Skin pathology, infectious, autoimmune diseases

Dr.Ashraf Abdelfatah Deyab
Assistant Professor
NORMAL SKIN, with labels
Lecture 37: Pathology of skin II
• At the end of session student should be able to :
• 1- enlist and describe etiology, morphology and
clinical features of infectious dermatoses (bacterial,
fungal and warts)
• 2- Enlist blistering (Bullous) disorders
• 3- Briefly discuss pathogenesis, morphology and
clinical features of pemiphigus , Bullous
• Robbins and Cortan 8th edition (843-847)
Blistering (Bullous) Diseases
= Vesiculobullous or Blistering bullous diseases
= Groups of disease chr. by “bullous” & “acantholysis”
= Bullous : epidermal separation levels:
A)Subepidermal bulla
B) Intraepidermal bulla.
= Intraepidermal type has two types:
1) Subcorneal)
2) Suprabasal
- What is a bulla? What is acantholysis?
- Bulla: Fluid-filled raised lesion greater than 5 mm across.
Acantholysis: Loss of intercellular connections resulting in
loss of cohesion between keratinocytes.
• Subcorneal
• Suprabasal
• Subepidermal
Blister Formation
• Subepidermal bullous dermatoses:
1-Dermatitis herpetiformis.
• 2- Bullous pemphigoid.
• 3- Erythema multiforme.
• 4- Porphyria cutanea tarda
• 5- Epidermolysis bullosa,
• Intraepidermal bullous dermatoses:
• 1- Pemphigus vulgaris
• 2- Pemphigus vegetans
Pemphigis Vulgaris
Bullous pemiphigoid
• Pemphigus is a “life threatining” blistering
disorder caused by autoantibodies that result
in the dissolution of intercellular attachments
within the epidermis and mucosal epithelium.
• Pemphigus vulgaris-most common type,
including multiple variants.
• Age: fourth to sixth decades of life,40-60 ]yrs
• Sex: men and women are affected equally
Pemphigus vulgaris- PV
• Commonest Chronic autoimmune Bullous disease
(Suprabasal acantholytic) Painful + rarely pruritic.
• Site: mucosa, skin, scalp, face, axilla, groin, trunk, and
points of pressure, oral ulcers
• Etiopathogenesis:
• Autoantibodies -IgG against epidermis& mucosa
(adehesion desmogleins1&3)&linkage to specific HLA types
(net-like pattern)>>Directly disrupting +Activate protease
• Morphologic features:
1- Superficial vesicles\bullae, rupture easily>> leaving shallow
erosions covered with dried serum and crusts.
2-superficial dermal infiltration by lymphocytes, histiocytes,
and eosinophils
• The mainstay of treatment
• Immunosuppressive agents>> decrease the titers of the Abs
Pemphigis Vulgaris- morphology
Clinical : skin with
varying sizes blisters in
skin, Transudative fluid
The surfaces are
glistening, transparent
thin roof.
The blisters content is
clear serum. Nikolsky’s
sign) is positive***
According to the duration:
rupture, crust, errosions
Pemphigus, fresh bullae
Pemphigus, ruptured, scabbed bullae
Eroded plaques are formed on rupture of confluent,
thin-roofed bullae, “suprabasal acantholytic blister”
Acantholysis – stratum spinosum,- cells lysis
adhesions- keratinocytes change to round
suprabasal acantholytic blister”
IF test of skin biopsy: Fish net pattern , indicate
immunoglobulin (IgG) deposition
• Acute or chronic autoimmune skin disease, involving
the formation of large blisters\bulla, age: in elderly
• Sizes: up to 2 cm ,also may reach 4 to 8 cm
• Clinically:
tense large blister\bullae, filled with clear
fluid, in normal or erythematous skin. Not rupture easily.
• - If not secondarily infected, heal without scarring
• - Can present as urticarial plaques &pruritus.
