Dermatology · PANCE / PANRE

Pemphigus Vulgaris

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.

🔒 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, 3,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.

Start your 7-day free trial → Sign in

Free to start · No credit card · Cancel anytime

Risk factors

Genetic predisposition (HLA-DRB1*04, DRB1*14)
Drug-induced: penicillamine, captopril, rifampin, NSAIDs
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)
CBC, CMP, baseline glucose, hepatitis B/C, TB screen prior to immunosuppression
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

Second-line / adjunct

Steroid-sparing agents: azathioprine (check TPMT first), mycophenolate mofetil, methotrexate, cyclophosphamide (severe refractory)
IVIG 2 g/kg per cycle for refractory disease or when immunosuppression contraindicated
Plasmapheresis or immunoadsorption for fulminant disease
Dapsone (mainly for IgA pemphigus variant)

Complications

Secondary bacterial infection of erosions; sepsis
Fluid, electrolyte, and protein loss (similar to burns in extensive disease)
Steroid-related morbidity (osteoporosis, diabetes, infections, AVN)
Esophageal stricture; laryngeal scarring; chronic ocular involvement
Mortality historically 60-90% pre-steroids; now <10% with modern therapy, mostly from infection

PANCE pearls

Positive Nikolsky sign is shared with TEN and SSSS; combine with clinical context and biopsy.
Oral lesions almost always precede skin disease — unexplained chronic oral erosions in a middle-aged adult should prompt biopsy.
Desmoglein 3 antibodies → mucosal disease; addition of desmoglein 1 antibodies → mucocutaneous disease.
Always exclude paraneoplastic pemphigus in patients with severe stomatitis or hematologic malignancy.
Rituximab has shifted PV from a chronic steroid-dependent disease toward durable remission in many patients.

References

AAD/EADV 2020 — Updated S2K guidelines on the management of pemphigus vulgaris (Joly et al., JEADV 2020)
RITUX 3 Trial — First-line rituximab combined with short-term prednisone versus prednisone alone for pemphigus (Joly et al., Lancet 2017)
International Panel — Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus (Murrell et al., JAAD 2008)

Practice Dermatology questions on FirstPassPA

Turn this outline into retention. 3,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.

Start studying free → Browse all 514 diagnoses

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. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.