Complete Resolution of Atypical Paraneoplastic Pemphigus Following Treatment With Dupilumab

TL;DR

A rare autoimmune skin condition called paraneoplastic pemphigus was completely resolved in a patient using dupilumab, a drug targeting the IL-4/13 pathway.

Contribution

This is the first reported case of complete resolution of atypical paraneoplastic pemphigus using dupilumab.

Findings

Dupilumab led to complete resolution of skin lesions and pruritus in a patient with atypical paraneoplastic pemphigus.

The patient's condition met diagnostic criteria for PNP, including autoantibodies and histopathological findings.

Traditional immunosuppressants were unsuitable due to comorbidities, making dupilumab a novel therapeutic option.

Abstract

Paraneoplastic pemphigus (PNP) is a rare autoimmune mucocutaneous blistering condition associated with underlying malignancies. While severe stomatitis is usually a hallmark feature of PNP, it may present with the absence of oral manifestations. Proposed diagnostic criteria include the presence of mucosal lesions with or without cutaneous involvement, concomitant internal neoplasm, anti-plakin autoantibodies, histopathology with acantholysis and/or lichenoid interface changes, and direct immunofluorescence (DIF) with intercellular and/or basement membrane deposition of immunoglobulin G (IgG) or complement component-3 (C3). Management of PNP traditionally involves immunosuppressants; however, prognosis remains poor.

This report presents a 77-year-old male patient with an ongoing, intensely painful, and pruritic rash with diffuse scaling, erythema, crust, bullae, and erosions covering 90% body surface area that notably lacked mucosal involvement. Biopsies revealed acantholysis with mixed infiltrate lichenoid interface dermatitis and DIF with 3+ intercellular and basement membrane deposition of C3 and IgG. Additional workup revealed elevated desmoglein-1 and bullous pemphigoid antigen-1 (BPAG1/BP230) autoantibodies and intramucosal gastrointestinal adenocarcinoma, satisfying the diagnostic criteria for PNP.

Due to his history of type 2 diabetes mellitus, chronic non-healing ulcers, and untreated malignancy, he was a poor candidate for first-line immunosuppressants. Additionally, the patient experienced significant pruritus resistant to topical corticosteroids and oral antihistamines. For these reasons, dupilumab was elected to control the patient's pruritus. After two months, there was significant improvement in skin lesions, and after four months, there were complete resolution of pruritus and 100% clearance of skin lesions.

This report highlights a unique and previously unreported case of complete resolution of atypical PNP following empiric treatment with dupilumab, a monoclonal antibody against interleukin 4/13 receptor-α.

Figures