Pathologie Prof. Dr. med. Katharina Glatz

Vesiculobullous Diseases

2014-01-30

History

Histopathology Of Blistering Diseases M. Megahead Springer 2004

Nomenclature

Vesicle: Fluid-filled epidermal elevation <1cm in diameter Serous exudate, serum with blood, seropurulent (vesicopustule)

Bulla: Fluid-filled blister >1cm in diameter Serous exudate, seropurulent fluid Erosions after rupture

• Clinical picture

• Serology

• Histology / DIF / IF (split skin)

Diagnosis

Causes

• Bacterial and viral infection

• Inflammation

• Trauma

• Hereditary diseases

• Autoimmune disease

• Anatomic level of split

• Mechanism of split

– Spongiotic

– Acantholytic

– Ballooning degeneration

• Cell infiltrate (subepidermal blisters)

– Little inflammation

– Eosinophils, neutrophils, lymhocytes predominate

Histologic Algorithm

Classification

• Subepidermal blister or bulla

• Intraepidermal blister or bulla

• Diseases occasionally or frequently associated with blister/bulla formation

Autoimmune Bullous Diseases

Akt Dermatol 2008; 34(8/09): 301-312

Biopsy

Small blister Perilesional & intact skin for DIF in Michels Intact blister for H&E in formaldehyde

Large blister Perilesional & intact skin for DIF in Michels Part of the blister for H&E in formaldehyde

Intraepidermal blistering diseases

Pemphigus Vulgaris

Pemphigus vulgaris

Rows of tombstones

Pemphigus vulgaris

DIF IgG DIF: IgG, IgA, IgM, C3 Circulating IgG autoantibodies against Desmoglein 3

Bullous Impetigo

Staphylococcus aureus or streptococcus Subcorneal blister with serum and neutrophils

Herpes Simplex/Zoster

Necrotic, dyskeratotic, acantholytic keratinocytes

Multinucleated keratinocytes with steel blue nuclei and nucleoplasm margination.

Intraepidermal subepidermal blister formation

Pale ballooned keratinocytes

Dyshidrotic Eczema (Pompholyx)

Contributing factors: • Atopic diathesis • Contact sensitivity to metals (nickel) • Fungal infection (id reaction) • Emotional stress • Seasonal change (hot/cold/humidity)

Friction Blister

Rubbing of the skin against another object

Friction Blister

Rubbing of moist skin against another object

J Korean Med Sci. 2013 Dec;28(12):1814-21. Choi SC et al. Injuries Associated with the 580 km University Student Grand Voluntary Road March: Focus on Foot Injuries.

Subepidermal blistering diseases

Bullous Pemphigoid

Large tense serous and haemorrhagic blisters on normal and erythematous skin Predilection sites: inner or anterior thighs, groin, flexor surfaces of the upper extremities and lower abdomen. Any skin area may be involved. Oral lesions are rare.

Bullous Pemphigoid

• Early: eosinophilic spongiosis

• Subepidermal blister with intact roof

• Vacuolisation of the basal zone adjacent to bulla

• Eosinophils in superficial dermis and within bulla

DIF in Bullous Pemphigoid

DIF C3 DIF IgG 80-90%

No discrimination of autoimmune blistering diseases of the pemphigoid group in direct immunofluorescence except for linear IgA disease (IgA instead of IgG deposits)

Bullous Pemphigoid

DIF IgG Blister mapping Type IV collagen: Intralamina lucida blister Lamina densa situated At the blister floor

Toxic Epidermal Necrolysis

Syn. Drug induced Lyell syndrome >30% of the body surface 30% mortality (sepsis) DD clinically: SSSS DD histologically: EEM Stevens-Johnson syndrome Milder form of TEN <10% of the body surface SJS-TEN overlap 10-30% of the body surface

TEN or EEM

TEN and bullous erythema multiforme may be histologically indistinguishable

TEN EEM

Association with Blister Formation

Graft vs Host Disease

Histologic staging for acute GVHD of the skin: Grade 0 - Normal skin

Grade 1 - Basal cell layer diffuse or focal vacuolar alteration

Grade 2 - Grade 1 with epidermis and/or hair follicle dyskeratotic squamous cells

Grade 3 - Grade 2 with subepidermal vesicle Formation

Grade 4 - Complete dermal and epidermal separation

Lichen Sclerosus

Edema of the papillary dermis or excessive vacuolar degeneration of the basal membrane zone

Arthropod Bite Reaction

Spongiosis, spongiotic vesicles Edema of papillary dermis with subepidermal blister formation

Solar Dermatitis

Solar Dermatitis

Mild: Superficial sun burn cells Sparse perivascular and interstitital lymphocytes & neutrophils Severe: Many sunburn cells Epidermal necrosis Neutrophils in the epidermis Vacuolar degeneration Intraepidermal blister formation Cave: reactive melanocytic atypia