• Site: skin (locally or generally), mucosa. Inner aspects of
the thighs, flexor of the forearms, axillae, groin,&lower abdomen.
• Microscopic:
1) Subepidermal, nonacantholytic bulla.
2) Superficial& deep perivascular infiltrate of lymphocytes and
variable numbers of eosinophils, occ. Neutrophils.
3)Superficial dermal edema, with basal cell layer vacuolization
Bullous Pemphigoid Pathogenesis
• Pathogenesis:
• 1) Deposition of Auto-antibodies Igs &complement
in the basement membrane, featuring linear
deposition “plaques” .
• 2) Inflammatory mediated-tissue injury associated
with recruited neutrophils and eosinophils.
Bullous Pemphigoid
• Older Pts
• Multiple Bullae
• (Nikolsky’s
sign) is
because there
is no
Bullous Pemphigoid
• Sub-epidermal bulla with serum and degenerating
eosinophils. Note bulla is non-acantholytic,
Vcuolated dermis- mixed inflammatory cells
Bullous Pemphigoid
• Linear deposition of IgG & C3 in the
basement membrane as seen in this IF image
is typical of bullous pemphigoid.
Dermatoses- Infections
1- Bacterial infection (impetigo)
2- Fungal infection(superficial- Tinea)
3- Viral infection (e.g. Warts)
4- Parasitic infection
5- Insects
Factors affecting clinical presentation:
Host immunity + infectious agents
Viral dermatoses- WARTS
- Warts: Most common skin viral infection, define as
cutaneous or mucosal VERRUCAE = wart =
papilloma-like squamous lesion, caused by HPV
(DNA virus)= > 100 variants, precancerous
- Etiology: several types of HPV, members papova.
Age: common in children& adolescents or any age
Transmission: direct contact (sexual),auto- inoculation.
Clinical course: generally self-limited, regressing
spontaneously within 6 months to 2 years. HPV lead to
cancer (penis, cervix, vagina, anus, orophyrnx)
Viral WARTS classification :
- Classification: based on appearance and
location Warts are classified:
- 1-Verruca vulgaris: most common type of wart,
anywhere, on hand, dorsal surfcae periungual
- 2-Verruca plana,(flat wart), common on face or
the dorsal surfaces of the hands
- 3-Verruca plantaris - soles and palms,
- 4- Verruca palmaris - soles and palms.
- 5- Condyloma acuminatum (venereal wart)
the penis, female genitalia, urethra, perianal areas,
and rectum
Viral WARTS-morphology
Gross: color-(gray-white to tan), shape-(“VV” flat to
convex, papules with a rough, pebble-like surface, “CA”
cauliflower-like, scaly ), size- (varying 0.1- to 1-cm, up2cm)
The histologic characteristics:
1) - Focal epidermal hyperplasia.
2) - Verrucous or papillomatous
3) - Hyperkeratosis and parakeratosis.
4) - Acanthosis varying degrees.
5) - Cells cytoplasmic vacuolization (koilocytosis)
6) = perinuclear hallo\zones.
- EM- clear zone reveal numerous keratohyaline
Verruca vulgaris- Cutaneous Warts
• Common wart (verruca
vulgaris): typically
occur on hands, face
anywhere as elevated,
hard, rough, peeled off,
leaving a pink .
• Caused by infection
with various strains of
the human
papillomavirus (HPV)
Bacterial dermatoses- Impetigo
- Impetigo - common superficial bacterial infection
of skin. (strept. & staph)
-- Age: more in children than adult
-Sites: involves exposed skin, the face and hands.
-Transmission - It is highly contagious and is frequently
seen in children and in adults in poor health.
- classification: classically Two forms exist, referred to as:
1) Impetigo contagiosa caused by group A β-hemolytic
streptococci (non-bullous)
2) Impetigo bullosa; by Staphylococcus aureus (bullous)
they differ from each other by the size of the pustules
Now: both are usually caused by Staphylococcus aureus.
