Chronic granulomatous diseases of nose and
paranasal sinuses
DR. Kamlesh Dubey
definition
• term "granuloma" is derived from the Latin "granulum", referring to a small particle such
as a grain
• a focal area of chronic inflammation produced by circulating monocytes as part of an
immunologic process
Pathophysiology
• Neutrophils usually remove agents that incite acute inflammatory responses by phagocytosis and digestion
• if an agent is indigestible, yet provokes an acute response- vicious cycle
 deplete the body’s white count
 cause severe damage to local normal tissues
 body deals with such indigestible substances and prolonged inflammatory reactions by forming granulomas
 principal cells involved in granulomatous inflammation are macrophages and lymphocytes
 Upon phagocytosis of an indigestible substance, macrophages:
 lose their motility and accumulate at the site of injury
 undergo a structural change to become epithelioid cells
 Nodular collections of these epithelioid cells form the heart of the granuloma
 multinucleated giant cells, formed by the fusion of up to fifty macrophages
 "Langhans Giant cell“-nuclei arranged in a horseshoe pattern
 foreign body giant cell-fungal spore or silica particle, is found within the giant cell
Classification
• Immunologic : autoimmune diseases
 Wegener’s granulomatosis
 Relapsing polychondritis
 SLE
 Churg-Strauss syndrome(allergic granulomatosis & vasculitis)
 Crohns disease
Classification
• Unknown etiology:
 Sarcoidosis
 Idiopathic midline disease
• Neoplastic granulomatous diseases:
 Langerhans cell histiocytosis
 Hand-Schuller-Christian disease
 Eosinophilic granuloma
 Fibrous histiocytoma
 Pyogenic granuloma
 Giant cell granuloma
 Cholesterol granuloma
Classification
• Infectious :
• Bacterial:
 Tuberculosis
 Leprosy
 Rhinoscleroma
 Syphilis
 Actinomycosis
• Fungal :
 Aspergillus
 Histoplasmosis
 Blastomycosis
 Zygomycosis
 Dermatocietes
 Sporotrichiasis
 Coccididomycosis
• Protozoa :
 Leishmaniasis
• Miscellaneous:
 Rhinosporidiosis
Tuberculosis
• least liable to invasion by acute tuberculosis of any part of the respiratory tract:
 structure of mucosa
 respiratory movements of the cilia
 bactericidal secretions
• Route of spread:
 Direct :
 air current by people sneezing or coughing
 direct inoculation by finger borne infections and by instrumentation
 Indirectly (secondarily):
 through the blood and lymph vessels
M. tuberculosis
Tuberculosis
• Types :
Nodular : lupus vulgaris
 Begins in vestibule
 Direct inoculation
 Strong immunity
 Pain unusual
 Ulcer: pale granular base , undermined edges
 Progressive scarring & deformity
Ulcerative
tuberculosis
• Paranasalsinus TB:
 Tuberculosis of paranasal sinuses: S. Sanehi Chandrashekhar Dravid Neena Chaudhary V. P.
Venkatachalam: Indian J. Otolaryngol. Head Neck Surg(January-March 2008) 60:85–87:
much rarer
Maxillary and ethmoid sinus most susceptible
disease is nearly always secondary to pulmonary or
extra pulmonary tuberculosis
Pathologically, three types can be recognized:
 confined to the mucosa only
 bony involvement and fistula formation
 hyperplastic type
Tuberculosis
• Site :
 Nasal vestibule
 anterior portions of the inferior turbinate, nasal septum
 Involvement of posterior nares is rare
 nasal floor is almost always spared
 Direct extension of infection from nose to sinuses
• Clinical presentation:
 nasal tuberculosis may not manifest themselves until the disease is well on its way
 Earliest: Bloody nasal discharge, possibly the only, presenting symptom
 Others: Pain, nasal obstruction and dryness in the nose or throat
 eye symptoms : involvement of NLD
 Headache: sinus involvement
 rapidly growing ulcer or tumour mass in the quadrangular cartilage of the nasal septum
 Septal perforation
Tuberculosis
• Workup :
 DDx:
 midline granulomas (i.e. wegners granulomatosis, leprosy, sarcoidosis, subcutaneous
phycomycosis, granulomatous syphilis etc.)
