Complete Resolution of Atypical Paraneoplastic Pemphigus Following Treatment With Dupilumab

Area of Science:

• Dermatology
• Autoimmune diseases
• Oncology

Background:

• Paraneoplastic pemphigus (PNP) is a rare, severe autoimmune blistering disease linked to internal malignancies.
• Typical PNP presents with painful oral erosions, but atypical presentations without mucosal involvement occur.
• Standard management with immunosuppressants offers a poor prognosis, necessitating alternative therapeutic strategies.

Observation:

• A 77-year-old male presented with a widespread, intensely pruritic rash (90% body surface area) featuring scaling, erythema, crusting, bullae, and erosions, notably lacking oral lesions.
• Histopathology and direct immunofluorescence confirmed PNP, with biopsies showing acantholysis and lichenoid interface dermatitis, and DIF revealing IgG and C3 deposition.
• The patient had elevated autoantibodies (desmoglein-1, BPAG1/BP230) and was diagnosed with intramucosal gastrointestinal adenocarcinoma.

Findings:

• The patient was unsuitable for conventional immunosuppressive therapy due to comorbidities including diabetes and non-healing ulcers.
• Empiric treatment with dupilumab, an interleukin-4/13 receptor-α inhibitor, was initiated to manage severe, refractory pruritus.
• Dupilumab therapy led to significant skin lesion improvement within two months and complete resolution of pruritus and skin lesions by four months.

Implications:

• This case demonstrates the potential efficacy of dupilumab in treating atypical paraneoplastic pemphigus, particularly in patients with contraindications to standard treatments.
• The successful outcome suggests dupilumab may be a valuable therapeutic option for managing severe cutaneous symptoms and pruritus in refractory PNP.
• This report highlights a unique, previously undocumented response to dupilumab, expanding treatment possibilities for this rare and challenging condition.