Dasatinib-Induced Transverse Melanonychia

Abstract

Introduction

Transverse melanonychia, characterized by grey to black pigmented bands traversing the nail plate, can occur as a side-effect of certain medications. While no documented reports specifically associate dasatinib, a tyrosine kinase inhibitor used in the treatment of chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia, with nail changes, we present a case of transverse melanonychia possibly related to dasatinib therapy.

Case Report

A 54-year-old male with CML, receiving dasatinib for 1.5 years, presented with transverse pigmented lines involving all fingernails and toenails. Clinical examination revealed discrete bands of transverse melanonychia in the nails. Onychoscopy of all finger- and toenails revealed multiple longitudinal grey lines within transverse grey bands of homogeneous chromonychia. Based on clinical presentation, onychoscopic features, and temporal association with dasatinib therapy, a provisional diagnosis of dasatinib-induced transverse melanonychia was made.

Discussion

The exact mechanisms underlying melanonychia are not fully understood but may involve nail matrix or toxicity, stimulation of nail-matrix melanocytes, or drug deposition within the nail plate. This case highlights the possibility of dasatinib-induced transverse melanonychia and underscores the importance of monitoring and evaluating nail changes in patients undergoing dasatinib treatment.

Established Facts

• •Transverse melanonychia is characterized by the presence of grey to black pigmented bands that traverse the width of the nail plate.
• •It is a rare nail alteration that can occur as a side-effect of certain medications.

Novel Insights

• •Dasatinib-induced transverse melanonychia has not been reported previously.
• •Multiple longitudinal grey lines within transverse grey bands of homogeneous chromonychia are seen on onychoscopy.

Introduction

Transverse melanonychia or melanonychia transversa is characterized by the presence of grey to black pigmented bands that traverse the width of the nail plate. It is a rare nail alteration that can occur as a side-effect of certain medications, in addition to other diseases like thyroid disorders and iron deficiency. While there are no documented reports of nail changes specifically associated with dasatinib, a tyrosine kinase inhibitor, used for the treatment of Philadelphia chromosome-positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia, we present a case of transverse melanonychia possibly related to dasatinib therapy [1, 2].

Case Report

A 54-year-old male plumber on dasatinib chemotherapy for 1.5 years for CML presented to the dermatology outpatient department with transverse pigmented lines involving all finger- and toenails for the past 6 months. The patient was diagnosed with Philadelphia chromosome-positive CML in chronic phase around 1.5 years back and started on dasatinib 100 mg once daily. The patient has responded favourably to dasatinib and has achieved “deep molecular response,” defined as ≤ 0.1% BCR-ABL1 on the international reporting scale, 3 months back. The patient did not reveal any other significant medical history and was not on any other concurrent medication.

Clinical examination of nails showed transverse melanonychia involving all finger- and toenails (Fig. 1). Additionally, no signs of trauma, infection, or inflammatory conditions affecting the nails were observed upon examination. The pigmentation was evenly distributed and appeared as discrete bands of similar width across each nail (Fig. 2). The mucosal and cutaneous examination did not reveal any abnormality. Onychoscopy of all finger- and toenails revealed multiple longitudinal grey lines within transverse grey bands of homogeneous chromonychia (Fig. 3). The routine laboratory investigations were within normal limits. Further, no abnormalities were observed in the patient's thyroid function tests, serum iron, or ferritin levels. Based on the clinical presentation, onychoscopic features, the absence of other identifiable causes, and the temporal association with dasatinib therapy, a provisional diagnosis of dasatinib-induced transverse melanonychia was made.

Fig. 1.

Transverse melanonychia involving all finger- and toenails.

Fig. 2.

Evenly distributed pigmentation appearing as discrete bands of similar width across each nail.

Fig. 3.

Onychoscopy showing multiple longitudinal grey lines within transverse grey bands of homogeneous chromonychia [polarized, ×30].

