Energy-Based Devices for Exogenous Ochronosis: A Systematic Review of Randomized Controlled Trials and Primary Studies

Energy-Based Devices for Exogenous Ochronosis: A Systematic Review of Randomized Controlled Trials and Primary Studies

Authors

  • Stephanie Anastasia Handono Faculty of Medicine, Universitas Pelita Harapan, Indonesia
  • Verika Christabela Tansuri Faculty of Medicine, Universitas Pelita Harapan, Indonesia

Keywords:

Exogenous ochronosis, Q-switched laser, picosecond laser, hydroquinone, dermal hyperpigmentation

Abstract

Introduction

Exogenous ochronosis (EO) is an acquired cutaneous disorder characterized by progressive dermal hyperpigmentation resulting from prolonged topical hydroquinone exposure. The deeply deposited ochronotic pigment within dermal collagen renders conventional therapies ineffective. Energy-based devices (EBDs) have emerged as the primary interventional strategy. This systematic review synthesizes evidence on EBD efficacy, safety, and patient-reported outcomes for EO treatment.

Methods

This systematic review followed PRISMA 2020 guidelines. A comprehensive search was conducted from inception to June 2025. Studies evaluating any EBD for confirmed EO with quantifiable outcomes were included. Risk of bias was assessed using Newcastle-Ottawa Scale and Cochrane RoB-2 tools.

Results

Fifteen primary studies (147 patients) were included. Q-switched alexandrite (755 nm) laser achieved 85–100% pigment clearance after 4–6 sessions. Q-switched Nd:YAG (1064 nm) and picosecond lasers demonstrated excellent outcomes in Fitzpatrick skin types III–VI. Combination therapies showed synergistic benefit in refractory cases. Adverse events were predominantly mild and transient.

Discussion

EBDs exploit selective photothermolysis to fragment dermal ochronotic pigment. Q-switched alexandrite remains the most validated monotherapy, while picosecond technologies offer superior precision with lower post-inflammatory hyperpigmentation rates. Significant heterogeneity and absence of standardized outcomes limit evidence comparability.

Conclusion

Q-switched lasers, particularly alexandrite and Nd:YAG, represent the most effective interventions for EO. Picosecond lasers and combination therapies show promising results. Standardized multicenter RCTs are urgently needed to establish evidence-based guidelines.

References

Wick N, Bresser A, Brenner R, et al. Exogenous ochronosis: an epidemiological study. Br J Dermatol. 1989;120(2):229-238. [Consensus: https://consensus.app/papers/details/81148b6db66f546498a89f7ae2ffad93/?utm_source=claude_desktop]

Lazar M, Comstock J, Harrington A, et al. Exogenous Ochronosis: Characterizing a Rare Disorder in Skin of Color. J Clin Med. 2023;12(4):1370. [Consensus: https://consensus.app/papers/details/c5f144a60d175bdba6ec11241adaa212/?utm_source=claude_desktop]

Simmons BJ, Griffith RD, Bray FN, et al. Exogenous Ochronosis: A Comprehensive Review of the Diagnosis, Epidemiology, Causes, and Treatments. Am J Clin Dermatol. 2015;16(3):205-212. [Consensus: https://consensus.app/papers/details/c493a9df11c9513a8c3fcc04a4556aaf/?utm_source=claude_desktop]

Levin CY, Maibach H. Exogenous Ochronosis. Am J Clin Dermatol. 2001;2(4):213-217. [Consensus: https://consensus.app/papers/details/bd5febb9291e587e9120079e0cfce959/?utm_source=claude_desktop]

Findlay GH, Morrison JG, Simson IW. Exogenous ochronosis and pigmented colloid milium from hydroquinone bleaching creams. Br J Dermatol. 1975;93(6):613-622. [Consensus: https://consensus.app/papers/details/ead8414ffcb258d88ea2873467322cee/?utm_source=claude_desktop]

Bellew SG, Rosen T. Treatment of Exogenous Ochronosis With a Q-Switched Alexandrite (755 nm) Laser. Dermatol Surg. 2004;30(4):555-558. [Consensus: https://consensus.app/papers/details/26ff480515175fb380d637aee880f859/?utm_source=claude_desktop]

Dover JS, Jeffrey SFM, et al. The History and Advancement of Light, Lasers, and Energy-Based Devices in Dermatologic Surgery. Dermatol Surg. 2025;51(1):1-12. [Consensus: https://consensus.app/papers/details/91e13fec6ec45334804171dd0dea325e/?utm_source=claude_desktop]

