Autoimmune intraepidermal blistering disease with flaccid bullae and painful mucosal erosions.
Also known as: pemphigus, PV, intraepidermal blistering disease
Overview
Autoimmune mucocutaneous blistering disorder caused by IgG autoantibodies against desmoglein 1 and 3, producing loss of keratinocyte adhesion (acantholysis) in the suprabasal epidermis. Flaccid bullae rupture easily, leaving painful erosions; oral mucosa is almost always involved.
Epidemiology
Rare (1-5 cases per million per year). Peak onset 40-60 years. Increased prevalence in Ashkenazi Jewish, Mediterranean, and South Asian populations. Associations with HLA-DR4 and HLA-DR14.
Try two board-style Pemphigus Vulgaris questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1DermatologyMedium
A 52-year-old woman of Ashkenazi Jewish descent presents with 3 months of painful oral erosions followed by flaccid bullae and raw, ragged-bordered erosions on her scalp, axillae, and trunk. The blisters rupture with minimal pressure, and lateral traction on adjacent normal-appearing skin produces shearing of the epidermis. A perilesional skin biopsy is sent for direct immunofluorescence. Which of the following findings best supports the suspected diagnosis?
AGranular IgA deposition within the tips of the dermal papillae
BIntercellular IgG and C3 deposition in a chicken-wire pattern
CLinear IgG and C3 deposition along the basement membrane zone
DSubepidermal separation with absent immunoreactant deposition
Reveal answer & full explanation
Correct answer: B — Intercellular IgG and C3 deposition in a chicken-wire pattern
AGranular IgA deposition within the tips of the dermal papillae
BIntercellular IgG and C3 deposition in a chicken-wire pattern✓
CLinear IgG and C3 deposition along the basement membrane zone
DSubepidermal separation with absent immunoreactant deposition
Why Intercellular IgG and C3 deposition in a chicken-wire pattern is correct
The vignette is classic pemphigus vulgaris: a middle-aged adult of Ashkenazi descent with painful oral erosions preceding flaccid cutaneous bullae and a positive Nikolsky sign (epidermal shearing on lateral pressure on perilesional skin).
PV is driven by IgG autoantibodies against desmoglein 1 and 3 within the desmosomes between keratinocytes, causing suprabasal acantholysis. Perilesional direct immunofluorescence therefore shows IgG and C3 deposited in the intercellular spaces of the epidermis, producing the characteristic net-like "chicken-wire" pattern.
This intercellular (not basement-membrane) localization is the confirmatory immunofluorescence finding; serum anti-desmoglein 1/3 ELISA further confirms the diagnosis and tracks disease activity.
Why the others are wrong
Linear IgG and C3 deposition along the basement membrane zone — This is the DIF pattern of bullous pemphigoid (anti-BP180/230), which causes tense subepidermal bullae on flexural skin with pruritus and usual mucosal sparing, the opposite localization from PV.
Granular IgA deposition within the tips of the dermal papillae — This is the finding of dermatitis herpetiformis, an intensely pruritic vesicular eruption linked to celiac disease, not an acantholytic mucocutaneous blistering disorder.
Subepidermal separation with absent immunoreactant deposition — A subepidermal split without intercellular IgG points to a non-immune or pemphigoid-group subepidermal process rather than the suprabasal acantholysis with intercellular IgG seen in PV.
Question 2DermatologyMedium
A 54-year-old man with biopsy-confirmed pemphigus vulgaris has widespread flaccid bullae and raw erosions covering roughly 40% of his trunk and scalp, plus painful oral erosions. He was started on high-dose prednisone two weeks ago. He now presents with fever to 39.1°C, tachycardia, and hypotension. The eroded skin is malodorous with purulent, crusted borders. Which of the following complications is most likely responsible for his deterioration?
AAvascular necrosis of the femoral head
BSepsis from secondary cutaneous infection
CUnderlying lymphoproliferative malignancy
DEsophageal stricture from mucosal scarring
Reveal answer & full explanation
Correct answer: B — Sepsis from secondary cutaneous infection
AAvascular necrosis of the femoral head
BSepsis from secondary cutaneous infection✓
CUnderlying lymphoproliferative malignancy
DEsophageal stricture from mucosal scarring
Why Sepsis from secondary cutaneous infection is correct
The denuded epidermis in pemphigus vulgaris is a large open wound that loses its barrier function, so extensive erosions are readily colonized and invaded by skin flora (Staphylococcus aureus, Streptococcus, gram-negatives).
Secondary bacterial infection of erosions progressing to sepsis is the leading cause of death in pemphigus vulgaris; modern mortality is under 10%, and most of those deaths are infectious.
High-dose corticosteroids (and other immunosuppression) further blunt the immune response, and the fever, tachycardia, hypotension, and purulent malodorous erosions here point to wound-derived sepsis.
Why the others are wrong
Esophageal stricture from mucosal scarring is a recognized late, chronic complication of mucosal disease, but it causes dysphagia over time, not acute fever and hemodynamic collapse.
