Paraneoplastic Pemphigus Unveiling Occult Lung Adenocarcinoma: A Rituximab‐Responsive Case With Diagnostic and Therapeutic Implications

TL;DR

A rare case of paraneoplastic pemphigus linked to lung cancer shows that rituximab can help manage the condition when standard treatments fail.

Contribution

This case expands the known malignancy spectrum of PNP to include lung adenocarcinoma and highlights rituximab as a potential treatment.

Findings

PNP can be an early sign of occult lung adenocarcinoma.

Rituximab achieved sustained improvement in PNP symptoms and autoantibody levels.

Tumor resection and immunomodulation are both critical for managing PNP linked to solid tumors.

Abstract

Paraneoplastic pemphigus (PNP) is a rare autoimmune disorder typically associated with hematologic or squamous cell malignancies. Its association with lung adenocarcinoma (LUAD) is exceptionally uncommon, with only sporadic cases reported. This report highlights PNP as a sentinel manifestation of occult LUAD, emphasizing diagnostic challenges and therapeutic implications in this underrecognized association. A 73‐year‐old Asian woman presented with refractory mucocutaneous erosions, confirmed as PNP through histopathology (intraepidermal acantholysis), direct immunofluorescence (IgG/C3 deposits), and elevated anti‐desmoglein‐3 antibodies (172 U/mL). Persistent symptoms prompted malignancy screening, which revealed stage IA EGFR‐mutated LUAD. Initial immunosuppression (corticosteroids, intravenous immunoglobulin) failed to control disease. Tumor resection induced transient remission, but postoperative recurrence required rituximab therapy, achieving sustained clinical and serologic improvement (anti‐Dsg3 decline to 60 U/mL). This case expands the known malignancy spectrum of PNP to include LUAD and underscores the necessity of rigorous tumor screening even in atypical presentations. The temporal correlation between tumor resection, rituximab response, and autoantibody decline supports synergistic neoplastic/immune mechanisms. Persistent B‐cell activity post‐resection suggests adjunctive immunomodulation is critical for durable remission. Our findings advocate for (1) multidisciplinary collaboration to address diagnostic pitfalls (e.g., lesion mimicry, delayed tumor detection) and (2) consideration of rituximab in refractory PNP with solid tumors.

Overview time line of the patient's clinical history.

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