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.