Evaluation of the additive effect of peeling with 15% TCA on the response to phototherapy in patients with acral vitiligo referred to dermatology clinics of Mashhad University of Medical Sciences, Iran

Evaluation of the additive effect of peeling with 15% TCA on the response to phototherapy in patients with acral vitiligo referred to dermatology clinics of Mashhad University of Medical Sciences, Iran | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of the additive effect of peeling with 15% TCA on the response to phototherapy in patients with acral vitiligo referred to dermatology clinics of Mashhad University of Medical Sciences, Iran Yasaman Rastegar, Shatila Torabi, Maryam Emadzadeh, Masoumeh Hosseininezhad, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6689842/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background; Vitiligo is a chronic skin disease with pigmentation disorder resulting in excessive psychological stress for patients with discolored spots. Despite methods including phototherapy, local and systemic immunosuppressants, and surgical techniques, the treatment of vitiligo is still one of the most difficult dermatology challenges. This study aimed to evaluate the additive effect of peeling with 15% TCA trichloroacetic acid solution on the response to phototherapy in patients with acral vitiligo. Methods; Patients with vitiligo referred to Imam Reza Hospital in Mashhad were examined for the extent of organ involvement by the disease using photography. Phototherapy was performed as a standard treatment and one limb was treated with chemical peeling with 15% TCA for 4 sessions once a week before receiving phototherapy. Then, the rate of repigmentation of the patient's limbs after treatment with phototherapy along with chemical peeling was measured with 15% TCA and compared with the side that received only phototherapy treatment. Results; 40 patients with acral vitiligo were studied, 55% of whom were female. Data regarding the percentage of healing of skin lesions in the intervention and control groups were evaluated by specialists. According to the results, the highest number of lesions, 37 from the control group and 26 from the intervention group, had a recovery percentage of less than 25%, followed by 6 lesions from the intervention group with an improvement of 25 to 50%. Assessing the therapeutic effect using the final score the mean score was 1.6 in the intervention, and 1 in the control group. The final scores of the intervention and control groups were compared using paired t-tests and a significant difference was found. Conclusions; The results of this study support the effectiveness of TCA in causing repigmentation in acral vitiligo patches. Vitiligo phototherapy 15% trichloroacetic acid solution chronic skin disease chemical peeling Figures Figure 1 Introduction Vitiligo is an acquired pigmentation disorder characterized by discolored spots on the skin due to the loss of melanocytes 1 . Colorless spots may appear in localized or generalized forms 2 . This chronic disease, which affects both sexes and all races between 0.1% and 2% of the general population 3 – 7 . Men and women are equally affected, although women and girls are often more likely to seek medical advice, which may be due to a greater potential for negative social impact 6 – 8 . Several theories have been proposed about the pathogenesis of this disorder 9 . The physiopathology of vitiligo is complex and involves a combination of factors. Such as - autoimmunity theory, cytotoxic metabolite theory, neurological theory, and genetic theory 10 . The association of vitiligo with other autoimmune disorders has been widely reported and is one of the first clues to the origin of vitiligo. A recent study of 2,624 patients with vitiligo from North America and the United Kingdom confirmed a significant increase in the incidence of six autoimmune disorders in people with vitiligo and their first-degree relatives: vitiligo itself, an autoimmune thyroid disease (especially Hypothyroidism), pernicious anemia, Addison's disease, lupus erythematosus, and possibly inflammatory bowel disease 11 . This association suggests that vitiligo has genetic etiological links in common with other autoimmune disorders 12 . CD8 + T cells from vitiligo lesions produce several cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor and other cytokines 13 – 16 . IFN-γ plays a central role in the pathogenesis of the disease and helps to adsorb CD8 + T cells on its own in the skin 14 . According to the neural hypothesis, the cause of vitiligo is the destruction of melanocytes secondary to the dysfunction of neurotransmitters and dysfunction of the nervous system. During severe emotional stress or mental illness. Other arguments in support of this hypothesis in the development of vitiligo include the common embryological origin of melanocytes and the nervous system and the occurrence of re-pigmentation in vitiligo macules in cases of administration of catecholamine metabolism inhibitors as neurotransmitters affecting the function of the sympathetic nervous system. Such as nialamide drugs and oral monoamine oxidase inhibitors 17 , 18 . Strong evidence from numerous studies suggests the importance of genetic factors in the development of vitiligo, although it is clear that these effects are complex. Epidemiological studies have shown that vitiligo is found in family members 8 , 11 , 19 , 20 . However, genetic risk is not absolute. About 20% of vitiligo patients have at least one first-degree relative with vitiligo, and the relative risk of vitiligo for first-degree relatives increases 7 to 10-fold. Single-egg twins have a 23% matching rate, indicating the importance of additional random or environmental factors in causing vitiligo 20 . It has been suggested that physical or chemical damage to the skin may lead to increased oxidative stress including accumulation of hydrogen peroxide (H2O2) 21 . Oxidative stress and accumulation of hydrogen peroxide (H2O2) are believed to be involved in vitiligo. High levels of H2O2 accumulate in the epidermis of lesions (these are toxic to melanocytes, inhibit tyrosinase, and inactivate catalase (a peroxisome enzyme that catalyzes the reduction of H2O2 into water and oxygen) 22 , 23 . Melanocytes in patients with vitiligo are more sensitive than in people with oxidative stress, and it is more difficult to culture these cells outside the body than in healthy people 24 . The pathogenesis of the koebner phenomenon KP in vitiligo is interesting but unclear. Most tests for KP have been performed in patients with psoriasis, although some research has been done on vitiligo. Several etiological theories have been considered for KP in vitiligo (including immune mechanisms, incomplete melanocyte adhesion, and increased oxidative stress). The pathophysiology of KP in various skin diseases is divided into two stages. These stages are derived from their observations in lupus erythematosus and not from vitiligo. The first step in the development of KP, they cite, is the release of several common inflammatory agents (e.g., TNF-α, IL1, IL6, Hsp70, Hsp72, Hsp90, and ICAM-1), which are triggered by environmental stimuli such as shock. Irritating to skin. Second, disease-specific antigens themselves may be the target of local flare-ups of skin disease 25 – 27 . Cleansing the affected area of the skin after an injury is called the reverse koebner phenomenon and is more commonly reported in psoriasis 28 . Re-pigmentation of vitiligo lesions can similarly occur following damage to that lesion. A "reverse Koebner phenomenon" reaction