAVITY – DIFFERENTIAL DIAGNOSTIC REMARKS
Diseases with an ulcer as the major symptom in the clinical picture can be divided into the
following 3 groups:
1) Diseases primarily affecting the gingiva
2) Diseases that do not affect the gingiva primarily
3) Ulcers associated with specific inflammations
8.4.1 Diseases primarily affecting the gingiva
The first group contains diseases that primarily affect the gingiva and occur in other regions of the
oral mucosa only very rarely, usually at the simultaneous affliction of the gingiva). Diseases such as
ulcerative gingivostomatitis, or changes on the mucosa associated with agranulocytosis and leukemia
belong to this group.
8.4.1.1 Ulcerative gingivostomatitis (gingivitis ulcerosa, gingivostomatitis ulceronecrotisans,
Vincent’s stomatitis)
It is assumed that this disease is caused by mixed bacterial microflora of the subgingival plaque,
particularly Gram-negative rods of the genus Bacteroides, Prevotella, Porphyromonas, Fusobacterium,
Actinobacillus, and by oral spirochetes of the genus Treponema. It is assumed that microorganisms
multiply in predisposed individuals, with the simultaneous involvement of multiple local (dental
plaque, improperly made fillings, semiretained teeth, etc.) and general factors (age, hormone changes,
immune imbalance, mental stress). However, it is currently assumed that general factors do not play a
major role. Typically, it affects young people of both genders, at the age of 17-25 years (the disease is
unlikely to occur at the age outside this range!).
Clinical picture: General symptoms are not part of the disease. In the absence of prodromal symptoms
(the differential diagnostic sign in contrast to gingivostomatitis herpetica is important!), the disease
presents suddenly in a completely healthy individual as acute catarrhal gingivitis localized in some
part of the dentition. The typical localization of the disease is in the frontal section of the dentition
around incisors and canines, or in the region of lower third molars. Major changes are found at sites
with the local irritation of the gingiva. Initially, the gingiva is red, very painful (spontaneously and
also on touch), and bleeds slightly. Later, the picture will change, showing greyish necrotic areas on
the tips of interdental papillae progressing to the whole marginal gingiva (circumdentally). After the
separation of necrotic tissue, the ulcerated margin with typical “bevelled” interdental papillae can be
found. The process is usually limited only to the gingiva but it can also spread to the alveolar mucosa,
buccal, lingual and palatine mucosa. It can heal spontaneously without the initiation of adequate
therapy (risk of recurrence), or it can become chronic – either as painless ulcerative gingivostomatitis
or very painful ulcerative gingivoperiodontitis associated with the fast destruction of the alveolar
bone. The swelling of submandibular nodes is an accompanying symptom. Hypersalivation and mouth
odour are also typical. Major subjective difficulties occur during eating a meal or when performing
oral hygiene that can be very difficult or even impossible. This may further deteriorate the condition.
Dg.: The diagnosis can be established on the basis of a clinical finding (changes on the papillae occur
on the 2nd or 3rd day). For differential diagnosis, it is necessary to check the blood count (leukemia,
agranulocytosis, etc.) and anti-HIV antibodies!
73
Therapy: Depending on the intensity, extent and duration of the disease, therapy is either local or
general. Local therapy is based on the effect of oxygen from the air on anaerobic bacteria. The dentist
will remove the necrotic covering using a cotton swab soaked with 30 % of hydrogen peroxide
whereas early patches are washed by 3 % H2O2 using a syringe with a blunt cannula. Treatment is
repeated every day for 2-5 days. When the condition is acute, surgical procedures in the oral cavity,
including the removal of dental plaque, are contraindicated. In home care, the patient can wash the
oral cavity with 6 % H2O2,. Treatment can also include antiseptic washes (hexetidine, chlorhexidine)
with the application of a local anaesthetic in spray before a meal. A pulpy and non-irritating diet is
recommended. When subjective difficulties disappear, local irritating factors such as dental crowns
and overhanging fillings are removed. The main goal is to reduce the subgingival plaque.
In chronic forms of the disease, it is recommended that local therapy is combined with general
antibiotics (PNC, tetracyclines, macrolides) or nitroimidazoles (metronidazol) at normal dosage.
Dif. dg: Acute viral stomatitis usually begins with the prodromal stage and does not affect largely the
gingiva (except for herpetic gingivostomatitis!). Hyperplasia and lesions in other sections of the oral
mucosa are found in patients with blood diseases. The major alteration of the general condition
(tiredness!) occurs at the same time. General diseases should be taken into account particularly in
individuals with a untypical age (children, elderly) and when the condition does not improve upon
adequate therapy (blood count!). It may happen that it will not be possible to distinguish HIVperiodontopathies if there are no other signs present in the oral cavity during HIV (the serological test
to detect anti-HIV antibodies!)
8.4.1.2 Leukemia and lymphoma
It is not rare that patients with acute hemoblastosis first come with their oral problems to the
dentist. The most common manifestation is extensive gingival hyperplasia that is edematously
thickened and hyperplastic (besides inflammatory changes, this also includes the infiltration of
connective tissue with immature blood elements). It can show a livid discolouration, with a tendency
to bleed, and usually covers dental crowns either partially or completely. Other manifestation is
ulceration with undermined margins, accompanied with a strong mouth odour (foetor ex ore).
Necrosis can affect not only the gingiva and tongue but also tonsils, which can be very enlarged and
cause respiratory problems. Surgical procedures in the oral cavity are contraindicated. The picture can
also be altered by the occurrence of opportunistic infections (usually candidiasis). The blood count,
the examination of bone marrow and biopsy are necessary.
8.4.1.3 Agranulocytosis
It is a hematological syndrome characterized by a decline in the total white blood count, with the
significantly decreased count of granulocytes or complete disappearance of granulocytes. The
etiology can be idiopathic (primary agranulocytosis) or associated with known causes (secondary
agranulocytosis). It is altered immunoallergic reaction to some drugs (analgesics, antidiabetics,
antiepileptics, antirheumatics, antibiotics). In predisposed patients, this will lead to damage to
hemopoiesis after some time (several weeks or years). Other causes include some bacterial infections
(TB, typhoid, septicemia), viral infections (hepatitis, rubeola, influenza), protozoal infections
(malaria), ionizing radiation, benzene and its derivatives. The condition typically shows major general
symptoms such as fever, tiredness, sore throat and dyspnoea. Petechia and necroses differing in
severity occur on the mucosa of the gingiva, soft and hard palates, pharynx, tonsils, and sometimes on
74
the tongue, lips and cheeks. Oral lesions are often accompanied with increased salivation, and
mastication can be painful. Necrosis may also affect the bone and cause its separation and the release
of teeth. When establishing the diagnosis, the physician should adhere to the rule that all cases of
ulcerative necrotic gingivostomatitis that are refractory to therapy may indicate a disease of the
hemopoietic system. Similar changes often occur as one of the symptoms of AIDS and other diseases
associated with disorders of the immune system.
Th: Local symptomatic, general therapy is controlled by a hematologist.
Dif. dg.: From a differential diagnosis point of view, the finding of ulcerative decay on the pale base
is important - the red surroundings are absent.