Discussion

Melanonychia occurs due to activation of nail-matrix melanocytes and is the most common type of chromonychia caused by antineoplastic agents. It can manifest as diffuse, longitudinal, or, less commonly, transverse band patterns. While there can be multiple causes of longitudinal melanonychia like drugs or systemic illnesses, only a few causes of transverse melanonychia have been reported. Chemotherapeutic agents including doxorubicin, bleomycin, pemetrexed, dacarbazine, imatinib and hydroxyurea, low dose radiation, electron beam therapy, PUVA therapy, infliximab, melanotan, antimalarials, zidovudine have all been reported to cause transverse melanonychia [2–7].

The exact mechanism underlying drug-induced melanonychia is not fully understood and it may involve various factors. One possible mechanism is direct toxicity to the nail matrix leading to altered melanocyte function and subsequent melanin deposition in the nail plate. Another proposed mechanism is the stimulation of nail-matrix melanocytes. Some medications may interact with melanocyte signalling pathways or receptors, leading to the activation and/or proliferation of melanocytes. Furthermore, drug deposition within the nail plate itself can contribute to nail pigmentation leading to diffuse melanonychia. When the melanocyte activation occurs throughout the matrix, it may lead to either diffuse or transverse melanonychia, depending on where the melanocyte activation is sustained or transient, respectively, whereas focal melanocyte activation leads to longitudinal melanonychia [2–9]. Onychoscopy features are suggestive of melanocyte activation, including pale bands of homogeneous greyish background pigmentation with regular grey lines [9].

Imatinib, also a tyrosine kinase inhibitor, has a potential molecular mechanism to explain pigmentary changes. Imatinib specifically targets tyrosine kinases associated with BCR-ABL, c-kit, and platelet-derived growth factor receptor (PDGFR)-α. C-kit is naturally present in basal cells of the skin, melanocytes, epithelial cells in breast tissue, and mast cells. It plays a regulatory role in processes such as melanogenesis, maintaining melanocyte balance, and pigmentation. Imatinib disrupts the functioning of c-kit, which could potentially result in the activation of melanocytes in the distal nail matrix [4]. In comparison, dasatinib inhibits many kinases (BCR-ABL, SRC family, c-kit, EPHA2, and PDGFR-β) to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, in addition to inhibiting alternate signalling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression [10]. The adverse effects of dasatinib include myelosuppression, fluid retention, diarrhoea, headache, musculoskeletal pain, mucocutaneous rash, and pigmentary changes including both hypo- and hyperpigmentation. Pigmentary changes are less frequent with dasatinib due to lower affinity to c-kit and PDFGR-α [11]. While there are no reported cases of nail changes specifically associated with dasatinib, individual variations in drug response and idiosyncratic reactions are possible. Dasatinib-induced immune dysregulation, in addition to the action on c-kit and PDFGR-α in susceptible patients, may account for these changes. However, a comprehensive evaluation to rule out other potential causes is necessary before diagnosing drug-induced melanonychia. Concurrent medications, other medical conditions, and external factors also merit consideration.

In conclusion, we present a case of transverse melanonychia possibly related to dasatinib therapy. While there are no previous reports of nail changes specifically associated with dasatinib, this case highlights the need for vigilance in monitoring and evaluating patients undergoing dasatinib treatment. Collaborative efforts between dermatologists, oncologists, and researchers are necessary to gather more evidence and establish a clearer understanding of this rare nail alteration in the context of dasatinib treatment.

Statement of Ethics

The study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The subject has given her written informed consent to publish the case (including the publication of images). Institutional Ethical Review Board approval was not required for this study in accordance with national guidelines.

Conflict of Interest Statement

The authors have no conflicts of interest to declare. None of the authors report any form of support or financial involvement. There are no nonfinancial relationships (personal, political, or professional) that may potentially influence the writing of the manuscript.

Funding Sources

The authors did not receive any funding.

Author Contributions

Dr. Mehul Tyagi, Dr. Vishal Gaurav, and Dr. Japnoor Kaur contributed equally to the concept, design, and definition of intellectual content, data acquisition, and data analysis. Dr. Mehul Tyagi, Dr. Vishal Gaurav, and Dr. Japnoor Kaur prepared the first draft of the manuscript. Dr. Vishal Gaurav did manuscript editing and review. Dr. Vishal Gaurav shall act as guarantor.

Funding Statement

The authors did not receive any funding.

Data Availability Statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.