Nilotinib-Induced Extensive Skin Rashes and Alopecia in a Patient with Chronic Myeloid Leukemia: A Case Report and Herbal Medicine Approach

Introduction

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome. While these targeted therapies have significantly improved patient outcomes, they are associated with various adverse effects, including dermatological manifestations. This case report highlights the occurrence of extensive skin rashes and alopecia in a patient receiving nilotinib, a second-generation TKI, and discusses the management strategies employed to alleviate these side effects.

Case Presentation

A 65-year-old female patient with chronic myeloid leukemia presented with a 3-year history of skin rashes. Initially, the patient was started on imatinib, the first-line TKI for CML, but was later switched to nilotinib (300 mg twice daily) due to therapeutic considerations. Following the initiation of nilotinib therapy, the patient developed extensive skin rashes, prompting the use of topical steroid creams, cetirizine (a non-sedating antihistamine), longifene (an antihistamine and antiemetic), and buclizine (an antihistamine) to manage the rashes, nausea, and vomiting associated with imatinib and nilotinib.

Nilotinib_A4

Over the past two years, the patient had been taking over-the-counter turmeric tablets and flaxseed oil supplements in an attempt to alleviate her symptoms. However, the skin rashes continued to spread, affecting the trunk, arms, legs, and forehead area. Furthermore, two alopecia patches, each measuring approximately 5 cm in diameter, appeared on the patient’s scalp, prompting her to seek a third-party opinion.

Upon examination, the patient presented with multiple erythematous rashes and diffuse follicular papules over the trunk, limbs, and forehead area, as well as two patches of alopecia.

Nilotinib_B4

Management and Outcome

Despite the dermatological manifestations, nilotinib therapy was continued without dose adjustment. Topical steroids, turmeric tablets, and flaxseed oil supplements were discontinued. Instead, an herbal medicine was prescribed, and after 12 months of treatment, the rashes had disappeared, and the patient’s hair had regrown.

Nilotinib_C4

Discussion

Nilotinib, a second-generation Bcr-Abl tyrosine kinase inhibitor, is approved for first-line treatment of CML or as a second-line therapy for imatinib-resistant CML. While generally well-tolerated, like all TKIs, nilotinib has off-target side effects. Skin reactions are among the common non-hematological side effects reported with nilotinib, with the incidence of rash varying from 22% to 62% in clinical trials [1-3]. Other dermatological side effects include pruritus, dry skin, and, rarely, alopecia [4-9].

The pathogenesis of TKI-induced skin rashes and alopecia are not fully understood, but it is thought to involve various mechanisms, such as its action on tyrosine kinase receptor in the hair follicles, reproducing the same rash induced by vemurafenib through the same ERK/MAPK pathway [10,11].

In this case, the patient’s skin rashes and alopecia were likely related to the nilotinib therapy, as the symptoms developed following the initiation of the drug and persisted despite the use of various supportive measures, including topical steroids and antihistamines. The patient had no atopic family history or other significant medical history, further supporting the association between the dermatological manifestations and nilotinib therapy. The decision to continue nilotinib without dose adjustment was based on the assessment of the risk-benefit ratio, as discontinuation of the TKI could compromise the patient’s leukemia treatment outcomes.

The management approach involved discontinuing the topical steroids and aggravating supplements (turmeric and flaxseed oil) and introducing an herbal compound, which ultimately led to the resolution of the skin rashes and hair regrowth over 6 months. While the precise mechanism of action of the herbal compound is unknown, it may have modulated the inflammatory pathways or targeted the off-target effects of nilotinib, thereby alleviating the dermatological manifestations.

Conclusion

This case report highlights the importance of recognizing and managing dermatological adverse effects associated with TKI therapy in patients with chronic myeloid leukemia. While nilotinib has proven efficacy in treating CML, its potential to cause skin rashes and alopecia should be considered, and appropriate management strategies should be implemented to alleviate these side effects without compromising the primary treatment goals. The successful resolution of the patient’s symptoms through the use of an herbal compound underscores the potential for complementary and alternative therapies in managing TKI-induced dermatological toxicities, although further research is warranted to elucidate the underlying mechanisms and establish their safety and efficacy.

Reference

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  2. Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, Cervantes F, et al. Chronic myeloid leukemia: An update of concepts and management recommendations of European LeukemiaNet. J ClinOncol. 2009;27(35):6041-6051.
  3. Cortes JE, Jones D, O’Brien S, Jabbour E, Konopleva M, Ferrajoli A, Kadia T, et al. Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J ClinOncol. 2010;28(3):392-397.
  4. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, Ossenkoppele GJ, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007;110(10): 3540–3546.
  5. Nicolini FE, Masszi T, Shen Z, Gallagher NJ, Jootar S, Powell BL et al. Expanding Nilotinib Access in Clinical Trials (ENACT), an open-label multicenter study of oral nilotinib in adult patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase or blast crisis. Leuk Lymphoma. 2012;53:907–914.
  6. Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, Tanaka C, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542–2551.
  7. Saglio G, Kim DW, Issaragrisil S, le CP, Etienne G, Lobo C, Pasquini R,Clark RE, et al. Nilotinib versus imatinib for newlydiagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251-2259.
  8. Hansen T, Little AJ, Miller JJ, Ioffreda MD. A case of inflammatory nonscarring alopecia associated with the tyrosine kinase inhibitor nilotinib. JAMA Dermatol. 2013;149:330–2.
  9. Patel AB, Solomon AR, Mauro MJ, Ehst BD. Unique cutaneous reaction to second- and third-generation tyrosine kinase inhibitors for chronic myeloid leukemia. Dermatology. 2016;232:122–5.
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Privacy

In situations where the disease information had already been made publicly available (as evidenced by prior articles), genuine names of individuals have been utilized. Conversely, in instances where there was no pre-existing public disclosure or at the explicit request of patients for privacy, pseudonyms have been employed. Furthermore, identities have been deliberately obscured, and certain contextual details and diagnoses have been modified to hinder any attempts at identification. It is essential to emphasize that the patients and encounters described in this work are authentic, and their consent for publication was duly obtained. As responsible authors, we earnestly implore all our readers to honor the privacy and confidentiality of these individuals. Additionally, certain scenarios, assessments, and clinical interventions have been altered to safeguard the anonymity of both patients and healthcare providers.