Association of oral mucosa hyperpigmentation with imatinib mesylate use: a cross-sectional study and a systematic literature review

Abstract

Objectives To assess the association between oral mucosa hyperpigmentation in patients with leukemia and imatinib mesylate use. Additionally, we compared our data to those obtained from a systematic review. Materials and methods A cross-sectional study was conducted with 74 patients undergoing treatment with imatinib mesylate. Sociodemographic characteristics, oral mucosa alterations, and medical history were evaluated. Oral hyperpigmentation was scored. The use of imatinib mesylate and hydroxyurea was evaluated. Association between oral hyperpigmentation and imatinib mesylate was assessed. A systematic review was also conducted to retrieve case reports or case series of patients with oral hyperpigmentation associated with imatinib mesylate. Results Among the 74 participants, 41 were male (55.4%) and 33 were female (44.6%). Participants' mean age was 49.3 years. Sixty-six (89.2%) patients developed hyperpigmented lesions in the hard palate mucosa. In multivariate analysis, patients who had used imatinib mesylate for > 72 months had a hyperpigmentation score 1.62 times higher than those who had used this medication during a shorter period. Patients who had used hydroxyurea for > 30 days had a hyperpigmentation score 1.43 times higher than those who had used this medication during a shorter period. The systematic review retrieved 20 clinical cases of patients undergoing imatinib mesylate treatment and exhibiting oral hyperpigmentation. Conclusions The development of oral hyperpigmentation is associated with imatinib mesylate use. Hydroxyurea seems to increment such an association. Clinical relevance To assist providers in the differential diagnosis of hyperpigmented lesions associated with imatinib mesylate, as well as in the clinical management of such lesions.

<p>Medication-Induced Oral Hyperpigmentation: A Systematic Review</p>

“…Included cohort studies achieved a moderate level of quality, 5 , 11 , 28 , 40 , 60 while the cross-sectional study achieved a high level of quality. 39 , 59 The quality of each included study is summarized in Supplementary Table 2–4 .…”

“…Imatinib-associated hyperpigmentation was described by several studies that reported treatment duration as a major risk factor leading to larger and darker lesions. 59 , 68 , 69 In addition, antimalarial was the second most common category caused MIOH. A long duration (up to 15 years) of use of antimalarial drugs was observed to be associated with severe blue-black and gray diffused lesions in the hard palate with cutaneous involvement.…”

“…11 The risk of oral pigmentation in association with imatinib therapy increased as the duration of intake increased (an average of 7 years) and occurred most commonly in the hard palate. 59 Other affected sites included the gingiva and tonsils. 53,57 Zidovudine, an antiviral agent, was associated with melanotic macules in the buccal mucosa and lips in 14 cases.…”

Oral hyperpigmentation associated with hydroxyurea in a patient with polycythemia vera: A case report

“…However, the exact duration of use and dosage of both drugs were not determined in the study. 14 Our literature search revealed only nine reports of HUassociated oral pigmentation (four female patients and five male patients; eight adults and one child). 9,[15][16][17][18][19][20][21][22] The age of the affected individuals ranged between 10 and 68 years (mean, 50.6 years of age).…”

“…The results of this cross‐sectional study supported that hyperpigmentation extent and intensity were related to IM use especially when combined with HU. However, the exact duration of use and dosage of both drugs were not determined in the study 14 …”