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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Pemphigus vulgaris: IgG against desmoglein 3 +/- 1 causing intraepidermal acantholysis, flaccid bullae, painful oral erosions, positive Nikolsky sign
- Bullous pemphigoid: IgG against BP180/BP230 hemidesmosomal proteins causing subepidermal tense bullae in older adults, usually mucosa-sparing
- Best diagnostic test: biopsy lesional skin for H&E plus perilesional skin for direct immunofluorescence
- PV DIF: intercellular fishnet IgG/C3; BP DIF: linear IgG/C3 along basement membrane
- PV is more dangerous and often needs systemic steroids + rituximab; BP often responds to high-potency topical steroids or systemic therapy if widespread
Overview
Pemphigus vulgaris and bullous pemphigoid are autoimmune blistering diseases frequently contrasted on Step 2 CK. Pemphigus vulgaris disrupts desmosomes between keratinocytes, creating fragile intraepidermal blisters and erosions. Bullous pemphigoid targets hemidesmosomes at the dermal-epidermal junction, creating deeper subepidermal blisters that remain tense. The clinical distinction is high-yield: PV has painful oral lesions and flaccid bullae; BP affects older adults with itchy urticarial plaques and tense bullae, usually sparing mucosa.
Epidemiology
Pemphigus vulgaris is uncommon and often presents in middle-aged or older adults; risk is higher in people of Ashkenazi Jewish, Mediterranean, Middle Eastern, or Indian ancestry. Bullous pemphigoid is the most common autoimmune blistering disease and mainly affects elderly patients. BP is associated with neurologic disease, dementia, Parkinson disease, stroke, and some medications such as loop diuretics, DPP-4 inhibitors, immune checkpoint inhibitors, and antibiotics.
Clinical Features
Symptoms
PV: painful oral erosions often precede skin lesions by weeks to months
PV: fragile blisters rupture quickly, leaving painful erosions and crusting
BP: intense pruritus may precede bullae; urticarial/eczematous plaques common
Eye, airway, or extensive mucosal involvement requires urgent specialist care
Fever, skin pain, mucosal erosions after new drug may suggest SJS/TEN rather than autoimmune blistering disease
Signs
PV: flaccid bullae, erosions, crusts, positive Nikolsky sign
PV: oral, pharyngeal, nasal, conjunctival, genital mucosal erosions
BP: tense bullae on erythematous or urticarial base, often trunk, flexures, thighs
BP: Nikolsky sign usually negative and mucosal involvement absent or mild
Secondary infection signs: purulence, spreading erythema, fever
Investigations
First-line
Two skin biopsiesLesional biopsy for H&E and perilesional normal-appearing skin for direct immunofluorescence. Do not place DIF specimen in formalin
Direct immunofluorescencePV: intercellular fishnet/chicken-wire IgG and C3. BP: linear IgG and C3 along basement membrane zone
HistopathologyPV: suprabasal acantholysis with tombstone basal cells. BP: subepidermal blister with eosinophils
Second-line
SerologyELISA for desmoglein 1/3 in PV; BP180/BP230 in BP. Useful for diagnosis and disease monitoring
Baseline therapy labsCBC, CMP, hepatitis B/C, TB testing, immunoglobulins or other labs before systemic immunosuppression/rituximab as appropriate
Specialist
Indirect immunofluorescence/salt-split skinMay help classify subepidermal blistering disease; BP antibodies bind epidermal side of salt split
Ophthalmology/ENT evaluationIf ocular, airway, or extensive mucosal symptoms; also consider mucous membrane pemphigoid in scarring mucosal disease
1
Pemphigus vulgaris
- Urgent dermatology referral; assess fluid loss, nutrition, infection, and mucosal/ocular involvement
- Systemic corticosteroids for induction, often with rituximab as first-line steroid-sparing therapy in moderate-severe PV
- Adjunct immunosuppressants may include mycophenolate mofetil or azathioprine depending on specialist plan
- Wound care, pain control, oral care, infection surveillance, bone/GI/PJP prophylaxis depending on steroid dose/duration
2
Bullous pemphigoid
- High-potency topical corticosteroids can be first-line for localized or even selected generalized BP if feasible
- Systemic prednisone for extensive disease when topical therapy is impractical or inadequate
- Steroid-sparing options include doxycycline/niacinamide, methotrexate, mycophenolate, azathioprine, omalizumab, dupilumab, or rituximab in refractory cases under specialist care
- Review and stop possible culprit drugs when temporally related
3
Safety and follow-up
- Monitor for skin infection, sepsis, dehydration, malnutrition, steroid adverse effects, and osteoporosis
- Vaccination review before rituximab or prolonged immunosuppression; avoid live vaccines during significant immunosuppression
- Taper therapy slowly based on disease control and antibody trends when used
Complications
- Pemphigus vulgaris mortality: Infection, fluid loss, malnutrition, and treatment toxicity if uncontrolled
- Secondary infection: Eroded skin barrier predisposes to cellulitis and sepsis
- Mucosal morbidity: Pain, dysphagia, poor intake; ocular or airway disease when involved
- Steroid toxicity: Hyperglycemia, hypertension, osteoporosis, adrenal suppression, infection
- Bullous pemphigoid morbidity: Pruritus, sleep loss, infection, frailty-related complications in older adults
USMLE Step 2 CK Exam Tips
- 1Pemphigus vulgaris = flaccid bullae + painful oral erosions + positive Nikolsky
- 2Bullous pemphigoid = elderly patient + tense bullae + pruritus + usually no mucosal involvement
- 3PV antibody target: desmoglein in desmosomes; BP target: hemidesmosomes at basement membrane
- 4PV histology: suprabasal acantholysis and tombstone basal cells
- 5BP histology: subepidermal blister with eosinophils
- 6Direct immunofluorescence: PV fishnet; BP linear basement membrane
- 7Biopsy perilesional skin for DIF, not ulcerated necrotic tissue
- 8SJS/TEN has drug prodrome, skin pain, dusky targets, and widespread mucosal erosions; distinguish from PV/BP
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