Elise Lupon
email: elupon@mgh.harvard.edu

Jérôme Laloze
email: jeromelaloze@hotmail.fr

Benoit Chaput
email: benoitchaput31@gmail.com

Paul Girard
email: paul.girard@hotmail.fr

Curtis L Cetrulo
email: ccetrulo@mgh.harvard.edu

Laurent A Lantieri
email: laurentlantieri@gmail.com

Jean Louis Grolleau
email: grolleau.jl@chu-toulouse.fro

Olivier Camuzard
email: camuzard.o@chu-nice.fr

Alexandre G Lellouch
email: alellouch@mgh.harvard.edu

MD Lupon Elise

MD Jérôme

MD Chaput Benoit

MD, MSc Girard Paul

Attending Plastic

MD Gaston Alexandre

TITLE PAGE: Treatment of post-burn hyperpigmentation: a literature review

Keywords: Dyschromia, skin burn, hyperpigmentation, post-burn sequelae, hydroquinone

Objectif: Skin pigmentation disorders are one of the most frequent sequelae post burn injury.

While these conditions often improve over time, some are permanent and cause severe psychological disorders (especially on the face). Given the frequency of these disorders and their benign nature, the scientific community has great difficulty postponing these patient follow-ups. Publications on their management are rare, and there is no consensus on the gold J o u r n a l P r e -p r o o f standard treatment for skin dyschromia. Herein, we performed a literature review including the various treatments currently proposed to manage these post-burn hyperpigmentations.

Methods: All reported articles up to February 2021 were reviewed on Pubmed. Studies on the treatment of hyperpigmented scars were included if they were secondary to burn injuries.

Excluded articles evaluated transient treatments, such as makeup, and articles on postinflammatory hyperpigmentation without etiological details or not secondary to burns.

Results: 201 articles were identified, and 13 studies were included. Topical creams used in post-inflammatory hyperpigmented lesions such as hydroquinone and first-line retinoids are controversial due to their inconstant efficacy. Various types of laser and pulsed light treatments have shown their effectiveness but can also aggravate pigmentation.

Conclusion:

Post-burn dyschromia still remains a therapeutic challenge. Post-burn hyperpigmentations should be treated on a case-by-case basis, using data from the literature, clinical experience and measuring the risk/benefit ratio.

INTRODUCTION

Pigmentation disorders are one of the most frequent sequelae post burn injury [START_REF] Greenhalgh | A primer on pigmentation[END_REF].

Hyperpigmented scars are more common in populations with dark skins, especially after skin grafting [START_REF] Greenhalgh | A primer on pigmentation[END_REF][START_REF] Halder | Management of dyschromias in ethnic skin[END_REF]. The pathophysiological mechanism of hyperpigmentation has not been fully elucidated [START_REF] Kaufman | Postinflammatory Hyperpigmentation: Epidemiology, Clinical Presentation, Pathogenesis and Treatment[END_REF]. Physiologically, melanin is produced by melanocytes in the basal layer of the epidermis, transported by melanosomes, and transferred to keratinocytes. The melanocytekeratinocyte interaction is responsible of the skin tone maintenance [START_REF] Cichorek | Skin melanocytes: biology and development[END_REF][START_REF] Serre | Intrinsic and extrinsic regulation of human skin melanogenesis and pigmentation[END_REF]. The proinflammatory cytokine storm released during the immune response following burns stimulates melanocyte proliferation and increases the level of melanogenesis [6 -10].

J o u r n a l P r e -p r o o f

In general, hyperpigmentation attenuates over time, but some cases are responsible for permanently delaying social reintegration [START_REF] Greenhalgh | A primer on pigmentation[END_REF] [START_REF] Wisely | Where to start? Attempting to meet the psychological needs of burned patients[END_REF][START_REF] Darji | Psychosocial Impact of Postinflammatory Hyperpigmentation in Patients with Acne Vulgaris[END_REF]. Aesthetic concerns are even more important for individuals when the affected areas are visible, such as the hands or face [START_REF] Darji | Psychosocial Impact of Postinflammatory Hyperpigmentation in Patients with Acne Vulgaris[END_REF].

Publications on the management of dyschromia are poorly reported, and the treatment of hyperpigmented scars after burns is not consensual [START_REF] Chaowattanapanit | Postinflammatory hyperpigmentation: A comprehensive overview: Treatment options and prevention[END_REF]. The objective of this review is to propose an algorithm for the management of hyperpigmented post-burn scars.

Materials and methods

Research Strategy

A literature review was performed on the management of post-burn hyperpigmentation using PubMed and lay media sources.

This review was conducted according to recommendations in the Cochrane Handbook for Intervention Reviews, version 5.1.0. The study complied with the AMSTAR checklist (Assessing the Methodological Quality of Systematic Reviews) and is reported in line with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement [START_REF] Moher | Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement[END_REF]. A protocol was developed, published, and is available in the PROSPERO National Institute of Health Research Prospective Register of Systematic Reviews at https://www.crd.york.ac.uk/PROSPERO, with registration number CRD42021255237.

