
==== Front
JAAD Case Rep
JAAD Case Rep
JAAD Case Reports
2352-5126
Elsevier

S2352-5126(24)00267-4
10.1016/j.jdcr.2024.06.038
Case Report
Imatinib-induced hyperpigmentation
Garraway Caroline MD cpgarraway@gmail.com
a∗
Yang Kevin MD a
Kantamneni Kavita BS b
Kissel Rebecca MD a
Pavlidakey Peter G. MD a
a Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
b UAB Heersink School of Medicine, Birmingham, Alabama
∗ Correspondence to: Caroline Garraway, MD, Department of Dermatology, University of Alabama at Birmingham, 510 20th St. S, FOT 858, Birmingham, AL 35233. cpgarraway@gmail.com
21 7 2024
10 2024
21 7 2024
52 2830
© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.
2024
American Academy of Dermatology, Inc.
https://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Key words

drug-induced pigmentation
hyperpigmentation
imatinib
==== Body
pmcIntroduction

Imatinib is a tyrosine kinase inhibitor used in several malignancies, including chronic myeloid leukemia. Imatinib acts on multiple targets, including BCR-ABL, c-KIT, platelet-derived growth factor receptor, and colony-stimulating factor receptor-1.1 Multiple cutaneous adverse effects have been reported with administration including nonspecific rash, pruritus, hypopigmentation, and rarely, hyperpigmentation, particularly of the oral mucosa.1 We present a case of significant blue-gray hyperpigmentation of the face and trunk.

Case report

A 46-year-old Korean woman with a history of chronic myeloid leukemia presented to dermatology clinic with progressive asymptomatic discoloration of the forehead, back, and right arm of 3-year duration. She began taking imatinib approximately 16 years prior to presentation for chronic myeloid leukemia and denied taking any other medications. Physical examination showed mottled blue-gray hyperpigmented patches of the bilateral temples extending posteriorly to the frontal scalp. Similar ill-defined blue-gray patches were scattered across diffusely on the back with accentuation around the middle portion (Fig 1). There was no mucosal or nail involvement noted on examination.Fig 1 Mottled blue-gray pigmented patches of the bilateral temples and back.

A biopsy was performed of the patient’s back with histopathology demonstrating deposition of dark-brown pigment in melanophages and dendritic mononuclear cells throughout the dermis in a perivascular and peri-eccrine distribution (Fig 2). Additional staining was negative for iron and positive for melanin highlighted by Fontana Masson. Immunostaining with SOX10 demonstrated retained melanocytes within the epidermis with a lack of dermal staining. Overall, pathology results were suggestive of medication-induced pigment deposition secondary to imatinib. Imatinib was subsequently discontinued by the oncology team but patient declined further management of the hyperpigmentation.Fig 2 Hematoxylin-eosin (H&E) staining demonstrated dark-brown pigment in melanophages perivascularly and around eccrine coils in the dermis.

Discussion

Hypopigmentation is known to be a side effect of imatinib; this is because of the role of c-KIT in proliferation and survival of melanocytes.2 Conversely, hyperpigmentation is a rare side effect of imatinib therapy and in most cases has been reported in involvement of oral mucosa, teeth, and nails.3 Cases affecting the skin have rarely been reported in the literature with varying degrees of pigmentation ranging from small hyperpigmented macules to localized patches distributed on the face or back.4, 5, 6 In 1 case, a patient with vitiligo had repigmentation of depigmented lesions after initiation of imatinib therapy for gastrointestinal stromal tumors.7 In our case, the body surface area involvement was greater than previously reported cases, likely because of the long duration over which the patient had been taking imatinib as well as the 3-year delay in presentation since the initial onset of the pigmentation.

The mechanism for hyperpigmentation is unclear, and multiple histologic patterns of pigment deposition have been identified, reflecting various possible mechanisms. Alexandrescu et al5 demonstrated a case with increased basal layer pigmentation. Kagimoto et al6 reported a case of hyperpigmentation with pathology showing pigment incontinence secondary to a lichenoid drug eruption. In fact, other tyrosine kinase inhibitors such as nilotinib and dasatinib have been associated with eruption of follicular lichen planus and lichen planopilaris lesions, suggesting the consideration of lichen planus pigmentosus given the distribution of the pigmentation and some of the histologic findings.8 In contrast, there was lack of inflammatory infiltrate noted on histology despite clinical progression of pigmentation. Furthermore, the depth of pigmentation in the dermis of our case was greater than would be expected for postinflammatory pigment alteration. In cases from Singapore and South Korea, histologic patterns showed dermal melanocytes, consistent with acquired dermal melanocytosis.9 Others have suggested that metabolites of imatinib may chelate with melanin and/or iron to cause pigment deposition in a manner similar to hydroxychloroquine, although this has not been specifically demonstrated for imatinib.10 In general, the pathogenesis behind hyperpigmentation remains poorly understood with multiple potential contributing clinical and pathologic patterns existing.