has been reported in patients with vitiligo who have undergone a mini-punch transplant. Spontaneous repainting of untreated lesions was observed after successful mini-puncture transplantation. This phenomenon is called the “remote reverse koebner phenomenon” 29 .In 2004, Agarwal et al. found the same phenomenon in untreated vitiligo lesions after puncture transplantation and proposed the term "satellite pigment remodeling". The pathophysiology of this phenomenon remains unknown 30 . Vitiligo treatment is still one of the most difficult skin challenges. An important step in the management of vitiligo is to first acknowledge that it is not just a cosmetic disease and that there are safe and effective treatments 31 . These therapies include phototherapy, topical and systemic immunosuppressants, and surgical techniques that together may help stop the disease, stabilize the pigment-free lesions, and re-stimulate the pigment 9 , 32 .In patients who do not respond to medical treatment or in addition to medical treatment, surgical treatments are used 33 – 36 . Other treatments for vitiligo include treatments based on skin trauma, such as dermabrasion, isolated or with 5FU, skin micro-needling, or thermal trauma with fractional lasers 37 – 41 . These new treatments for vitiligo, which work by modifying certain cytokines and metalloproteinases, are emerging. For example, the effect of chemical peeling of trichloroacetic acid (TCA), dermapen and fractional CO2 laser in the treatment of stable non-segmental vitiligo whose effects on IL-17 and MMP-9 levels have been evaluated. And their levels almost increased with the repetition of the traumatic methods mentioned earlier. 25% TCA peeling is the most effective method both clinically and in vitro and can be used before or in combination with other conventional treatments for vitiligo 42 , 43 . Despite the reference to different treatments for vitiligo, this depigmenting disease that deforms the patient's appearance is still a major challenge for patients and physicians, so it is necessary to suggest new combination therapies alongside previous treatments. Apart from the Koebner phenomenon in patients with vitiligo, it is well established that in normal individuals there is pigmentation associated with the wound healing process. On the other hand, the reverse Koebner phenomenon has been described in patients with vitiligo, during which spontaneous repigmentation of vitiligo patches occurs following skin rash. These two phenomena (wound pigmentation and reverse Koebner phenomenon in vitiligo) have paved the way for the introduction of new treatment modalities for vitiligo 44 , 45 . trichloroacetic acid solution TCA is safe and has no systemic absorption or toxicity. A brief feeling of burning or discomfort occurs temporarily. The use of this solution is possible in the doctor's office and does not require anesthesia or monitoring of the patient 46 . Some sources state that the TCA peel can penetrate deeper in some areas for unknown reasons and create hot spot areas. Therefore, higher concentrations of TCA can produce an unexpected response 47 . Puri et al., who used 100% TCA, reported bacterial infections and scarring. TCA also tends to cause hyperpigmentation (PIH) in the skin with types 4 and 5 and above 48 . Method This study was performed in the dermatology clinic of Imam Reza Hospital, Mashhad University of Medical Sciences, from February 2020 to February 2021. This project was performed on 40 patients with acral vitiligo referred to the dermatology clinic of Imam Reza Hospital of Mashhad University of Medical Sciences. In all patients with inclusion criteria, after completing the informed consent form and explaining the objectives of complete clinical information of patients, including age, family history, skin type, and duration of vitiligo patients were recorded in the preparation checklist. Clinical examination to find skin type. And disease spread was performed. BCG scars or old scars were examined for Keloid formation. Complete information and the extent of limb involvement were recorded by Vitiligo using photography. Phototherapy was performed twice a week as bath PUVA 1 as a standard treatment for vitiligo. After random assignments were performed by Excel software, patients were divided into two categories (even / odd code or A / b code). One of the codes was set as the right limb of the intervention, the left limb of the routine treatment (phototherapy), and the other code was set as the right limb of the routine treatment, the left limb of the intervention. The codes were written in a sequence arranged on separate sheets, the sheets were updated in such a way that they were not clear inside them (they were placed in separate envelopes). After visiting each patient with inclusion criteria who agreed to participate in the project, take an envelope and according to the code in it (right limb intervention, left limb routine treatment (phototherapy) or right limb routine treatment, left limb intervention) with the patient was hit. Interventional limbs of patients underwent chemical peeling with 15% TCA before phototherapy. The opposite limb was also compared as a control group by photography only after phototherapy. After cleaning the patient's skin with alcohol, the TCA15 was rubbed evenly on all depigmented parts of one limb of the patient until uniform frost was obtained. Patients were then asked to thoroughly wash the lesions with saline and apply zinc oxide ointment twice a day on the lesions and refrain from manipulating and tearing the crusts. We performed peeling sessions 4 times a week and after completing the peeling sessions, after 10–15 days, the patient was referred to the phototherapy unit of Imam Reza (AS) Hospital for phototherapy by PUVA bath method, and phototherapy was continued twice a week for 6 months.. Then the rate of re-pigmentation of the patient's limbs after treatment with phototherapy with chemical peeling with TCA 15% was measured according to the photograph taken before and after the intervention and also with the opposite side as a control. Examples of lesions included perifollicular, marginal, or diffuse repigmentation decreased or increased lesion size, and Koebner occurrence. At the end of six months, the percentage of repigmentation after the intervention was compared with that before by two outpatient dermatologists who were unaware of the intervention. Differences were evaluated with the third physician and data were entered. Evaluation of repigmentation amount was defined as scoring from 1 to 4. Score1 (weak): indicates the rate of repigmentation in the range of 1–25%. Score2 (good): indicates the rate of repigmentation in the range of 26–50%. Score3 (very good): indicates the rate of repigmentation in the range of 51–75%. Score4 (excellent): indicates the rate of repigmentation in the range of 76–100%. Also, patients' satisfaction with response to treatment was numerically recorded between 0 and 10. In addition, age and sex variables may act as confounders, which were tried to be controlled after the study at the analysis stage. Among the cases not included in the study are cases such as phototherapy contraindications such as eye problems, photosensitivity, patients with a history of the Koebner phenomenon, and history of keloid and pregnancy. Inclusion criteria: Patients with acral vitiligo, Age over 12, Completion of the informed consent form by the patient or legal guardian who volunteers to participate in this study. Exclusion criteria: Contraindications to phototherapy such as eye problems, photosensitivity, Patients