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KembaraXtra -Medicine- Emergency and Acute Medicine – Pemphigus
Pemphigus is a rare, IgG-mediated autoimmune blistering disorder of the skin and mucous membranes characterized by loss of keratinocyte cell-to-cell adhesion (acantholysis). The term is derived from the Greek word for “bubble” or blister. It most commonly affects older adults, with a median age of 71 years, and has a slight female predominance. Although rare, it can occur in neonates, children, and adolescents. If untreated, mortality historically reached 60–90%, but with modern therapy this has decreased to approximately 5%. Mortality is highest in patients with extensive mucocutaneous involvement.
There are three major subtypes. Pemphigus vulgaris accounts for 70–80% of cases and is the most serious form, with deeper mucocutaneous involvement. Up to 70% of patients initially present with painful oral lesions before cutaneous involvement develops. Autoantibodies are directed against desmoglein (Dsg) 1 and 3. Pemphigus foliaceus is more superficial, limited primarily to the skin, and associated with antibodies to Dsg1 only; oral lesions are uncommon and prognosis is generally better. Paraneoplastic pemphigus is often severe and associated with lymphoreticular malignancies. Endemic pemphigus foliaceus (fogo selvagem) is reported most commonly in South America and may be associated with environmental triggers such as insect bites.
The pathogenesis involves IgG autoantibodies targeting desmosomal cadherins (desmoglein 1 and 3) on keratinocytes. This immune attack results in acantholysis, cytoskeletal disruption, and apoptosis, leading to intraepidermal blister formation. Genetic predisposition is associated with certain HLA haplotypes, including DR4 and DRw6. Drug-induced pemphigus-like reactions have been reported with agents such as penicillamine, captopril, rifampin, piroxicam, and phenobarbital.
Clinically, patients present with flaccid bullae that rupture easily, leaving painful erosions with shreds of detached epithelium. Mucosal involvement, especially painful oral erosions, is common in pemphigus vulgaris and may precede skin findings. Lesions may spread to the scalp, chest, axillae, and groin. Crusted erosions, exfoliative plaques, and postinflammatory hyperpigmentation are common. The Nikolsky sign—epidermal separation with lateral pressure—is characteristic but not highly sensitive or specific. Without treatment, lesions persist and may lead to dehydration, malnutrition, infection, or sepsis.
Diagnosis is suspected clinically but requires confirmation with skin biopsy and direct immunofluorescence testing, which demonstrate intraepidermal blistering and intercellular IgG deposition. Serum antibody titers (indirect immunofluorescence or ELISA) may correlate with disease activity but are not typically obtained in the emergency setting. The differential diagnosis includes bullous pemphigoid, toxic epidermal necrolysis, dermatitis herpetiformis, erythema multiforme, lupus erythematosus, herpes simplex infection, and other blistering or erosive dermatoses.
Emergency management depends on severity. Mild-to-moderate disease may be managed with oral prednisone and urgent dermatology follow-up. Systemic corticosteroids remain the cornerstone of therapy. Severe disease may require high-dose corticosteroids, pulse intravenous methylprednisolone, or admission for plasmapheresis. Adjuvant immunosuppressive therapies such as azathioprine, mycophenolate, cyclophosphamide, cyclosporine, IV immunoglobulin, or rituximab may be added in refractory cases. Patients presenting with hypotension or sepsis require aggressive fluid resuscitation, broad-spectrum antibiotics if infection is suspected, and stress-dose steroids in those on chronic corticosteroids.
Admission is indicated for first-time presentations requiring biopsy and diagnostic confirmation, extensive mucocutaneous involvement, intractable pain, secondary infection, or signs of systemic compromise. ICU or burn unit admission may be necessary in cases of shock, sepsis, or large body surface involvement requiring intensive wound care. Patients with mild disease who are stable may be discharged with prompt dermatology follow-up.
Key clinical principles include recognizing early mucosal involvement, understanding that long-term immunosuppression is often required, and maintaining vigilance for complications such as adrenal crisis, severe infection, or steroid-induced metabolic derangements. Early diagnosis and coordinated dermatologic management significantly improve outcomes.
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