Associação entre a hiperpigmentação da mucosa oral com o uso de mesilato de imatinibe: estudo transversal e revisão sistemática da literatura

Abstract

Hyperpigmented lesions are commonly observed in the oral mucosa. Although they often present similar clinical characteristics, these lesions present different etiopathogenesis and diagnosis. Thus, for the correct diagnosis, it is necessary to investigate the medical history of the patient, use of drugs. Clinical examination and biopsy may also be necessary. A number of medications can cause pigmentation in the oral mucosa. The pathogenesis of pigmentation may vary depending on the causative agent. Chemotherapeutic agents such as Imatinib Mesylate, used in the treatment of chronic myeloid leukemia and acute lymphoblastic leukemia pH +, may be associated with the development of hyperpigmented oral lesions in particular in the hard palate. The objective of this study was to evaluate the association between hyperpigmentation of the oral mucosa and the use of imatinib mesylate in patients with leukemia. In addition, we also aimed to compare our data with those obtained from a systematic review of the literature. The study was approved by the Research Ethics Committee of the Federal University of Minas Gerais under the protocol number 48317515.6.0000.5149. A cross-sectional study was conducted with 74 patients undergoing treatment with imatinib mesylate. The sociodemographic characteristics, clinical history of the patients and data regarding the use of drugs used during the treatment of leukemia were collected. In addition, an intra-oral clinical examination and photographic record of the hard palate region were performed. The association between the use of imatinib mesylate and the presence of hyperpigmented oral lesions was also investigated. Descriptive statistics, bivariate analysis and multivariate (Poisson regression) analysis were carried out. In the Poisson regression, confidence intervals (CI) were provided. A systematic review of the literature was conducted in the main electronic databases with the objective of retrieving case reports or case series of patients using imatinib mesylate, who developed hyperpigmented lesions in the oral mucosa. Among the 74 participants, 41 were male individuals (55.4%) and 33 were female individuals (44.6%). The mean age of the participants was 49.3 years. Sixty-six (89.2%) patients developed hyperpigmented lesions in the oral mucosa. In the multivariate analysis, in which Poisson regression was employed, patients who had used imatinib mesylate for more than 72 months had a hyperpigmentation score 1.62 (1.12 – 2.33 95% CI) times greater than those who had used this drug for a shorter period. Patients who had used Hydroxyurea associated Imatinib Mesylate over a period of more than 30 days had a hyperpigmentation score 1.43 (1.02 – 2.01 95% CI) times higher than those who had used this drug for a shorter period. The systematic review of the literature retrieved 20 clinical cases of patients submitted to treatment with imatinib mesylate and exhibiting hyperpigmented lesions in the oral mucosa. Based on the analysis of these data, it was possible to conclude that the development of hyperpigmented oral lesions was associated with the use of imatinib mesylate. The use of hydroxyurea seemed to increment this association.