with a history of Koebner phenomenon, keloid history, Positive ANA test, Pregnancy, Breastfeeding Also, in case of drug side effects during the intervention that are not tolerable for the volunteer, he was excluded from the study. It’s also worth noting that this study was performed as a clinical trial, so according to the nature of the study and the need for intervention in the study process and different stages, its possible side effects, and benefits for each patient were explained separately before entering the study. The informed consent form for each patient was completed after providing a complete explanation. Patients' secrets were completely preserved until the end of the study and patient information was entered into the statistical software in coded form Results In the present study, 40 vitiligo patients referred to the dermatology clinic of Imam Reza Hospital were included, of which 22 (55%) were female and 18 (45%) were male. The mean age of patients was 30.9 years with a standard deviation of 7.6 (minimum 18 years and maximum 50 years). The mean duration of disease in this study was 9.45 years with a standard deviation of 5.6 (minimum 2 and maximum 18 years). 23 patients (57.5%) had a positive family history of vitiligo and 17 patients (42.5%) were negative in this regard. In the study of the frequency of different types of Fitzpatrick skin phototypes, according to this study in Iran, types 1, 5, and 6 were not found among patients and the highest frequency was related to type 3 (24 people, 60%), type 2, respectively. (11 people, 37.5%) and type 4 (5 people, 12.5%), (Table 1 ). Table 1 Demographic information of patient and different types of Fitzpatrick skin phototypes Number Percentage Gender Female 22 18 55% 45% Male Family history Positive 23 17 57/5% 42/5% Negative Skin phototype 1 0 11 24 5 0 0 0/00% 27/5% 60/0% 12/5% 0/00% 0/00% 2 3 4 5 6 Each patient's Acral lesion was treated with phototherapy and one side was randomly intervened with TCA. According to random numbers prepared with Excel software, in which A is the left limb of the intervention and B is the right limb of the intervention, after randomization, 19 people (47.5%) in group A and 21 people (52.5%) ) Were in group B. Skin lesions in the two intervention groups (skin lesions that received TCA in addition to routine phototherapy) and the control group (lesions that received only phototherapy) were examined by two relevant physicians after the treatment they got. According to the first physician, most lesions had a recovery of less than 25%, which was assigned to 36 lesions in the control group and 24 lesions in the intervention group, respectively. After that, 9 lesions with a recovery percentage of 25 to 50% and 6 lesions with a recovery of 50 to 70% were observed, respectively (Table 2 ). Table 2 According to the first physician, most lesions had a recovery of less than was assigned to 36 lesions in the control group and 24 lesions in the control group 25%. Percentage of improvement Treated only with phototherapy Number (%) Treated with phototherapy and TCA Number (%) Below 25% 36 (0/90%) 24 (0/60%) Between 25% and 50% 2 (0/5%) 9 (5/22%) Between 50% and 75% 1 (5/2%) 6 (0/15%) More than 75% 1 (5/2%) 1 (5/2%) Total 40 (100%) 40 (100%) According to the second physician, the highest number of lesions showed less than 25% recovery rate, which was assigned to 33 lesions in the control group and 26 lesions in the control group, respectively. After that, 6 lesions with an improvement of more than 75%, 5 lesions with improvement between 50 to 75%, and 4 lesions with an improvement of more than 75% were observed by the second physician, respectively (Table 3 ). Table 3 According to the second physician, the highest number of lesions showed less than 25% recovery rate, which was assigned to 33 lesions in the control group and 26 lesions in the control group, respectively. Percentage of improvement Treated only with phototherapy Number (%) Treated with phototherapy and TCA Number (%) Below 25% 33 (5/82%) 26 (0/65%) Between 25% and 50% 2 (0/5%) 3 (5/7%) Between 50% and 75% 1 (5/2%) 5 (5/12%) More than 75% 4 (0/10%) 6 (0/15%) Total 40 (100%) 40 (100%) Due to the differences observed in the results of the previous two tables, the agreement between the two physicians for patients was evaluated. The recovery rate was the same (80%) in 32 cases and different in 8 cases (20%) according to the two physicians. Therefore, according to the third physician, help was used to score the percentage of healing of lesions in 20% of disagreement, and the equivalent data of the opinions of three specialist physicians about the percentage of healing of skin lesions in the control and intervention groups were examined. According to the results, the highest number of lesions, 37 lesions from the control group and 26 lesions from the intervention group had a recovery percentage of less than 25%, followed by 6 lesions from the intervention group with an improvement of 25 to 50% and again 6 lesions from this group. They were observed with an improvement of between 50 and 70% (Table 4 ). Table 4 The differences observed in the results of the previous two tables. Percentage of improvement Treated only with phototherapy Number (%) Treated with phototherapy and TCA Number (%) Below 25% 37 (5/92%) 26 (0/65%) Between 25% and 50% 1 (5/2%) 6 (0/15%) Between 50% and 75% 1 (5/2%) 6 (0/15%) More than 75% 1 (5/2%) 2 (0/5%) Total 40 (100%) 40 (100%) In the study of the therapeutic effect using the final score in the intervention group, the average score was 1.6 and in the control group was 1. In which 75% of the intervention group received less than 2 and 75% of the control group received less than 1 score. According to these results, the final scores of the intervention and control groups were compared using paired t-tests and a significant difference was found (p-value = 0/004) (Table 5 ). Table 5 Group Average score Standard deviation Intervention (treated with phototherapy and TCA) 1/60 0/92 Control (treated with phototherapy only) 1/15 0/57 P-value * 0/004 * Checked by paired-t-test It is also worth mentioning that in general, the patients' satisfaction with the treatment process on a scale of 10 had an average of 4.8 with a standard deviation of 2.1. In the study of the final score by gender in the intervention and control groups, it was observed that in both subgroups of patients, male and female, the mean final score of the intervention group was higher than the control group (Table 6 ). Table 6 * Checked by Mann-Whitney test Group Average female score (standard deviation) The average score of sir (standard deviation) p-value Intervention (treated with phototherapy and TCA) 1/59 (± 0/09) 1/61 (± 0/97) 0/949* Control (treated with phototherapy only) 1/22 (± 0/75) 1/05 (± 0/23) 0/634* . Then, the correlation between the final scores of the intervention and control groups with age and skin phototypes was measured. As can be seen in the table, there was a significant but weak correlation between the final score of the intervention and the skin phenotype (r = 0.328, p = 0.039). The skin phototypes in this study were phototypes 2, 3, and 4. Kruskal-Wallis test showed that the final score of the intervention group did not differ significantly between different skin phenotypes (p-value = 0.4) and in the control group (p-value = 0.4) there was a significant difference between these three groups of skin phototypes (Table 7 ). Table 7 Group Age Skin phototype Intervention (treated with phototherapy and TCA) The correlation coefficient -0/146 0/328 p-value * 0/369 