 Carcinoma
 rhinoscleroma, rhino- sporidium seeberi, rhinitis sicca, suppurative sinus disease and foreign
bodies
 History
 Clinical examination: nasal endoscopy
 Hemogram, ESR, CXR PA view, Monteux skin test
 AFB staining , Culture
 Serological : TB PCR
 Radiological: CECT PNS
 Biopsy: usually required to establish the diagnosis
• Nasal secretions and swab specimens have a very low yield and should not be
used to rule out nasal TB: Goguen LA, Karmody CS. Nasal tuberculosis. Otolaryngol
Head Neck Surg 1995;113:131–5
• Biopsy :
LABORATORY TESTS FOR EXTRA-PULMONARY TB
Test
Sensitivity (%)
Specificity(%)
Timescale
Diffs atyp
myco?
Comments
Skin test
79
76
72h
72 h
PPD
Microscopy
>98
41–65
1–2 h
No
ZN stain most
common
Culture
46–63
98
∼21 d
Yes
Faster results
with liquidbased media
NAAT(nucleic acid
amplification test)
78
96
<24 h
Yes
High unit cost
Interferon γ
85
95
16–24 h
Yes
Requires
whole blood
sample
Tuberculosis
• Treatment :
adequate anti-tuberculosis therapy
excisional surgery: if obstruction is significant
 reconstruction plastic surgery for perforation of nasal septum and cosmetic purpose
Leprosy
• Obligate intracellular Gram positive and acid fast bacilli
• Short, thick, pink stained rods
• Size: 5 X 0.5 
• Arrangement: Single or in cigar-shaped bundles or in “globi”
• Affinity for Schwan cells & cells of R-E system
• Cannot grow in vitro but can grow in
• mice and
• nine banded armadillos
Reservoir of infection
• Main reservoir: Human being
• Lepromatous case> Non lepromatous cases
• Animal reservoirs
• 9-banded armadillos
• Chimpanzees
• Mangabey monkeys
Portal of entry:
• Major portal of exit: Nose
• LL cases harbour millions of M. leprae in their nasal mucosa
• Ulcerated or broken skin of bacteriologically positive cases
Mode of transmission:
• Transmission by inhalation
• Droplet infection
•
Transmission by contact
• Skin to skin contact with infectious cases
• Skin contact with soil & fomites
WHO classification
• Clinical features: depend on type of leprosy
Tuberculoid:
 No mucosal involvement
 Skin of nasal vestibule can be involved
Borderline : no mucosal involvement
Lepromatous :
 Nasal mucosal involvement occurs early
 Nasal obstruction
 Crust formation
 Blood stained discharge
 hyposmia
 Late disease: atrophic rhinitis, septal perforation, dorsal saddling
diagnosis
• Early diagnosis essential : nasal discharge principle route of transmission
• Diagnosis :
Clinical findings
 Skin anesthesia
 Thickened peripheral nerves, skin lesions
Bacteriological examination:
 Microscopy : nasal discharge, scrappings of nasal mucosa
 Histopathology of nasal mucosa
 Skin biopsy in TT, IL
Treatment
• Anti leprosy therapy
WHO treatment regimen:
 Tuberculoid : x 6 months
 Dapsone 100mg x od –unsupervised, 1-2mg/kg in children not more than 100mg/day
 Rifampicin 600mg x monthly – supeprviced
 Lepromatous : 1-2 years
 Dapsone 100mg x od – unsuperviced
 Clofazimin 50mg x od – unsuperviced
 Clofazimin 300mg x od – superviced
 Rifampicin 600mg x monthly – superviced
Direct intranasal rifampicin reduce bacterial load much faster than oral

Rhinoscleroma
• chronic granulomatous condition of the nose and other structures of the upper respiratory
tract
• caused by Klebsiella rhinoscleromatis—subspecies of Klebsiella pneumoniae— a gram-
negative, encapsulated, nonmotile, rod-shaped bacillus (diplobacillus)
• Historical facts:
• Hans von Hebra (1847–1902) wrote classical description of disease in a paper published
January 1870
 Polish surgeon Johann von Mikulicz in Wroclaw described histologic features in 1877
 von Frisch identified the organism in 1882
 In 1932, Belinov proposed the use of the term scleroma respiratorium
 1961, Steffen and Smith demonstrated that K rhinoscleromatis conformed to Koch's
postulates
Syphilis
• Congenital :
• Acquired :
Early
Primary (chancre)
Secondary
Late
Tertiary (gumma)
Clinical features
• Early congenital :
 Purulent nasal discharge
 Fissuring & excoriation of nasal vestibule
• Late congenital:
 Gummatous lesion destroy nose structure
 Corneal opacity
 Deafness
 Hutchinson’s teeth
Complications
• Vestibular stenosis
• Perforation nasal septum
• Secondary atrophic rhinitis
• Saddle nose deformity
Investigations
• Specific treponemal tests:
 Treponemal enzyme immunoassay (EIA)
 Fluorescent treponemal antibody absorbed test (FTA-abs)
• Cardiolipin or non-treponemal tests:
 VDRL
• Demonstration of T. pallidum:
 Dark field microscopy.