8.4.2 Diseases that do not affect the gingiva primarily
The typical feature of the second group of diseases is that ulcers do not affect the gingiva
primarily and are usually localized in other regions of the oral cavity. This group of diseases includes
decubital ulcer, periadenitis mucosa, ulcers associated with blistering diseases, ulcers of toxic-allergic
origin and carcinoma.
8.4.2.1 Traumatic ulcer (decubitus ulcer)
It is the most common ulcer on the mucosa in the oral cavity arising due to mere mechanical
irritation. It often presents as a flat or dish-shaped ulceration with distinct margins. Defects can occur
anywhere in the oral cavity - the respective localization is associated with a traumatizing factor. It
usually develops on the lateral side of the tongue, on the buccal mucosa, lips or gingiva. It is painful,
the surrounding area is usually red and can be covered by a greyish pseudomembrane. Patients report
major pain; regional lymph nodes can be swollen. The ulcer develops due to the traumatization of the
oral mucosa caused by unsuitable dental prosthesis, carious or destructed teeth with sharp edges,
hygienic dental tools, or orthodontic apparatus, surgical splints, tools used in dental treatment or
externally applied medicines. The causes of traumatic defects on the oral mucosa can be recognized
and established easily in most cases, on the basis of clinical findings and medical records in the
patient history. However, the traumatization of the oral mucosa in some patients can only be
established indirectly or with difficulties.
Th.: Traumatic defects of the oral mucosa cannot be cured (fully and permanently) without the
elimination of their causal factor. When the cause is eliminated, mucosal defects should heal
spontaneously in 1-2 weeks, depending on their particular size, depth and localization. Treatment may
last longer at sites with keratinized sections of the mucosa (the gingiva, the dorsum and edge of the
tongue, hard palate). Sometimes, it is necessary to revise hygiene habits in patients and eliminate
unsuitable hygienic tools and improper cleaning techniques. Healing can be accelerated by irrigation
using antiseptic solutions or solutions that support epithelial cell growth. Herbal infusions are often
used (chamomile, agrimony, yarrow, sage, etc.). Chlorhexidine as an antiseptic can also be used.
Treatment can be initiated by applying superficial anesthetics (usually before a meal).
Dif. dg: It is very comprehensive. Autoaggressive diseases from the group of pemphigus and
pemphigoid: Symptoms in the oral cavity are usually extensive and prolonged. They often occur at
sites exposed to chronic irritation, sometimes together with skin symptoms which they may precede.
The condition afflicts older patients. The disease is recurrent, spreads, does not heal at common
indifferent local therapy using antiseptics, formulations supporting epithelial cell growth, etc. When
this kind of a disease is assumed, laboratory and bioptic tests should be carried out (direct
75
immunofluorescence!) Herpetic stomatitis: It is often recurrent and very painful. In rare cases, a
blister on the mucosa of the oral cavity can be found, lesions on the lip red are quite common and
have a characteristic pattern. Lesions usually heal spontaneously or after non-specific indifferent
therapy, in one week. The virological test can be positive. Acute hemoblastosis and marrow
suppression: They can be of a different origin. Symptoms in the oral cavity (bleeding, gingival
hyperplasia, the ulceration of the mucosa) are associated with general alteration (tiredness!) and
generalized lymphadenopathy. It follows from medical records in the patient history that the duration
of mucosal changes is short (several days) and mucosal ulcerations are painful. When such general
diseases are suspected, it is necessary to perform the thorough biochemical analysis of blood.
Carcinoma of the oral mucosa: Its history is usually longer (months or longer) and it progresses
without pain. Some patients may show enlarged regional lymph nodes (submandibular, cervical).
When carcinoma is suspected, it is necessary to perform a histopathological examination.
8.4.2.2 Suction injury to the palatine mucosa
The suction injury to the palatine mucosa is a specific kind of traumatic defects of the oral mucosa
and gingiva. It arises from the repeated exposure of soft tissues to pressure, and possibly from the
negative pressure on the mucosa. This action probably causes the ruptures of tiny blood vessels
located in the submucosal connective tissue of traumatized mucosa, which lead to bleeding into the
mucosa. This affliction has a typical appearance and localization. It is not painful, the finding in
surrounding parts of the oral mucosa is negative. The origin of the affliction can be identified in the
patient medical history but not every patient is willing to speak about causes. Healing usually lasts 1-2
weeks, therapy is not necessary.
Individual nosological units associated with trauma to the oral mucosa include:
8.4.2.3 Cheek bite stomatitis (morsicatio buccalis)
It is caused by a bad habit such as biting the buccal or labial mucosa. The clinical picture shows
damage to the epithelium in the respective area that is “ruptured" to some extent, being sporadically
hyperplastic or detached. The finding is not always clear - the histological examination is
recommended in the case of doubts since it can prove chronic inflammation. Prognosis is sometimes
problematic and depends on patient compliance.
8.4.2.4 Cotton-roll stomatitis
It can arise due to the dental examination where the cotton roll used during treatment has adhered
to the vestibular mucosa of the oral cavity. During removal, it tears away the surface layer of the
epithelium.
8.4.2.5 Recurrent aphthae (stomatitis apthosa)
See Chapter Erosions in the oral cavity – differential diagnostic remarks
8.4.2.6 Ulcers of toxic-allergic origin
See Chapter Erosions in the oral cavity – differential diagnostic remarks
8.4.2.7 Electrogalvanic stomatitis
See Chapter External causes of diseases
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8.4.2.8 Stomatitis caused by thermal factors
Burning can occur by accident due to drinking hot beverages, eating hot meals, or carelessness
during manipulation with some medical tools. Low temperatures (frost, snow) can result in frozen lips
in skiers, etc. The clinical picture shows various changes ranging from simple erythema with edema to
necrosis of tissue with a subsequent ulcer, depending on the temperature and duration of action.
Hyperkeratotic changes may occur at chronic heat. Damage due to low temperatures depends on the
duration of a thermal effect. Initially, it presents as a pale to livid discolouration, later as edema with
mucosal defects such as ulcers. Diagnosis is clear on the basis of medical records in the patient
history.
Th.: Local therapy.
8.4.2.9 Stomatitis caused by chemical factors (chemical burning)
It arises due to chemical burning of the mucosa caused by laboratory accidents, carelessness when
manipulating with chemicals in surgery rooms, or as a result of chronic occupational exposure to
harmful substances. Depending on their concentration and duration of action, acids and bases cause
necrosis that has a variable depth, being initially manifested by a pale discolouration of tissue. Later,
the colour of the damaged mucosa will change, depending on a chemical substance (nitric acid causes
a yellow discolouration of the skin, hydrochloric acid produces white spots, sulfuric acid causes black
burns). The skin surface after exposure to lye is greyish and watery. After the separation of necrotic
tissue, painful ulcers will develop. They heal very slowly and cause scars. Chronic exposure mostly
affects the mucosa of the eye and nose; the mucosa of the oral cavity shows hyperkeratic changes.
Th.: The principle of therapy is to neutralize the chemical substance as soon as possible. In the case of
acid burning, the affected area is rinsed with 5 % sodium hydrocarbonate. In the case of lye burns, the
affected are is rinsed with a diluted solution of citric acid. If no suitable neutralizing substances are
available, the affected site is rinsed with a stream of water, for at least 20 minutes. Measures to
prevent secondary infection and relieve pain should then be taken.