0/039 Control (treated with phototherapy only) The correlation coefficient 0/115 0/214 p-value * 0/482 0/184 * Checked by Spearman statistical test Discussion In the present study, the comparative effect of phototherapy alone and phototherapy with topical TCA in vitiligo in acral areas were investigated. In total, 40 patients with acral vitiligo were studied in this study, 55% of whom were female and the rest were male. About half of the patients had a positive family history of vitiligo. In the study of the frequency of different types of Fitzpatrick skin phototypes, according to this study in Iran, types 1, 5, and 6 were not found among patients and the highest frequency was related to type 3 (24 people, 60%), type 2, respectively. (11 people, 37.5%) and type 4 (5 people, 12.5%). Data were evaluated by the opinions of 3 specialist physicians about the percentage of healing of skin lesions in the control and interventionc groups. According to the results, the highest number of lesions, 37 lesions from the control group and 26 lesions from the intervention group had a recovery percentage of less than 25%, followed by 6 lesions from the intervention group with an improvement of 25 to 50% and again 6 lesions from this group. They were observed with an improvement of between 50 and 70%. In the study of the therapeutic effect using the final score in the intervention group, the mean score was 1.6 and in the control group was 1. In which 75% of the intervention group received less than 2 and 75% of the control group received less than 1 score. According to these results, the final scores of the intervention and control groups were compared using paired t-tests and a significant difference was found. In a 2016 study by Hunter et al in Cairo, 10 patients with stable vitiligo of segmental bread and acral bread received two TCA-treated lesions per patient (one with 15% TCA and the other with 25% TCA). Patients then underwent phototherapy with NBUVB. TCA-treated lesions had a significant improvement in 70%, moderate improvement in 10%, and minimal improvement in 20%, while TCA-treated lesions had a significant improvement in 25% in 20%, moderate improvement in 40%, and 10%. They had a slight improvement and concluded that a TCA of 15% would increase the clinical response with phototherapy 49 . In this study, the aim was to compare 2 different concentrations of TCA (15% and 25%) which resulted in the improvement of some lesions with complications and improvement of TCA 15, and the treatment of BASE was phototherapy. It was performed on acral lesions that are more resistant to various treatments and if the response is more likely to respond to other areas. And in our study, there was no comparison of different percentages of TCA, and vice versa, the comparison of the effect of phototherapy alone and TCA was that we could distinguish the effect of phototherapy as a separate variable in response and add the effect of TCA separately to the response of lesions with more confidence. Also, due to the increase of local complications in TCA with a higher percentage, we used 15% TCA to reduce complications and reduce systemic absorption. With the same percentage, fewer results were obtained. In a 2016 study by Mofty et al. In Egypt on 30 patients with stable vitiligo, patients were divided into three groups: a chemical peel group with 25% TCA, another group treated with dermapen, and a third group treated with fractional CO2 laser. The effects of these therapies on the serum levels of IL-17 and MMP-9 were evaluated 50 . In this study, to be effective, instead of clinical response, the immune response was used in response to treatments such as TCA, which was the highest response with TCA among other recombinant methods such as dermapen and CO2 laser, and we also used the clinical response of this substance in the study, we used it ourselves and examined it. In another study by Puri et al. In India in 2012, 30 patients with vitiligo stable who had not previously responded or had little response to topical or oral steroid therapy were divided into two groups of 15. With 100% TCA and the other group treated with Phenol 88%. Significant pigmentation was observed in 66.6% of the TCA group in 80% of the phenol group. Moderate pigmentation was seen in 13.3% of both groups and mild pigmentation was seen in 20% of the TCA group and 6.6% of the phenol group 48 . In this study, the aim was to compare the effects and side effects of TCA and phenol, both of which were used with high percentages, which due to the significant response in both groups indicated the relative effectiveness of both substances, but in the study, We observed lower excellent response and relatively moderate response, which could be due to the use of lower concentrations of the solution, but these studies also had higher side effects due to the use of high concentrations of high substances, which in our study had no skin side effects. No response was observed. Also, another reason for more response to solutions such as TCA in the study than can be used in acral areas that have a lower resistance response than acral areas in our study. Conclusion The results of this study support the effectiveness of TCA in causing repigmentation in acral vitiligo patches. Further studies are needed on this matter. Declarations Ethics approval The study protocol was approved by the Regional Medical Ethics Committee at MUMS (IR.MUMS.MEDICAL.REC.1399.622) conducted according to the Declaration of Helsinki principles. All participants provided written informed consent before participating in this investigation. Author Contributions Statement Yasaman Rastegar: Data collection and writing the manuscript text. Maryam Emadzadeh: Statistical analysis of data. Seyede Zahra Ghasemi: English editing of the manuscript text. Masoumeh Hosseininezhad and Shatila Torabi: Data collection and cooperation in writing the manuscript text. Yalda Nahidi: Study designer, supervisor, and reviser of the manuscript text. Author Contribution Yasaman Rastegar: Data collection, writing the manuscript text, prepared figures and tables. Maryam Emadzadeh: Statistical analysis of data. Seyede Zahra Ghasemi: English editing of the manuscript text. Masoumeh Hosseininezhad and Shatila Torabi: Data collection and cooperation in writing the manuscript text. Yalda Nahidi: Study designer, supervisor, and reviser of the manuscript text. Acknowledgement The authors would like to express their sincere gratitude to all the Colleagues and patients for their participation in this study. This research was supported by the Mashhad University of Medical Sciences (code number: 990674). References Ezzedine K, Eleftheriadou V, Whitton M, van Geel N (2015) Vitiligo Lancet 386:74–84 Grimes PE, Hensin T, Rosamaria C, Vitiligo (2017) Pathogenesis, clinical features, and diagnosis. UpToDate Accedido Marzo 19:2019 Bacigalupi RM, Postolova A, Davis RS (2012) Evidence-based, non-surgical treatments for vitiligo. Am J Clin Dermatol 13:217–237 Howitz J, Brodthagen H, Schwartz M, Thomsen K (1977) Prevalence of vitiligo: epidemiological survey on the Isle of Bornholm, Denmark. 