Skip to main content
Top
Published in: European Journal of Medical Research 1/2023

Open Access 01-12-2023 | Hypopigmentation | Review

Laser treatment for Cafe-au-lait Macules: a systematic review and meta-analysis

Authors: Zi-Zhen Guo, Zhi-Chao Wang, Dun Wang, Ling-Ling Ge, Yue-Hua Li, Yi-Hui Gu, Wei Wang, Cheng-Jiang Wei, Bin Gu, Min Yao, Ji-Ying Dong, Qing-Feng Li

Published in: European Journal of Medical Research | Issue 1/2023

Login to get access

Abstract

Nowadays, laser is the mainstay treatment for cafe-au-lait macules (CALMs), but no systematic review has been published to demonstrate the overall efficacy and it’s still controversial which type of laser is optimal. Thus, we conduct the meta-analysis to evaluate the effectiveness and side effects of various types of lasers in treating CALMs. Original articles reporting the efficacy and side effects for CALMs in laser treatment were identified in PubMed, EMBASE, and Web of Science from 1983 to April 11, 2023. Using R software and the ‘meta’ package, meta-analysis was conducted for clearance and recurrence for evaluation of efficacy. And the occurrence of hypopigmentation and hyperpigmentation rate was pooled for safety evaluation. We used RoB2 and ROBINS-I tools to assess the risks of bias in RCT studies and non-RCT studies, respectively. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of the evidence. Nineteen studies involving 991 patients were included, which had a very low to moderate quality of evidence. The pooled 75% clearance rate was 43.3% (95% CI 31.8–54.7%, I2 = 96%), 50% clearance rate was 75% (95% CI 62.2–85.9%, I2 = 89%) and the recurrence rate was 13% (95% CI 3.2–26.5%, I2 = 88%). The pooled hypopigmentation and hyperpigmentation rates were 1.2% (95% CI 0.3–2.1%, I2 = 0%) and 1.2% (95% CI 0.3–2%, I2 = 0%), respectively. Subgroup analysis revealed that QS-1064-nm Nd:YAG laser treatment not only achieved more than 75% clearance rate in 50.9% of patients (95% CI 26.9–74.4%, I2 = 90%) but also resulted in the lowest hypopigmentation and hyperpigmentation rate of 0.5% (95% CI 0.0–2.5%, I2 = 26%) and 0.4% (95% CI 0.0–2.5%, I2 = 0%). To draw a conclusion, the laser treatment could reach an overall clearance rate of 50% for 75% of the patients with CALMs, for 43.3% of the patients, the clearance rate could reach 75%. When looking at different wavelength subgroups, QS-1064-nm Nd:YAG laser exhibited the best treatment capability. Laser of all the wavelength subgroups presented acceptable safety regarding of the low occurrence of side effects, namely, hypopigmentation and hyperpigmentation.
Literature
1.
go back to reference Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834–43.CrossRefPubMed Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13(8):834–43.CrossRefPubMed
3.
go back to reference Anderson S. Café au Lait Macules and Associated Genetic Syndromes. J Pediatr Health Care. 2020;34(1):71–81.CrossRefPubMed Anderson S. Café au Lait Macules and Associated Genetic Syndromes. J Pediatr Health Care. 2020;34(1):71–81.CrossRefPubMed
4.
go back to reference Grossman MC, Anderson RR, Farinelli W, Flotte TJ, Grevelink JM. Treatment of cafe au lait macules with lasers. A clinicopathologic correlation. Arch Dermatol. 1995;131(12):1416–20.CrossRefPubMed Grossman MC, Anderson RR, Farinelli W, Flotte TJ, Grevelink JM. Treatment of cafe au lait macules with lasers. A clinicopathologic correlation. Arch Dermatol. 1995;131(12):1416–20.CrossRefPubMed
6.
go back to reference Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science. 1983;220(4596):524–7.CrossRefPubMed Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation. Science. 1983;220(4596):524–7.CrossRefPubMed
7.
