Iatrogenic Hyperpigmentation: Pathogenesis, Risk Factors, and Advances in Prevention

Abstract

Background: Iatrogenic hyperpigmentation is an acquired pigmentary change associated with medications, dermatologic procedures, surgery, radiotherapy, and other medical interventions. Although many cases are benign, visible or persistent discoloration can impair quality of life, reduce treatment satisfaction, and occasionally complicate the management of an otherwise necessary therapy [42,43]. The term encompasses mechanistically distinct disorders, including post-inflammatory hyperpigmentation (PIH), drug-induced pigmentation, phototoxic pigmentation, and deposition of non-melanin pigments. Objective: To summarize current understanding of the mechanisms and risk factors of iatrogenic hyperpigmentation and critically review emerging preventive strategies, with emphasis on evidence published in recent years. Methods: This narrative review was developed using targeted searches of PubMed and reference lists of relevant reviews and clinical studies. Priority was given to literature published from 2022 through October 2026, while earlier mechanistic studies and clinical trials were retained when they remain important to the interpretation of current evidence. As this is a narrative rather than systematic review, no meta-analytic pooling or formal evidence grading was performed. Results: Major mechanisms include inflammation-driven melanogenesis, disruption of the dermoepidermal junction with pigment incontinence, altered melanosome transfer, ultraviolet- and visible-light-associated pigment induction, and direct tissue deposition of drugs or metabolites. Risk is influenced by baseline skin phototype and pigmentary history, active inflammation, medication exposure and cumulative dose, treatment energy and depth, anatomical site, and post-procedure care. Recent evidence supports individualized procedural planning and careful control of inflammation. A 2026 network meta-analysis of randomized trials suggested that selected interventions—including topical corticosteroids, tranexamic acid (TXA), vasoconstrictors, and epidermal cooling—may reduce laser-associated PIH, but the small and heterogeneous evidence base limits generalization. A 2024 randomized trial found a lower incidence of laser-induced PIH with pre-treatment isobutylamido thiazolyl resorcinol (ITR) used twice daily, whereas evidence for epidermal growth factor-containing products and systemic TXA remains inconsistent. Photoprotection is central to prevention but cannot prevent pigmentation caused predominantly by dermal drug deposition. Conclusions: Prevention should be mechanism-based rather than uniform. A practical approach combines pre-treatment risk assessment, treatment of active inflammation, conservative and indication-specific procedures, medication review, barrier-supportive aftercare, photoprotection, and structured follow-up. Better-designed prospective studies using standardized pigmentary outcomes are needed, particularly for drug-induced pigmentation and for patients with darker skin phototypes.