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Sci Transl Med 6:223ra23–ra23 Bertolotti A, Boniface K, Vergier B, Mossalayi D, Taieb A, Ezzedine K et al (2014) Type I interferon signature in the initiation of the immune response in vitiligo. PCMR 27:398–407 Kotb El-Sayed M-I, Abd El-Ghany AA, Mohamed RR (2018) Neural and Endocrinal Pathobiochemistry of Vitiligo: Comparative Study for a Hypothesized Mechanism. Front Endocrinol (Lausanne) 9:197 Enkhtaivan E, Lee CH (2021) Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication. Int J Mol Sci 22:8071 Majumder PP, Nordlund JJ, Nath SK (1993) Pattern of familial aggregation of vitiligo. Arch Dermatol 129:994–998 Nath SK, Majumder PP, Nordlund JJ (1994) Genetic epidemiology of vitiligo: multilocus recessivity cross-validated. AJHG 55:981 Silva SAME, Michniak-Kohn B, Leonardi GR (2017) An overview about oxidation in clinical practice of skin aging. Bras Dermatol 92:367–374 Laddha NC, Dwivedi M, Mansuri MS, Gani AR, Ansarullah M, Ramachandran AV et al (2013) Vitiligo: interplay between oxidative stress and immune system. Exp Dermatol 22:245–250 Speeckaert R, Dugardin J, Lambert J, Lapeere H, Verhaeghe E, Speeckaert MM et al (2018) Critical appraisal of the oxidative stress pathway in vitiligo: a systematic review and meta-analysis. JEADV 32:1089–1098 Puri N, Mojamdar M, Ramaiah A (1987) In vitro growth characteristics of melanocytes obtained from adult normal and vitiligo subjects. J Invest Dermatol 88:434–438 Westerhof W, d'Ischia M (2007) Vitiligo puzzle: the pieces fall in place. Pigment Cell Res 20:345–359 Ueki H (2005) Koebner phenomenon in lupus erythematosus with special consideration of clinical findings. Autoimmun Rev 4:219–223 van Geel N, Speeckaert R, Taieb A, Picardo M, Böhm M, Gawkrodger DJ et al (2011) Koebner's phenomenon in vitiligo: European position paper. Pigment Cell Melanoma Res 24:564–573 Eyre RW, Krueger GG (1982) Response to injury of skin involved and uninvolved with psoriasis, and its relation to disease activity: Koebner and 'reverse' Koebner reactions. Br J Dermatol 106:153–159 Lahiri K, Malakar S, Sarma N, Banerjee U (2006) Repigmentation of vitiligo with punch grafting and narrow-band UV-B (311 nm)--a prospective study. Int J Dermatol 45:649–655 Agarwal US, Gulati R, Shukla SR, Mathur N (2004) Satellite repigmentation after punch grafting. Int J Dermatol 43:273–274 Ezzedine K, Sheth V, Rodrigues M, Eleftheriadou V, Harris JE, Hamzavi IH et al (2015) Vitiligo is not a cosmetic disease. J Am Acad Dermatol 73:883–885 Ezzedine K, Whitton M, Pinart M (2016) Interventions for Vitiligo. JAMA 316:1708–1709 Majid I, Imran S (2012) Ultrathin split-thickness skin grafting followed by narrowband UVB therapy for stable vitiligo: an effective and cosmetically satisfying treatment option. Indian J Dermatol Venereol Leprol 78:159–164 Lu N, Xu A, Wu X (2014) Follow-up study of vitiligo patients treated with autologous epidermal sheet transplants. J Dermatolog Treat 25:200–204 Feetham HJ, Chan JL, Pandya AG (2012) Characterization of clinical response in patients with vitiligo undergoing autologous epidermal punch grafting. Dermatol Surg 38:14–19 Cortelazzi C, Pellacani G, Raposio E, Di Nuzzo S (2020) Vitiligo management: combination of surgical treatment and phototherapy under reflectance confocal microscopy monitoring. Eur Rev Med Pharmacol Sci 24:7366–7371 Arora S, Gupta P (2012) Automated microneedling device - A new tool in dermatologist's kit -. Rev JPAD 22:354–357 Shin J, Lee JS, Hann SK, Oh SH (2012) Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study. Br J Dermatol 166:658–661 Yuan J, Chen H, Yan R, Cui S, Li Y-H, Wu Y et al (2016) Fractional CO2 lasers contribute to the treatment of stable non-segmental vitiligo. Eur J Dermatol 26:592–598 El Mofty M, Esmat S, Hunter N, Mashaly HM, Dorgham D, Shaker O et al (2017) Effect of different types of therapeutic trauma on vitiligo lesions. Dermatol Ther 30:e12447 Salloum A, Bazzi N, Maalouf D, Habre M (2020) Microneedling in vitiligo: A systematic review. Dermatol Ther 33:e14297 Lotti T, Gori A, Zanieri F, Colucci R, Moretti S (2008) Vitiligo: new and emerging treatments. Dermatol Ther 21:110–117 Migayron L, Boniface K, Seneschal J, Vitiligo (2020) From Physiopathology to Emerging Treatments: A Review. Dermatol Ther (Heidelb) 10:1185–1198 Nahhas AF, Braunberger TL, Hamzavi IH (2019) Update on the Management of Vitiligo. Skin Therapy Lett 24:1–6 Abdel-Malek ZA, Jordan C, Ho T, Upadhyay PR, Fleischer A, Hamzavi I (2020) The enigma and challenges of vitiligo pathophysiology and treatment. Pigment Cell Melanoma Res 33:778–787 Dayal S, Sahu P, Yadav M, Jain VK (2017) Clinical efficacy and safety on combining 20% trichloroacetic acid peel with topical 5% ascorbic acid for melasma. JCDR 11:WC08 El-Mofty M, Mostafa WZ, Esmat S, Zayed A, Mashaly H, Hussien MF et al (2019) Site‐oriented depigmentation in vitiligo patients using Q‐switched Nd: YAG laser (1,064/532 nm), cryotherapy and chemical peels: A comparative study. Dermatol Ther 32:e13052 Puri N, Puri A (2012) A comparative study on 100% tca versus 88% phenol for the treatment of vitiligo. Our Dermatology Online 3:184–186 Hunter N, Mashaly H, Dorgham D, Ismail S (2016) Trichloroacetic acid peel 15%+ NB-UVB versus trichloroacetic acid peel 25%+ NB-UVB for stable non-segmental vitiligo. Med J Cairo Univ 84:1959–1963 El Mofty M, Essmat S, Youssef R, Sobeih S, Mahgoub D, Ossama S et al (2016) The role of systemic steroids and phototherapy in the treatment of stable vitiligo: a randomized controlled trial. Dermatol Ther 29:406–412 Footnotes bathwater Psoralen + ultraviolet light A Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Jul, 2025 Reviews received at journal 02 Jul, 2025 Reviewers agreed at journal 01 Jul, 2025 Reviewers agreed at journal 29 Jun, 2025 Reviewers agreed at journal 24 Jun, 2025 Reviewers agreed at journal 10 Jun, 2025 Reviewers invited by journal 10 Jun, 2025 Editor assigned by journal 19 May, 2025 Submission checks completed at journal 19 May, 2025 First submitted to journal 18 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6689842","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":469524225,"identity":"317ddce3-032a-48b5-a3ed-ade73f1ed5b8","order_by":0,"name":"Yasaman Rastegar","email":"","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yasaman","middleName":"","lastName":"Rastegar","suffix":""},{"id":469524231,"identity":"687a60c2-55f2-4108-85a9-d041dc19c13c","order_by":1,"name":"Shatila Torabi","email":"","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Shatila","middleName":"","lastName":"Torabi","suffix":""},{"id":469524232,"identity":"d5145563-b604-4daa-96cc-9568fc8ff106","order_by":2,"name":"Maryam Emadzadeh","email":"","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Maryam","middleName":"","lastName":"Emadzadeh","suffix":""},{"id":469524233,"identity":"7eb1c0aa-4b0c-4eaa-8285-5d1bea137ebb","order_by":3,"name":"Masoumeh Hosseininezhad","email":"","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Masoumeh","middleName":"","lastName":"Hosseininezhad","suffix":""},{"id":469524234,"identity":"23f5dcd1-7e24-4e67-8098-9fff55dbb7d3","order_by":4,"name":"Yalda Nahidi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYBACgwM8DAd4DA7LwUXYCGmxgGoxJl6LDVALAw9DWmID0Q6zOX724IE3BTbpa2dkJ39gqLFj4JM+gF+L2Zm8hINzDCRyt93I3SbBcCyZgY0vgYCWAzkGh3mgWoAeOcDAxkPAYcbn34C1pJvdyN38geEfEVoMb0BsSQBq2SDB2EaUljcGIL8YbjvzdptEYl8yD0EtBudzjD+8+SMhb3Yc6LAP3+zk5HsIaEEFCaA4GgWjYBSMglFAOQAALMNEEVPC9YYAAAAASUVORK5CYII=","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Yalda","middleName":"","lastName":"Nahidi","suffix":""},{"id":469524235,"identity":"af005e0a-3fb8-4f5a-87a0-8a2d4f4ce6bc","order_by":5,"name":"Seyede Zahra Ghasemi","email":"","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Seyede","middleName":"Zahra","lastName":"Ghasemi","suffix":""}],"badges":[],"createdAt":"2025-05-18 05:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6689842/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6689842/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84531647,"identity":"c58f3aa5-21b3-4206-a2c8-ecc630deb1d9","added_by":"auto","created_at":"2025-06-13 06:16:05","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":501317,"visible":true,"origin":"","legend":"\u003cp\u003eIn the picture number 1 : the right hand of the patient was intervention(TCA + photo) and the left hand was control(phototherapy alone) , as the results showed the right hand has more pigmentation compared to the control side. In the picture number 2 : the left hand of the patient was intervention and the right hand was control as in the picture shows the right hand(TCA applied) becomes more pigmented.