8.4.3 Ulcers associated with specific inflammations
The third group consists of ulcers associated with specific inflammations such as tuberculosis and
syphilis, in our geographical conditions. Specific inflammations pose a risk for dentists as they can
cause occupational infections. For a dentist, it is important to be acquainted and comply with the
hygienic regimen and have thorough training in the diagnosis of oral forms of these diseases.
8.4.3.1 Syphilis (lues, French disease)
It is caused by the spirochetal bacteria Treponema pallidum. The clinical picture of the symptoms
of syphilis in the oral cavity is very varied and may resemble symptoms associated with completely
different diseases. The mucosa of the oral cavity can be affected at all stages of acquired syphilis and
a number of manifestations are highly infectious! Congenital forms are also associated with intraoral
symptoms such as afflicted teeth and jaw bones (the typical Hutchinson’s triad: keratitis, labyrinthitis
and Hutchinson’s teeth) but without the affliction of mucous membranes!
The disease is transmitted almost exclusively by direct contact with a patient. Sexual contact is the
most common form of the transmission of this disease (the oral cavity can be affected as a result of
the orogenital form of sexual contact). When the infection is present in the oral cavity, it may spread
through other forms of contact (for example kissing). Indirect transmission can occur rarely. The oral
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cavity is the most common extragenital site of primary infection (10 % of cases)! The oral cavity is
afflicted in the primary stage (ulcus durum, hard ulcer) only when it is the gate for entry of infection
(together with the lips). Infection presents after the incubation time (approximately 3 weeks) as a
shallow ulcer with an elevated margin (initially, it consists of a flat, red papule with a diameter of 1
cm that turns into a pink, glossy (like lard), tangential bevelled ulcer) or as erosion whose surface
looks watery and can be coated with tissue detritus and precipitated blood proteins. When on the red
lip, it presents as a crust. A major collateral edema is formed in its surroundings (initial sclerosis).
One typical finding is that the defect is completely painless and the base of the erosion is hardened
upon palpation (use gloves!). There is noticeable disproportion between subjective problems and a
clinical finding. The defect heals spontaneously in 6-8 weeks after infection; lymphangiitis and
regional lymphadenitis occur during progression. Nodes are freely movable, elastic, painless, the
primary complex is formed. After healing, the generalized affliction of lymph nodes is observed. The
disease progresses into the stage of early latency, followed by the secondary stage. In the secondary
stage, the disease is generalized and manifests itself in 8-10 weeks after infection by mild general
symptoms that resemble viral infection, followed by general lymphadenopathy with the enlarged
spleen, specific laryngitis and tonsilitis. General unspecific symptoms include fatigue, elevated
temperature, headache, loss of appetite and weight loss, polyarthralgia and polymyalgia. Macular
exanthema (roseola syphylitica) will develop. Other skin symptoms may be varied. However, the skin
(mucosa) usually shows one particular type of lesion for a certain period of time (monomorphic
exanthema). In the oral cavity, plain enanthema (red spots) can be found, including smoothed patches
in the physiological coating of the tongue (plaques lisses), yellow-white, slightly prominent patches
(plaques opalines) with the opalescent surface on the dark red base that later transform into erosive
plaques (plaques muqueuses). The macerated mucosa can be found in mouth corners, like in the first
stage (painless bilateral angular cheilitis with crevices), or there may be warts resembling
condylomata on the outer genitals or in the perianal region which are highly infectious. Painless
tonsilitis (syphilitic angina) can be present. Tonsils are red, edematous, with coatings, sometimes with
hoarseness (syphilitic laryngitis). General symptoms are mostly absent! It should be pointed out that
all above-mentioned syphilitic lesions are painless and very varied. Manifestations of the 2nd stage of
syphilis in the oral cavity are frequent and highly infectious! After the secondary stage (which may
last for a different period of time, usually 2-5 years), the disease will become latent and may last for a
number of years (at least 3 years). The tertiary stage of the disease is not infectious, showing localized
organ-specific affliction. In the early tertiary stage, the affliction of the facial skin at syphilis tuberoserpiginosa and syphilis ulcero-serpigninosa can propagate into the oral cavity, with the formation of
infiltrates of a different size that tend to decompose and form scars. Both separated (gummata) and
nonseparated infiltrates of soft tissues, or jaw bones with destructions can develop, resembling benign
tumours. The colliquation and decomposition of infiltrates result in fistulas, with the formation of
scars. When the hard palate is affected, the oronasal communication will occur. Glossitis interstitialis
luetica is another manifestation of tertiary syphilis in the oral cavity and can occur either in the
superficial form (with prominent infiltrates and hyperkeratosis-leukoplakia of the mucosa and
atrophic patches) or in the deep form (glossitis interstitialis luetica profunda), which involves the
whole tongue that becomes stiff and has a limited mobility. It is also associated with the atrophy of
lingual muscles and scarring that may transform into squamous cell carcinoma. In the past, the
78
terminal stage of the disease was associated with damage to the cardiovascular and nervous systems
(tabes dorsalis, progressive paralysis).
Examination: The microscopic examination of the native material in the dark field (mucosal lesions
must not be treated with any antimicrobial agent for at least 2 days, repeated examination is
necessary) is needed in order to confirm primary infection. Serological examinations are still
negative. The second stage of syphilis can be excluded (or confirmed) only by performing serological
tests to prove the presence of specific antibodies in the body (TPHA, TPIT)- see Chapter 2.1.3.
Suspected lesions can be subjected to microscopic examination. Serological and histopathological
tests can be used to confirm the third stage of syphilis.
Therapy is provided at dermatological clinics; different regimens are available with exactly defined
criteria of treatment. The disease is subject to mandatory reporting!
Dif. dg: Difficulties with establishing the diagnosis can occur due to clinical symptoms of all three
stages of acquired syphilis.
The traumatic ulcer of the oral mucosa is detected in the first stage of the disease. It differs from
primary infection by pain, short duration, medical records on injury, and indistinct indurations of the
base. The neurodystrophic ulcer develops as a result of damage to the insensitive oral mucosa after
the application of a local anaesthetic - it occurs particularly in children (in whom syphilis is not a
typical finding). Periadenitis type of recurrent aphthae are multiple, very painful and recurrent.
Herpes labialis (usually with prodromes) and skin pyoderma (furuncle on the skin side of the lips) are
also very painful, with a tendency to colliquation, with major response in regional nodes and elevated
temperature.
It does not need to be difficult to recognize intraororal manifestations at the secondary stage of the
disease using the differential diagnosis approach, if they are taken into account. The targeted medical
history and clinical examination of the condition of the oral mucosa will help in differentiation, with
subsequent verification based on serological tests. Lesions can resemble a number of congenital
mucosal diseases – the geographic tongue (patient medical history), aphthae, stomatitis herpetica,
erythema multiforme and autoaggressive diseases.
The symptoms of the third stage of syphilis in the oral cavity should be distinguished from the
symptoms of TB (the diagnosis of these two diseases is known), tumours and lingual cysts,
leukoplakia and carcinoma.