All reported article up to July 2021 were verified between publications and news reports (as applicable) before inclusion for analysis. The keywords used on Pubmed were: dyspigmentation, dyschromia, hyperpigmentation, hyperpigmented burn scars, hyperpigmentation peels, laser hyperpigmentation, hydroquinone creams burn, laser hyperpigmentation, pigmentation disorders, dermabrasion burn hyperpigmentation, hydroquinone burn, post-burn scars.

J o u r n a l P r e -p r o o f

Selection of articles and inclusion and exclusion criteria

English-language publications on dyschromia were selected from the title and abstract. We have included clinical studies exclusively on the permanent management of post-burn hyperpigmented scars. Work on scar pathophysiology, erythematous scars, and work on postburn dyschromia transitional treatment, such as makeup, were excluded from the analysis.

Treatments for dyschromic scars other than for burns, such as melasma or post-inflammatory hyperpigmentation not secondary to burns (acne, eczema, etc.) or unspecified, were excluded from the analysis. Given the differences between the various pathological processes, only post-burn pigmentation was accepted as an appropriate model to study these currently proposed pigmentations treatments.

Data Collection

For each publication, we have listed the number of patients, their origin, the location of dyschromic scars and their surface area, the treatment evaluation modalities, follow-up, results, and complications after treatment. The treatment details were also specified, i.e., the time between injury and treatment, the use of a pre-treatment, and the treatment modalities (duration, doses, etc.).

Results

General comment

Out of 201 initially selected publications, 13 articles [START_REF] Raulin | Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby laser[END_REF][START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF][START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Eberlein | Erbium:YAG laser treatment of post-burn scars: potentials and limitations[END_REF][START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF][START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF][START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF][START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF][START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF][START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF] -comprising 444 patients -on the therapeutic management of post-burn pigmentation disorders were included in this review (Figure 1). One hundred eighty-seven articles were not retained because they were off topic [START_REF] Grimes | Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study[END_REF] or dealing with erythematous scars (3). One article meeting the inclusion criteria J o u r n a l P r e -p r o o f

was not included because it was inaccessible [START_REF] Cho | Treatment of burn scar using a carbon dioxide fractional laser[END_REF]. The selected articles included 4 case reports [16, 18-20, 22-25, 27], 8 descriptive cohort studies (non-randomized, non-controlled, single-cohort studies) [START_REF] Raulin | Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby laser[END_REF][START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF][START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF] and 2 comparative studies [START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF] (Table 1). Five different types of treatments were highlighted: topical lightening agents (n=3) [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF], lasers (n=5) [START_REF] Raulin | Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby laser[END_REF][START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF][START_REF] Eberlein | Erbium:YAG laser treatment of post-burn scars: potentials and limitations[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF][START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF][START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF], microplasma radio frequency (n=1) [START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF], intense pulsed light (IPL) (n=2) [START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF][START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF], and surgery (n=1) [START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF]. The patient phototypes were reported in 8/13 studies and were most often Fitzpatrick (FTZ) III or IV (n=123/128 patients in studies reporting FTZ score). The etiology of burns, reported in 9/13 studies, was diverse (fire, acid, boiling water, etc.). The grade of burns causing the hyperpigmented lesion was specified in only six studies [START_REF] Eberlein | Erbium:YAG laser treatment of post-burn scars: potentials and limitations[END_REF][START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF][START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF][START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF] and was at least second degree in four of these six studies. The majority of the studies (11/13) specified the burn locations, which were very heterogeneous (head, trunk, extremities). Eight studies stated that they did not use any prior treatment [START_REF] Raulin | Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby laser[END_REF][START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF][START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF][START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF][START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF], and three studies stated that they evaluated their treatment after prior failure of another treatment [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF]. Assessment of improvement used scales in five studies [START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF][START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF][START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF], and percentage assessment in three studies [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF]. Photography was mentioned in 7/13 studies [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF]. The follow-up period varied across studies from 6 weeks [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF] to 3.6 years [START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF]. The majority of the articles presented a treatment that was concluded to be effective and applicable, except for one study that studied IPL treatment and concluded that the benefit/risk ratio was negative [START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF]. Complications were minor, mainly as local manifestations (local peri-procedure pain, erythema, phlycten, irritation, and burning sensations). Two studies reported recurrence of hyperpigmentation (n=6 cases) and involved treatment with Erbium ablative laser [START_REF] Eberlein | Erbium:YAG laser treatment of post-burn scars: potentials and limitations[END_REF] and IPL [START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF].

Details of the articles are available in tables 2 and 3. A study by Mohammed Ali in 2016 [START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF] evaluated the efficacy, safety, and tolerability of salicylic acid peeling compared to topical tretinoin in the treatment of post-burn hyperpigmentation. This study included forty-five patients with post-inflammatory hyperpigmentation (PIH) lesions. Twelve of these 45 patients experienced post-burn hyperpigmentation. Patients were divided into three groups: Group I with 20-30% salicylic acid peel, Group II with 0.1% topical tretinoin, and Group III with a salicylic acid peel /topical tretinoin combination. The combined salicylic acid peel/topical tretinoin treatment showed a significant clinical improvement for hyperpigmentation compared to each treatment alone (with Group I, p=0.016 and with Group II, p=0.019), without complications. There was no significant difference in the recurrence of hyperpigmentation rate between the three J o u r n a l P r e -p r o o f groups. There was a non-significant difference between treatment efficacy and the type of PIH in the groups studied. There was no significant difference between treatment efficacy and duration of treatment, except for Group III. From this study, salicylic acid appears to be an inexpensive, safe, well-tolerated drug suitable for darker skin but a less effective therapeutic modality for treating hyperpigmentation. Topical tretinoin is an effective treatment for postburn hyperpigmentation compared to salicylic acid but with lower tolerance. The combination of low-dose salicylic acid and topical tretinoin has been significantly more effective in treating post-burn hyperpigmentation than either modality alone and with low side effects, low recurrence rate, and good tolerability.