 Direct fluorescent antibody (DFA) test.
 Polymerase chain reaction (PCR).
Management
• Primary, secondary, early latent syphilis:
 benzathine penicillin 2.4 mega units (intramuscular (IM), single dose)
 oral azithromycin single dose
 procaine penicillin 600,000 units (IM, once daily for 10 days)
 doxycycline 100 mg twice daily for 14 days
• Late latent syphilis:
 benzathine penicillin weekly for three weeks is first-line
Clinical stages
• 1. catarrhal :
 Foul smelling, purulent nasal discharge(carpenter glue), no response to conventional
antibiotics
• 2. atrophic :
 Foul smelling, honey comb colored crusting in stenosed nasal cavity(in contrast to roomy
nasal cavity in atrophic rhinitis
• 3. nodular :
 Non ulcerative painless nodules (soft bluish red →pale, hard) → widen lower nose(hebra nose)
• 4. cicatrizing:
 Coarse & distorted external nose (Tapir nose)
 Lower external nose & upper lip → wooden feel
• Epidemiology :
 Slightly more females than males are affected
 Age : usually 10 to 30 years of age
 Africa (Egypt, tropical areas), Southeast Asia, Mexico, Central and South America, and
Central and Eastern Europe
 Five percent of all cases occur in Africa
 Risk factors: crowded conditions, poor hygiene, and poor nutrition
 Mortality/Morbidity: rarely lethal, unless it causes airway obstruction
Diagnosis
• Culture :
 in MacConkey agar is diagnostic
 culture results are positive in only 50-60% of patients
• Staining : periodic acid-Schiff, Giemsa, Gram, and silver stains
• Immunoperoxidase technique: of a biopsy specimen
• HPE:
Mikulicz (foam cells):
 Histiocytes with foam vacuolated cytoplasm + central nucleus & containing frisch bacilli
 Warthin-Starry stain
Russel (hyaline) body:
 Degenerated plasma with large round eosinophil material
Treatment
• Medical treatment:
 Total duration: 6 weeks-6 months
Negative culture from two consecutive biopsy materials
Streptomycin 1gm x OD I.M + Tetracycline 500mg x QID
Rifampicin 450mg x OD
2% Acroflavin solution apply locally x OD
RT: 35 Gy over 3 weeks + antibiotics → to halt progress of resistant cases
Sx :
 removal of granulation & nodular lesion
 Dilatation of airway combined with insertion of airway tube for 6-8 weeks
 Plastic reconstruction surgery after three negative cultures from biopsy
Rhinosporodiosis
• chronic granulomatous infection of the mucous membranes
• described by Seeber in 1900 in an individual from Argentina
• reported from about 70 countries with diverse geographical features
• highest incidence has been from India and Sri Lanka
• India : Kerala, Karnataka, Tamil Nadu
• activated macrophage :
 increase in the functional activity of the macrophage
 a new functional activity has appeared
 increase their nuclear euchromatin content
 develop prominent nucleoli
 extensive cytoplasm
 free ribosomes
 abundant Golgi apparatus
 large lysosomes
Etiology
• Rhinosporidiosis is an infective disease in the sense that the tissue lesions are always
