Hydroxychloroquine-Associated Skin Lesions: Clinical Features and Mechanisms.

Area of Science:

• Dermatology and Rheumatology
• Pharmacovigilance

Background:

• Hydroxychloroquine (HCQ) is a vital medication in rheumatology and dermatology.
• While generally safe, HCQ can cause cutaneous adverse reactions (CARs), ranging from pigmentation to severe cutaneous adverse reactions (SCARs).

Purpose of the Study:

• To review and synthesize data on hydroxychloroquine-induced cutaneous adverse reactions.
• To explore the mechanisms, clinical manifestations, and management strategies for HCQ-related skin reactions.

Main Methods:

• Comprehensive literature search of PubMed, Web of Science, Embase, and Cochrane Library up to December 2025.
• Inclusion of original studies, reviews, and case reports focusing on HCQ skin reactions.
• Independent screening and quality assessment of selected literature.

Main Results:

• Common HCQ CARs include pigmentation, maculopapular rash, and pruritus.
• Severe reactions such as AGEP, DRESS, SJS, and TEN are rare but critical.
• Potential mechanisms involve pigment metabolism alteration, lysosomal ion trapping, and T-cell hypersensitivity.

Conclusions:

• Early identification and appropriate management, including dose adjustment or discontinuation, are essential for HCQ CARs.
• Desensitization may be considered for mild reactions.
• Continuous pharmacovigilance is crucial for monitoring and early detection of adverse events.