A topical agent, methimazole (MMI), was tested in a study of a 27-year-old man with postinflammatory hyperpigmentation due to acid burn [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF]. It was successfully treated with topical MMI as a novel skin depigmenting agent. The 5% topical MMI produced very moderate to a marked improvement for hyperpigmented lesions within six weeks after oncedaily application and was well tolerated by the patient with no change in serum thyroid hormone levels.

Lasers

The Q-switched laser showed an excellent result in one patient when used on an old facial burn [START_REF] Raulin | Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby laser[END_REF]. The scar was first partially treated, making it easy to compare the laser effectiveness on the treated area compared to the native adjacent scar.

In 2005, Eberlein et al. [START_REF] Eberlein | Erbium:YAG laser treatment of post-burn scars: potentials and limitations[END_REF] showed an improvement for hyperpigmentation using Erbium:

YAG lasers tested for the first time on 96 hyperpigmented scars in 24 patients aged 16-55 years old. Black powder tattoos were eliminated in all cases. Smaller dark spots or frecklelike lesions improved in 93% of the cases. Hyperpigmentation was observed in a patient with darker type III skin. Recurrence was noted in 5 cases. Another fractional non-ablative Erbium J o u r n a l P r e -p r o o f laser was used with 80% improvement for dyschromia in 8 patients with hyperpigmentation after deep second or third-degree burns [START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF]. Nine of the ten subjects treated experienced improved skin texture, and 8 patients showed improvement for hypertrophy/atrophy. In 2012, Bach et al. [START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF] described a 22-year-old woman with a hyperpigmented scar and type IV Fitzpatrick's skin, initially treated with local agents without success, who improved significantly after treatment with a fractional erbium-doped fiber laser. The improvement was maintained at least 1 year after the last procedure. Two Fitzpatrick III phototype patients with burn scars were successfully treated with a combination of pulsed dye laser (PDL) and nonablative fractional lasers in a 2018 study [START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF]. A combination of the non-ablative laser with a fat micrograft has been proposed for the treatment of burns. Erol OO in 2018 [START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF] presented a case series report over eight years using the combined treatments of Fraxel Restore (fractional laser) and "micro-fat graft" injection in 288 patients with burn scars. The laser treatment reduced the intensity of the scars and reduced skin irregularities and hyperpigmentation. A 40-80% improvement was noted in this series. All patients and their families expressed satisfaction with the results.

Intense pulsed light (IPL)

HO WS et al. [START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF] conducted a prospective study evaluating the efficacy of IPL in the treatment of post-burn hyperpigmentation in a series of 19 cases. More than 78% of the patients showed >50% clinical improvement and nearly 32% of the patients achieved >75% depigmentation including a patient with 100% hyperpigmentation disappearance. Three patients developed phlyctens, and one patient experienced erythema that resolved within one week without leaving permanent marks. Siadat et al. [START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF] recommend 3-7 IPL sessions to apply the modified Kligman cream for better efficacy.

J o u r n a l P r e -p r o o f

However, in 2015, Hultman et al. [START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF] did not reach the same conclusions. Despite a high level of satisfaction among the patients tested (4.5/5), the authors advise against treatment with IPL, given its lack of efficacy at a high cost to the patient and its risks, particularly that of the initial lesion aggravation. Indeed, out of the 20 Asian patients tested (FTZ score=3.9), one patient experienced hyperpigmentation after treatment. Pain (4 patients) was also reported as well as phlyctens (2 patients). These patients benefited from fewer sessions than in the previous study [START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF], with one session performed most often (17 cases) and two sessions (3 cases).

Micro-plasma radiofrequency technology

DISCUSSION

As commonly admitted in the literature [START_REF] Halder | Management of dyschromias in ethnic skin[END_REF][START_REF] Taylor | Postinflammatory hyperpigmentation[END_REF][START_REF] Taylor | Postinflammatory hyperpigmentation[END_REF][START_REF] Halder | Ethnic skin disorders overview[END_REF][START_REF] Shokeen | Postinflammatory hyperpigmentation in patients with skin of color[END_REF], FTZ II and IV skins are at higher risk of hyperpigmentation due to increased reactivity of melanocytes within the skin and represented the majority of patients in these studies when their FTZ classes were mentioned.