associated with the presence of the pathogen
• Rhinosporidium seeberi, has never been successfully propagated in vitro
• Initially thought to be a parasite, for more than 50 years
• Bizarre fungus: obsolete theory
Alhuwalia KB, Maheshwari N, Deka RC. Rhinosporidiosis: a study that resolves etiologic
controversies. Am J Rhinol. 1997;11:479-83:
 R. seeberi is a prokaryote cyanobacterium within the genus Microcystis
Herr RA, Tarcha EJ, Taborda PR, Taylor JW, Ajello L, Mendoza L. Phylogenetic analysis of
Rhinosporidium seeberi's 18S small-sub unit ribosomal DNA groups this pathogen among
members of the protistan Mesomycetozoa clade. J Clin Microbiol. 1999;37:2750-4 :
 R. seeberi is a eukaryote microbe within the Mesomycetozoa
• The taxonomy and phylogenetics of the human and animal
pathogenRhinosporidium seeberi: A critical review(Vilela,
Raquel; Mendoza, Leonel Rev Iberoam Micol. 2012;29:185-99:
 is a mesomycetozoa microbe based on DNA and phylogenetic analysis
Epidemiology
• Age : 15-40 years
• Sex : M/F 4:1
• Curious feature:
 while several hundreds of persons bathe in the stagnant waters, as in Sri Lanka,
only a few develop progressive disease
 existence of predisposing factors:
 only patient factor on which there is some data is blood groups
• In India the highest incidence of rhinosporidiosis was in Group O (70%)
• Jain S. Aetiology and Incidence of Rhinosporidiosis. Indian Journal of Otorhinology, :
 reported that the blood group distribution was too variable to draw any
conclusion
• In a small series of 18 Sri Lankan patients, the distribution was different; Groups
A Rh+ and O Rh+ having 33% each, Group B Rh+ with 22%, and Group AB Rh+
with the lowest of 11%
• Mode infection:
 through the traumatised epithelium ('transepithelial infection')most commonly
in nasal sites:Karunaratne WAE. The pathology of rhinosporidiosis. J Path Bact
 occurrence of rhinosporidiosis in river-sand workers, in India and in Sri Lanka, is
particularly relevant to such a mode of infection
• Mode of spread:
 'Auto-inoculation‘(Karunaratne WAE. Rhinosporidiosis in Man: (The Athlone
Press, London) 1964):
 explanation for the occurrence of satellite lesions adjacent to granulomas
especially in the upper respiratory sites and for local spread
• Haematogenous spread:
 evidence for haematogenous spread of rhinosporidiosis to anatomically distant
sites i.e development of subcutaneous granulomata in the limbs, without breach
of the overlying skin
• Lymphatic spread :
 is controversial
 first report on the occurrence of inguinal lymphadenitis in a case of
disseminated rhinosporidiosis which involved the lower limbs was made in 2002
 rarity might be related to the diverse mechanisms of immune evasion
by R.seeberi
Clinical features
• polyps are pink to deep red, are sessile or pedunculated, and are often
described as strawberrylike in appearance.
