Diltiazem-Associated Hyperpigmentation

Abstract

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.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. Conflict of Interest:The authors declare that they do not have a conflict of interest.

The phenomenon of phototoxicity and long-term risks of commonly prescribed and structurally diverse drugs

“…In a retrospective 10-year study of individuals taking HCTZ, alone or in combination with other drugs, nonhispanic black men and women were observed to be at increased risk of phototoxic sunburn compared to those not taking such drugs [ 135 ]. That is to note, that unlike other phototoxic medications, a unique feature of thiazides (and diltiazem) is the increased likelihood of reactions in darker skin types [ 135 , 136 , 205 ]. HCTZ-induced photoleukomelanoderma presents primarily in Asian populations as hypo- and hyper-pigmented macules, papules, and scaly plaques with eczematous or psoriasiform features but may resolve with normal pigmentation after discontinuation of the drug [ 134 ].…”

Photodermatoses in skin of colour

“…Photodistributed hyperpigmentation caused by diltiazem, most often the extended release formulation, while rare, has been reported primarily in patients with SOC. This is a rare side‐effect with only twenty cases reported . It has been seen most commonly in black females, but can also affect black males, Asians and Hispanics .…”

“…This is a rare sideeffect with only twenty cases reported. [47][48][49][50][51][52][53][54][55][56][57][58] It has been seen most commonly in black females, but can also affect black males, Asians and Hispanics. 49,[51][52][53][54]56,58 The age of presentation ranges from 49 to 86 years with hyperpigmentation beginning from 1.5 to 150 months after initiation of diltiazem and invariably involves the face.…”