Four of the 13 studies [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Eberlein | Erbium:YAG laser treatment of post-burn scars: potentials and limitations[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF] performed treatment in some patients before 12 months, the time of scar maturation, and four studies did not specify this critical information [START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF][START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF][START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF]. Topical lightening agents appear to be typically used as first-line treatment and of moderate efficacy. Combination treatments reported good results in 4 studies [START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF][START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF][START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF]. The heterogeneity of the number of patients and treatment evaluation methods in each study (Table 3) makes it challenging to demonstrate a treatment superiority. We recommend that any investigator wishing to evaluate the efficacy of a treatment on post-burn hyperpigmentation do the following: 1) Make pre-treatment and post-treatment standardized photographs in terms of lighting and camera settings; 2) Use the VSA for the evaluation of As it has been done in some studies regarding PIH [START_REF] Isedeh | An in vivo model for postinflammatory hyperpigmentation: an analysis of histological, spectroscopic, colorimetric and clinical traits[END_REF][START_REF] Fell | The Scarbase Duo(®): Intra-rater and inter-rater reliability and validity of a compact dual scar assessment tool[END_REF], colorimetry and spectroscopic evaluation could be used for better treatment comparisons. Moreover, the burn grade was only specified in 6/13 publications [START_REF] Eberlein | Erbium:YAG laser treatment of post-burn scars: potentials and limitations[END_REF][START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF][START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF][START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF][START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF], and the depth of the lesion and the level of damage are also essential in prioritizing treatment [START_REF] Chaowattanapanit | Postinflammatory hyperpigmentation: A comprehensive overview: Treatment options and prevention[END_REF]. Our approach to the management of post-burn hyperpigmentation is illustrated in the algorithm (Figure 2).

In the case of hyperpigmentation less than one year after the initial injury, we recommend patience before any treatment. This time interval of 12 months has to be given for the maturation of burn scars. Topical lightening agents, the least invasive and most comfortable to use, can then be used as first-line treatment. The main strategy to treat PIH is to inhibit melanogenesis enzymes. The best-known treatment consists of inhibiting tyrosinase activity, the enzyme that converts tyrosine into melanin, by acting as an alternative substrate with hydroquinone cream [START_REF] Chaowattanapanit | Postinflammatory hyperpigmentation: A comprehensive overview: Treatment options and prevention[END_REF][START_REF] Kolbe | 4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation[END_REF][START_REF] Palumbo | Mechanism of inhibition of melanogenesis by hydroquinone[END_REF][START_REF] Callender | Postinflammatory hyperpigmentation: etiologic and therapeutic considerations[END_REF][START_REF] Ebanks | Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration[END_REF] in countries where it is still authorized [START_REF] O'donoghue | Hydroquinone and its analogues in dermatology -a riskbenefit viewpoint[END_REF][START_REF] Palm | Hydroquinone and the FDA--the debate?[END_REF]. The use of the most active tyrosinase inhibitor, 4n-butyl resorcinol has not been published in post-burn hyperpigmentation [START_REF] Kolbe | 4-n-butylresorcinol, a highly effective tyrosinase inhibitor for the topical treatment of hyperpigmentation[END_REF]. Chemical peels, tretinoin, corticosteroids, azelaic acid, kojic acid, arbutin, ascorbic acid, and soy extract can also be proposed in combination for better efficacy in the treatment of post-inflammatory hyperpigmentation [START_REF] Halder | Management of dyschromias in ethnic skin[END_REF][START_REF] Chaowattanapanit | Postinflammatory hyperpigmentation: A comprehensive overview: Treatment options and prevention[END_REF][START_REF] Callender | Postinflammatory hyperpigmentation: etiologic and therapeutic considerations[END_REF][START_REF] Chandra | Hydroquinone therapy for postinflammatory hyperpigmentation secondary to acne: not just prescribable by dermatologists[END_REF][START_REF] Davis | Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color[END_REF][START_REF] Lawrence | Postinflammatory Hyperpigmentation[END_REF]. Few studies are evaluating the use of these topical agents in patients with hyperpigmentation, specifically in the context of burn sequelae [START_REF] Kasraee | Topical methimazole as a new treatment for postinflammatory hyperpigmentation: report of the first case[END_REF][START_REF] Ali | Evaluation of salicylic acid peeling in comparison with topical tretinoin in the treatment of postinflammatory hyperpigmentation[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF], and some articles reporting the use of these agents in PIH do not specify the precise PIH etiologies [START_REF] Bulengo-Ransby | Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients[END_REF][START_REF] Kakita | Azelaic acid and glycolic acid combination therapy for facial hyperpigmentation in darker-skinned patients: a clinical comparison with hydroquinone[END_REF][START_REF] Grimes | The safety and efficacy of salicylic acid chemical peels in darker racial-ethnic groups[END_REF][START_REF] Grimes | A microsponge formulation of hydroquinone 4% and retinol 0.15% in the treatment of melasma and postinflammatory hyperpigmentation[END_REF][START_REF] Burm | Superficial dermabrasion and suction blister epidermal grafting for postburn dyspigmentation in Asian skin[END_REF][START_REF] Cook-Bolden | An open-label study of the efficacy and tolerability of microencapsulated hydroquinone 4% and retinol 0.15% with antioxidants for the treatment of hyperpigmentation[END_REF][START_REF] Sarkar | Treatment of Postinflammatory Hyperpigmentation With a Combination of Glycolic Acid Peels and a Topical Regimen in Dark-Skinned Patients: A Comparative Study[END_REF][START_REF] Bae | Treatment of Post-Inflammatory Hyperpigmentation in Patients With Darker Skin Types Using a Low Energy 1,927 nm Non-Ablative Fractional Laser: A Retrospective Photographic Review Analysis[END_REF]. Scars may remain refractory to these first-line treatments. It should be kept in mind that bleaching creams may be associated with adverse effects such as hydroquinone halo, irritation, erythema, hyperpigmentation, and exogenous ochronosis [START_REF] Schwartz | Hydroquinone[END_REF][START_REF] Draelos | Skin lightening preparations and the hydroquinone controversy[END_REF][START_REF] Sánchez-Martínez | Exogenous ochronosis: the failure of depigmenting creams[END_REF][START_REF] Tse | Hydroquinone for skin lightening: safety profile, duration of use and when should we stop?[END_REF][START_REF] Masub | Cosmetic skin lightening use and side effects[END_REF][START_REF] Simmons | Exogenous ochronosis: a comprehensive review of the diagnosis, epidemiology, causes, and treatments[END_REF]. However, a recent review has been reassuring about these side J o u r n a l P r e -p r o o f effects if the use is controlled [START_REF] Searle | Hydroquinone: myths and reality[END_REF]. Lasers can be considered as the second line treatment after failure of topical agents. The role of laser therapy for post-burn hyperpigmentation remains unclear [START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF]. PIH can be a complication of many laser systems, so they have to be used with appropriate parameters and adequate care should be provided after laser treatment. The Qswitch and long-pulse specific pigment laser have shown good improvements for PIH [START_REF] Dierickx | Laser treatment of erythematous/hypertrophic and pigmented scars in 26 patients[END_REF][START_REF] Cho | Treatment of postinflammatory hyperpigmentation using 1064-nm Q-switched Nd:YAG laser with low fluence: report of three cases[END_REF][START_REF] Kim | Treatment of procedure-related postinflammatory hyperpigmentation using 1064-nm Q-switched Nd:YAG laser with low fluence in Asian patients: report of five cases[END_REF][START_REF] Masub | Cosmetic skin lightening use and side effects[END_REF]. While the Q-switch ruby laser is an effective and safe therapeutic device for treating tattoos and well-defined skin lesions of the pigmented epidermis and dermis [START_REF] Raulin | Q-switched ruby laser treatment of tattoos and benign pigmented skin lesions: a critical review[END_REF], only one publication shows efficacy in post-burn hyperpigmentation [START_REF] Raulin | Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby laser[END_REF].

