This is the answer and explanation for a USMLE practice question from the Dr. Ray Makar Facebook page. Try it first, then check your answer below.
The Question
A 50-year-old man has painful mouth erosions and flaccid blisters on his trunk that rupture easily. Rubbing normal-looking skin makes the top layer slide off (positive Nikolsky sign). Antibodies against which target are responsible?
A. Desmoglein 1 and 3
B. Hemidesmosomes (BP180/BP230)
C. Type VII collagen
D. Tissue transglutaminase
Correct Answer: A. Desmoglein 1 and 3
This is pemphigus vulgaris. IgG antibodies attack desmogleins, the proteins in desmosomes that hold keratinocytes together. The cells separate (acantholysis), creating a fragile blister inside the epidermis just above the basal layer. Direct immunofluorescence shows a net-like (fishnet) pattern between the cells. The mouth is often involved first. Treatment is systemic corticosteroids plus rituximab.
Why the Other Answers Are Wrong
- Hemidesmosomes: Bullous pemphigoid: tense blisters in older adults, negative Nikolsky sign, linear IgG/C3 along the basement membrane, and the mouth is usually spared.
- Type VII collagen: Epidermolysis bullosa acquisita: blisters at sites of trauma that heal with scarring.
- Tissue transglutaminase: Celiac disease. Its skin form, dermatitis herpetiformis, causes itchy grouped vesicles on the elbows and knees.
High-Yield Pearl
From the dermatology clinic: flaccid blisters plus mouth sores suggest pemphigus; tense blisters in an elderly patient suggest pemphigoid.
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