Hyperpigmented rash of imatinib

INTRODUCTION

Imatinib mesylate, a selective tyrosine kinase inhibitor, changed the way chronic myeloid leukemia (CML) is treated. Despite its favorable safety profile, dermatologic side effects including hyperpigmented rashes have been increasingly recognized. We discuss an uncommon instance of face hyperpigmentation caused by imatinib therapy, and we also provide an analysis of the literature that focuses on the clinical aspects, diagnostic issues, and management. Imatinib mesylate is a key part of treating CML since it targets the BCRABL, c-KIT, and platelet-derived growth factor receptor pathways.^[1] Dermatologic side effects happen in 9–28% of patients, mostly as maculopapular eruptions, hypopigmentation, and less often hyperpigmentation.^[2,3] Hyperpigmentation is not common, yet it can have a big impact on a person’s quality of life.

CASE REPORT

A 37-year-old woman with intermediate-risk CML started using imatinib (400 mg/day). She reported progressive facial hyperpigmentation within 2 months, which was characterized by gray-brown macules and patches that were primarily located over the malar regions [Figures 1-3]. The clinical examination showed no redness, scaling, or hardening that went along with it. The rash just affected the face and did not spread to other parts of the body or mucous membranes. There was no history of photosensitivity or other drugs that could have caused hyperpigmentation. Hyperpigmentation appeared progressively darker, prompting considerations of melasma, post-inflammatory hyperpigmentation, Addison’s disease, and drug-induced causes. Clinical history, physical examination, and endocrine tests ruled out these other possibilities. Given the classic presentation and the benign nature, skin biopsy was deferred respecting patient preference. Three months later, there was a complete molecular response; thus, imatinib was continued with precautions to protect against light.

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Figure 1:

Image showing hyperpigmented rash in the malar area after imatinib therapy for chronic myeloid leukemia.

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Figure 2:

Image showing hyperpigmented rash on the right side of face.

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Figure 3:

Image showing hyperpigmented rash on the left side of face.

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DISCUSSION

Compared to hypopigmentation,^[4] hyperpigmentation caused by imatinib is rare and not often documented. Previous studies described hyperpigmentation manifesting as melasma-like macules predominantly in facial convexities, sparing mucosal areas, similar to our patient’s clinical presentation.^[5,6] The reasons why imatinib causes hyperpigmentation are yet not fully understood:

Melanocyte dysregulation – paradoxical stimulation or migration of melanocytes, despite c-KIT inhibition;^[7] drug metabolite deposition – chelation of iron and melanin inside dermal macrophages and melanophages leading to pigmentation;^[8] and lichenoid reactions – other publications’ histopathological findings show a lichenoid inflammatory process linked to pigment incontinence.^[9] Li et al. reported imatinib-induced mucosal hyperpigmentation. They employed positive Fontana-Masson and Prussian blue stains to show that iron and melanin were deposited, which is similar to minocycline pigmentation.^[10] Garraway et al. also documented severe hyperpigmentation on the face and trunk, which was caused by long-term exposure to imatinib therapy.^[3] Clinically, the rash presents as well-defined hyperpigmented macules predominantly on sun-exposed areas, underscoring phototoxicity as a possible contributing mechanism. Patients tolerate the pigmentation without significant discomfort, and imatinib is rarely discontinued unless severe cosmetic distress or dermatologic complications occur.^[11]

Management and prognosis: Management involves using broad-spectrum sunscreens to protect the skin from the sun, avoiding the sun, and topical depigmenting chemicals if needed. Pigmentation usually goes down slowly once the dose of imatinib is lowered or stopped.^[12] Our patient, on the other hand, wanted to continue treatment with cautious management because of a good hematologic response.

CONCLUSION

Facial hyperpigmentation induced by imatinib is a rare yet clinically relevant dermatologic event. Awareness of this manifestation aids in early diagnosis, exclusion of differentials, and appropriate patient counseling. Conservative management with photoprotection is still effective without lowering the effectiveness of the treatment.