Dermatology · Autoimmune Bullous Diseases
The facts most likely to be tested
Pemphigus vulgaris is caused by IgG autoantibodies against desmoglein 1 and 3, which are components of desmosomes that maintain cell-to-cell adhesion.
Patients typically present with flaccid bullae and mucosal erosions that rupture easily due to the loss of intercellular connections.
A positive Nikolsky sign is present, where the epidermis separates and sloughs off with lateral pressure on perilesional skin.
Oral mucosal involvement is the most common initial presentation and often precedes cutaneous lesions by months.
Direct immunofluorescence of perilesional skin reveals a classic net-like or fishnet pattern of IgG and C3 deposition in the intercellular spaces.
Histopathology demonstrates acantholysis, which is the loss of intercellular connections between keratinocytes, resulting in a tombstone appearance of the basal layer.
The first-line treatment for pemphigus vulgaris is systemic corticosteroids, often requiring the addition of rituximab or other immunosuppressive agents for long-term management.
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A 52-year-old woman presents with a 3-month history of painful, non-healing oral ulcers that have made eating difficult. She now reports the development of multiple flaccid, thin-walled bullae on her trunk and axillae that rupture easily, leaving behind painful erosions. Physical examination reveals that firm lateral pressure on normal-appearing skin adjacent to a blister results in epidermal sloughing. A biopsy of the perilesional skin is performed for direct immunofluorescence.
What is the most likely diagnosis?
Pemphigus vulgaris
The presence of flaccid bullae, oral involvement, and a positive Nikolsky sign is classic for pemphigus vulgaris, which is confirmed by the finding of IgG autoantibodies against desmogleins.
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High yield triage
Etiology / Epidemiology
Autoimmune disorder targeting desmoglein 1 and 3 in middle-aged adults.
Clinical Manifestations
Flaccid bullae with Nikolsky sign; mucosal involvement is universal.
Diagnosis
Direct immunofluorescence showing IgG/C3 in a net-like pattern.
Treatment
Systemic corticosteroids are first-line; secondary infection is the primary mortality risk.
Prognosis
Historically fatal; mortality <10% with modern immunosuppression.
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Epidemiology & Etiology
Typically presents in patients aged 40–60 years. It is a type II hypersensitivity reaction caused by autoantibodies against desmosomal proteins. No strong gender predilection exists, though it is more common in patients of Ashkenazi Jewish or Mediterranean descent.
Pertinent Anatomy
Targets the desmosomes within the epidermis. Specifically, it disrupts the intercellular adhesion between keratinocytes, leading to the loss of structural integrity in the skin and mucous membranes.
Pathophysiology
Autoantibodies (IgG) target desmoglein 3 (mucosal) and desmoglein 1 (cutaneous). This leads to acantholysis, the loss of cell-to-cell adhesion. The resulting separation of keratinocytes creates intraepidermal, suprabasal bullae.
Clinical Manifestations
Patients present with painful, flaccid bullae that rupture easily, leaving raw, weeping erosions. The Nikolsky sign (lateral pressure on skin causes blistering) is positive. Oral mucosal involvement is often the initial presenting symptom and can lead to severe dysphagia and malnutrition.
Diagnosis
The gold standard is direct immunofluorescence of perilesional skin, revealing net-like (chicken wire) IgG and C3 deposition. ELISA is used to detect circulating anti-desmoglein antibodies. Histopathology shows suprabasal acantholysis.
Treatment
Initiate high-dose systemic corticosteroids as the first-line therapy. Add rituximab or other steroid-sparing agents (azathioprine, mycophenolate mofetil) to minimize long-term steroid toxicity. Avoid systemic steroids if there is evidence of severe, uncontrolled sepsis.
Prognosis
The primary cause of death is secondary infection or sepsis due to extensive skin barrier loss. Patients require long-term monitoring for immunosuppression-related complications and metabolic side effects of chronic steroid use.
Differential Diagnosis
Bullous Pemphigoid: tense bullae, negative Nikolsky sign, spares mucosa
Stevens-Johnson Syndrome: acute drug reaction, targetoid lesions, full-thickness necrosis
Erythema Multiforme: target lesions, usually post-infectious (HSV)
Cicatricial Pemphigoid: scarring, primarily ocular/mucosal involvement
Dermatitis Herpetiformis: pruritic vesicles on extensor surfaces, associated with celiac disease