8.4.3.2 Tuberculosis
Tuberculosis is mostly caused by Mycobacterium tuberculosis or less often by Mycobacterium
bovis. It is a general infectious disease whose incidence rate has increased in recent years.
Predispositions include the weakened organism due to malnutrition, immunosuppression or cachexia
of different origin – HIV, drug abuse. The affliction of the oral cavity is rare. It is associated with the
following three factors: the primary penetration of mycobacteria in the body through the damaged
epithelial covering of the mucosa of the oral cavity, secondarily due to autoinoculation at active TB
(usually pulmonary TB), or the spread of skin TB on the oral mucosa.
Clinical picture: In the case of primary infection, a painless ulcer develops in 14 days (anywhere on
the oral mucosa), regional lymph nodes are affected (they are enlarged, painless or may show
colliquation) and the primary complex is formed (ulcus and regional node). Either the primary
complex will heal at simultaneous indistinct general symptoms, or generalized miliary TB will arise.
At active pulmonary tuberculosis and the inoculation of mycobacteria in the mucosal defects in the
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oral cavity (usually in the dorsum of the tongue, buccal mucosa, gingiva), a single, deep and painful
ulcer with rolled margins (tuberculoma) will develop. The ulcer will not heal at common local
indifferent therapy, and can spread slowly into the surroundings (it behaves like carcinoma - it cannot
be distinguished clinically). When it is deposited deep in muscles, a chronic fistula will develop.
When the gingiva is afflicted, bleeding granulations and vegetations can be present. Diagnosis of
active TB is usually known! (Patients show cachexia, are weak and have distinct general symptoms).
There is a risk of occupational TB infection in health professionals! The skin form of TB known as
tuberculosis cutis luposa (lupus vulgaris) is very rare nowadays. It presents in the oral cavity as red
patches, sometimes with greyish nodes that tend to break down and bleed. Lupus vulgaris is generally
considered to be a precancerosis.
Th: Therapy is provided at specialized clinics of lung diseases.
Atypical mycobacteria such as M. avium, M. kansasii, M. Scrophulaceum, and M. ulcerans can also
cause mucosal defects that look like ulcers in the oral cavity and can be found particularly in HIVpositive individuals.
Fig. 11: Differential diagnosis of the disease with an ulcer as the basic skin manifestation
(taken from Onemocnění sliznice dutiny ustní (Oral mucosal diseases), Škach et al., 1975).
Česky:
Vlivy fyzikální (dekubitální vřed)
Gingivostomatitis ulcerosa
periadenitis mucosa
zoster
Multiformní erytém
Lichen ruber planus (bulosní forma)
Toxickoalergické reakce
Arteritidy
Erythematodes
Infekční mononukleosa
Agranulocytosa
Vředy trofické
ULCUS
Hemoblastosy
Karcinom
Mykosy
Tuberkulosa
Syfilis I. a III. st.
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English:
Physical factors (decubitus ulcer)
Ulcerative gingivostomatitis
Periadenitis mucosa
Zoster
Erythema multiforme
Lichen ruber planus (bullous form)
Toxic-allergic reactions
Arteritis
Erythematosus
Infectious mononucleosis
Agranulocytosis
Trophic ulcers
ULCER
Hemoblastosis
Carcinoma
Fungal infections
Tuberculosis
Stage I and III syphilis
9 SYMPTOMS OF SYSTEMIC DISEASES IN THE ORAL CAVITY
9.1 MUCOSAL CHANGES IN THE ORAL CAVITY IN PATIENTS WITH HIV-INFECTION/AIDS
(ACQUIRED IMMUNE DEFICIENCY SYNDROME)
....Acquired immunodeficiency syndrome was first described in 1981. The range of manifestations of
HIV-infection is extremely broad and may overlap with many diseases of the oral mucosa of different
origin. Schematically, these diseases can be divided into 2 groups: infectious diseases of the oral
mucosa and tumour diseases of the oral mucosa (the diseases of unspecified origin such as recurrent
aphthae could be included in the third group, respectively). Infectious diseases of the oral mucosa can
occur within the ARC (the AIDS-related complex) and are common in patients with manifested AIDS.
However, none of these manifestations is among the clinical criteria for the determination of HIV
infection. The disease of the oral mucosa can manifest itself several months earlier than other HIV
manifestations. Respective changes in the oral cavity can be the first clinical symptoms of the disease,
none of them being specific only for HIV infection! This poses a problem from both the diagnostic
and epidemiological point of view. Diseases with different etiologies may occur in one patient at the
same time (mostly at a level of CD4+ T-lymphocytes below 200/mm3); patients with elevated levels
of CD4+ T-lymphocytes (but still below 400/mm3) usually show only one kind of intraoral affliction
in the oral cavity. Generally, infectious diseases of the oral mucosa can be divided into viral
infections, bacterial infections and fungal infections.
9.1.1 Viral infections
Herpesviruses, papovaviruses or poxviruses are the most common etiological agents. Viral
infections in HIV-positive individuals are usually more serious and prolonged than in HIV-negative
individuals.
Symptoms of primary infection in the oral cavity
2-6 weeks after transmission of HIV infection, 50-80 % of patients show clinical signs of acute
HIV infection. However, these symptoms are not characteristic (fever, myalgia and athralgia, fatigue,
skin exanthema, lymphadenopathy – mononucleosis-like syndrome). The oral cavity shows the
symptoms of acute pharyngitis, the eruption of superficial painful erosions on the hard palate that
resemble aphthae (minor apthosis) but occur at unusual locations (recurrent aphthae never develop on
the keratinized mucosa of the hard palate!). Erosions heal spontaneously in a week together with other
symptoms of acute infection.
Gingivostomatitis herpetica
This disease is usually extensive, with serious progression. It heals more slowly even at general
antiviral therapy.
Stomatitis herpetica
This disease is also serious and prolonged. It is always very painful and shows multiple
recurrences. The disease can develop to a chronic condition and when it lasts more than one month, it
can be considered as opportunistic infection in HIV positive patients. In order to prevent possible
recurrences, the general prophylactic use of acyclovir is recommended.
Herpes simplex (labialis)
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Herpes simplex usually progresses from the lip red to the facial skin, which it affects to a different
extent. The affliction may persist for a long period of time even at therapy.
Herpes zoster cephalicus
This disease is usually recurrent. When present in the oral cavity, it can lead to osteonecrosis of
the alveolar bone. Sometimes, it involves a larger number of sensitive nerves or may occur bilaterally,
which is very rare in HIV-negative persons.
Cytomegaloviral ulcerations
They occur in patients with very serious immune deficiency and are considered a sign of potential
organ-specific complications (CMV-retinitis, etc.). Their diagnosis is difficult when they are among
the first clinical symptoms of immunodeficiency (histopathological verification).
Viral acanthoma
Condyloma acuminata with multiple manifestations and chronic progression occurs in the oral
cavity relatively frequently. They affect the genitals and the perianal region at the same time.