• anterior nares, the nasal cavity - the inferior turbinates, septum and floor
• Posteriorly, rhinosporidial polyps occur in the nasopharynx, larynx, and
soft palate
• buccal cavity is only rarely affected
Suggestion : that the primary site of rhinosporidiosis is the lacrimal sac
with downward spread to the nasal passages through the naso-lacrimal
duct(disputed)
• H/o: epistaxis, viscid nasal discharge, nasal block
Features of nasal rhinosporidiosis
• Chronicity
• Recurrence
• Dissemination
Chronicity :
 immune suppression
 Immune Deviation
Pathology
• Appearance :
 polypoidal, granular, red in colour due to pronounced vascularity
 with a surface containing yellowish pin head-sized spots(represent
underlying mature sporangia)
 Naso-pharyngeal polyps are often multi-lobed
Diagnosis
• definitive diagnosis: by histopathology on biopsied or resected tissues
with the identification of the pathogen in its diverse stages
• Pitfalls in the histopathological diagnosis of rhinosporidiosis:
• Microscopic examination of nasal discharge for spore
• Serologic testing:
 Immunoblot (dot – enzyme-linked immunosorbent assay [ELISA])
identification of antirhinosporidial antibody
• Life cycle :
a)
release of the endoconidia
b) increase in size (10–70(μm)
c)
juvenile sporangia (JS)
d) JS increases in size 70–150(μm) IS
e)
early mature sporangia
f) Mature sporangia
Treatment
• cases of spontaneous regression have been recorded
• Total excision of the polyp, preferably by electro-cautery
 Pedunculated polyps permit of radical removal
 excision of sessile polyps with broad bases : recurrence due to spillage of
endospores
• dapsone (4,4-diaminodiphenyl sulphone):
 arrest the maturation of the sporangia and to promote fibrosis in the
stroma
 100 mg/day x 1year
 No innovations in treatment since surgery and dapsone were introduced
Nasal leishmaniasis
• Presentation of cutaneous leishmaniasis (CL)
• Infecting organism :
 protozoan parasites belonging to the genus Leishmania
• Vector :
 bite of a tiny – only 2–3 mm long – insect vector, thephlebotomine sandfly
 500 known phlebotomine species: 30 only transmit infection
 Only the female sandfly transmits the parasites.
 Over a period of between 4 and 25 days, parasites develop in the sandfly
Nasal leishmaniasis
• frequently been mentioned in the literature as a presentation of CL
• nasal affliction in CL: most exposed and unprotected part of the face
• can have a variety of appearances:
 psoriasiform plaques
 furunculoid nodules
 lupoid plaques
 erysipeloid or mucocutaneous
 Rhinophymous(rhinophyma-like plaque)
• Visceral and cutaneous leishmaniasis in patients with AIDS
A proposed new clinical staging system for patients with
mucosal leishmaniasis (Hélio A. Lessa et.al Trans R Soc Trop
Med Hyg. 2012 June; 106(6): 376–381
• Stage I: nodular lesion
• Stage II: Fine granular lesions:
• superficial ulcerations observed at the inferior conchae and the floor of the nasal fossa
• Stage III:Deep ulceration
• more intense tissue reaction and clearly visible tissue granulation and mucosa infiltration
• Stage IV: Septal perforation
• visible tissue granulation and mucosa infiltration of the posterior nasal septum and
inferior conchae
• Stage V:
Destruction of nasal architecture and altered facial structure
Nasal clinical features
Symptoms
Signs
Rhynorrhea
Mucosal infiltration
Pruritus
Ulcer
Obstruction
Septum perforation
Epistaxis
Cartilagenous septum destruction
Diagnosis
• Montenegro skin test :
 similar to the purified protein derivative (PPD)
 to determine delayed-type hypersensitivity reactions
 made locally from killed promastigotes
• Biopsy :
 from the raised edge of an active lesion
 aline aspiration, tissue scrapings, or slit incisions
Direct visualization: hematoxylin and eosin staining, Giemsa staining
Culture tissue samples and aspirates: Nicolle-Novy-MacNeal (NNN) medium
inoculating tissue into the footpad and nose of hamsters
• Serology : PCR, isoenzyme electrophoresis, or monoclonal antibody speciation
Treatment