Hull PR, De Beer HA. The melanocyte: an essential link in hydroquinone-induced ochronosis. J Am Acad Dermatol. 1990;22(3):529-531. [Consensus: https://consensus.app/papers/details/0a3cc52cc1185a4ba0918a0e8562860b/?utm_source=claude_desktop]

Garg S, Nair KA, Maheshwari M, et al. Advancements in Laser Therapies for Dermal Hyperpigmentation in Skin of Color. J Clin Med. 2024;13(2):468. [Consensus: https://consensus.app/papers/details/a81f64324e4c57ae8b15538b060dc9f2/?utm_source=claude_desktop]

Ito S, Nakanishi Y, Watt AAR, et al. Exogenous Ochronosis by Hydroquinone is not caused by Inhibition of Homogentisate Dioxygenase but potentially by Tyrosinase-catalyzed Metabolism of Hydroquinone. Br J Dermatol. 2025;192(4):678-685. [Consensus: https://consensus.app/papers/details/080ca8e4f34056789a0e5bf9b5bd4eef/?utm_source=claude_desktop]

Mornchan R, Charoenporn P. Low-Fluence Q-Switched Neodymium-Doped Yttrium Aluminum Garnet (1,064 nm) Laser for the Treatment of Facial Melasma in Asians. Dermatol Surg. 2010;36(1):76-87. [Consensus: https://consensus.app/papers/details/53c1cbb5c27f56a6b2ef1fce7992ec68/?utm_source=claude_desktop]

Wang CC, Sue YM, Yang CH, et al. A comparison of Q-switched alexandrite laser and intense pulsed light for the treatment of freckles and lentigines in Asian persons. J Am Acad Dermatol. 2006;54(5):804-810. [Consensus: https://consensus.app/papers/details/3af2dad6c54b505c8a14a33df098afbb/?utm_source=claude_desktop]

Park BJ, Jung HJ, Lee JH, et al. Therapeutic Effects of New Pulsed-Type Microneedling Radiofrequency for Refractory Facial Pigmentary Disorders. Dermatol Surg. 2022;48(9):1002-1008. [Consensus: https://consensus.app/papers/details/28175a3f860a5c758589f02b3f617f50/?utm_source=claude_desktop]

Evangelista MT, Abad-Casintahan MF. Clinical Evaluation of Safety and Efficacy of a 670-nm Picosecond Laser for Treatment of Benign Pigmented Lesions in Asians. Dermatol Surg. 2020;46(11):1389-1394. [Consensus: https://consensus.app/papers/details/9b2341b0a58054f9b4e5b8a6881eeb23/?utm_source=claude_desktop]

Friedmann DP, Goldman MP, Fabi SG. Prospective Study of 532-nm Picosecond Laser for the Treatment of Pigmented Lesions of the Face and Dorsal Hands. Dermatol Surg. 2022;48(6):673-678. [Consensus: https://consensus.app/papers/details/a6df4aa380b65ecb85013c204306736a/?utm_source=claude_desktop]

Ungaksornpairote C, Lueangarun S, Tanrattanakorn S, et al. A Prospective, Split-Face, Randomized Study Comparing Picosecond to Q-Switched Nd:YAG Laser for Treatment of Epidermal and Dermal Pigmented Lesions in Asians. Dermatol Surg. 2020;46(12):1671-1676. [Consensus: https://consensus.app/papers/details/d186296170a0506ea0ad6c7f97a1dc14/?utm_source=claude_desktop]

Sowash MG, Abudu O, Goldenberg G. Review of Laser Treatments for Post-Inflammatory Hyperpigmentation in Skin of Color. Am J Clin Dermatol. 2023;24(3):435-443. [Consensus: https://consensus.app/papers/details/a9715ea9aea554ad8919c79f7a3a0d15/?utm_source=claude_desktop]

Zhang AD, Torbeck RL, Shihab N, et al. Treatment of Benign Pigmented Lesions Using Lasers: A Scoping Review. J Clin Med. 2025;14(3):788. [Consensus: https://consensus.app/papers/details/3b827e2fa6c35297b9e023179dd889b4/?utm_source=claude_desktop]

Chen SX, Leong K, Kauvar ANB. Review of Lasers and Energy-Based Devices for Skin Rejuvenation and Scar Treatment With Histologic Correlations. Dermatol Surg. 2022;48(7):733-742. [Consensus: https://consensus.app/papers/details/764f8a991be856d5b515601bc8049047/?utm_source=claude_desktop]

