(44) Oral and Dermatologic Manifestations of Imatinib Mesylate: A Case Report

Abstract: Imatinib, sold under the brand name Gleevec, belongs to a class of medications known as small molecule tyrosine kinase inhibitors, which have the mechanism of action by binding to the kinase domain of BCR-ABL. FDA approved since 2001, Gleevec is utilized to treat malignancies and proliferative disorders, including Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, KIT positive gastrointestinal stromal tumors. The side effect profile is well documented includ-ing melanonychia, oral melanosis, dental hyperpigmentation, and keratocanthoma formation. This paper reviews several case reports which detail the aforementioned side effects.
This case report highlights a 75-year-old male patient presenting to an oral maxillofacial surgeon for a tooth extraction. On examination, the presence of a 2 cm x 2.5 cm, flat, non-tender lesion with grayish-blue hue on the palate was identified, and similar lesions were observed on the nails. The use of antimalarials and tobacco use, both known causes of oral mucosal hyper-pigmentation, were excluded from the patient’s history. A clinical diagnosis of drug induced oral melanosis was made.
Imatinib has the ability to cause both hypo and hyper-pigmented lesions 1. Hyper-pigmented lesions are reported in 3.6% of patients prescribed this medication 1. Only 8 total cases of oral melanosis related to Imatinib have been reported, and this is the ninth 2. Imatinib inhibits c-KIT tyrosine kinase in melanocytes, and inactivation of c-KIT can cause an increase in melanocyte production in rare scenarios 3. An accurate patient history helped the surgeon exclude diagnoses from her differential and accurately diagnose this patient.
Imatinib has been shown to produce other oral cavity and dermatologic manifestations. A study conducted prior to FDA approval revealed dental lesions as one of the long-term toxicities noted in rats 4. One case report published in 2013 details the dental complications endured by a patient prescribed Imatinib for treatment of a gastrointestinal stromal tumor, which resulted in he lost seven teeth and developed widespread dental erosion .
Many patients receiving Imatinib have experienced metabolic imbalances including hypophosphatemia, hypocalcemia, and secondary hyperparathyroidism . Additionally, bone mineral density has been noted in nearly 50% of patients . This is postulated to be the result of Imatinib’s impact on bone homeostasis .
Dental hyperpigmentation is a noted side-effect rarely seen in patients taking Imatinib 5. A 2015 case report detailed the findings in a 32-year-old female taking Imatinib for treatment of CML, presenting with hyperpigmentation of her teeth. She was not taking any other medications with this known side effect profile. It is theorized that Imatinib’s mechanism in these stem cells may be the causative agent of this discoloration .
In addition to the aforementioned oral manifestations, dermatologic manifestations have been documented including maculopapular eruptions. One study published in 2010 reviewed several case reports of keratocanthoma formation in patients receiving this medication .
The ability of Imatinib and similar medications to cause these intraoral and dermatologic manifestations have not been well elucidated. When managing patients undergoing treatment with Imatinib, it is necessary to perform a thorough physical exam, as subtle findings may be present as a sequelae of treatment. Future studies should strive to elucidate, with conviction, the mechanistic pathways involved in these side effects.

References

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2. Kyriazoglou et al. “Severe dental erosion associated with imatinib mesylate therapy.” Acta Oncologica, Vol. 53, no. 7, 2014, pp 988-990..
3. Balagula et al. “Keratocanthomas associated with imatinib mesylate.” Acta Oncologica, Vol. 50, 2011, pp: 593-595.