• Medical :
Injectable :
Pentavalent antimony compounds:
 Sodium stibogluconate
 Meglumine antimmonate
Amphotericine B
Pentamidine
Oral :
 Dapsone x 6 weeks, ketoconazole, fluconazole
 Miltefosine : 2.5mg/kg x 4-6 weeks
Topical :
 Parmomycin : ointment 15% parmomycin+12% methylbenzethonium chloride
• Surgical therapy:
 Leishmania : are temperature sensitive
 Local treatment with cold/heat :
Cryotherapy : 15-20 seconds freeze-thaw-refreeze cycle x 1-2 weeks
Thermosurgery : heats skin by radiofrequency waves (directed to
specified area and depth)
Autoimmune disorder
Wegener’s granulomatosis
• Definition :
A condition, characterized by granulomatous inflammation involving
 Respiratory tract
 Necrotizing vasculitis affecting small-medium sized vessels
 Necrotizing vasculitis
• Dr Friedrich Wegener, a German pathologist who first described the disease
as rhinogenic granulomatosis in 1936:
o Wegener, F.1939: A peculiar rhinogenic granulomatosis with particular
involvement of the arterial system and the kidneys. Beitraege zur Pathologie 102:
36-68
Profile of Organ Involvement in Wegener Granulomatosis
Organ Site
Frequency at Presentation, %
Frequency During Disease
Course, %
Upper airway
73
92
Lower airway
48
85
Kidney
20
80
Joint
32
67
Eye
15
52
Skin
13
46
Nerve
1
20
Variants
• Head and neck alone
• Head and neck and pulmonary
• Head and neck, pulmonary, and renal
 Cadoni G, Prelajade D, Campobasso E. Wegener's granulomatosis: a
challenging disease for otorhinolaryngologists. Acta Otolaryngol. Oct
2005;125(10):1105-10.
 Cummings CW, Haughey BH, Thomas JR, et al. Otolaryngology - Head and
Neck Surgery. 4th ed. St. Louis, MO: Mosby, Inc; 2005:934-936; 1493-1508.
Etiology
• belongs to the heterogeneous group of systemic vasculitides.
• multifactorial pathophysiology of WG supposedly caused by yet unknown
environmental influence(s) on the basis of genetic predisposition
• Presence of ANCA in the plasma of ~90%→autoimmune
• ANCAs are mostly directed against proteinase 3 (PRTN3)
 primary azurophil granules of polymorph nuclear neutrophils (PMN)
 lysosomes of monocytes
Clinical features
• nose and paranasal sinuses are involved in up to 80% of Wegener granulomatosis (WG)
cases
• Gubbels SP, Barkhuizen A, Hwang PH. Head and neck manifestations of Wegener's
granulomatosis.Otolaryngol Clin North Am. Aug 2003;36(4):685-705:
 Chronic sinusitis affects 40-50% of patients
 mucosal edema with obstruction, rhinorrhea, ulcerations, crusting, and epistaxis
 osteocartilaginous destruction :
• Saddle nose deformity
• Septal perforation
• Pain at the nasal dorsum, which suggests chondritis
• Osteocartilaginous destruction does not correlate closely with active disease
Diagnosis
• c-ANCA +ve in 95%-generalized: 60%- localized disease
• The American College of Rheumatology 1990 criteria for the classification of Wegener's
granulomatosis(Leavitt RY. Et.al. Arthritis Rheum. 1990 Aug;33(8):1101-7. )
• presence of 2 or more of these 4 criteria was associated with a sensitivity of 88.2% and
a specificity of 92.0%
Treatment
• Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic
review. Clin Exp Rheumatol. September-October 2008;26:S94-S104:
 Untreated generalized or severe Wegener granulomatosis (WG) typically
carries poor prognosis
 with up to 90% of patients dying within 2 years, usually of respiratory or
renal failure
 Even non-renal WG carries a mortality rate of up to 40%.
• Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of
primary small and medium vessel vasculitis. Ann Rheum Dis. March 2009;68:310-317:
 European Vasculitis Study Group recommends grading disease :
I.
Localized - Upper and/or lower respiratory tract disease without any other systemic
involvement or constitutional symptoms
II.
Early systemic - Any, without organ-threatening or life-threatening disease
III. Generalized - Renal or other organ-threatening disease, serum creatinine level less than
5.6 mg/dL
IV. Severe - Renal or other vital-organ failure, serum creatinine level exceeding 5.6 mg/dL
V.
