Melasma-like facial hyperpigmentation associated with long-term dasatinib therapy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia: a rare cutaneous adverse event

Abstract

Tyrosine kinase inhibitors (TKIs) have significantly improved survival in Philadelphia chromosome-positive leukemias, including chronic myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib, a second-generation TKI, is frequently used in Ph+ ALL due to its potent BCR-ABL inhibition and ability to cross the blood-brain barrier. While common adverse effects of dasatinib include cytopenias and fluid retention, cutaneous side effects are rare, particularly pigmentary changes, and among these, melasma-like hyperpigmentation has seldom been reported. We report the case of a 29-year-old woman diagnosed with high-risk Ph+ B-cell ALL with baseline CNS-III involvement, who was treated with the augmented BFM 2009 protocol along with dasatinib (100 mg once daily). After achieving complete molecular remission and transitioning to maintenance therapy, the patient developed progressive, asymptomatic, brown-gray hyperpigmented macules and patches over the malar areas, forehead, nasal bridge, and upper lip consistent with a centrofacial melasma-like pattern. No history of sun exposure, hormonal therapy, cosmetic products, or systemic illness was identified. A dermatologic evaluation attributed the lesions to dasatinib-induced hyperpigmentation, and the patient was treated with topical fluticasone and 2% hydroquinone, along with strict photoprotection. Cutaneous pigmentary changes induced by TKIs are typically hypopigmentary and most commonly associated with imatinib, whereas hyperpigmentation, especially with melasma-like features, remains a rare adverse effect of dasatinib; the pathogenesis is believed to involve inhibition of the c-KIT/stem cell factor signaling pathway, which is vital for melanocyte function. In this patient, the delayed onset of pigmentation nearly four years after dasatinib initiation highlights the unpredictable nature of TKI-induced skin changes, and given the importance of dasatinib in disease control, continuation of therapy with symptomatic dermatologic management was deemed appropriate. This case underscores the importance of recognizing rare dermatologic adverse effects of TKIs, such as melasma-like hyperpigmentation associated with dasatinib; early identification and management are essential to prevent cosmetic distress and ensure treatment adherence, and further research is needed to elucidate the mechanisms underlying such pigmentary changes and to guide optimal management strategies.