B108 Blistering skin disorders, Pemphigus, Bullous pemphigoid, Dermatitis hepatiformis.

Question 1

What causes Pemphigus, what are the subtypes?

Answer 1

It is a rare autoimmune disorder,

• caused by Type 2 hypersensitivity reaction
• IgG anti-bodies against desmoglein 1 and desmoglein 3 intercellular attachment proteins.
• Disrupts attachment between stratum spinosum cells, the general term for this type of process is acantholysis.
• The squamous epithelium becomes loose, fluid gathers from the inflammation forming a blister, or in medicle terms, a vesicle (less than 5mm) or bulla (more than 5mm).

Pemphigus Vulgaris -

• The most common type by far.
• The suprabasal stratum spinosum cells are most affected.
• vesicle and bullae form on the scalp and face, axillae and groin, periumbilical region, and intertrigonal regions *areas where skin rubs together, and on the oral mucosa.

Pemphigus Foliaceus

• Rare and less severe form.
• Blisters only form on the skin and spare the mucous membranes/oral mucosa.
• The separation occurs much higher in the st. squaous epithelial layer, in the subcorneal zone (the most superficial layer)
• So only very limited erythema is seen, and mostly just skin crusting of ruptured blisters that never get very large.

Paraneoplastic pemphigus.

• Most associated with Thymoma and Castleman’s disease, lymphoproliferative neoplasia

Question 2

What causes bullous pemphigoid,

pathogeneis

morphology

symptoms and patient populations

Answer 2

An autoimmune disorder. Can occur any age but is more frequent in elderly, and during pregnancy.

Caused by linear deposition of IgG and complement in the basement membrane of the epithelium in the skin and mucous membranes. (subepidermal deposition)

The IgG is directed against Type 17 collagen *XVII.

IgG rection also against the hemidesmosomes of basal cells.

This forms large bullae on skin that may or may not be erythematous and inflamed. The fluid inside is clear and without pus. The blister is covered by the entire layer of epidermis, and is thus tougher than most blisters and does not rupture as easily.

The bullae heal without scarring if they do not get complicated by infection.

Responds to topical or systemic immunosuppresion

A distinct variant of bullous pemphigoid occurs during pregnancy in the 2nd or 3rd trimester, and resolves after pregnancy, but may recur in future pregnancies.

Question 3

Dermatitis herpetiformis morphology, presentation

Answer 3

An uncommon autoimmune disease.

Predominantly in males in their 20’s and 30’s.

80% of dermatitis herpetiformis cases occur in association with celiac disease. (but only a small minority of celiac patients get dermatitis herpetiformis). Interstingly, DH is responsive to a gluten free diet.

Forms a bilaterally symmetric, itchy, rash of urtricaria and vesicles

urtricaria - hives. Raised, flat areas of skin that are solid and not blisters.

vesicles - small blisters <5mm.

The rash forms on the extensor surface of the elbows, knees, upper back, and butt.

Question 4

Pathogenesis of dermatitis herpetiformis

Answer 4

In genetically predisposed people, IgA antibodies are formed against dietary gluten, specifically against its metabolic product Gliadin.

Some of these IgA antibodies cross-react against epidermal transglutaminases found in keratinocytes.

There is granular IgA deposition in the tips of dermal papillae. Causes immune reaction and inflammation, producing the hives and subepidermal blisters, and pruritus