Refractory - Progressive disease unresponsive to glucocorticoids and
cyclophosphamide
Treatment
• Remission Induction:
Cyclophosphamide
 daily oral route or intermittent intravenous route in combination with high-dose glucocorticoids.
 daily oral dose of cyclophosphamide is 2mg/kg/day (not to exceed 200mg/day)
 Pulsed (intravenous) cyclophosphamide (15mg/kg every 2 weeks for the first 3 pulses, then every
3 weeks for the next 3-6 pulses)
 continued until there is significant disease improvement or remission, typically 3-6 months
 Prophylaxis against Pneumocystis (carinii) jiroveci pneumonia: TMP-SMZ at 160/800 mg 3 times
weekly
Rituximab
 375 mg/m2 weekly times 4
 with high-dose glucocorticoids represents an alternative to cyclophosphamide for induction of
remission
Plasma exchange
 in patients with rapidly progressive renal disease (serum creatinine level >5.65mg/dL)
 mechanism of action of plasma exchange in AAV includes removal of pathologic
circulating factors (eg, ANCA, activated lymphocytes)
 removal of excess physiologic factors (eg, complement, coagulation factors,
cytokines/chemokines)
 Adverse effects:
o electrolyte disturbances, anaphylaxis, hemorrhage, and transfusion-related lung injury
• Methotrexate
• Localized, milder disease
• 20-25 mg/wk, oral or subcutaneous + Daily folic acid 1 mg/day
• Remission Maintenance
 continued for at least 18 months, often longer
 Azathioprine:
o 2 mg/kg/day)
o higher relapse rates than cyclophosphamide
 Methotrexate
 Leflunomide
o 20-30 mg/day
o may be used in patients with renal insufficiency
o associated with increased peripheral neuropathy symptoms
Alternative or Promising Therapies
Intravenous immunoglobulin
Etanercept
Infliximab
Mycophenolate mofetil
Alemtuzumab
Abatacept
Stem cell transplantation
sarcoidosis
• Synonyms : boeck’s sarcoidosis, besner-boeck-schoumann syndrome
• Definition :
A disease characterized by formation in all of several affected organs or tissues of
epithelioid cell tubercules, without caseation though fibronoid necrosis may be present at
centres of a few proceeding either to resolution or to conversion into hyaline fibrous
tissue( Scalding & Mitchell 1985)
Similar histologic features seen in :
 Berylliosis
 Fungal diseases
Epidemiology
• Age : young adults , 3-5th decades
• Sex : F/M -2:1
• Aetiology :
 Unknown
 Suspicion :
o Various infective agents :
 (?special form of TB)
 Propionibacterium acnes: 70% active disease after bronchoalveolar lavage
 disease has also been reported by transmission via organ transplants
o Chemicals : beryllium, zirconium
o Pine pollen, peanut dust
o Possible : Vitamin D dysregulation, Hyperprolactinemia, Thyroid disease
o Autoimmune
Clinical features
• Wilson R. et.al. Upper respiratory tract involvement in sarcoidosis and its management.
European Respiratory Journal. 1998;1:269-7
• 90% will have evidence of thoracic involvement : lung/ affecting lymphnodes
Clinical features
• Mucosal :
 Yellow nodules surrounded by hyperaemic mucosa on anterior septum& turbinate
• Skin : lupus pernio
 Nasal tip: symmetrical bulbous, glistening violaceous lesion
 Similar lesion on cheeks, lip, ear (turkey ear)
Diascopy : yellowish brown appearance
Probe test:
 Probing of nodular lesion to look for penetration
 Negative in sarcoidosis/positive in lupus vulgaris
Diagnosis
• No test pathognomic
• Most reliable: Kveim-Siltzbach test
 Spleen extract from cases of sarcoid → intradermal injection
 Followed 6 weeks later by skin biopsy→ non-caseating granulomas
 Hemogram , ESR, ACE(↑83% active sarcoid)
 Imaging :
CXR, CT , MRI
 Perfusion studies
 Bronchoalvelar lavage
 Gallium-67 scanning
 Biopsy : nasal mucosa (92% negativity on random biopsy)
Treatment
• Spontaneous remission
• Systemic therapy:
Prednisolone :
 1mg/kg x 6 weeks , taper over 3 months
