D3.27 - Nivolumab-Induced Psoriasiform Eruption: Diagnostic Challenge Between Immune-Related Toxicity and Drug Allergy

Background:

Nivolumab, an anti–PD-1 immune checkpoint inhibitor approved for multiple oncologic indications, is frequently associated with cutaneous immune-related adverse events (irAEs).

The most common manifestations include maculopapular rash, pruritus, and vitiligo, while psoriasiform, eczematous, lichenoid, and bullous lesions are less common. These immune-mediated reactions may clinically resemble drug-induced allergic eruptions, posing diagnostic challenges for allergists. Distinguishing between immune-related toxicity and true drug hypersensitivity is essential to ensure optimal oncologic management without unnecessary discontinuation.

Methods:

A 61-year-old man with high-grade urothelial carcinoma of the bladder (cT4N0, with prostatic invasion) received neoadjuvant cisplatin–gemcitabine for four cycles, achieving partial response, followed by radical cystoprostatectomy and pelvic lymphadenectomy. Given PD-L1 expression >1%, adjuvant therapy with Nivolumab was initiated on a monthly basis. During the fourth infusion, the patient developed a pruritic erythematous eruption without systemic symptoms. He was referred to our Allergy Department to rule out hypersensitivity to Nivolumab. Skin prick testing with Nivolumab 1 mg/mL (1/10) and intradermal testing at 0.1 mg/mL (1/100) were negative on both immediate and delayed readings. Laboratory evaluation, including complete blood count, renal and hepatic function tests, and inflammatory markers, was unremarkable (no eosinophilia, normal biochemistry, normal acute-phase reactants). A skin biopsy of active lesions was performed.

Results:

Examination revealed well-demarcated erythematous plaques with silvery scaling on the scalp, face, trunk, arms, and flanks (Image 1). Histopathology showed hyperkeratosis and focal parakeratosis with neutrophil aggregates, psoriasiform acanthosis, thinning of suprapapillary plates, and dermal vascular dilatation with perivascular mononuclear infiltrate; PAS staining was negative for fungal pathogens—findings consistent with psoriasis. Based on clinical, histologic, and immunoallergologic results, the eruption was classified as a psoriasiform immune-related adverse event rather than an IgE-mediated drug allergy. The patient was treated with topical corticosteroids, continued Nivolumab, and remains stable with partial improvement while awaiting biologic therapy for psoriasis control.

Conclusion:

This case highlights the importance of differentiating immune-related cutaneous toxicity from hypersensitivity reactions when evaluating eruptions under immunotherapy. Negative skin tests, absence of systemic allergic or inflammatory markers, and characteristic histology supported an immune-mediated mechanism. Collaboration between allergists and oncologists is critical to maintain effective cancer therapy while managing AEs safely.