Avascular necrosis of the femoral head is a long-term corticosteroid complication causing hip pain after prolonged therapy, not an acute septic presentation two weeks into treatment.
Underlying lymphoproliferative malignancy defines paraneoplastic pemphigus (anti-plakin antibodies, severe stomatitis, CLL/NHL/Castleman), not classic biopsy-confirmed pemphigus vulgaris, and would not explain acute infected erosions.
🔒 Free preview limit reached
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Pemphigus Vulgaris outline — plus all 514 diagnoses, 6,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Other autoimmune disease (myasthenia gravis, thymoma)
Middle-aged adults of Mediterranean or Ashkenazi descent
Pathophysiology
IgG4 autoantibodies against desmoglein 3 (mucosa-dominant) or both desmoglein 1 and 3 (mucocutaneous) disrupt desmosomal adhesion between keratinocytes. The resulting acantholysis produces flaccid intraepidermal blisters that rupture, leaving raw erosions prone to secondary infection and fluid/protein loss.
Clinical presentation
Symptoms
Painful, persistent oral erosions (often the presenting symptom, precede skin disease by months)
Burning, painful skin lesions rather than itch
Dysphagia, odynophagia, weight loss from oropharyngeal involvement
Hoarseness if laryngeal involvement
Signs / physical exam
Flaccid bullae that rupture easily on scalp, face, axillae, groin, trunk
Erosions with ragged borders, slow to heal, may crust
Positive Nikolsky sign (lateral pressure on perilesional skin produces shearing)
Positive Asboe-Hansen sign (pressure on intact bulla extends it peripherally)
Classic findings
Painful oral erosions preceding flaccid cutaneous bullae in a middle-aged adult; positive Nikolsky.
Differential diagnosis
Bullous pemphigoid — Tense subepidermal bullae on flexural skin, intense pruritus, mucosa usually spared, elderly; anti-BP180/230 antibodies; linear C3 + IgG along basement membrane
Paraneoplastic pemphigus — Severe stomatitis, polymorphic skin lesions, underlying lymphoproliferative malignancy (CLL, NHL, Castleman disease); antibodies against multiple plakin proteins
Stevens-Johnson syndrome / TEN — Acute febrile drug reaction, dusky targetoid macules, full-thickness epidermal necrosis, mucosal involvement, positive Nikolsky on inflamed skin only
Mucous membrane pemphigoid — Scarring erosions of mucosa (oral, ocular, genital), risk of blindness and esophageal strictures; subepithelial split
Erythema multiforme major — True targetoid lesions, post-HSV or Mycoplasma, limited mucosal involvement, self-limited
Aphthous stomatitis — Recurrent small round ulcers limited to non-keratinized oral mucosa; no skin involvement; not progressive
Diagnostic workup
Diagnostic criteria
Diagnosis requires clinical findings plus histology and immunofluorescence. Lesional biopsy: suprabasal acantholysis with 'tombstone' row of basal cells. Perilesional direct immunofluorescence (DIF): intercellular 'chicken-wire' IgG and C3 deposition. Serum anti-desmoglein antibodies confirm and track activity.
Labs
Serum indirect immunofluorescence and ELISA for anti-desmoglein 1 and 3 IgG (titers correlate with disease activity)
Wound cultures from eroded skin if secondary infection suspected
Imaging
No routine imaging required
Esophagogastroduodenoscopy if dysphagia or odynophagia suggests esophageal involvement
Chest imaging and age-appropriate cancer screening to exclude paraneoplastic pemphigus in atypical cases
Diagnostic algorithm
Feature
Pemphigus Vulgaris
Bullous Pemphigoid
Age
40-60
>60
Bulla type
Flaccid, ruptures easily
Tense, intact
Mucosal involvement
Almost always (often first)
Rare (10-30%)
Pruritus
Pain > itch
Intense itch
Histology split
Intraepidermal (suprabasal)
Subepidermal
Target antigen
Desmoglein 1 and 3
BP180 (BPAG2), BP230 (BPAG1)
DIF pattern
Intercellular 'chicken-wire' IgG/C3
Linear IgG/C3 at basement membrane
Nikolsky sign
Positive
Negative (usually)
Mortality untreated
High (60-90%)
Lower but morbid
Pemphigus vulgaris vs bullous pemphigoid — key clinical and immunopathologic distinctions.
Treatment
First-line
Systemic corticosteroid: prednisone 1 mg/kg/day, methylprednisolone IV for severe disease; taper slowly over months
Rituximab (anti-CD20) — now first-line with steroids per 2020 international consensus and Joly et al. 2017 RITUX 3 trial; 1 g IV days 0 and 14 (rheumatoid arthritis dosing) or 375 mg/m² weekly × 4 (lymphoma dosing)
Wound care: nonadherent dressings, gentle cleansing, treatment of secondary bacterial infection (mupirocin topical, oral cephalexin or doxycycline)
Nutritional support, soft diet, viscous lidocaine and 'magic mouthwash' for oral pain
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.