 Good response in mucosal disease only
Methotrexate :
 5mg /weekly x 3 months
Chloroquine :
 250mg /alternate day
Churg-Strauss syndrome
• Churg & Strauss described in 1951
 Syndrome of: systemic vasculitis , asthma
• Eosinophil rich & granulomatous inflammation involving respiratory tract and
necrotizing vasculitis + asthma +eosinophilia
• Nasal clinical features:
 Nasal polyps
 Nasal crusting
 Septal perforation
• DD’s: Wegener's granulomatosis
• Treatment : oral steroids
Giant cell granuloma
• first described by Jaffe in 1953
• Benign granuloma like aggregates of giant cell in fibrovascular stroma
• Giant cell reparative granuloma/giant cell reaction of bone
• Age : children, young adults
• Sex : F/M- 2:1
• Imaging: soap bubble center and well demarcated edges
 Not true giant cells tumor: do not contain multiple nuclei
 B/L symmetrical involvement jaw-cherubism
 DD’s: aneurysmal bone cyst, hyperparathyroidism
• Treatment:
 Curettage ( 15% recurrence)
 Total excision (where possible)
Cholesterol granuloma
• Definition :
Granulomatous reaction to cholesterol crystals precipitated in tissues (presumed to
result from haemorrhage and/or trauma)
• Age /Sex: 26-56 years(mean-38) / male predominant
• Clinical features:
 Affect maxilla, frontal sinuses
 Expansion of bone cosmetic deformity, displacement of adjacent structures
• Imaging :CT/MRI
 Cyst like expansion
 Opaque , does not enhance on contrast
 High signal on all MRI sequences
Choleterol granuloma
• Histology :
 Typical appearance of granulation tissue with foreign body type giant cells
• Treatment :
 Surgical excision
Neoplastic granulomatous disease
Granulomatous neoplasia
• Synonyms :
Stewart’s granuloma
Lethal midline granuloma
Non healing midline granuloma
Idiopathic midline destructive disease (IMDD)
Sinonasal T-cell lymphoma
Necrosis with atypical cellular exudate (NACE)
Midline malignant reticulosis
Introduction
• T/NK cell lymphoma
• Responsible for classical destruction of midface
• Great controversy and pathological debate
• MacBride P. A case of rapid destruction of nose ad face. Journal of Laryngology and
Otology.1897;12:64-6: first description of disease
• Death resulted from:
 Intercurrent infection of disseminated lymphoma:
Failure of diagnosis
Insufficiently aggressive oncologic treatment
DD’s: substance abuse (Cocaine)
Epidemiology
• Age : 10-90years ( meadian 5th/6th decade)
• Sex : male predominance
• Location: south-east asia, south & central america
• Etiology :
Suzuki R, Yamaguchi M, Izutsu K, et al. Prospective measurement of Epstein-Barr
virus-DNA in plasma and peripheral blood mononuclear cells of extranodal NK/Tcell lymphoma, nasal type. Blood 2011; 118:6018.:
 positivity for Epstein-Barr virus (EBV)
 exact mechanism of malignant transformation via EBV has not been elucidated.
designated NK/T because of uncertainty regarding its cellular lineage
 Gene rearrangement studies support a natural killer cell origin in most cases
small minority has clonal T cell receptor gene rearrangements and appears to be
derived from cytotoxic T cells
Clinical features
• Polymorphic neoplastic infiltrate with angioinvasion and angiodestruction
• Classical division in three stages:
1. Prodromal :
 Last for many years
o Persistent nasal obstruction, rhinnorhoea
2. Active stage:
o Nasal crusting, ulceration, septal perforation
3. terminal stage:
o Haemorrhage
o Gross mutilation of face
 DD’s: Wegener’s granulomatosis , BCC
Diagnosis
• Histopathology :
Good quality representative biopsy material( from beneath slough and crust
Immunohistochemistry : (against T-cell differentiation)
Granulomas and giant cells are not present
Thrombosis & necrosis
• EBV serology
• Imaging
Treatment
• RT:
Radical radiotherapy: 55Gy or more
• CT
Disseminated/Recurrence
 5 year survival : 46-63 %
 Relapse : within few months-20 years