Blistering diseases are among the most tested dermatology topics on USMLE Step 1. You must know where the blister forms, which protein is attacked, and what immunofluorescence shows. These three practice questions compare pemphigus vulgaris, bullous pemphigoid and dermatitis herpetiformis. Pick your answer first, then open the explanation.
Question 1: Painful oral erosions and flaccid blisters
A 45-year-old woman has had painful erosions in her mouth for 2 months, followed by flaccid blisters on her trunk that rupture easily. Gentle pressure on normal-looking skin causes the epidermis to slide off. Which of the following is the target of the autoantibodies in this condition?
A. Hemidesmosomes (BP180)
B. Desmoglein 3
C. Type VII collagen
D. Tissue transglutaminase
E. Laminin 332
Correct answer: B. Desmoglein 3
This is pemphigus vulgaris: IgG autoantibodies against desmoglein 3 (and often desmoglein 1), components of the desmosomes that hold keratinocytes together. Loss of adhesion (acantholysis) causes an intraepidermal, suprabasal split, so the blisters are thin and flaccid, the Nikolsky sign is positive, and mucosa is almost always involved.
Why the other options are wrong:
BP180 (hemidesmosomes) is the target in bullous pemphigoid.
Type VII collagen is the target in epidermolysis bullosa acquisita.
Tissue transglutaminase antibodies are seen in celiac disease and dermatitis herpetiformis.
Laminin 332 is targeted in mucous membrane pemphigoid.
High-yield: Direct immunofluorescence: net-like (fishnet) IgG between keratinocytes. Histology: “row of tombstones” (basal cells left attached to the basement membrane). Treat with systemic corticosteroids and rituximab. Pemphigus is a type II hypersensitivity reaction.
Question 2: Elderly patient with tense, itchy blisters
An 80-year-old man has had intense itching for months, followed by large, tense blisters on his thighs, groin and forearms. His mouth is not affected, and the Nikolsky sign is negative. A biopsy is most likely to show which of the following?
A. Intraepidermal acantholysis with net-like IgG
B. Subepidermal blister with linear IgG and C3 along the basement membrane
C. Granular IgA deposits in the dermal papillae
D. Full-thickness epidermal necrosis
E. Spongiosis with eosinophils only
Correct answer: B. Subepidermal blister with linear IgG and C3 along the basement membrane
This is bullous pemphigoid, the most common autoimmune blistering disease, typically in the elderly. IgG antibodies target hemidesmosome proteins (BP180 and BP230), causing a subepidermal split. Because the whole epidermis forms the roof, the blisters are tense and do not rupture easily, the Nikolsky sign is negative, and the mouth is usually spared. Biopsy shows eosinophils in the blister.
Why the other options are wrong:
Intraepidermal acantholysis with net-like IgG is pemphigus vulgaris.
Granular IgA in the dermal papillae is dermatitis herpetiformis.
Full-thickness epidermal necrosis is toxic epidermal necrolysis.
Spongiosis is eczema, not a blistering autoimmune disease.
High-yield: Bullous pemphigoid can be triggered by drugs, especially DPP-4 inhibitors (gliptins) and furosemide. It usually starts with an itchy, urticarial phase before blisters appear. Treat with potent topical or systemic steroids.
Question 3: Itchy vesicles on the elbows and knees with GI symptoms
A 28-year-old woman has extremely itchy, grouped vesicles and excoriations on her elbows, knees and buttocks. She also reports bloating and loose stools. Which of the following is the best long-term management of her skin disease?
A. Systemic corticosteroids
B. Gluten-free diet, with dapsone for symptom control
C. Oral acyclovir
D. Topical antifungal cream
E. Phototherapy
Correct answer: B. Gluten-free diet, with dapsone for symptom control
This is dermatitis herpetiformis, the skin form of celiac disease. Biopsy shows neutrophils in the dermal papillae, and direct immunofluorescence shows granular IgA in the dermal papillae. Dapsone controls the itch within days, but a strict gluten-free diet treats the underlying disease and allows dapsone to be stopped over time.
Why the other options are wrong:
Systemic corticosteroids do not work well and are not used.
Acyclovir treats herpes virus; despite the name, dermatitis “herpetiformis” is not viral – the lesions are just grouped like herpes.
Antifungals treat fungal infections.
Phototherapy is not a standard treatment.
High-yield: Check G6PD before starting dapsone (risk of hemolysis). Dapsone also causes methemoglobinemia. Celiac disease is linked to HLA-DQ2/DQ8 and increases the risk of enteropathy-associated T-cell lymphoma.
As an Amazon Associate, I earn from qualifying purchases.
Written and reviewed by Dr. Ray Makar, MD, dermatologist with 20 years of clinical practice. Last reviewed: October 2026. For exam preparation only, not medical advice.
FREE USMLE PDFs
Get 80 free practice questions
Four free sampler PDFs by Dr. Ray Makar: Step 1 (Pathology & Pharmacology) and Step 2 CK (Medicine, Surgery & Pediatrics), in both Review style and USMLE style, with answers and explanations. Also useful for NEET-PG, INI-CET and FMGE.