“Hairy” leukoplakia (condyloma plana)
It is characterized by changes on the oral mucosa, usually on the lingual mucosa. It appears as
fuzzy looking white patches with an evenly arranged, folded mucous surface on the tongue’s edges in
the two frontal thirds of the tongue (pars oralis linguae). Leukoplakia can also occur on the tongue’s
dorsum and apex. Sometimes, it can also occur on the labial, buccal or palatine mucosa but it does not
have a typical appearance there (the folding of the mucous epithelium typical of the tongue is absent).
The finding is usually stationary and may disappear spontaneously or after therapy.
Histopathology: It is hyperkeratosis, acanthosis and ballooning degeneration of epithelial cells of the
mucosa with pycnotic nuclei in the stratum spinosum. Pseudohyphae of yeast of the genus Candida
often grow into the superficial layers of the extensively keratinized mucous epithelium. Epithelial
cells show the presence of eosinophilic inclusions (classified as the Epstein-Barr virus with PCR).
Th: General administration of virostatic agents (acyclovir); when yeast is detected, antimycotic
treatment is usually successful. However, the current, widely accepted opinion is that therapy is not
necessary if the patient has no subjective problems.
The occurrence of hairy leukoplakia means a bad prognosis for the disease and progression from HIV
infection to AIDS. More than 80% of patients show progression within 30 months of diagnosis.
Dif. dg: When localized on the edges of the tongue, it must be distinguished from frequently
occurring changes due to chronic injuries to the lingual mucosa (friction injury) such as teeth
impressions or changes due to cheek or lip biting. The tongue can be sensitive and painful. The
typical smokers’ leukoplakia can affect any part of the lingual mucosa. The histopathological
examination usually reveals changes such as hyperkeratosis. The geographic tongue (lingua
geographica) in the phase of the healing of the epithelium may resemble "hairy” leukoplakia.
However, the clinical picture changes quickly within a few days. Oral candidiasis in the acute or
chronic pseudomembranous form can also resemble this affliction. However, it affects other parts of
the oral mucosa and the surroundings of white patches are noticeably red at oral candidiasis. Patients
have subjective problems such as burning sensation and pain.
9.1.2 Bacterial infections
82
They are caused by mixed flora, usually consisting of anaerobic rods and cocci (Bacteroides,
Fusobacterium , Actinobacillus and Peptococcus) or oral spirochetes (the genus Treponema).
Linear marginal edema (HIV-gingivitis)
This disease of the gingiva presents as intense red, 2-3 mm stripes on the marginal gingiva,
accompanied with bleeding and petechiae. From an etiological point of view, this inflammation is
associated with the presence of the microbial plaque in the oral cavity. It differs from the “normal”
plaque-induced gingivitis by the absence of a chronic inflammatory infiltrate and by the abnormal
build-up of vessels in the submucosal connective tissue.
Th: Proper and consistent hygiene of the oral cavity, or the use of antiseptics (such as chlorhexidine)
Dif. dg.: Desquamative gingivitis within the manifestation of lichen ruber planus or pemphigoid
Acute necrotizing gingivitis and stomatitis
It resembles ulcerative gingivostomatitis with the breakdown of interdental papillae and the spread
of white-grey necrosis to adjacent tissues. The surroundings of necroses are red and edematous.
Necroses can also affect the alveolar bone in the form of superficial ostitis but osteomyelitis will not
develop. Initial mild pain will change to intense pain. The premolar sections of the jaws are mostly
affected. Present periodontitis is a predisposition.
Th: The hygiene of the oral cavity (mechanical and chemical – chlorhexidine, the local application of
metronidazole, or general application of antibiotics – tetracycline). The surgical removal of necroses,
symptomatic therapy (analgesics).
Necrotizing ulcerative periodontitis
It is quickly progressing periodontitis with the premature loss of teeth that occurs in a short period
of time (in approximately half a year after the diagnosis has been established). The disease can affect
either certain groups of teeth or the whole dentition.
Clinical picture: The affliction of the supporting apparatus of teeth (the periodontium) is uneven,
usually with purulent exudation from periodontal pockets. Soft tissues covering the alveoli also show
necrotic changes. Severe gingitivis with the necrotic decay of papillae is always present. The disease
is very painful. The X-ray image reveals the uneven loss of bone, sometimes osteonecrosis with the
formation of sequesters.
Th: Initially, analgesics are required (approximately 2 weeks). General antimicrobial therapy is
applied (nitroimidazole, TTC – Warning! A risk of secondary oral candidiasis due to dysmicrobia in
the GIT). Surgical treatment is not performed.
Bacterial ulceration of the oral mucosa
HIV-positive individuals often show painful and deep mucosal defects with the clinical picture of
ulcerations (histopathological and microscopic examinations are necessary). It is not clear whether the
ulcers are formed by the action of microorganisms or whether this involves the secondary
colonization of mucosal defects of a different origin.
Th: Local and/or general use of antibiotics, topical anesthetics to be applied on the mucous membrane
before a meal.
Specific inflammations
83
Oral manifestations of TB in HIV-positive patients have not yet been investigated in detail.
However, they are usually associated with "multiple-drug resistant” tuberculosis (i.e. TB refractory to
therapy). Lues occurs relatively frequently in HIV-positive individuals (the same routes of the
transmission of infection). The general clinical picture in patients including mucosal changes can be
altered due to the presence of a particular immune disorder (lues maligna).
Bacillary angiomatosis
This disease seems to occur only in HIV-positive individuals. It is caused by Rochalimaea henselae
(the genus Rickettsia). It particularly affects the endothelial cells of capillaries, small vessels in the
skin and mucosa, or in internal organs. It presents in the oral cavity as red, nodular, soft hypertrophy
on different locations whereas on the skin it is manifested by maculo-papular exanthema, sometimes
with ulcerations.
Th: Macrolide or tetracycline antibiotics.
Dif. dg: It can easily be confused with Kaposi’s sarcoma (the histopathological examination and/or
immunofluorescent test are necessary for differentiation).
9.1.3 Fungal infections
Recurrent candidiasis is the most common manifestation in the oral cavity in HIV-positive
patients. However, the range of fungal diseases is much broader and also includes deep, systemic
mycoses.
Oral candidiasis
Practically, any of the above-mentioned forms can be found in HIV-positive patients. It is usually
part of the more extensive affliction of the GIT and respiratory tract (candidiasis of the esophagus is
described as a diagnostic criterion of HIV infection). Pseudomembraneous candidiasis can occur on
the oral mucosa practically in all localities, including the gingiva. Chronic, atrophic, hyperplastic or
erythematous forms can lead to the development of superficial, very painful ulcerations that are
difficult to diagnose. HIV-positive patients also show nodular and papillary forms of Candida
infection that do not occur in HIV-negative individuals. Median rhomboid glossitis (glossitis
rhombica mediana) is also present more frequently (Candida-associated lesions).
Th: Third-generation azole antimycotics (fluconazole, etc.) are mainly used in therapy, clotrimazole is
used in local therapy for a period of at least 2 weeks. Fluconazole (applied generally) combined with
locally applied nystatin or chlorhexidine appears to be the optimum treatment. Prophylaxis using
fluconazole or clotrimazole is recommended in HIV-positive individuals after healing.
