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Copyright (c) 2025 Luay Alnughaymishi, Fayez Homod AlSahabi, Rawan Abdo Othman, Sabah Hamoud O Alsuwat , Moneerah Mohammed Humood Alzoman, Faisal Abdullah Alghamdi, Fahad Sami Abdulaziz Alfehaid, Abdulaziz Salem Shafi Alshammari, Hussam Ahmed Alhassan Alnami, Saad Saud Saad Alrashoud, Mufarh Abdullah Aldosari, Mashael Abdullah Fahad Alamer, Saleh Hassan M. Leslom
This work is licensed under a Creative Commons Attribution 4.0 International License.
Mechanisms, Assessment, and Management of Drug-Induced Pigmentation in Clinical Pharmacology
Corresponding Author(s) : Luay Alnughaymishi
Saudi Journal of Medicine and Public Health,
Vol. 2 No. 2 (2025)
Abstract
Background: Drug-induced pigmentation (DIP) is a clinically significant adverse effect resulting from diverse pharmacologic agents. It manifests through mechanisms such as melanogenesis stimulation, drug/metabolite deposition, and postinflammatory changes, often leading to cosmetic and psychosocial concerns.
Aim: To review the mechanisms, clinical assessment, and management strategies for DIP, emphasizing preventive and therapeutic approaches.
Methods: A comprehensive literature review was conducted, analyzing pharmacologic classes implicated in DIP, pathophysiologic mechanisms, histopathologic features, and treatment modalities. Clinical evaluation protocols and interprofessional management strategies were synthesized from current evidence.
Results: Over 50 drug classes, including antimicrobials, antimalarials, psychotropics, chemotherapeutics, and heavy metals, are associated with DIP. Mechanisms include enhanced melanogenesis, dermal deposition of lipophilic drugs, and inflammatory sequelae. Histopathology reveals nonspecific but diagnostic patterns, such as melanin-laden macrophages or drug granules. Management involves drug substitution or dose reduction, photoprotection, topical depigmenting agents, and procedural interventions like laser therapy. Prognosis is generally favorable, though pigmentation may persist, especially with dermal deposition or extracutaneous involvement.
Conclusion: Early recognition and individualized management of DIP are essential to prevent progression and optimize patient outcomes. Preventive strategies, patient education, and multidisciplinary collaboration remain critical components of care.
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- 1. Tisack A, Mohammad TF. Drug-Induced Pigmentation: A Review. Drugs. 2024 Sep:84(9):1071-1091. doi: 10.1007/s40265-024-02062-z.
- 2. Giménez García RM, Carrasco Molina S. Drug-Induced Hyperpigmentation: Review and Case Series. Journal of the American Board of Family Medicine : JABFM. 2019 Jul-Aug:32(4):628-638. doi: 10.3122/jabfm.2019.04.180212.
- 3. Nahhas AF, Braunberger TL, Hamzavi IH. An Update on Drug-Induced Pigmentation. American journal of clinical dermatology. 2019 Feb:20(1):75-96. doi: 10.1007/s40257-018-0393-2.
- 4. Halder RM, Nandedkar MA, Neal KW. Pigmentary disorders in ethnic skin. Dermatologic clinics. 2003 Oct:21(4):617-28, vii
- 5. Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. American journal of clinical dermatology. 2001:2(4):253-62
- 6. Schaefer JK, Ramnath N. Fluorouracil-Induced Hyperpigmentation. The New England journal of medicine. 2020 Jan 23:382(4):e6. doi: 10.1056/NEJMicm1909329.
- 7. Peng JP, Yang XY, Luo F, Yuan XM, Xiong H, Ma WK, Yao XM. Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review. Frontiers in immunology. 2024:15():1383343. doi: 10.3389/fimmu.2024.1383343.
- 8. Nishikubo M, Yamashita D, Nishioka H. Minocycline-induced skin hyperpigmentation. BMJ case reports. 2025 Mar 25:18(3):. pii: e264463. doi: 10.1136/bcr-2024-264463. Ep
- 9. Bell AT, Roman JW, Gratrix ML, Brzezniak CE. Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non-Small Cell Lung Adenocarcinoma. Case reports in oncology. 2017 Jan-Apr:10(1):156-160. doi: 10.1159/000452146.
- 10. Granstein RD, Sober AJ. Drug- and heavy metal--induced hyperpigmentation. Journal of the American Academy of Dermatology. 1981 Jul:5(1):1-18
- 11. Kounis NG, Frangides C, Papadaki PJ, Zavras GM, Goudevenos J. Dose-dependent appearance and disappearance of amiodarone-induced skin pigmentation. Clinical cardiology. 1996 Jul:19(7):592-4
- 12. Behera B, Palit A, Sethy M, Nayak AK, Dash S, Ayyanar P. Dermoscopic features of clofazimine-induced pigmentation in a borderline tuberculoid leprosy plaque. Indian journal of dermatology, venereology and leprology. 2021 Jan-Feb:88(1):85-87. doi: 10.25259/IJDVL_1421_20.
- 13. Hamri L. Hyperpigmentation Induced by Hydroxychloroquine. Dermatology practical & conceptual. 2023 Oct 1:13(4):. doi: 10.5826/dpc.1304a235.
- 14. Baaklini C, Kesav N, Reinhart W. Minocycline-Induced Ocular Ochronosis. Cureus. 2023 Aug:15(8):e43307. doi: 10.7759/cureus.43307.
- 15. Suvirya S, Agrawal A, Parihar A. 5-Fluorouracil-induced bilateral persistent serpentine supravenous hyperpigmented eruption, bilateral mottling of palms and diffuse hyperpigmentation of soles. BMJ case reports. 2014 Oct 21:2014():. doi: 10.1136/bcr-2014-206793.