Patel N, Bhatt S, Reddy N. Exogenous Ochronosis from Skin-Lightening Cream. N Engl J Med. 2024;390(6):547. [Consensus: https://consensus.app/papers/details/88d03d2d3fdc5b4a975365f19a0076ed/?utm_source=claude_desktop]

Wat H, Wu DC, Rao J, Goldman MP. Application of Intense Pulsed Light in the Treatment of Dermatologic Disease: A Systematic Review. Dermatol Surg. 2014;40(4):359-377. [Consensus: https://consensus.app/papers/details/c0d3d9126fdf582eb50ff2eddef322f8/?utm_source=claude_desktop]

Dlova NC, Hamed SH, Tsoka-Gwegweni J, Grobler A. Skin lightening practices: an epidemiological study of South African women of African and Indian ancestries. Br J Dermatol. 2015;173 Suppl 2:2-9. [Consensus: https://consensus.app/papers/details/5988fbfbc3eb5096a6bd2a79604d8577/?utm_source=claude_desktop]

Torbeck RL, Pan M, DeMaria S, Tyring S. Evolution of the Picosecond Laser: A Review of Literature. Dermatol Surg. 2019;45(2):183-194. [Consensus: https://consensus.app/papers/details/6a1d7d8e4afa5dd4bfe0311c4ad20497/?utm_source=claude_desktop]

Zawodny P, Bienias A, Buśko K, et al. The Efficacy of 532/755 nm Laser Therapy for Facial Pigmented and Vascular Lesions: A Systematic Review and Meta-Analysis. J Clin Med. 2025;14(4):1219. [Consensus: https://consensus.app/papers/details/281e64149c9252e5a184fa2bba5cef6c/?utm_source=claude_desktop]

Lee MSY, Martin CP, Ross EV, et al. Lasers and Energy-Based Devices for Treatment of Pigmented Lesions With Histologic and Ultrastructural Imaging Correlation: A Systematic Review. Dermatol Surg. 2025;51(2):145-157. [Consensus: https://consensus.app/papers/details/eb8685a639c6569a836ec86e84a6bece/?utm_source=claude_desktop]

Haimovic A, Brauer JA, Cindy Bae YS, Geronemus RG. Safety of a picosecond laser with diffractive lens array (DLA) in the treatment of Fitzpatrick skin types IV to VI. J Am Acad Dermatol. 2016;74(2):386-388. [Consensus: https://consensus.app/papers/details/fa49d3e220fd52c38a449304d0d617d3/?utm_source=claude_desktop]

Beaumet M, Ito S, Wakamatsu K, et al. Hydroquinone causes exogenous ochronosis through tyrosinase catalytic activity and highlights the need for genuine human tyrosinase inhibitors. Br J Dermatol. 2025;192(3):500-507. [Consensus: https://consensus.app/papers/details/eccba09de240505598acf109b6801165/?utm_source=claude_desktop]

Lawrence N, Bligard CA, Reed R, Perret WJ. Exogenous ochronosis in the United States. J Am Acad Dermatol. 1988;18(5 Pt 2):1207-1211. [Consensus: https://consensus.app/papers/details/2ac5ee01f33754d7b49607a41e4217e8/?utm_source=claude_desktop]

Bruce S, Wolf JE Jr. Exogenous ochronosis resulting from quinine injections. J Am Acad Dermatol. 1986;15(2 Pt 2):357-361. [Consensus: https://consensus.app/papers/details/544c2e7b342f51619297d5b3a12ef9a4/?utm_source=claude_desktop]

Ito S, Nakanishi Y, Wakamatsu K. Mechanistic Insights into Tyrosinase-Catalyzed Metabolism of Hydroquinone: Implications for the Etiology of Exogenous Ochronosis and Cytotoxicity to Melanocytes. Int J Mol Sci. 2025;26(3):1043. [Consensus: https://consensus.app/papers/details/0a7a67e9a46c52368197537ff664c948/?utm_source=claude_desktop]

Downloads

Published

2026-08-02

How to Cite

Stephanie Anastasia Handono, and Verika Christabela Tansuri. 2026. “Energy-Based Devices for Exogenous Ochronosis: A Systematic Review of Randomized Controlled Trials and Primary Studies”. The International Journal of Medical Science and Health Research 48 (4): 497-535. https://doi.org/10.70070/edfzrq56.