SYSTEMATIC REVIEW article
Front. Med.
Sec. Dermatology
Drug Induced Hyperpigmentation: Systematic Review and Meta-Analysis
Roaa Alharithy 1,2
Kayan AlOtaibi 3
Rawan Bin Salamah 3
Reem Altamimi 3
Norah Alqntash 3
Reem Alsarhan 3
Leen Khosyfan 3
Shahad Alrowais 3
1. Assistant Professor, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
2. Dermatology Consultant, Security Forces Hospital, Riyadh, Saudi Arabia
3. Princess Nourah bint Abdulrahman University College of Medicine, Riyadh, Saudi Arabia
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Abstract
Background: Drug-induced hyperpigmentation (DIH) represents a significant subset of acquired pigmentation disorders and poses diagnostic challenges due to delayed onset and polypharmacy. This systematic review and meta-analysis aimed to identify medications significantly associated with DIH and evaluate their reported incidence. Methods: A systematic search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library for studies published between 2002 and June 2024. Eligible studies reported DIH as an outcome with incidence or descriptive data. Pooled proportions were calculated using a random-effects model, and heterogeneity was assessed via the I² statistic. Results: Twenty-two studies met the inclusion criteria. The overall pooled incidence of DIH was 36.7% (95% CI: 0.291–0.444). Subgroup analyses revealed the highest incidences with tyrosine kinase inhibitors (89.2%) and MC4R agonists (71.4%), followed by antibiotics (52.0%), antineoplastic agents (35.5%), and antimalarials (29.0%). Commonly implicated agents included minocycline, hydroxychloroquine, and hydroxyurea. Conclusion: DIH is a prevalent adverse drug reaction with considerable variation in incidence across drug classes. Recognition of high-risk medications is essential for prompt diagnosis and clinical management.
Summary
Keywords
5-fluorouracil, Adverse Drug Reaction, Antimalarial agents, Cutaneous side effects, Dermatology, Drug-induced hyperpigmentation, Hydroxychloroquine, Meta-analysis
Received
27 July 2025
Accepted
30 January 2026
Copyright
© 2026 Alharithy, AlOtaibi, Bin Salamah, Altamimi, Alqntash, Alsarhan, Khosyfan and Alrowais. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Kayan AlOtaibi
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