Ichthyosiform Pityriasis Rubra Pilaris-Like Eruption Secondary to Ponatinib Therapy: Case Report and Literature Review

Abstract

Tyrosine kinase inhibitors have revolutionized the chemotherapy arena as targeted therapies for a multitude of malignancies. They are more selective than conventional chemotherapy, and often elicit fewer systemic adverse events, however toxicities still exist. Cutaneous toxicities are common and their management presents a novel challenge to physicians and patients. Ponatinib is a third-generation tyrosine kinase inhibitor increasingly reported to cause cutaneous eruption. A 50-year-old woman with a history of chronic myelogenous leukemia presented with a 4-month history of worsening atrophic and ichthyosiform pink plaques involving the axillae, thighs and abdomen; red patches were also observed on the cheeks and forehead. She was started on the third-generation, ponatinib, 5 months earlier because of disease refractory to previous therapies including interferon, imatinib, dasatinib and bosutinib. A skin biopsy revealed perifollicular fibrosis, alternating orthokeratosis and parakeratosis, and a sparse perivascular lymphocytic infiltrate consistent with a pityriasis rubra pilaris-like reaction. Topical tretinoin 0.025% cream was initiated, resulting in resolution within 3 weeks without discontinuation of ponatinib. A review of previous reports identified significant similarities among the ponatinib-induced drug reactions. Here, we highlight not only that cutaneous eruptions occur on ponatinib therapy, but that the dermatologic manifestations are characteristic and unique, and benefit from retinoid therapy, without requiring interruption of vital chemotherapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s40800-017-0055-y) contains supplementary material, which is available to authorized users.

Use of Biologics in Pityriasis Rubra Pilaris Refractory to First-Line Systemic Therapy: A Systematic Review

“…More recently, there has been an increasing number of articles reporting the safe and efficacious use of biological agents in patients with PRP who fail to respond sufficiently to oral retinoid or MTX therapy, or who have comorbidities that preclude use of systemic therapy. 7,8 These include antagonists of tumor necrosis factor alpha (TNFα), and interleukins (ILs) 12, 23, and 17. 5 Given the rarity of the disease, available data on the use and efficacy of biologics in treatment-refractory PRP limited to published case series and case reports.…”

Cutaneous eruption in a patient of color

“…While discontinuation of the causative agent often leads to resolution, this is often difficult in refractory cases of leukemias resistant to first‐line therapy. Clearance of cutaneous lesions has been achieved without interruption of TKI therapy in previously reported cases, with only one patient requiring a dose reduction 4,5 . Other therapeutic options that have shown some efficacy include topical corticosteroids, topical or systemic retinoids, and keratolytics 5 …”

“…Clearance of cutaneous lesions has been achieved without interruption of TKI therapy in previously reported cases, with only one patient requiring a dose reduction 4,5 . Other therapeutic options that have shown some efficacy include topical corticosteroids, topical or systemic retinoids, and keratolytics 5 …”

A patient with maculopapular rash and lichenoid skin damage caused by ponatinib

“…5 Published case reports have described lamellar ichthyosislike, keratosis pilaris-like, lichen planopilaris-like, and pityriasis rubra pilaris-like eruptions, as well as folliculocentric and seborrheic changes after the initiation of ponatinib. [6][7][8][9][10][11] Suggested treatment options for these skin reactions include topical steroids, retinoids, keratolytics, and antifungals, as well as systemic retinoids in more severe cases. 4 Unlike the current patient, most previously reported cases described an ichthyosiform appearance, as well as follicular involvement on histopathological examination.…”

“…Some researchers have suggested that retinoids may strengthen the local chemotherapeutic resistance of keratinocytes by upregulating heparinbinding epidermal growth factor. 7 Dermatological adverse reactions are common after treatment with TKIs. The impacts of these side effects on the patient's appearance and quality of life may ultimately lead to interruption of their anticancer therapy.…”