Letter to the Editor: Chlorpromazine-Induced Skin Pigmentation in a Pediatric Patient

Introduction

Skin changes and photosensitivity are potential side effects of chlorpromazine, with previous reports of photosensitivity in one in seven individuals taking chlorpromazine (Adams et al. 2005) and of pigmentation changes in 1%–2.9% of hospitalized adult patients with schizophrenia taking chlorpromazine (Ban et al. 1985). Various mechanisms have been proposed. With exposure to ultraviolet (UV) light, chlorpromazine changes to free radical form and interacts with melanin (Mitkov et al. 2014). It is suspected that dissociation of chlorpromazine's chlorine bond occurs with irradiation by UV light, resulting in this free radical form, as many chlorine-containing drugs that undergo photodechlorination can cause photosensitivity (Moore 2002). Chlorpromazine can also activate the enzyme tyrosinase, which is involved in melanin production (Mitkov et al. 2014).

There have been case reports of chlorpromazine-associated skin pigmentation in adults, but none in a child. In this study, we describe a case of chlorpromazine-associated skin changes in a child.

Case Presentation

The patient was an 11-year-old male with autism spectrum disorder (ASD), intellectual disability, and intermittent explosive disorder with significant self-injurious behavior and aggression toward others. Prior medication trials included clonidine, quetiapine, risperidone, and aripiprazole, including risperidone and aripiprazole together. He transitioned from risperidone to chlorpromazine with improvement in behaviors on dose of 675 mg divided three times daily (TID). After 9 months, he experienced sun burning, so transitioned to haloperidol. Aggression and self-injury worsened, prompting transition back to chlorpromazine after only 2 months on haloperidol. He again showed improvement in aggressive and self-injurious behaviors with use of chlorpromazine, so he was continued on chlorpromazine 700 mg divided TID. His other medications included amitriptyline, buspirone, clonidine, benztropine, and diphenhydramine.

After 10 months back on chlorpromazine, parents reported discoloration of his fingernails, followed by blue/purple discoloration of his legs, but were unable to bring him to clinic for examination due to other factors and stressors within the patient's family including issues with transportation, and chlorpromazine was continued. Given previous severe behaviors, inpatient admission was recommended for medication changes. Parents subsequently reported worsening skin discoloration that spread to his entire body, most notable in sun-exposed areas (Fig. 1).

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Fig. 1.

Photograph of patient's skin hyperpigmentation associated with chlorpromazine use.

Seven months after the initial discoloration, family was able to bring patient for admission, and he was transitioned off of chlorpromazine. He was prescribed perphenazine, which was not effective, so he was then transitioned to clozapine, which he remains on with adequate symptom control. Laboratory work obtained during this time period, including complete blood count (CBC), comprehensive metabolic panel (CMP), lipid profile, hemoglobin A1C, insulin, and thyroid studies, was unremarkable. Pharmacogenetic testing was not completed at the time, but subsequent studies showed the patient to be a normal Cytochrome P450 2D6 (CYP2D6) metabolizer. The patient was not seen by dermatology. Three months after chlorpromazine was discontinued, an undilated eye examination noted mild lenticular opacities, thought to be secondary to chlorpromazine. Skin pigmentation is still present, though has improved significantly over time.

Discussion

This case appears unique in many ways. This is the first report of significant skin pigmentation change associated with chlorpromazine use in a pediatric patient. In addition, regarding cumulative exposure, the length of time on this dose is less than described in adult literature, suggesting that cumulative exposure may not be the main determinant of skin changes. Chlorpromazine is primarily metabolized through CYP2D6. Given the patient's normal CYP2D6 function, it is unlikely altered metabolism of chlorpromazine played a role in his presentation, though he has not had a full pharmacogenetic profile completed.

Other factors, such as polypharmacy and multiple medication changes, may have contributed to his presentation, though aside from transitioning to and from chlorpromazine, other medication had little change over this period. In addition, skin concerns were present with both chlorpromazine trials (sun burning with the first and skin pigmentation with the second), with improvement in skin symptoms after chlorpromazine was stopped each time.

This case also highlights limitations in caring for patients with aggression and developmental delays. The family was counseled on limiting sun exposure, but it proved difficult for the patient to regularly wear sunscreen or tolerate clothing that provided adequate coverage. It was challenging for the family to attend appointments due to behavioral concerns and distance to the clinic, leading to delay in skin examination and appreciation of the extent of hyperpigmentation. As in-home telemedicine has become more available during the COVID-19 pandemic, we imagine this would have been a valuable tool to assess skin changes in a more timely manner. Furthermore, the previous trial off chlorpromazine resulted in significant worsening of unsafe behaviors, requiring planned admission for subsequent medication changes, adding delay in tapering the chlorpromazine.

Lastly, consistent with reports in adult literature, switching from chlorpromazine to another antipsychotic did lead to improvement in hyperpigmentation over time.