go back to reference Cen Q, Gu Y, Luo L, Shang Y, Rao Y, Zhu J, et al. Comparative effectiveness of 755-nm picosecond laser, 755- and 532-nm nanosecond lasers for treatment of Café-au-Lait Macules (CALMs): a randomized, split-lesion clinical trial. Lasers Surg Med. 2021;53(4):435–42.CrossRefPubMed Cen Q, Gu Y, Luo L, Shang Y, Rao Y, Zhu J, et al. Comparative effectiveness of 755-nm picosecond laser, 755- and 532-nm nanosecond lasers for treatment of Café-au-Lait Macules (CALMs): a randomized, split-lesion clinical trial. Lasers Surg Med. 2021;53(4):435–42.CrossRefPubMed
8.
go back to reference Zhuang Y, Huang M, Shen J, Wang L, Yang L, Jiang A, et al. Comparison of the efficacy and safety between a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser and a conventional Q-switched 532-nm laser for the treatment of cafe-au-lait macules in 40 Chinese children: a prospective, randomized, parallel-controlled, evaluator-blinded trial. Lasers Med Sci. 2022;37(1):279–86.CrossRefPubMed Zhuang Y, Huang M, Shen J, Wang L, Yang L, Jiang A, et al. Comparison of the efficacy and safety between a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser and a conventional Q-switched 532-nm laser for the treatment of cafe-au-lait macules in 40 Chinese children: a prospective, randomized, parallel-controlled, evaluator-blinded trial. Lasers Med Sci. 2022;37(1):279–86.CrossRefPubMed
9.
go back to reference Gu T, Yuan J, Zhang Y, Li YH, Wu Y, Gao XH, et al. A retrospective study of FQSRL and IPL in the treatment of Café-au-lait macule. J Dermatol Treat. 2021;32(5):544–7.CrossRef Gu T, Yuan J, Zhang Y, Li YH, Wu Y, Gao XH, et al. A retrospective study of FQSRL and IPL in the treatment of Café-au-lait macule. J Dermatol Treat. 2021;32(5):544–7.CrossRef
10.
go back to reference Lin Y, Liu HX, Shi WH, Wang HX, Geng JH, Guo X, et al. Preliminary experience of the Q-switched 1064-nm neodymium:yttrium aluminum garnet laser in the treatment of Café-au-lait macules. J Eur Acad Dermatol Venereol. 2019;33(4):e185–6.CrossRefPubMed Lin Y, Liu HX, Shi WH, Wang HX, Geng JH, Guo X, et al. Preliminary experience of the Q-switched 1064-nm neodymium:yttrium aluminum garnet laser in the treatment of Café-au-lait macules. J Eur Acad Dermatol Venereol. 2019;33(4):e185–6.CrossRefPubMed
11.
go back to reference Artzi O, Mehrabi JN, Koren A, Niv R, Lapidoth M, Levi A. Picosecond 532-nm neodymium-doped yttrium aluminium garnet laser-a novel and promising modality for the treatment of café-au-lait macules. Lasers Med Sci. 2018;33(4):693–7.CrossRefPubMed Artzi O, Mehrabi JN, Koren A, Niv R, Lapidoth M, Levi A. Picosecond 532-nm neodymium-doped yttrium aluminium garnet laser-a novel and promising modality for the treatment of café-au-lait macules. Lasers Med Sci. 2018;33(4):693–7.CrossRefPubMed
12.
go back to reference Balaraman B, Ravanfar-Jordan P, Friedman PM. Novel use of non-ablative fractional photothermolysis for café-au-lait macules in darker skin types. Lasers Surg Med. 2017;49(1):84–7.CrossRefPubMed Balaraman B, Ravanfar-Jordan P, Friedman PM. Novel use of non-ablative fractional photothermolysis for café-au-lait macules in darker skin types. Lasers Surg Med. 2017;49(1):84–7.CrossRefPubMed
13.
go back to reference Belkin DA, Neckman JP, Jeon H, Friedman P, Geronemus RG. Response to laser treatment of café au lait macules based on morphologic features. JAMA Dermatol. 2017;153(11):1158–61.CrossRefPubMedPubMedCentral Belkin DA, Neckman JP, Jeon H, Friedman P, Geronemus RG. Response to laser treatment of café au lait macules based on morphologic features. JAMA Dermatol. 2017;153(11):1158–61.CrossRefPubMedPubMedCentral
14.
go back to reference Alster TS. Complete elimination of large café-au-lait birthmarks by the 510-nm pulsed dye laser. Plast Reconstr Surg. 1995;96(7):1660–4.CrossRefPubMed Alster TS. Complete elimination of large café-au-lait birthmarks by the 510-nm pulsed dye laser. Plast Reconstr Surg. 1995;96(7):1660–4.CrossRefPubMed
15.
go back to reference Baek JO, Park IJ, Lee KR, Ryu HR, Kim J, Lee S, et al. High-fluence 1064-nm Q-Switched Nd:YAG laser: Safe and effective treatment of café-au-lait macules in Asian patients. J Cosmet Dermatol. 2018;17(3):380–4.CrossRefPubMed Baek JO, Park IJ, Lee KR, Ryu HR, Kim J, Lee S, et al. High-fluence 1064-nm Q-Switched Nd:YAG laser: Safe and effective treatment of café-au-lait macules in Asian patients. J Cosmet Dermatol. 2018;17(3):380–4.CrossRefPubMed
