A Case of Chlorpromazine-Induced Skin Pigmentation and Ophthalmic Lesions

Abstract

Chlorpromazine (CPZ) was widely used for schizophrenia, but was replaced by other antipsychotics due to deleterious effects on cardiovascular and central nervous systems1. CPZ can also cause dermatologic problems, including blue-gray pigmentation in sun-exposed areas, mainly the face, with a marked sparing of wrinkles, and ophthalmic lesions, such as corneal and lenticular deposits, and rarely decreased visual acuity2. A 45-year-old man with usual exposure to the sun, but without sunscreen use, presented with a 1-year history of blue-gray colored facial pigmentation (Fig. 1A, B). He had been diagnosed with schizophrenia, and treated with various antipsychotics before achieving maintenance with CPZ for the last 5 years. The dose of CPZ was gradually increased from 100 mg daily to 900 mg daily. At presentation, his treatment regimen included quetiapine, clonazepam, flunitra- zepam, and trazodone. After 4 years of CPZ treatment, he developed blue-gray pigmentation all over his face, except on the facial wrinkles and the cleft below the lower lip. There was no evidence of pigmentation or other dermatologic problems when CPZ was initiated. A skin biopsy taken from the cheek showed accumulation of golden-brown granular pigments in macrophages near superficial dermal vessels (Fig. 2A∼C), and Fontana-Masson staining resulted in black stain (Fig. 2D). Laboratory tests were normal and other systemic causes of pigmentation including Wilson disease and Addison disease were excluded. Although he denied ocular symptoms and didn’t get his visual acuity checked before, ophthal- mological assessment revealed visual acuity of 0.3 in both eyes and slit-lamp examination demonstrated bilateral corneal and lenticular deposits (Fig. 1C, D). A diagnosis of CPZ-induced hyperpigmentation was made, and CPZ discon- tinuation and strict sun protection were recommended. However, the patient was noncompliant to follow-up. Common drugs that can cause blue-gray pigmentation include CPZ, silver, and minocycline3. The patient didn’t take other medications except antipsychotics, and the drugs that he took together were less likely to cause hyperpig- mentation. Therefore, a diagnosis of CPZ-induced hyperpig- mentation was made. However, there is no specific treatment and CPZ discontinuation with sun protection is recommended4. Skin pigmentation is reversible but ocular changes could persistent after CPZ discontinuation1. The pathogenesis of and dosage associated with CPZ-in- duced hyperpigmentation remain poorly understood3. A recent study indicated that deposition of dermal melanin, CPZ, and its metabolites may provoke skin pigmentation3. Further, an in vitro study has revealed that CPZ increases melanin, microphthalmia-associated transcription factor, and tyrosinase activity in human melanocytes2. Most cases report pigmenta- tion after 500 mg of CPZ daily or more for more than 1 year, but pigmentation was also reported at lower doses1,5. Further evaluation is thus warranted. Many cases of CPZ-induced skin or ocular pigmentation have been reported; however, reduced drug use has led to fewer recent case reports. Further, while some cases describe ocular symptoms, a few had asymptomatic ophthalmic lesions, similar to our patient1,5. In conclusion, physicians must be aware that CPZ can induce not only skin pigmentation but also asymptomatic ocular deposits that can decrease visual acuity if left unchanged. Therefore, early ophthalmological examination should be performed when treating CPZ-induced hyperpig- mentation.