Non-ablative fractional erbium laser showed promising results in three selected studies [START_REF] Waibel | Treatment of burn scars with the 1,550 nm non-ablative fractional Erbium Laser[END_REF][START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF][START_REF] Onur Erol | Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF]. In 2020 a case series of 11 subjects supported the effectiveness of fractional ablative Er:YAG laser in treating the multiple characteristics of scars, including dyschromia but without specifying the hypo-or hyper-side of the dyschromia [START_REF] Wulkan | Treatment of Hypertrophic Burn and Traumatic Scars With a 2,940-nm Fractional Ablative Erbiumdoped Yttrium Aluminium Garnet Laser: A Pilot Study[END_REF].

Pulsed dye lasers are a type of laser that is attractive in PIH [START_REF] Alster | Improvement of facial acne scars by the 585 nm flashlamp-pumped pulsed dye laser[END_REF] but has not been published as single treatment in post-burn hyperpigmentation. They were combined with a non-ablative fractional erbium/thulium-based laser in 2018 [START_REF] Tao | Treatment of burn scars in Fitzpatrick phototype III patients with a combination of pulsed dye laser and non-ablative fractional resurfacing 1550 nm erbium:glass/1927 nm thulium laser devices[END_REF] to improve hyperpigmentation. Scanning CO2 lasers have been used to debride burn wounds, but sometimes without clinical improvement of the scar outcome [START_REF] Schwartz | Long-term assessment of CO2 facial laser resurfacing: aesthetic results and complications[END_REF] or even an aggravation [START_REF] Rokhsar | Fractional photothermolysis for the treatment of postinflammatory hyperpigmentation after carbon dioxide laser resurfacing[END_REF]. Moreover, while treating pigmented disorders with fractional ablative lasers, it is necessary to avoid the early removal of scabs to prevent PIH development [START_REF] Oram | Refractory Postinflammatory Hyperpigmentation Treated Fractional CO2 Laser[END_REF].

Intense pulsed light has been reported in 3 studies with heterogeneous results [START_REF] Ho | Prospective study on the treatment of postburn hyperpigmentation by intense pulsed light[END_REF][START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF][START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF]. Its benefit/risk ratio is reported to be unfavorable [START_REF] Hultman | Efficacy of intense pulsed light for the treatment of burn scar dyschromias: a pilot study to assess patient satisfaction, safety, and willingness to pay[END_REF], and they seem to be more effective in combination with topical lightening agents [START_REF] Siadat | The comparison between modified kligman J o u r n a l P r e -p r o o f formulation versus kligman formulation and intense pulsed light in the treatment of the post-burn hyperpigmentation[END_REF]. Microplasma radiofrequency seems to show good results at the facial level but it has only been reported for one study subject [START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF].