Dif.dg.: Hairy leukoplakia
Manifestations of systemic mycoses on the oral mucosa
They are usually characterized by a single, very painful ulcer with edematous surroundings.
Histoplasmosis, cryptococcosis, mucormycosis, geotrichosis and aspergillosis can also be present,
which usually indicates a bad prognosis. Candida dubliniensis is a newly identified causative agent of
oral candidiasis in HIV-positive patients.
9.1.4 Neoplasms
Kaposi’s sarcoma, malignant non-Hodgkin lymphoma and squamous-cell carcinoma of the oral
mucosa (particularly of the tongue) are among the most common neoplasms.
84
Kaposi’s sarcoma (sarcoma idiopathicum multiplex)
It is the most common neoplasm in AIDS patients. It occurs in 20 % of these patients. It is
currently considered an infectious disease caused by the HHV-8 human herpesvirus. It primarily
affects the skin, lymph nodes and oral mucosa, with a higher incidence rate in men than in women
(8:1). It presents on the skin as purple or livid multiple papules, nodules and tumour lesions. The oral
mucosa is affected only in some patients, usually after the clinical manifestation of Kaposi’s sarcoma
on the skin. However, in rare cases, the disease can affect the oral mucosa primarily. Lesions in the
mouth present as single or multiple, red or red-brown macules or papules. Later, they develop into
elevated plaques or tumours that can ulcerate. The palate, gingiva, tongue, lips and buccal mucosa are
the most frequently affected sites.
Th: Radiotherapy, interferon-alpha, chemotherapy, or surgical excision of small lesions
Dif. dg: Pyogenic granuloma, hemangioma, pigmented naevi and malignant melanoma
Malignant non-Hodkin lymphoma
This kind of lymphoma is the second most common malignancy in HIV-positive individuals. The
great majority of lymphomas originate from B-lymphocytes, being clinically manifested by an
inflammatory bulge in the oral cavity that can ulcerate. It usually affects the gingiva and the palate.
9.1.5 Diseases of the mucosa of nonspecific etiology in HIV-positive patients
Recurrent aphthae (minor, major, herpetiformes), drug-induced reactions (ulcerative, lichenoid,
toxic epidermolysis) and salivary gland diseases are among the most typical diseases included in this
group.
9.1.5.1 Cystic lymphoid hyperplasia associated with AIDS
It affects the lymph nodes of salivary glands (usually the parotic gland). Its symptoms resemble the
Sjögren’s syndrome.
9.1.6. Guidelines for the treatment of HIV positive patients
Since the clinical symptoms of the disease may appear long after the contact with the HIV virus
(even laboratory tests may not give a reliable result for a certain period of time - 3-6 months), the
medical staff should observe basic hygienic precautions and use protective gloves and a mouthpiece,
when treating HIV patients. Most HIV-positive patients and patients with AIDS symptoms are treated
in specialized clinics for infectious diseases. Every dentist is obliged to provide acute dental
treatment. Precautions that must be observed during dental treatment are based on Regulation No.
440/2000:
a) The patient is scheduled to have a dental treatment at the end of working hours.
b) Tools for single use should be used as much as possible.
c) The assisting nurse must decontaminate and wash the used tools after use, avoiding the formation
of aerosol. Dry tools are sterilized in an autoclave or hot-air sterilizer.
d) The attending physician and other medical staff should use a mouthpiece, cap, safety glasses, fullface shield, disposable clothing and two pairs of gloves (surgical and non-sterile protective!).
e) The use of a turbine should be limited (aerosol) during preparation.
85
f) After prosthetic treatment, all materials which were placed in the patient’s mouth are transported
in a closed container to the laboratory and disinfected and sterilized prior to further processing
(the laboratory technician should be protected in the same manner as the medical staff),
g) X-ray images must be sealed in a plastic foil and submerged into an alcohol solution for
disinfection, prior to development,
h) All materials intended for disposal must be labelled as infectious (including clothing unless it is
intended for single use only),
i) The dental kit must be washed with a disinfectant solution (for example Incidur, Presept) and the
germicidal lamp must be switched on in the room (preferably overnight, after working hours until
the morning).
If a healthcare worker sustains an injury, the wound must be washed and disinfected immediately
(using alcohol solutions – Biotensid, etc.) and allowed to bleed freely! The AIDS centre in the
respective catchment area of the clinic of infectious diseases must be notified of the accident. It will
initiate targeted antiviral prophylaxis after performing laboratory tests (prophylaxis within 1-2 hours
after the injury is effective in up to 100 % of cases).
9.2
MUCOSAL CHANGES IN THE ORAL CAVITY ASSOCIATED WITH DISEASES OF THE
HEMATOPOIETIC SYSTEM
The first symptoms of some of the blood diseases, for example myeloproliferative diseases
characterized by the rapid proliferation of immature blood cells, may first manifest themselves in the
oral cavity. Immature blood cells are malfunctioning. The complications that occur result from a lack
of normal blood elements. In addition, patients are treated with a wide range of drugs that may
produce toxic effects on the oral mucosa.
9.2.1 White blood cell diseases
9.2.1.1 Leukemia and lymphoma
See Chapter 8.4.1.2
9.2.1.1.1 Medicines
Some medicines used in the treatment of myeloproliferative diseases can have toxic effects on the
oral mucosa (methotrexate, daunomycin, cyclophosphamide, 6-mercaptopurine, etc.). The most
common clinical symptoms include white, painful patches with red margins on the gingiva, buccal
mucosa, palate and pharynx. The vast areas of the epithelium can become necrotic. The exposed
erosive areas formed after scaling are often infected with Candida sp. Severe dysphagia is usually
present.
9.2.1.2 Plasmocytoma
The extramedullary forms of plasmocytoma rarely occur in the oral cavity (they are more common
in the upper airways – in the nasal and jaw cavities and in the epipharynx (nasopharynx)). Greyish
nodes are formed, with a tendency to ulcerate.
9.2.1.3 Agranulocytosis
86
Agranulocytosis manifested by leukopenia and granulocytopenia (up to agranulocytosis) presents
local changes on the oral mucosa that are nearly a constant finding. For further details, see Chapter
8.4.1.3
9.2.2 Red blood cell diseases
9.2.2.1. Anemia
This chapter will only mention some forms of anemia whose symptoms occur typically in the oral
cavity although the etiology of these forms can be very different.
Pernicious anemia
It is caused by Castle's intrinsic factor deficiency in irreversible atrophic gastritis - see Chapter
5.4.3.
Sideropenic anemia
It is associated with iron deficiency. It is typical hypochromic anemia - see Chapter 5.4.3.
Aplastic anemia
It occurs when hemopoiesis in the bone marrow is suppressed. General and local symptoms are
similar to those of agranulocytosis – see Chapter 8.4.1.3.
9.2.2.2 Polyglobulia ( polycythemia vera, Vaquez-Osler disease)
It is the opposite of anemia. The face, lips and oral mucosa have a very noticeable, deep red
discolouration (almost cyanosis). The patients suffer from nose bleeding and gingival bleeding. The
tongue is smoothed, filiform papillae are atrophic. The patient can bleed heavily after surgical
procedures in the mouth (for example after tooth extraction).