- 16. Hamid RN, Yang RG, Munavalli GS. Treatment of imipramine-induced hyperpigmentation with quality-switched ruby and picosecond lasers. JAAD case reports. 2021 Nov:17():12-17. doi: 10.1016/j.jdcr.2021.09.004.
- 17. Yamaguchi Y, Hearing VJ. Melanocytes and their diseases. Cold Spring Harbor perspectives in medicine. 2014 May 1:4(5):. doi: 10.1101/cshperspect.a017046.
- 18. Kleinegger CL, Hammond HL, Finkelstein MW. Oral mucosal hyperpigmentation secondary to antimalarial drug therapy. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2000 Aug:90(2):189-94
- 19. Sant'Ambrogio S, Connelly J, DiMaio D. Minocycline pigmentation of heart valves. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 1999 Nov-Dec:8(6):329-32
- 20. Weiss SR, Lim HW, Curtis G. Slate-gray pigmentation of sun-exposed skin induced by amiodarone. Journal of the American Academy of Dermatology. 1984 Nov:11(5 Pt 1):898-900
References
1. Tisack A, Mohammad TF. Drug-Induced Pigmentation: A Review. Drugs. 2024 Sep:84(9):1071-1091. doi: 10.1007/s40265-024-02062-z.
2. Giménez García RM, Carrasco Molina S. Drug-Induced Hyperpigmentation: Review and Case Series. Journal of the American Board of Family Medicine : JABFM. 2019 Jul-Aug:32(4):628-638. doi: 10.3122/jabfm.2019.04.180212.
3. Nahhas AF, Braunberger TL, Hamzavi IH. An Update on Drug-Induced Pigmentation. American journal of clinical dermatology. 2019 Feb:20(1):75-96. doi: 10.1007/s40257-018-0393-2.
4. Halder RM, Nandedkar MA, Neal KW. Pigmentary disorders in ethnic skin. Dermatologic clinics. 2003 Oct:21(4):617-28, vii
5. Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. American journal of clinical dermatology. 2001:2(4):253-62
6. Schaefer JK, Ramnath N. Fluorouracil-Induced Hyperpigmentation. The New England journal of medicine. 2020 Jan 23:382(4):e6. doi: 10.1056/NEJMicm1909329.
7. Peng JP, Yang XY, Luo F, Yuan XM, Xiong H, Ma WK, Yao XM. Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review. Frontiers in immunology. 2024:15():1383343. doi: 10.3389/fimmu.2024.1383343.
8. Nishikubo M, Yamashita D, Nishioka H. Minocycline-induced skin hyperpigmentation. BMJ case reports. 2025 Mar 25:18(3):. pii: e264463. doi: 10.1136/bcr-2024-264463. Ep
9. Bell AT, Roman JW, Gratrix ML, Brzezniak CE. Minocycline-Induced Hyperpigmentation in a Patient Treated with Erlotinib for Non-Small Cell Lung Adenocarcinoma. Case reports in oncology. 2017 Jan-Apr:10(1):156-160. doi: 10.1159/000452146.
10. Granstein RD, Sober AJ. Drug- and heavy metal--induced hyperpigmentation. Journal of the American Academy of Dermatology. 1981 Jul:5(1):1-18
11. Kounis NG, Frangides C, Papadaki PJ, Zavras GM, Goudevenos J. Dose-dependent appearance and disappearance of amiodarone-induced skin pigmentation. Clinical cardiology. 1996 Jul:19(7):592-4
12. Behera B, Palit A, Sethy M, Nayak AK, Dash S, Ayyanar P. Dermoscopic features of clofazimine-induced pigmentation in a borderline tuberculoid leprosy plaque. Indian journal of dermatology, venereology and leprology. 2021 Jan-Feb:88(1):85-87. doi: 10.25259/IJDVL_1421_20.
13. Hamri L. Hyperpigmentation Induced by Hydroxychloroquine. Dermatology practical & conceptual. 2023 Oct 1:13(4):. doi: 10.5826/dpc.1304a235.
14. Baaklini C, Kesav N, Reinhart W. Minocycline-Induced Ocular Ochronosis. Cureus. 2023 Aug:15(8):e43307. doi: 10.7759/cureus.43307.
15. Suvirya S, Agrawal A, Parihar A. 5-Fluorouracil-induced bilateral persistent serpentine supravenous hyperpigmented eruption, bilateral mottling of palms and diffuse hyperpigmentation of soles. BMJ case reports. 2014 Oct 21:2014():. doi: 10.1136/bcr-2014-206793.
16. Hamid RN, Yang RG, Munavalli GS. Treatment of imipramine-induced hyperpigmentation with quality-switched ruby and picosecond lasers. JAAD case reports. 2021 Nov:17():12-17. doi: 10.1016/j.jdcr.2021.09.004.
17. Yamaguchi Y, Hearing VJ. Melanocytes and their diseases. Cold Spring Harbor perspectives in medicine. 2014 May 1:4(5):. doi: 10.1101/cshperspect.a017046.
18. Kleinegger CL, Hammond HL, Finkelstein MW. Oral mucosal hyperpigmentation secondary to antimalarial drug therapy. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. 2000 Aug:90(2):189-94
19. Sant'Ambrogio S, Connelly J, DiMaio D. Minocycline pigmentation of heart valves. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 1999 Nov-Dec:8(6):329-32
20. Weiss SR, Lim HW, Curtis G. Slate-gray pigmentation of sun-exposed skin induced by amiodarone. Journal of the American Academy of Dermatology. 1984 Nov:11(5 Pt 1):898-900