Because of the need to create a scar at the donor site, we recommend skin graft surgery only

J o u r n a l P r e -p r o o f

for treating hyperpigmentation as a treatment for hyperpigmentation after skin grafting on burns, as was done in a Moon SH et al. study [START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF]. This review's main limitation is the small number of studies and the non-inclusion of studies due to the lack of information on etiology of the injury. Indeed, some publications on the treatment of hyperpigmentation classify post-burn hyperpigmentation as PIH without any details [START_REF] Lacz | Postinflammatory hyperpigmentation: a common but troubling condition[END_REF][START_REF] Callender | Postinflammatory hyperpigmentation: etiologic and therapeutic considerations[END_REF][START_REF] Oram | Refractory Postinflammatory Hyperpigmentation Treated Fractional CO2 Laser[END_REF][START_REF] Chang | Disorders of hyperpigmentation[END_REF].

We have selected only articles presenting treatments for hyperpigmentations with a specified post burn etiology. On one hand, because PIH does not include the same causes, according to the articles. For example, for Grimes PE [START_REF] Grimes | Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study[END_REF] and Roberts WE [START_REF] Roberts | Chemical peeling in ethnic/dark skin[END_REF], acne is not considered as PIH, whereas it is considered as PIH for Callender VD [START_REF] Palumbo | Mechanism of inhibition of melanogenesis by hydroquinone[END_REF] and Oram Y. [START_REF] Oram | Refractory Postinflammatory Hyperpigmentation Treated Fractional CO2 Laser[END_REF]. Similarly, post melasma hyperpigmentations are considered as PIH for Silpa-Archa [START_REF] Silpa-Archa | Postinflammatory hyperpigmentation: A comprehensive overview: Epidemiology, pathogenesis, clinical presentation, and noninvasive assessment technique[END_REF], while they are considered as a differential diagnosis of PIH for Taylor S. [START_REF] Taylor | Postinflammatory hyperpigmentation[END_REF] Lawrence E. [START_REF] Lawrence | Postinflammatory Hyperpigmentation[END_REF]. As Bach DQ pointed out in his discussion [START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF], we cannot extrapolate with certainty the effect of a treatment on a specific type of PIH to all PIHs because not all PIHs have the same pathophysiological mechanisms and may therefore respond differently to treatment [START_REF] Tiwari | Burn wound: How it differs from other wounds?[END_REF][START_REF] Lee | Recent progress in melasma pathogenesis[END_REF].

Moreover, descriptions of altered post-burn pigmentation have been less documented than another dermatosis causing hyperpigmentations [START_REF] Tyack | Postburn dyspigmentation: its assessment, management, and relationship to scarring--a review of the literature[END_REF]. Despite this, alternative treatments used to correct hyperpigmentation in other indications should be kept in mind, tested on post-burn hyperpigmentation, and reported. Also, several studies [74 -81] have proposed a recent treatment, microneedling, also known as collagen induction therapy, as an alternative to conventional treatment in pigmentation disorders affecting darker skin types, including melasma, vitiligo, and periorbital hyperpigmentation [START_REF] Iriarte | Review of applications of microneedling in dermatology[END_REF].

J o u r n a l P r e -p r o o f

The use of laser assisted drug delivery [START_REF] Ali | Laser-assisted drug delivery in dermatology: from animal models to clinical practice[END_REF][START_REF] Searle | Lessons Learned from the First Decade of Laser-Assisted Drug Delivery[END_REF] such as hydroquinone [START_REF] Badawi | Fractional erbium-doped yttrium aluminum garnet laser-assisted drug delivery of hydroquinone in the treatment of melasma[END_REF], kojic acid [START_REF] Al-Dhalimi | Evaluation of the of the efficacy of Fractional Erbium-Doped Yttrium Aluminum Garnet Laser-Assisted Drug Delivery of Kojic Acid in the Treatment of Melasma; A split face, comparative clinical study[END_REF],

tranexamic acid [START_REF] Wang | Laser-assisted delivery of tranexamic acid for melasma: Pilot study using a novel 1927 nm fractional thulium fiber laser[END_REF] tested for melasma, could be the subject of the same hopes for a treatment. Precautions should be taken with corticosteroids. Indeed, in 2020, the most common adverse event was hyperpigmentation (14.4%) for 1,026 lesions in 684 patients with stable vitiligo who underwent treatment with fractional Er:YAG laser-assisted delivery of a topical betamethasone solution. Likewise, hyperpigmentation was also treated in a 2013 clinical trial on hypertrophic scars resulting from burns, surgery, or traumatic injuries with the use of an ablative fractional laser with topically applied triamcinolone acetonide suspension in the immediate post-operative period [START_REF] Waibel | Treatment of hypertrophic scars using laser and laser assisted corticosteroid delivery[END_REF]. They mentioned that dyschromia showed the least amount of improvement while texture showed the most improvement.

Other therapy delivery systems could be tested in burned patients with dyschromia, e.g., nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), that can modulate drug permeation through the skin and improve drug action [START_REF] Gonçalez | Skin delivery of kojic acidloaded nanotechnology-based drug delivery systems for the treatment of skin aging[END_REF].