9.2.3 Hemorrhagic diseases (bleeding diathesis)
Hemorrhagic diseases are characterized by abnormal bleeding that can be spontaneous,
posttraumatic or may occur after surgical procedures. Blood coagulation disorders can also be
associated with the use of some medicines (analgesics, antipyretics).
The symptoms of hemorrhagic diseases are very distinct in the orofacial region and can be the first
indication of a potential blood disorder. Hemorrhagic diseases can be divided into coagulopathies,
platelet disorders and vessel wall disorders.
9.2.3.1 Coagulopathy (disorders of plasmatic factors)
It is caused by plasma factor deficiency. Hemophilia is quite common. Hemophilia A is a
congenital disorder of the procoagulant activity of the low-molecular-weight component of Factor
VIII. Hemophilia B is associated with Factor IX (Christmas factor) deficiency. Both diseases only
occur in men (whereas women are only carriers). A certain percentage of the disease can be caused by
the new mutation (i.e. the patient has no familial history of the disease). Hemophilia C is
characterized by Factor XI deficiency (it can occur in both men and women).
Clinical picture: Bleeding into the GIT is among the first symptoms, together with bleeding into
joints and muscles. In the oral cavity, the disease presents as bleeding into mucous membranes and
muscles, particularly the muscles of tongue (macroglossia haemorrhagica), bleeding into the oral base
and gingival bleeding. Bleeding after tooth extraction can be very dangerous (the dentist should know
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that even a minor surgical procedure must not be performed without a previous hematological
examination and the preparation of a patient). Intramuscular application of injections or drugs that
affect blood coagulation (aspirin, non-steroidal antiinflammatory drugs) should be avoided.
Dg: PTT is prolonged, the Quick’s test is normal.
Th: General therapy is prescribed by a hematologist; drugs that stop bleeding and fibrin foams are
used locally. Preferably, surgical procedures should be performed on an inpatient basis under close
supervision.
9.2.3.2 Disorders of thrombocytes
These disorders can be either quantitative (thrombocytopenia) or qualitative (platelet defects,
thrombocytopathy). Bleeding depends on the number of platelets and can be manifested by bleeding
into the skin and mucous membranes with the formation of small petechiae (they never develop in
hemophilic patients!) or bleeding into internal organs. The most common disorder is idiopathic
autoimmune thrombopenic purpura (Werlhof's disease, morbus maculosus Werlhofi); the clinical
picture of this disease is characterized by bleeding with petechiae, suffusion and hematomas at
different sites, including the oral mucosa. Laboratory tests show a decreased number of thrombocytes,
the result of the Quick’s test is pathological, PTT is normal.
Th.: Therapy is prescribed by a hematologist, local therapy is similar to that for hemophilia.
9.2.3.3 Disorders of the vessel wall (vasculopathy)
They can occur after bacterial or viral infections (sepsis), after some drugs or because of vitamin
C deficiency (scurvy). They particularly affect capillaries. These disorders are characterized by the
development of differently large hematomas, from dot petechiae up to extensive ecchymosis. In
addition, bleeding from different organs and tissues occurs. Hereditary hemorrhagic telangiectasia
(teleangiectasia hereditaria hemorhagica, Osler-Weber-Rendu disease) is the most common disorder,
with congenital dysplasia of the supporting tissue of minor vessels. Clinical examination shows
teleangiectasias of a different size on the skin and mucous membranes. Teleangiectasias on the oral
mucosa are usually located on the lips, tongue and soft palate, and bleed easily and spontaneously
after minor injuries.
Therapy: Symptomatic – coagulation of teleangiectasias.
Allergic-toxic purpura (Schönlein-Henoch syndrome) occurs relatively frequently. It usually
develops after the catarrh of the upper airways associated with a fever, first as urticarial later as
maculopapular exanthema (enanthema) with hemorrhagia. In the oral cavity, it usually presents on the
tongue and the base of the oral cavity as petechiae and hemorrhagias.
Th: Allergens should be eliminated, corticoids are used at the severe progression of the disease.
9.3 DISEASES OF THE HEART AND BLOOD CIRCULATION
The attending dentist should know whether his/her patient suffers from a heart disease or blood
circulation disorder for the following two reasons: patients (for example, patients with hypertension,
congenital heart defects, chronic heart failure, etc.) need special care and treatment after previous
preparation (for example, the prevention of bacterial endocarditis in patients with heart defects). The
second reason is that cardiovascular diseases may produce some changes directly in the oral cavity.
This particularly concerns the disorders of the terminal vascular bloodstream that are usually
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manifested by changes in the mucosal pattern of the tongue. Such changes are usually associated with
the formation of varices, complications may occur in rare cases (clotting, bleeding). The lower part of
the tongue is the most frequently affected site. In the case of right-sided cardiac failure, the tongue
can be enlarged and the mucous membranes have a blue-violet discolouration. In the case of left-sided
insufficiency, they are crimson red and the size of the tongue is not usually changed. Advanced
arteriosclerotic changes can manifest themselves by atrophy of the mucous membrane in the oral
cavity.
9.4 RESPIRATORY DISEASES
At the disease of the upper airways accompanied with a fever (rhinitis, pharyngitis, angina,
tracheitis), the mouth odour (foetor ex ore) can occur (the most common finding is acute or acutely
exacerbated chronic gingivitis - arising due to pain and discomfort in the mouth that reduce hygiene in
the oral cavity, causing plaque to develop). Mucous membranes can be dry, lips can be dry and
cracked. Besides gingivitis, the enlargement of the tongue coating is often observed in patients with
pneumonia. The eruptions of herpes labialis (also called herpes febrilis) are common. A typical mouth
odour occurs at bronchiectasis or pulmonary abscess. The secondary ulceration on the oral mucosa is
a rare complication of pulmonary TB.
9.5 RENAL DISEASES
A typical mouth odour occurs in the terminal stage of chronic renal failure, at uremia. Otherwise,
there are no typical changes on the mucosa. The tongue can be dry, with a brownish coating, the lips
can be crusty. Gingival bleeding is common and is caused by a disorder of thrombocyte function
(either as a symptom of a renal disease or secondarily due to damage to thrombocytes during dialysis).
9.6 GASTROINTESTINAL DISEASES
Basic pathological changes associated with the diseases of the gastrointestinal tract were
discussed in previous chapters. Recurrent aphthae occur typically in patients with diseases of the
gastrointestinal tract whereas patients with vitamin or trace element (Fe) deficiencies show the
smoothed tongue and painful mouth corners as typical symptoms. Besides the oral cavity, the
esophagus can also be affected, resulting in the symptoms of dysphagia. At acute inflammations of the
gastric mucosa, the coating of the tongue can be white, wet and enlarged, whereas at chronic
inflammations of the gastric mucosa, the coating of the tongue will disappear, showing atrophic
mucosa. Acute abdominal episodes (particularly when the peritoneum is irritated) are characterized by
the enlarged, brownish coating of the tongue, and the tongue is dry.
At hepatic diseases, the lingual mucosa may show atrophic changes. Particularly filiform papillae
may show atrophy which starts on the apex and will later spread through the whole surface of the
tongue. The tongue is dark red, wet, almost without any coating, with slight hyperkeratosis.