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6689842/v1/78cefeebb77b054251f20842.png"},{"id":84533957,"identity":"9da819f1-8f41-47ec-9834-0bcb36b524f8","added_by":"auto","created_at":"2025-06-13 06:40:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1396465,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6689842/v1/db390a2d-94f7-446e-8450-ad51352764f6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of the additive effect of peeling with 15% TCA on the response to phototherapy in patients with acral vitiligo referred to dermatology clinics of Mashhad University of Medical Sciences, Iran","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVitiligo is an acquired pigmentation disorder characterized by discolored spots on the skin due to the loss of melanocytes\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Colorless spots may appear in localized or generalized forms\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. This chronic disease, which affects both sexes and all races between 0.1% and 2% of the general population\u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Men and women are equally affected, although women and girls are often more likely to seek medical advice, which may be due to a greater potential for negative social impact\u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSeveral theories have been proposed about the pathogenesis of this disorder\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. The physiopathology of vitiligo is complex and involves a combination of factors. Such as - autoimmunity theory, cytotoxic metabolite theory, neurological theory, and genetic theory\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe association of vitiligo with other autoimmune disorders has been widely reported and is one of the first clues to the origin of vitiligo. A recent study of 2,624 patients with vitiligo from North America and the United Kingdom confirmed a significant increase in the incidence of six autoimmune disorders in people with vitiligo and their first-degree relatives: vitiligo itself, an autoimmune thyroid disease (especially Hypothyroidism), pernicious anemia, Addison's disease, lupus erythematosus, and possibly inflammatory bowel disease\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. This association suggests that vitiligo has genetic etiological links in common with other autoimmune disorders\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCD8\u0026thinsp;+\u0026thinsp;T cells from vitiligo lesions produce several cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor and other cytokines\u003csup\u003e\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. IFN-γ plays a central role in the pathogenesis of the disease and helps to adsorb CD8\u0026thinsp;+\u0026thinsp;T cells on its own in the skin\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAccording to the neural hypothesis, the cause of vitiligo is the destruction of melanocytes secondary to the dysfunction of neurotransmitters and dysfunction of the nervous system. During severe emotional stress or mental illness. Other arguments in support of this hypothesis in the development of vitiligo include the common embryological origin of melanocytes and the nervous system and the occurrence of re-pigmentation in vitiligo macules in cases of administration of catecholamine metabolism inhibitors as neurotransmitters affecting the function of the sympathetic nervous system. Such as nialamide drugs and oral monoamine oxidase inhibitors\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eStrong evidence from numerous studies suggests the importance of genetic factors in the development of vitiligo, although it is clear that these effects are complex. Epidemiological studies have shown that vitiligo is found in family members\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. However, genetic risk is not absolute. About 20% of vitiligo patients have at least one first-degree relative with vitiligo, and the relative risk of vitiligo for first-degree relatives increases 7 to 10-fold. Single-egg twins have a 23% matching rate, indicating the importance of additional random or environmental factors in causing vitiligo\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt has been suggested that physical or chemical damage to the skin may lead to increased oxidative stress including accumulation of hydrogen peroxide (H2O2)\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Oxidative stress and accumulation of hydrogen peroxide (H2O2) are believed to be involved in vitiligo. High levels of H2O2 accumulate in the epidermis of lesions (these are toxic to melanocytes, inhibit tyrosinase, and inactivate catalase (a peroxisome enzyme that catalyzes the reduction of H2O2 into water and oxygen)\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Melanocytes in patients with vitiligo are more sensitive than in people with oxidative stress, and it is more difficult to culture these cells outside the body than in healthy people\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe pathogenesis of the koebner phenomenon KP in vitiligo is interesting but unclear. Most tests for KP have been performed in patients with psoriasis, although some research has been done on vitiligo. Several etiological theories have been considered for KP in vitiligo (including immune mechanisms, incomplete melanocyte adhesion, and increased oxidative stress). The pathophysiology of KP in various skin diseases is divided into two stages. These stages are derived from their observations in lupus erythematosus and not from vitiligo. The first step in the development of KP, they cite, is the release of several common inflammatory agents (e.g., TNF-α, IL1, IL6, Hsp70, Hsp72, Hsp90, and ICAM-1), which are triggered by environmental stimuli such as shock. Irritating to skin. Second, disease-specific antigens themselves may be the target of local flare-ups of skin disease\u003csup\u003e\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCleansing the affected area of the skin after an injury is called the reverse koebner phenomenon and is more commonly reported in psoriasis\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Re-pigmentation of vitiligo lesions can similarly occur following damage to that lesion. A \"reverse Koebner phenomenon\" reaction has been reported in patients with vitiligo who have undergone a mini-punch transplant. Spontaneous repainting of untreated lesions was observed after successful mini-puncture transplantation. This phenomenon is called the \u0026ldquo;remote reverse koebner phenomenon\u0026rdquo;\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.In 2004, Agarwal et al. found the same phenomenon in untreated vitiligo lesions after puncture transplantation and proposed the term \"satellite pigment remodeling\". The pathophysiology of this phenomenon remains unknown\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eVitiligo treatment is still one of