16.
go back to reference Fitzpatrick RE, Goldman MP, Ruiz-Esparza J. Laser treatment of benign pigmented epidermal lesions using a 300 nsecond pulse and 510 nm wavelength. J Dermatol Surg Oncol. 1993;19(4):341–7.CrossRefPubMed Fitzpatrick RE, Goldman MP, Ruiz-Esparza J. Laser treatment of benign pigmented epidermal lesions using a 300 nsecond pulse and 510 nm wavelength. J Dermatol Surg Oncol. 1993;19(4):341–7.CrossRefPubMed
17.
go back to reference Kilmer SL, Wheeland RG, Goldberg DJ, Anderson RR. Treatment of epidermal pigmented lesions with the frequency-doubled Q-switched Nd:YAG laser. A controlled, single-impact, dose-response, multicenter trial. Arch Dermatol. 1994;130(12):1515–9.CrossRefPubMed Kilmer SL, Wheeland RG, Goldberg DJ, Anderson RR. Treatment of epidermal pigmented lesions with the frequency-doubled Q-switched Nd:YAG laser. A controlled, single-impact, dose-response, multicenter trial. Arch Dermatol. 1994;130(12):1515–9.CrossRefPubMed
18.
go back to reference Kim H-R, Ha J-M, Park M-S, Lee Y, Seo Y-J, Kim C-D, et al. A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet laser for the treatment of cafe-au-lait macules. J Am Acad Dermatol. 2015;73(3):477–83.CrossRefPubMed Kim H-R, Ha J-M, Park M-S, Lee Y, Seo Y-J, Kim C-D, et al. A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet laser for the treatment of cafe-au-lait macules. J Am Acad Dermatol. 2015;73(3):477–83.CrossRefPubMed
19.
go back to reference Kim J, Hur H, Kim YR, Cho SB. Treatment of café-au-lait macules with a high-fluenced 1064-nm Q-switched neodymium:yttrium aluminum garnet laser. J Cosmet Laser Ther. 2018;20(1):17–20.CrossRefPubMed Kim J, Hur H, Kim YR, Cho SB. Treatment of café-au-lait macules with a high-fluenced 1064-nm Q-switched neodymium:yttrium aluminum garnet laser. J Cosmet Laser Ther. 2018;20(1):17–20.CrossRefPubMed
20.
go back to reference Kung KY, Shek SY, Yeung CK, Chan HH. Evaluation of the safety and efficacy of the dual wavelength picosecond laser for the treatment of benign pigmented lesions in Asians. Lasers Surg Med. 2019;51(1):14–22.CrossRefPubMed Kung KY, Shek SY, Yeung CK, Chan HH. Evaluation of the safety and efficacy of the dual wavelength picosecond laser for the treatment of benign pigmented lesions in Asians. Lasers Surg Med. 2019;51(1):14–22.CrossRefPubMed
21.
go back to reference Shimbashi T, Kamide R, Hashimoto T. Long-term follow-up in treatment of solar lentigo and café-au-lait macules with Q-switched ruby laser. Aesthetic Plast Surg. 1997;21(6):445–8.CrossRefPubMed Shimbashi T, Kamide R, Hashimoto T. Long-term follow-up in treatment of solar lentigo and café-au-lait macules with Q-switched ruby laser. Aesthetic Plast Surg. 1997;21(6):445–8.CrossRefPubMed
22.
go back to reference Shimbashi T, Kojima T. Ruby laser treatment of pigmented skin lesions. Aesthetic Plast Surg. 1995;19(3):225–9.CrossRefPubMed Shimbashi T, Kojima T. Ruby laser treatment of pigmented skin lesions. Aesthetic Plast Surg. 1995;19(3):225–9.CrossRefPubMed
23.
go back to reference Somyos K, Boonchu K, Somsak K, Panadda L, Leopairut J. Copper vapour laser treatment of café-au-lait macules. Br J Dermatol. 1996;135(6):964–8.CrossRefPubMed Somyos K, Boonchu K, Somsak K, Panadda L, Leopairut J. Copper vapour laser treatment of café-au-lait macules. Br J Dermatol. 1996;135(6):964–8.CrossRefPubMed
24.
go back to reference Wang Y, Qian H, Lu Z. Treatment of café au lait macules in Chinese patients with a Q-switched 755-nm alexandrite laser. J Dermatol Treat. 2012;23(6):431–6.CrossRef Wang Y, Qian H, Lu Z. Treatment of café au lait macules in Chinese patients with a Q-switched 755-nm alexandrite laser. J Dermatol Treat. 2012;23(6):431–6.CrossRef
25.
