TITLE: HYPERPIGMENTATION AS AN ADVERSE EFFECT OF ANTIMALARIAL USE AND THE ASSOCIATION WITH RETINOPATHY AND PREDISPOSING FACTORS: A SYSTEMATIC REVIEW

PV273 / #773 Poster Topic: AS24 - SLE-Treatment Background/Purpose Antimalarials are essential in treating various dermatological and rheumatological conditions like systemic lupus erythematosus. Hyperpigmentation is a known side effect, most often seen with chloroquine than hydroxychloroquine, affecting over 25% of users after prolonged use. These drugs alter antigen processing and increase lysosomal pH, affecting the skin by modifying UV absorption and inflammatory mediators. Antimalarial drugs can bind to iron and melanin, which stimulates melanocytes and may cause increased pigmentation in the skin. While the exact link between hyperpigmentation and retinopathy is not fully established, reports have suggested a possible association. Retinal toxicity is more likely to occur with chloroquine and higher doses of hydroxychloroquine. Studies suggest that factors like ecchymosis and the use of anticoagulants or antiplatelet agents may influence hyperpigmentation. This study explores the relationship between antimalarial use and mucocutaneous hyperpigmentation, considering factors such as retinopathy, trauma/ecchymosis, and concurrent anticoagulant use. Methods We have conducted a systematic review to examine the association between antimalarial use and hyperpigmentation and the possible link to retinopathy and predisposing factors. A comprehensive search strategy was developed using a combination of database-specific subject headings and text words for the main concepts of hyperpigmentation and the drugs chloroquine or hydroxychloroquine. Results were limited to humans. Studies from 1960 to May 2024, including cohort, cross-sectional, case reports, and case series, were identified on September 5, 2024 through Ovid MEDLINE and Embase. A total of 1760 studies were screened, and 71 studies were extracted and included in the review. The reference lists of included publications were also searched and considered for inclusion. A supplementary search was conducted on Google Scholar on December 26, 2024, using the following search terms: hyperpigmentation, antimalarial, drug adverse effect, chloroquine, hydroxychloroquine, skin pigmentation, antimalarial side effects. The first 100 results from that search were screened. Results The analysis involved 71 studies with a total sample size of 318 patients. Of these, 89.6% were female and 7.2% were male. The most common diagnosis was systemic lupus erythematosus (SLE), accounting for 74.6% of patients, followed by rheumatoid arthritis (RA) at 8.8%. Other diagnoses included Sjögren’s syndrome (6%), discoid lupus erythematosus (DLE) (4.1%), undifferentiated connective tissue disease (0.9%), and subacute cutaneous lupus erythematosus (SCLE) (0.3%). There were 4.7% of patients with other conditions, and 0.3% had no report on the diagnosis. In terms of treatment, 70.4% of patients were treated with hydroxychloroquine (HCQ), 17.6% with chloroquine, and 6.3% with other combinations of antimalarials. Hyperpigmentation was mostly blue-gray (9.9%), with the face and neck (40.5%), legs (34.6%), and hands (21.6%) being the most affected areas. Preceding ecchymosis was reported in 23.5%, and 18.5% were using anticoagulants/antiplatelets. Biopsies were performed in 27.5% of cases. Retinopathy was noted in 3.1%, with no strong correlation to hyperpigmentation. Of those who discontinued antimalarials (52.2%), 35.5% experienced fading pigmentation, with partial (24.2%) or complete (10.6%) resolution. Conclusions Hyperpigmentation is a common side effect of antimalarials. No correlation was found with the presence of hyperpigmentation and retinopathy with use of hydroxychloroquine. The role of anticoagulants and ecchymosis remains uncertain. Discontinuation of antimalarials does not always lead to the resolution of pigmentation. Further research is needed to better understand the mechanisms of hyperpigmentation and improve its treatment.

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