The main challenge in treating post-burn hyperpigmentation is to improve coloring by preventing the occurrence of new scars, postoperative complications such as infections, pain, and the esthetic aggravation of these lesions. Care must be taken not to accentuate this treatment-related dyschromia. Indeed, more aggressive therapeutic interventions such as ablative resurfacing, chemical peels, and Q-switch laser therapy may worsen pigmentation [START_REF] Bach | Hyperpigmented burn scar improved with a fractionated 1550 nm non-ablative laser[END_REF][START_REF] Cho | Treatment of postinflammatory hyperpigmentation using 1064-nm Q-switched Nd:YAG laser with low fluence: report of three cases[END_REF][START_REF] Schwartz | Long-term assessment of CO2 facial laser resurfacing: aesthetic results and complications[END_REF]. Moving forward, the inclusion of large patient sample sizes, sub-analyses by skin type, which must be specified as we pointed out in 2019 [START_REF] Lupon | Comments on "Combined Non-Ablative Laser and Microfat Grafting for Burn Scar Treatment[END_REF], and use of skin spectroscopy for objective measurement of skin pigmentation will be essential for determining the safety and efficacy of commonly used treatments for post-burn hyperpigmentation.

J o u r n a l P r e -p r o o f Conclusion

There is no unambiguous codification or treatment of post-burn hyperpigmentation, with many articles on post-inflammatory hyperpigmentation but few articles dealing specifically with post-burn hyperpigmentation. Post-burn hyperpigmentations should be treated on a caseby-case basis, using data from the literature, clinical experience and assessing the risk/benefit ratio.

Abbreviation

Ref. Delay burntreatment

Treatment protocol and duration

Strategy of treatment

Treatment assesment Followup [START_REF] Raulin | Hyperpigmented burn injuries of the face: treatment with the Q-switched ruby laser[END_REF]

First intention

Patients were asked about their level of satisfaction with the procedure (very satisfied, satisfied, relatively satisfied, dissatisfied), and scar appearance was assessed using a five-point Likert scale and Vancouver scale.

12 months

[20] -Clinical outcomes were assessed by two independent physicians, blinded to the patients and their treatment. Assessments were performed by analyzing the preoperative and postoperative digital photographs, the hardness, texture, pliability, and color of the scars. The color match accuracy according to the preoperative and postoperative photographs were checked using the Mirror system, which compared the color of the undamaged skin. Improvements in J o u r n a l P r e -p r o o f the clinical appearance were rated using the following semi-quantitative scale (0-3).

-Histopathological examination of the burn scar tissue performed for six patients.

Highlights

(3 to 5 bullet points (maximum 85 characters, including spaces, per bullet point).

 Small numbers of clinical trials have proven the efficacy in reducing pigmentation for patients with postburn hyperpigmentation  Topical cream, non-invasive, should be used in the first intention with the cream de Kligman (hydroquinone, retinoic acid, and corticosteroids).  Lasers and IPL are being considered in second intentions with caution because they can also worsen post inflammatory hyperpigmentation.  A combination treatment appears to be more effective than monotherapy.

J o u r

  n a l P r e -p r o o f Topical agent In a randomized study in 2016, Siadat et al. [25] evaluated the efficacy of modified Kligman cream combined with IPL sessions compared to modified Kligman cream alone in the treatment of post-burn hyperpigmentation. The Kligman cream included hydroquinone, vitamin C, tretinoin, and triamcinolone in both treatment groups. The study involved 53 postburn lesion patches in 14 patients randomized to receive either two sessions of IPL plus the modified Kligman formula or the Kligman formula alone for two months. Patients were recommended to apply the modified Kligman cream for 12 hours in the evening. Patients in the IPL + Modified Kligman cream group had greater satisfaction with the modified Kligman cream alone (p=0.0001). Also, according to the physician's assessment, patients in the IPL + modified Kligman cream group had higher satisfaction than patients in the modified Kligman cream alone. Mild irritation, erythema, and exfoliation due to the modified Kligman cream were not observed in patients.

A

  2015 study conducted by Wang LZ et al.[START_REF] Wang | Treatment of facial post-burn hyperpigmentation using micro-plasma radiofrequency technology[END_REF], included[START_REF] Callender | Postinflammatory hyperpigmentation: etiologic and therapeutic considerations[END_REF] Asian patients with FTZ skin type III or IV and permanent hyperpigmentation after facial burn. Patients received three to five treatments eight weeks apart. A roller tip was used with a 60-90 W power setting, and 3-4 scans were made in different directions. Three to five treatments at 8-week intervals were necessary. The results showed that the post-burn hyperpigmentation responded favorably to microplasma radiofrequency treatment with very few complications. Using a Visual Analog Scale (VAS) from 0 to 10, the mean pain score was 6.7 ±0.7. After a series of treatments, 32 of the 35 patients experienced improvement for hyperpigmentation by more than 51%, and three patients had achieved a significant improvement. The mean improvement score for hyperpigmentation was 4.28 (with four being good and five excellent). Patient selfassessments indicated good satisfaction with the cosmetic results and a slight softening of scars.SurgeryJ o u r n a l P r e -p r o o fIn a 2019 study, Moon SH et al[START_REF] Moon | Use of split thickness plantar skin grafts in the treatment of hyperpigmented skin-grafted fingers and palms in previously burned patients[END_REF] treated patients with hyperpigmentation after finger and palm skin grafts. They were all injured by burns to the hand. Mechanical dermabrasion of the hyperpigmentation scar and transplantation of a split skin thickness graft harvested from the inner side of the plantar foot were performed. Patients were asked about their level of satisfaction with the procedure. The scar's appearance was assessed using a five-point Likert scale and a Vancouver Scar Scale (VSS). All 19 patients experienced complete graft acceptance. Fifteen patients were delighted, and four patients were relatively satisfied. The mean score for patient improvement in postoperative appearance was 4.5 (significant postoperative appearance improvement). The mean VSS score was improved from 9.53 to 2.53.

