Diltiazem-Associated Hyperpigmentation

A 59-year-old African American female presented with a one-year history of progressive skin darkening. Her only symptom was mild itching. Medications included diltiazem 180 mg daily (extended release), prescribed three years earlier. Examination revealed blue-gray reticular hyperpigmentation in a photodistributed pattern on the face, neck, “V of the chest,” and extensor forearms (Fig. 1a, b). Punch biopsy showed a predominantly lichenoid reaction with upper dermal melanophages. Figure 1. Blue-gray reticular hyperpigmentation on the face (a) and neck (b) at initial presentation (3 years after starting diltiazem). Lesions were not palpable. Diltiazem-associated hyperpigmentation was suspected and diltiazem was discontinued. Treatment with hydrocortisone 2.5 % cream for three months resolved the itching. Hydroquinone 4 % cream was applied twice daily to the face for 12 months with significant improvement in the hyperpigmentation. Eighteen cases of diltiazem-induced hyperpigmentation have been reported prior to this case.1–3 Darker skin types, especially those of African American and Asian descent, are more commonly affected. Onset of hyperpigmentation averages 25 months after starting diltiazem, but reports range from 1.5 months to 12.5 years. The extended release formulations have been implicated in most cases. This reaction to diltiazem may be under-recognized due to the delayed onset of hyperpigmentation. Discontinuing diltiazem is essential for improvement. Hydroquinone 4 % cream and strict sun protection can also help lighten the hyperpigmentation.