the most difficult skin challenges. An important step in the management of vitiligo is to first acknowledge that it is not just a cosmetic disease and that there are safe and effective treatments\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. These therapies include phototherapy, topical and systemic immunosuppressants, and surgical techniques that together may help stop the disease, stabilize the pigment-free lesions, and re-stimulate the pigment\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.In patients who do not respond to medical treatment or in addition to medical treatment, surgical treatments are used\u003csup\u003e\u003cspan additionalcitationids=\"CR34 CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOther treatments for vitiligo include treatments based on skin trauma, such as dermabrasion, isolated or with 5FU, skin micro-needling, or thermal trauma with fractional lasers\u003csup\u003e\u003cspan additionalcitationids=\"CR38 CR39 CR40\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. These new treatments for vitiligo, which work by modifying certain cytokines and metalloproteinases, are emerging. For example, the effect of chemical peeling of trichloroacetic acid (TCA), dermapen and fractional CO2 laser in the treatment of stable non-segmental vitiligo whose effects on IL-17 and MMP-9 levels have been evaluated. And their levels almost increased with the repetition of the traumatic methods mentioned earlier. 25% TCA peeling is the most effective method both clinically and in vitro and can be used before or in combination with other conventional treatments for vitiligo\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite the reference to different treatments for vitiligo, this depigmenting disease that deforms the patient's appearance is still a major challenge for patients and physicians, so it is necessary to suggest new combination therapies alongside previous treatments. Apart from the Koebner phenomenon in patients with vitiligo, it is well established that in normal individuals there is pigmentation associated with the wound healing process. On the other hand, the reverse Koebner phenomenon has been described in patients with vitiligo, during which spontaneous repigmentation of vitiligo patches occurs following skin rash. These two phenomena (wound pigmentation and reverse Koebner phenomenon in vitiligo) have paved the way for the introduction of new treatment modalities for vitiligo\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003etrichloroacetic acid solution TCA is safe and has no systemic absorption or toxicity. A brief feeling of burning or discomfort occurs temporarily. The use of this solution is possible in the doctor's office and does not require anesthesia or monitoring of the patient\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Some sources state that the TCA peel can penetrate deeper in some areas for unknown reasons and create hot spot areas. Therefore, higher concentrations of TCA can produce an unexpected response\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. Puri et al., who used 100% TCA, reported bacterial infections and scarring. TCA also tends to cause hyperpigmentation (PIH) in the skin with types 4 and 5 and above\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eThis study was performed in the dermatology clinic of Imam Reza Hospital, Mashhad University of Medical Sciences, from February 2020 to February 2021.\u003c/p\u003e \u003cp\u003eThis project was performed on 40 patients with acral vitiligo referred to the dermatology clinic of Imam Reza Hospital of Mashhad University of Medical Sciences. In all patients with inclusion criteria, after completing the informed consent form and explaining the objectives of complete clinical information of patients, including age, family history, skin type, and duration of vitiligo patients were recorded in the preparation checklist. Clinical examination to find skin type. And disease spread was performed. BCG scars or old scars were examined for Keloid formation. Complete information and the extent of limb involvement were recorded by Vitiligo using photography. Phototherapy was performed twice a week as bath PUVA\u003csup\u003e1\u003c/sup\u003e as a standard treatment for vitiligo. After random assignments were performed by Excel software, patients were divided into two categories (even / odd code or A / b code). One of the codes was set as the right limb of the intervention, the left limb of the routine treatment (phototherapy), and the other code was set as the right limb of the routine treatment, the left limb of the intervention. The codes were written in a sequence arranged on separate sheets, the sheets were updated in such a way that they were not clear inside them (they were placed in separate envelopes).\u003c/p\u003e \u003cp\u003e After visiting each patient with inclusion criteria who agreed to participate in the project, take an envelope and according to the code in it (right limb intervention, left limb routine treatment (phototherapy) or right limb routine treatment, left limb intervention) with the patient was hit. Interventional limbs of patients underwent chemical peeling with 15% TCA before phototherapy. The opposite limb was also compared as a control group by photography only after phototherapy. After cleaning the patient's skin with alcohol, the TCA15 was rubbed evenly on all depigmented parts of one limb of the patient until uniform frost was obtained. Patients were then asked to thoroughly wash the lesions with saline and apply zinc oxide ointment twice a day on the lesions and refrain from manipulating and tearing the crusts.\u003c/p\u003e \u003cp\u003eWe performed peeling sessions 4 times a week and after completing the peeling sessions, after 10\u0026ndash;15 days, the patient was referred to the phototherapy unit of Imam Reza (AS) Hospital for phototherapy by PUVA bath method, and phototherapy was continued twice a week for 6 months.. Then the rate of re-pigmentation of the patient's limbs after treatment with phototherapy with chemical peeling with TCA 15% was measured according to the photograph taken before and after the intervention and also with the opposite side as a control.\u003c/p\u003e \u003cp\u003eExamples of lesions included perifollicular, marginal, or diffuse repigmentation decreased or increased lesion size, and Koebner occurrence. At the end of six months, the percentage of repigmentation after the intervention was compared with that before by two outpatient dermatologists who were unaware of the intervention. Differences were evaluated with the third physician and data were entered. Evaluation of repigmentation amount was defined as scoring from 1 to 4.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eScore1 (weak): indicates the rate of repigmentation in the range of 1\u0026ndash;25%.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eScore2 (good): indicates the rate of repigmentation in the range of 26\u0026ndash;50%.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eScore3 (very good): indicates the rate of repigmentation in the range of 51\u0026ndash;75%.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eScore4 (excellent): indicates the rate of repigmentation in the range of 76\u0026ndash;100%.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eAlso, patients' satisfaction with response to treatment was numerically recorded between 0 and 10. In addition, age and sex variables may act as confounders, which were tried to be controlled after the study at the analysis stage. Among the cases not included in the study are cases such as phototherapy contraindications such as eye problems, photosensitivity, patients with a history of the Koebner phenomenon, and history of keloid and pregnancy.