Treatment is challenging and requires risk-benefit discussion with the patient to balance therapy for malignancy with benign pigmentary changes of the skin. Hyperpigmentation of the nails and teeth has been reported to resolve after cessation of imatinib and similar improvements have been seen in cutaneous involvement.4,5 Kok and Chua11 demonstrated a successful case of treatment of imatinib-induced hyperpigmentation after 5 sessions of treatment with a picosecond alexandrite laser. In summary, imatinib is a rare but potential culprit for medication-induced hyperpigmentation.

Conflicts of interest

None disclosed.

Funding sources: None.

Patient consent: The authors attest that they have obtained written consent from patient/s, their legal guardian/s or person/s with legal authority, for their photographs and medical information to be published in print and online and with the understanding that this information may be publicly available. Patient consent forms were not provided to the journal but are retained by the authors to be made available upon request.

IRB approval status: Not applicable.
==== Refs
References

1 Brazzelli V. Grasso V. Borroni G. Imatinib, dasatinib and nilotinib: a review of adverse cutaneous reactions with emphasis on our clinical experience J Eur Acad Dermatol Venereol 27 12 2013 1471 1480 10.1111/jdv.12172 23611501
2 Tsao A.S. Kantarjian H. Cortes J. O’Brien S. Talpaz M. Imatinib mesylate causes hypopigmentation in the skin Cancer 98 11 2003 2483 2487 10.1002/cncr.11812 14635084
3 Di Tullio F. Mandel V.D. Scotti R. Padalino C. Pellacani G. Imatinib-induced diffuse hyperpigmentation of the oral mucosa, the skin, and the nails in a patient affected by chronic myeloid leukemia: report of a case and review of the literature Int J Dermatol 57 7 2018 784 790 10.1111/ijd.13931 29417559
4 Rehman H. Hakim N. Sugarman R. Seetharamu N. Saif M.W. Hyperpigmentation due to imatinib: a rare case of cutaneous involvement J Oncol Pharm Pract 26 6 2020 1511 1515 10.1177/1078155220903364 32067560
5 Alexandrescu D.T. Dasanu C.A. Farzanmehr H. Kauffman L. Persistent cutaneous hyperpigmentation after tyrosine kinase inhibition with imatinib for GIST Dermatol Online J 14 7 2008 7
6 Kagimoto Y. Mizuashi M. Kikuchi K. Aiba S. Lichenoid drug eruption with hyperpigmentation caused by imatinib mesylate Int J Dermatol 53 3 2014 e161 e162 10.1111/ijd.12174 23786260
7 Han H. Yu Y.Y. Wang Y.H. Imatinib mesylate-induced repigmentation of vitiligo lesions in a patient with recurrent gastrointestinal stromal tumors J Am Acad Dermatol 59 5 Suppl 2008 S80 S83 10.1016/j.jaad.2008.06.029 19119132
8 Patel A.B. Solomon A.R. Mauro M.J. Ehst B.D. Unique cutaneous reaction to second- and third-generation tyrosine kinase inhibitors for chronic myeloid leukemia Dermatology 232 1 2016 122 125 10.1159/000437383 26352467
9 Jang J.W. Song C.H. Jung Y.J. Imatinib mesylate-induced acquired dermal melanocytosis and acquired bilateral nevus of Ota-like macules Ann Dermatol 33 3 2021 293 294 10.5021/ad.2021.33.3.293 34079193
10 Li C.C. Malik S.M. Blaeser B.F. Mucosal pigmentation caused by imatinib: report of three cases Head Neck Pathol 6 2 2012 290 295 10.1007/s12105-011-0325-4 22209988
11 Kok W.L. Chua S.H. Picosecond 755-nm alexandrite lasers are an effective treatment for imatinib-induced hyperpigmentation Dermatol Surg 45 4 2019 616 618 10.1097/DSS.0000000000001868 30893177
