Imatinib mesylate is a well-known tyrosine kinase inhibitor used to treat chronic myeloid leukemia, gastrointestinal stromal tumor, as well as a variety of other malignancies.
Management and outcome: As use of this medication continues to grow, providers must be aware of potential side effects and management thereof. The toxicity profile of imatinib has been well characterized with most patients experiencing a grade 1 or 2 adverse event. These side effects are usually mild, and most patients can continue treatment without interruption. Around 30% of patients on imatinib experience skin toxicity, with 5% being high grade. This rash is typically hypopigmented, which is explained by imatinib’s effect on melanocytes.
Discussion
Although there have been several case reports describing hyperpigmentation of the oral mucosa or nails, very few have described skin hyperpigmentation. We previously reported the first two cases of imatinib-related squamous cell carcinoma in patients undergoing treatment for gastrointestinal stromal tumors. In this paper, we present a case of a patient on imatinib for management of gastrointestinal stromal tumor who experienced extensive skin hyperpigmentation and review the literature.
DagherRCohenMWilliamsG, et al.
Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors.Clin Cancer Res2002;
8: 3034–3038.
2.
Ben AmiEDemetriGD.A safety evaluation of imatinib mesylate in the treatment of gastrointestinal stromal tumor.Expert Opin Drug Saf2016;
15: 571–578.
3.
TsaoASKantarjianHCortesJ, et al.
Imatinib mesylate causes hypopigmentation in the skin.Cancer2003;
98: 2483–2487.
4.
InayatFSaifMW.New drug and possible new toxicity – squamous cell carcinoma following imatinib in patients with gastrointestinal stromal tumors.Anticancer Res2016;
36: 6201–6204.
5.
CohenMHWilliamsGJohnsonJR, et al.
Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res2002;
8: 935–942.
6.
YanadaMTakeuchiJSugiuraI, et al. Japan Adult Leukemia Study Group.
High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group.J Clin Oncol2006;
24: 460.
7.
PardananiAReederTPorrataLF, et al.
Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders.Blood2003;
101: 3391.
8.
McArthurGADemetriGDvan OosteromA, et al.
Molecular and clinical analysis of locally advanced dermatofibrosarcoma protuberans treated with imatinib: imatinib target exploration consortium study B2225.J Clin Oncol2005;
23: 866.
9.
MughalTISchreiberA.Principal long-term adverse effects of imatinib in patients with chronic myeloid leukemia in chronic phase. Biologics2010;
4: 315–323.
10.
AroraBKumarLSharmaA, et al.
Pigmentary changes in chronic myeloid leukemia patients treated with imatinib mesylate. Ann Oncol2004;
15: 358–359.
11.
NaranjoCABustoUSellersEM, et al.
A method for estimating the probability of adverse drug reactions.Clin Pharmacol Ther1981;
30: 239–245.
12.
LiCCMalikSMBlaeserBF, et al.
Mucosal pigmentation caused by imatinib: report of three cases.Head Neck Pathol2012;
6: 290–295.
13.
ValeyrieLBastuji-GarinSRevuzJ, et al.
Adverse cutaneous reactions to imatinib (STI571) in Philadelphia chromosome-positive leukemias: a prospective study of 54 patients.J Am Acad Dermatol2003;
48: 201–206.
14.
LammieADrojnakMGeraldW, et al.
Expression of c-kit and kit ligands proteins in normal human tissues.J Histochem Cytochem1994;
42: 1417–1425.
15.
PrabhashKBiswasGPrasadN, et al.
Imatinib-induced nail hyperpigmentation in chronic myeloid leukemia.Ind J Dermatol Venerol Leprol2006;
72: 63–64.
AlexandrescuDTDasanuCAFarzanmehrH, et al.
Persistent cutaneous hyperpigmentation after tyrosine kinase inhibition with imatinib for GIST. Dermatol Online J2008;
14: 7.
18.
LewisDM.Diffuse pigmentation of the palate.J Okla Dent Assoc2009;
100: 24–25
19.
McphersonTShermanVTurnerR.Imatinib-associated hyperpigmentation, a side effect that should be recognized.J Eur Acad Dermatol Venereol2009;
23: 82–83.
20.
WongMSadeSGilbertM, et al.
Oral melanosis after tyrosine kinase inhibition with imatinib for chronic myelogenous leukemia: report of a case and review of the literature. Dermatol Online J2011;
17: 4.
21.
MattssonUHalbritterSMӧrner SerikoffE, et al.
Oral pigmentation in the hard palate associated with imatinib mesylate therapy: a report of three cases.Oral Surg Oral Med Pathol Oral Radiol Endod2011;
111: e12–e16.
22.
SteeleJCTriantafyllouARajlawatBP, et al.
Oral mucosal hyperpigmentation and horizontal melanonychia caused by imatinib.Clin Exp Dermatol2012;
37: 432–433.
23.
ResendeRGTeixeiraRGVasconcelos FdeO, et al.
Imatinibassociated hyperpigmentation of the palate in post-HSCT patient. J Craniomaxillofac Surg2012;
40: e140–e143.
24.
KhooTLCatalanoASuppleS, et al.
Hyperpigmentation of the hard palate associated with imatinib therapy for chronic myeloid leukemia with a genetic variation in the proto-oncogene c-KIT.Leuk Lymphoma2013;
54: 186–188.
25.
RoekerLEWolanskyjAP.Imatinib-associated melanosis of the palate.Am J Hematol2014;
89: 564.
26.
SongHSKangHY.Imatinib mesylate-induced hyperpigmentation of the nose and palate.Ann Dermatol2014;
26: 532–533.
27.
LyneACreedonABaileyBM.Mucosal pigmentation of the hard palate in a patient taking imatinib. BMJ Case Rep2015;
2015: bcr2015209335.
28.
RomeoUPalaiaGFantozziPJ, et al.
A rare case of melanosis of the hard palate mucosa in a patient with chronic myeloid leukemia.Case Rep Dent2015;
2015: 817094.
29.
BalasubramanianPJagadeesanSThomasJ.Imatinib-induced extensive hyperpigmentation in a case of chronic myeloid leukemia.Ind J Dermatol2015;
60: 523.
30.
AgrawalPSinghONigamAK, et al.
Imatinib-induced dental hyperpigmentation in chronic myeloid leukemia in an adult female.Ind J Pharmacol2015;
47: 685–686.
31.
BombeccariGPGaragiolaUPallottiF, et al.
Hyperpigmentation of the hard palate mucosa in a patient with chronic myeloid leukaemia taking imatinib. Maxillofac Plast Reconstr Surg2017;
39: 37.
32.
Di TullioFMandelVDScottiR, et al.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 Dermatol2018;
57: 784–90.