  J o u r n a l P r e -p r o o f pain related to the treatment; 3) Make a double evaluation by the patient and by blinded independent physicians; 4) Use several evaluation methods (questionnaire, scale, comparison of photographs and adjacent skin) including a validated evaluation scale (i.e., 5-point Likert scale, VSS).

Figure 1 . 3 -Inaccessible : 1 J

 131 Figure 1. Flow Chart

Figure 2 .

 2 Figure 2. Algorithm of post-burn hyperpigmentation mangement.

First intention -

 intention For each patient, improvement of hyperpigmentation was assessed by comparison of the difference in color between the burnt skin and the adjacent normal skin on pre-and post-treatment standardized digital photographs. Two months after the last treatment, patients were asked to evaluate their improvement using the same categories and a scale (1 to 5).

  the degree of improvement by percent was rated by patient and intervening physician weekly untill the end of treatment sessions, and monthly for 3 months during follow-up period. degree of improvement by percent was rated by patient and intervening physician by the comparison of the baseline and final color as rated by the patient and comparison of the photographs -Dermoscopy was carried out to the recurrent or non improved cases only.

Table 1 .

 1 Type of studies.

	Stu dy and refe ren ce	C. Ra uli n et al. PR S, 19 97 J o u r n a l P r e -p r o o f HO WS et al, laser s in Surg ery and Mede cine, Kasra ee et al, Derm atolog y, 2005 [17] Erbel ein et al, Burn s, 2005 [18] Moo n SH et al, Burn s, 2011 [19] Waib el et al. Laser s in Surg ery and Medi cine, Bach D et al, Derm atolog y, 2012 [21] Hult man et al, Anna ls of plasti c surge ry, 2014 Wan g LZ et al, Laser s Med Sci, 2014 [23] Moha med ali BM et al, Journa l of Cosme tic dermat ololog Siada t AH et al, Adv Biom ed Res 2016 [25]	Ta o J et al, Sca rs, Bur ns and hea	O.On ur Erol et al, Aesth etic Plast ic Surg ery,
		[1	2003				2012		[22]		y,		lin	2018
		5]	[16]				[20]				[24] 2016		201 g,	[27]
													8
													[2
													6]
	Typ	Ca	Prosp	Case	Non	Non	Prosp	Case	Non	Non	Clinic	Rand	Cas	Non
	e	se	ectiv	report	rando	rando	ectiv	report	rando	rando	al trial,	omiz	e	rando
	stud	re	e,		mize	mize	e,		mize	mize	non	ed	rep	mize
	y	po rt	non rando mize d, non		d, non contr olled, singl	d, non contr olled, singl	non rando mize d, non		d, non contr olled, singl	d, non contr olled, singl	blind, compa rative study.	non-blind ed comp	ort	d, non contr olled, singl

Table 2 .

 2 Subject characteristics and results of selected studies concerning the treatment of post-burn hyperpigmentation.

	Ref. Treatment [15 ] Q-switched ruby laser [16 ] Intense pulsed light J o u r n a l P r e -p r o o f Numb er of patient s Origine and/or phototy pe Burn etiology Grade of burn Localizati on of scars Results Complications 1 patient Unknow n Etiology: Boiling fat Grade : Unknown Forehead and left temple Excellent result with removal of all hyperpigmentati on Mild discomfort 19 patient s FTZ III (3), FTZ IV (16) Etiology: hyperpigmentat ion over grafted areas (9), healed wounds without skin graft (8), over donor sites (2) Grade : Unknown Unknown 78% of the patients showed more than 50% clinical clearance and nearly 32% of the patients were able to achieve more than 75% clearing. Although two patients had no clinical response, one patient had 100% clearing Phlyctenes (3), transient erythema (1)
	[17	Methimazol	1	FTZ III	Etiology: Acid	Face	Moderate	None
	]	e	lesion in one		burn		improvement (no cutaneous
			patient		Grade:		side effects, no
					Unknown		impact on the
							thyroid
							function)
	[18	Laser ablatif	96	Unknow	Etiology: hot	Face,	Improvement.	Delayed healing
	]	Erbium YAG	lesions on 24	n	liquids (scald burns) or fire	neck, lower	Grafted area	(3), local infection (1),
			patient		(flame burns)	neckline	could be	partial
			s		and one caused	and hands	smoothed in all	recurrence of
					by acid		cases	hypertrophy
					exposure			(42%),
								recurrence of

Table 3 .

 3 Characteristics of treatments used in the studies.

The authors received no specific funding for this work.

Declaration of interests

The authors declare that they have no links of interest.