Drug-associated hyperpigmentation of the oral mucosa: report of four cases.

OBJECTIVE: The aim of this study was to describe 4 patients with oral mucosa hyperpigmentation associated with 4 drug classes and to review the relevant literature.

STUDY DESIGN: Two patients under imatinib and hydroxychloroquine treatment exhibited diffuse palatal hyperpigmentation and 2 patients treated with minocycline and golimumab showed multifocal pigmented macules. In all cases, biopsy was performed.

RESULTS: Microscopically, in all cases, there was no increase in the number of melanocytes in the epithelium, and pigment granules were present in the lamina propria. The pigment granules in minocycline- and golimumab-associated hyperpigmentation were seen in the superficial lamina propria and reacted for silver but not iron, whereas in imatinib- and hydroxychloroquine-associated hyperpigmentation, pigment granules were found in the reticular lamina propria and reacted for both silver and iron. A review of the literature found 38 cases of hyperpigmentation of the oral mucosa attributed to minocycline, 23 to imatinib, 1 to hydroxychloroquine without microscopic documentation, and none to golimumab.

CONCLUSIONS: The temporal relationship between pigmentation and onset of drug effect, resolution following drug withdrawal, and exclusion of other causes support the diagnosis of drug-induced hyperpigmentation. Microscopic examination may be contributory to diagnosis, as there are differences among drugs with regard to the distribution of pigment granules and the histochemical reactions of the drugs.