go back to reference Zhang B, Chu Y, Xu Z, Sun Y, Li L, Han X, et al. Treatment of Café-Au-Lait spots using Q-switched Alexandrite laser: analysis of clinical characteristics of 471 children in Mainland China. Lasers Surg Med. 2019;51(8):694–700.CrossRefPubMedPubMedCentral Zhang B, Chu Y, Xu Z, Sun Y, Li L, Han X, et al. Treatment of Café-Au-Lait spots using Q-switched Alexandrite laser: analysis of clinical characteristics of 471 children in Mainland China. Lasers Surg Med. 2019;51(8):694–700.CrossRefPubMedPubMedCentral
26.
go back to reference Yoshida Y, Sato N, Furumura M, Nakayama J. Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed-radio frequency in combination with topical application of vitamin D3 ointment. J Dermatol. 2007;34(4):227–30.CrossRefPubMed Yoshida Y, Sato N, Furumura M, Nakayama J. Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed-radio frequency in combination with topical application of vitamin D3 ointment. J Dermatol. 2007;34(4):227–30.CrossRefPubMed
27.
go back to reference Chan NP, Ho SG, Shek SY, Yeung CK, Chan HH. A case series of facial depigmentation associated with low fluence Q-switched 1,064 nm Nd:YAG laser for skin rejuvenation and melasma. Lasers Surg Med. 2010;42(8):712–9.CrossRefPubMed Chan NP, Ho SG, Shek SY, Yeung CK, Chan HH. A case series of facial depigmentation associated with low fluence Q-switched 1,064 nm Nd:YAG laser for skin rejuvenation and melasma. Lasers Surg Med. 2010;42(8):712–9.CrossRefPubMed
28.
29.
go back to reference Wattanakrai P, Mornchan R, Eimpunth S. 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.CrossRefPubMed Wattanakrai P, Mornchan R, Eimpunth S. 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.CrossRefPubMed
30.
go back to reference Polnikorn N. Treatment of refractory dermal melasma with the MedLite C6 Q-switched Nd:YAG laser: two case reports. J Cosmet Laser Ther. 2008;10(3):167–73.CrossRefPubMed Polnikorn N. Treatment of refractory dermal melasma with the MedLite C6 Q-switched Nd:YAG laser: two case reports. J Cosmet Laser Ther. 2008;10(3):167–73.CrossRefPubMed
31.
go back to reference Ara G, Anderson RR, Mandel KG, Ottesen M, Oseroff AR. Irradiation of pigmented melanoma cells with high intensity pulsed radiation generates acoustic waves and kills cells. Lasers Surg Med. 1990;10(1):52–9.CrossRefPubMed Ara G, Anderson RR, Mandel KG, Ottesen M, Oseroff AR. Irradiation of pigmented melanoma cells with high intensity pulsed radiation generates acoustic waves and kills cells. Lasers Surg Med. 1990;10(1):52–9.CrossRefPubMed
32.
go back to reference Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372: n160.CrossRefPubMedPubMedCentral Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372: n160.CrossRefPubMedPubMedCentral
33.
go back to reference Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898.CrossRefPubMed Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366: l4898.CrossRefPubMed
34.
go back to reference Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355: i4919.CrossRefPubMedPubMedCentral Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355: i4919.CrossRefPubMedPubMedCentral
35.
go back to reference Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.CrossRefPubMed Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.CrossRefPubMed
36.
go back to reference Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–6.CrossRefPubMed Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–6.CrossRefPubMed
37.
go back to reference RCoreTeam. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2022. RCoreTeam. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2022.
Metadata
Title
Laser treatment for Cafe-au-lait Macules: a systematic review and meta-analysis
Authors
Zi-Zhen Guo
Zhi-Chao Wang
Dun Wang
Ling-Ling Ge
Yue-Hua Li
Yi-Hui Gu
Wei Wang
Cheng-Jiang Wei
Bin Gu
Min Yao
Ji-Ying Dong
Qing-Feng Li
Publication date
01-12-2023
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2023
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-023-01143-1

Other articles of this Issue 1/2023

European Journal of Medical Research 1/2023 Go to the issue