The pigmentation of lips and the oral mucosa can be diagnostically very useful in the case of
intestinal polyposis associated with the Peutz-Jehgers syndrome (see Chapter Pigmentation – dif. dg.
remarks).
Diabetes-associated changes on the mucosa of the oral cavity are very variable and usually occur
as secondary. They are characterized by the red discolouration and the smoothed pattern of the lingual
mucosa, the mucosa looks congested. Since patients with diabetes mellitus are very prone to
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infectious complications, bacterial infections (ulcerative gingivostomatitis) occur more frequently in
these patients, showing a decreased tendency to heal. Fungal infections (fungal stomatitis) are also
common in these patients. Diabetic patients also show a higher rate of leukoplakia, gingivitis and
periodontitis that usually progress more quickly than in healthy individuals.
10 PRECANCEROSES
Precanceroses are all pathological processes that are not carcinoma by itself but can turn into
malignancy at certain conditions. These lesions can show cell abnormalities and loss of the normal
maturation of cells, which indicates that they may later turn malignant. They are described as
epithelial dysplasia. Histological changes indicating the diagnosis of epithelial dysplasia include the
loss of cell polarity in the basal layer, an increase in the nucleoplasmic index, the increased number of
mitotic figures, the presence of atypical mitosis, cellular and nuclear polymorphism, hyperchromasia
of the nucleus and the enlargement of the nucleoli. The number of the above-mentioned changes
determines the degree of dysplasia - mild, medium and severe (lower-degree dysplasia is usually
associated with inflammations and regenerative processes). The development of epithelial dysplasia is
a prerequisite for the development of carcinoma where mild to medium dysplasia means an increased
risk for transformation into carcinoma and severe dysplasia means a high risk for transformation into
carcinoma.
Precanceroses in the region of the lips and oral mucosa particularly include leukoplakia and
erythroplakia, rarely senile keratoma and cornu cutaneum. On the basis of the correlation of
pathological, anatomical and clinical findings, precanceroses can be divided into 3 groups according
to severity:
1) The first group includes precanceroses in a more general sense, for example afflictions that
may turn into carcinoma. Homogenic leukoplakia is one of the forms of leukoplakia that
belongs to this group. It is characterized by regular hyperkeratosis and acanthosis without the
signs of epithelial dysplasia. However, even with this diagnosis, regular follow-ups and
preventive care are necessary (the process may progress even after many years of a stationary
finding).
2) The second group includes precanceroses in a narrower sense, showing structural unrest and
signs of proliferation activity. Cell and nuclear polymorphism and abnormalities can be
present. The entire epithelium shows structural irregularities with changes in keratinization
such as hyperkeratosis or dyskeratosis, but the basement membrane is not affected. This
group includes non-homogeneous leukoplakia, cornu cutaneum and senile keratoma.
3) The third group includes intraepithelial carcinoma (carcinoma spinocellulare in situ). It is a
neoplastic lesion where the squamous-cell epithelium in the whole layer shows all
histological signs of malignancy, except for invasion. It can easily transform into invasive
carcinoma. This group includes erythroplasia of Queyrat.
10.1 LEUKOPLAKIA
The term leukoplakia is used to describe whitish patches on the oral mucosa which can differ by
appearance and etiology (see Chapter 8.2.1). Definitive diagnosis can be established on the basis of
evaluating the macroscopic finding, etiological factors and histological examination.
10.2 ERYTHROPLAKIA
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Erythroplakia presents on the oral mucosa as a flame red patch (see Chapter 8.2.10), with a high
risk for the development of carcinoma.
10.3 SENILE KERATOMA (KERATOMA SENILE)
It belongs to a group of precanceroses that often turn malignant. Ultraviolet light is assumed to be
the major etiological factor. Senile keratoma can be found on the sites often exposed to sunlight, for
example on the facial skin and the lip red.
Clinically, it presents on the mucosa as a greyish spot with indistinct margins. Its surface peels off in
scales, sometimes with the formation of small erosions or crusts. When it turns into carcinoma, the
base will show induration; erosions will become deep and pustules will grow on the surface.
Léčba: Radical surgery.
Dif. dg: Particularly, in the beginning, one should distinguish the scaling of the lip red associated with
cheilitis, lichen ruber planus, erythematosus and psoriasis.
10.4 CUTANEOUS HORN (CORNU CUTANEUM)
Clinical findings are similar to those for senile keratoma in its early stages. It is hyperkeratosis
which initially resembles a papule. Later, the keratotic layer will grow to form a differently long,
corny outgrowth. It occurs on the face, lip red or rarely on the oral mucosa.
Th.: Radical surgery because of the nature of a lesion.
10.5 OTHER FACULTATIVE PRECANCEROSES
There is a wide range of other pathological conditions - general or local - which make the oral
mucosa more susceptible to carcinogens (histological examinations show the atrophy of the
epithelium), thereby posing a risk of tumours.
10.5.1. Sideropenic dysphagia (Paterson-Kelly, Plummer-Vinson syndrome)
It predominantly occurs in middle-aged women with iron deficiency in serum (see Chapter 5.4.3).
The whole mucosa in the oral cavity is glossy, red and atrophic. Leukoplakias are common and may
turn into carcinoma in some cases (particularly in the rear part of the oral cavity and the oropharynx).
10.5.2 Discoid lupus erythematosus (DLE)
It presents in the oral mucosa as pseudoepitheliomatous hyperplasia (see Chapter 8.2.8.1). Carcinoma
was reported to develop in the atrophic epithelium (particularly on the lower lip).
10.5.3 Xeroderma pigmentosum
It is a recessive inherited disease characterized by the hypersensitivity of the skin to UV radiation.
The atrophy of the epithelium, hyperkeratosis, teleangiectasias and hyperpigmentations occur on the
site after exposure. The disease particularly affects the lips and the oral mucosa where spinocellular
carcinoma may develop.
10.5.4 Epidermolysis bullosa
It is an inherited disease with autosomal dominant or recessive inheritance. It presents as blisters
on the skin or the oral mucosa. Subsequent scarring may cause ankyloglossia and microstomia. The
carcinoma of the tongue in the scar was reported.
10.5.5 Lues
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Leukoplakias may develop in the atrophic epithelium of the tongue dorsum in later stages of
syphilis, and may turn malignant (for details see Chapter 8.4.3.1).
10.5.6 Lichen ruber planus
It was described in Chapter 8.2.3. Malignant transformation of this disease was reported in 3% of
patients. Nesrozumitelné: Zvláště ženy jsou postiženy vznikem karcinomu dutiny ústní 50x častěji než
ostatní ženská populace. The carcinoma of the oral cavity occurs in women 50x more frequently than
in other female population.
10.5.7 Sjögren's syndrome
It also belongs to a group of precanceroses (see Chapter 6.3.2.1).
10.6 PARANEOPLASTIC SYNDROMES
Apart from precanceroses, there is another group of conditions that are not precanceroses in itself
but are the consequence of the presence of cancer in other parts of the body. These diseases are called
paraneoplastic syndromes, for example acanthosis nigricans (see Chapter 8.1.4) and the Peutz-Jeghers
syndrome (see Chapter 8.1.3).
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