Hydroxychloroquine-Associated Skin Lesions: Clinical Features and Mechanisms

Hydroxychloroquine (HCQ) is pivotal in rheumatology and dermatology for its potent antimalarial and immunomodulatory properties. Though generally safe, HCQ causes cutaneous adverse reactions ranging from mild pigmentation to life-threatening severe cutaneous adverse reactions. This review synthesizes data from studies indexed in PubMed, Web of Science, Embase, and the Cochrane Library through December 2025. Search keywords included "hydroxychloroquine," "adverse reactions," "skin lesions" (eg, pigmentation, maculopapular rash, psoriasiform eruption), and "mechanisms." We included original studies, reviews, and case reports, excluding duplicates and studies focused solely on noncutaneous reactions. Two reviewers independently screened the literature, and any discrepancies were resolved via discussion. Study quality was assessed based on methodological rigor and data completeness, with priority given to high-impact literature published within the last decade. Common adverse reactions include pigmentation, maculopapular rash, and pruritus; rare but severe reactions include acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Underlying mechanisms may involve alteration of pigment metabolism, lysosomal ion trapping, and T-cell-mediated hypersensitivity. Management depends on early recognition, dose adjustment, or drug discontinuation. For select mild cases, desensitization may be appropriate. Ongoing monitoring of pharmacovigilance databases is crucial for proactive surveillance and early detection.