BI36 Dose-dependent ponatinib-induced pityriasis rubra pilaris in chronic myeloid leukaemia

Abstract

Tyrosine kinase inhibitors are increasingly used in the management of haematological malignancy, with a growing spectrum of cutaneous adverse effects. Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis that can present with erythroderma and mimic psoriasis or drug hypersensitivity. Although cutaneous reactions are a well-recognized adverse event that can occur with tyrosine kinase inhibitors, PRP eruptions are rare, and evidence supporting dose dependence is limited. We present the case of a 79-year-old man with chronic myeloid leukaemia who had been treated with ponatinib for 1 year without adverse cutaneous effects. His ponatinib dose was increased to 45 mg daily due to disease progression, and 1 month following dose escalation he developed a rapidly progressive widespread erythematous eruption. Examination demonstrated diffuse confluent erythema with scaling and characteristic islands of sparing, clinically consistent with PRP. A 6-mm punch biopsy from the right upper arm demonstrated hyperkeratosis, parakeratosis, mild acanthosis and a superficial perivascular lymphocytic infiltrate, supporting the clinical impression of PRP. The patient was treated with emollients and topical corticosteroids (betamethasone valerate and clobetasone butyrate). Following multidisciplinary discussion with haematology, ponatinib was discontinued and replaced with an alternative agent. The rash had completely resolved at review 6 weeks later, with complete sustained clearance confirmed at ­follow-up 3 months after rash onset. This case supports a dose-­dependent PRP-like erythrodermic eruption secondary to ponatinib, occurring only after dose escalation despite previous long-term tolerance. It strengthens clinicopathological evidence for causality and expands the recognized spectrum of targeted therapy toxicity. Early recognition may prevent unnecessary systemic immunosuppression and enable prompt multidisciplinary medication review in immunosuppressed patients.