Palmoplantar psoriasis emerging during nilotinib treatment for chronic myeloid leukemia
Year: 2025
Type: article
Abstract: Dear Editor, Nilotinib, a second-generation tyrosine kinase inhibitor (TKI) introduced in 2007, is approved as first-line therapy for newly diagnosed chronic myeloid leukemia (CML) and as second-line therapy for imatinib-resistant or imatinib-intolerant CML.[1] We present the case of a patient who developed new-onset palmoplantar psoriasis (PP) after initiating nilotinib therapy, contributing to the understanding of its associated dermatologic manifestations. A 41-year-old female with chronic-phase CML presented to our dermatology department with an 18-month history of progressive scaling of the palms and soles. She had previously been treated with dasatinib for approximately 2.5 years, which was discontinued due to dasatinib-induced pulmonary arterial hypertension. She was subsequently started on nilotinib (300 mg) twice daily. She first experienced painful sensations on the palms and soles 6 weeks after initiating nilotinib therapy, with grade 2 pruritic skin rash initially suspected. She had no family history of psoriasis or prior dermatologic conditions, no concomitant medications, and no recent history of infection, stress, or trauma before the onset of skin lesions. Due to the gradual progression of the lesions and worsening pain, she was referred to our outpatient dermatology clinic for further evaluation. Physical examination revealed multiple well-demarcated erythematous plaques with overlying scale formation on the bilateral palms and soles. Nail examination demonstrated fingernail pitting, and additional erythematous scaly patches were noted on the shins [Figure 1]. A biopsy of the plantar lesion revealed psoriasiform acanthosis, confluent parakeratosis with Munro microabscesses, a diminished granular cell layer, and dilated tortuous vessels in the superficial dermis [Supplementary Figure 1]. Based on the clinical presentation and histopathologic findings, a diagnosis of PP was established. Although palmar-plantar involvement is rarely reported in TKI-related adverse events, this case highlights the need to recognize PP as a potential cutaneous toxicity of nilotinib.Figure 1: Clinical findings of nilotinib-induced palmoplantar psoriasis: (a) Erythematous plaques predominantly affecting the periungual areas, with associated fingernail pitting. (b) Hyperkeratosis, scaling, and pustule formation on bilateral soles. (c) Widespread erythematous, scaly plaques involving the palms, soles, and dorsal feet.Supplementary Figure 1: Histopathologic features (hematoxylin and eosin staining) of nilotinib-induced palmoplantar psoriasis: (a) Medium power view (×100) showing psoriasiform epidermal hyperplasia with thinning of the suprapapillary plates, confluent parakeratosis with loss of the granular layer, and prominent dilated capillaries within elongated dermal papillae. (b) High power view (×400) demonstrating classic Munro microabscesses within the stratum corneum, characterized by collections of neutrophils within the parakeratotic scale.The patient was treated with daily acitretin (10 mg), cyclosporine (200 mg), and topical calcipotriol-betamethasone combination ointment. She denied arthralgias or joint symptoms. After 1 year of follow-up, the cutaneous lesions showed clinical stabilization with persistent but tolerable symptoms that did not significantly impact quality of life, allowing continuation of nilotinib therapy without dose modification. This outcome underscores the importance of personalized immunomodulatory strategies in managing dermatologic toxicity while preserving the oncologic benefits of TKI therapy. CML is a myeloproliferative neoplasm characterized by the Philadelphia chromosome, which arises from a t (9;22) translocation creating the BCR::ABL1 fusion oncogene.[1] TKIs targeting BCR::ABL1 have revolutionized CML treatment outcomes. Compared to first-generation imatinib, nilotinib demonstrates superior potency as a BCR::ABL1 inhibitor. It maintains efficacy against most ABL1 kinase domain mutations that confer resistance to imatinib, with the notable exception of the T315I mutation.[1] While nilotinib demonstrates a generally favorable safety profile, the incidence of skin rashes with nilotinib therapy has been reported to range from 20% to 40%.[2] Despite this relatively high frequency of dermatologic side effects, detailed reports characterizing specific types of cutaneous reactions, such as Sweet syndrome, erythema nodosum, skin ulcer, and photosensitivity, remain limited in the literature.[2] PP accounts for 3%–4% of all psoriasis cases and may occur with or without psoriatic lesions elsewhere on the body.[3] Despite its localized distribution to palms and soles, PP leads to substantial functional impairment through painful fissuring and hyperkeratosis that significantly interfere with daily activities. The management of PP typically begins with potent topical therapies, although systemic treatment is often required.[3] Oral retinoids, cyclosporine, and methotrexate have conventionally been the systemic therapies of choice due to their anti-inflammatory and immunomodulatory properties.[3,4] Biologic agents, including guselkumab, bimekizumab, and adalimumab, have shown efficacy in managing PP and are utilized for refractory cases.[5] The pathogenesis of psoriasis is characterized by aberrant T-cell activation and the consequent inflammatory cascade. An in vitro study has demonstrated that at therapeutic concentrations, nilotinib inhibits phytohemagglutinin-induced CD8+ T-cell proliferation, impairing T-cell function.[6] However, regulatory T-cell suppression occurs primarily at supratherapeutic concentrations, with minimal effects at therapeutic doses.[7] These concentration-dependent effects suggest that nilotinib may disrupt immune homeostasis in a complex, dose-sensitive manner. A recent case of psoriasis regression during nilotinib therapy further highlights the possibility that clinical manifestations may depend on the shifting balance between its effects on regulatory and effector T-cell populations.[8] This case highlights new-onset PP temporally associated with nilotinib therapy, underscoring the importance of recognizing potential TKI-related cutaneous adverse effects. While temporality supports an association, causality cannot be definitively established. We compare this case with four previously reported cases in Supplementary Table 1. Although the underlying mechanisms remain unclear, documenting such atypical cutaneous manifestations may provide important clinical insights and guide future studies on TKI-induced immune dysregulation.Supplementary Table 1: Reported cases of nilotinib-induced psoriasisDeclaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Dermatologica Sinica
Authors: Wan-Chen Lin, Chun-Wei Lu
Language: English
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $70
OpenAlex ID: W4415495461