Impetigo-clinical appearance
1) Non-bullous impetigo:
1) Erythematous small red sores rapidly evolve to >>
breaks >> Shallow erosions with leaking pus or
serum, featuring honey-colored crust.
- - If the crust is not removed>> adjacent extensive
epidermal damage .
2) A bullous form of impetigo mainly occurs in
children< 2yrs, fluid-filled blisters > break,> form
yellow scabs
1- Strept. impetigo is a major cause of post-strept. acute
glomerular nephritis (AGN).
2- Develop skin scar if not treated
Bacterial Infection- Impetigo
• Risk: factors as warm, humidity, crowded conditions,
and poor hygiene increase the chance of spread
rapidly among large groups.
• Clinically: induces allergic and inflammatory eczematous
response in the host
• Morphology:
• The characteristic microscopic feature of impetigo:
• 1) In Blistering lesions- accumulation of fluid and
neutrophils beneath the stratum corneum >> TO
produce Subcorneal pustule.
2) Crusts- rupture pustules.
3) presence of bacteria
4) Nonspecific, reactive epidermal alterations.
4) Superficial dermal inflammation .
- -commonest superficial fungal skin infection
(confined to the stratum corneum), in human, domestic
animals. Ringworm is misnomer used to refer this infection.
- The etiology: number of different species of fungi.
Dermatophytes of the genera Trichophyton and Microsporum are
- Transmission:
- contact with infected soil animals and
- Predisposing factors:
- Excessive heat ,humidity, exposure to animals, soil.
- Morphologic features- Tinea- has different clinical presentations& types depend on
the infected sites of the body- annular, reddish, scaly
- The fungal colonized in form of hyphae& arthospore are
found in the stratum corneum and in hair shafts.
Dermatophytoses disease patterns
• Dermatophytosis = (tinea or ringworm)
• Tinea Capitis (Scalp)
• Tinea Barbae (facial hair)
• Tinea Corporis (arm, leg, trunk)
• Tinea Cruris (groin- Jock itch)
• Tinea Pedis (Feet- Athlete’s foot)
• Tinea unguium ( fingernails and toenails)
• Tinea Manuum (hand and palm area)
• Tinea Faciei (face fungus)
laboratory diagnosis: Skin Scrapings,nail scrapings, hairs
Direct Microscopy\ Culture\ Serology
Fungal Infections - Dermatophytes
• Scaly patches and plaques, often annular in
Tinea capitis (scalp dermatophytosis)
• Age: usually in children, rarely in infants& adults.
• Clinically: It is characterized by:
1) Asymptomatic, often hairless patches of skin .
2) Associated with mild erythema,
3) Crust formation,
4) Scaling.
Ringworm of scalp, Tinea capitis
Tinea barbae
Tinea barbae is infection of the beard area that
affects adult men; it is uncommon disorder
Ringworm of the body, Tinea corporis
common fungal infection of the body surface that
affects all ages, but particularly children
Tinea cruris, or jock itch
Frequently in the inguinal areas of obese men during
warm weather.
Infected moist, red patches, scaling borders
Athlete’s foot, or tinea pedis.
Diffuse erythema and scaling, occasional
bacterial superinfection
Onychomycosis (Note the LACK of the
word tinea)
Dermatophytes primary infection or spread to
the nails is referred to as onychomycosis
Tinea - morphology
Gross: Characteristic reddish plaque or ring
worm, annular or lack of ring shaped
1- Inflammation of dermal and subcutaneous tissue.
intraepidermal neutrophils
2- Fungal colonies (viable arthrospores or hyphae) in
the anucleate cornified layer of lesional skin, etc..
3- Pseudoepitheliomatous hyperplasia.
4- Features of Bacterial superinfections+\- Cellulitis,
PAS stain of hyphae, probably scrap
PAS stain of hyphae, histologic section