\u003c/p\u003e \u003cp\u003eInclusion criteria: Patients with acral vitiligo, Age over 12, Completion of the informed consent form by the patient or legal guardian who volunteers to participate in this study.\u003c/p\u003e \u003cp\u003eExclusion criteria: Contraindications to phototherapy such as eye problems, photosensitivity, Patients with a history of Koebner phenomenon, keloid history, Positive ANA test, Pregnancy, Breastfeeding\u003c/p\u003e \u003cp\u003eAlso, in case of drug side effects during the intervention that are not tolerable for the volunteer, he was excluded from the study.\u003c/p\u003e \u003cp\u003eIt\u0026rsquo;s also worth noting that this study was performed as a clinical trial, so according to the nature of the study and the need for intervention in the study process and different stages, its possible side effects, and benefits for each patient were explained separately before entering the study. The informed consent form for each patient was completed after providing a complete explanation. Patients' secrets were completely preserved until the end of the study and patient information was entered into the statistical software in coded form\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn the present study, 40 vitiligo patients referred to the dermatology clinic of Imam Reza Hospital were included, of which 22 (55%) were female and 18 (45%) were male. The mean age of patients was 30.9 years with a standard deviation of 7.6 (minimum 18 years and maximum 50 years). The mean duration of disease in this study was 9.45 years with a standard deviation of 5.6 (minimum 2 and maximum 18 years). 23 patients (57.5%) had a positive family history of vitiligo and 17 patients (42.5%) were negative in this regard. In the study of the frequency of different types of Fitzpatrick skin phototypes, according to this study in Iran, types 1, 5, and 6 were not found among patients and the highest frequency was related to type 3 (24 people, 60%), type 2, respectively. (11 people, 37.5%) and type 4 (5 people, 12.5%), (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic information of patient and different types of Fitzpatrick skin phototypes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e55%\u003c/p\u003e \u003cp\u003e45%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFamily history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e57/5%\u003c/p\u003e \u003cp\u003e42/5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eSkin phototype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e24\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0/00%\u003c/p\u003e \u003cp\u003e27/5%\u003c/p\u003e \u003cp\u003e60/0%\u003c/p\u003e \u003cp\u003e12/5%\u003c/p\u003e \u003cp\u003e0/00%\u003c/p\u003e \u003cp\u003e0/00%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEach patient's Acral lesion was treated with phototherapy and one side was randomly intervened with TCA. According to random numbers prepared with Excel software, in which A is the left limb of the intervention and B is the right limb of the intervention, after randomization, 19 people (47.5%) in group A and 21 people (52.5%) ) Were in group B.\u003c/p\u003e \u003cp\u003eSkin lesions in the two intervention groups (skin lesions that received TCA in addition to routine phototherapy) and the control group (lesions that received only phototherapy) were examined by two relevant physicians after the treatment they got.\u003c/p\u003e \u003cp\u003eAccording to the first physician, most lesions had a recovery of less than 25%, which was assigned to 36 lesions in the control group and 24 lesions in the intervention group, respectively. After that, 9 lesions with a recovery percentage of 25 to 50% and 6 lesions with a recovery of 50 to 70% were observed, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAccording to the first physician, most lesions had a recovery of less than was assigned to 36 lesions in the control group and 24 lesions in the control group 25%.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePercentage of improvement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreated only with phototherapy\u003c/p\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTreated with phototherapy and TCA\u003c/p\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBelow 25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (0/90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (0/60%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBetween 25% and 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0/5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5/22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBetween 50% and 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5/2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0/15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5/2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (5/2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAccording to the second physician, the highest number of lesions showed less than 25% recovery rate, which was assigned to 33 lesions in the control group and 26 lesions in the control group, respectively. After that, 6 lesions with an improvement of more than 75%, 5 lesions with improvement between 50 to 75%, and 4 lesions with an improvement of more than 75% were observed by the second physician, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAccording to the second physician, the highest number of lesions showed less than 25% recovery rate, which was assigned to 33 lesions in the control group and 26 lesions in the control group, respectively.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePercentage of improvement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreated only with phototherapy\u003c/p\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTreated with phototherapy and TCA\u003c/p\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBelow 25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (5/82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (0/65%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBetween 25% and 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0/5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (5/7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBetween 50% and 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5/2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (5/12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0/10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0/15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eDue to the differences observed in the results of the previous two tables, the agreement between the two physicians for patients was evaluated. The recovery rate was the same (80%) in 32 cases and different in 8 cases (20%) according to the two physicians. Therefore, according to the third physician, help was used to score the percentage of healing of lesions in 20% of disagreement, and the equivalent data of the opinions of three specialist physicians about the percentage of healing of skin lesions in the control and intervention groups were examined. According to the results, the highest number of lesions, 37 lesions from the control group and 26 lesions from the intervention group had a recovery percentage of less than 25%, followed by 6 lesions from the intervention group with an improvement of 25 to 50% and again 6 lesions from this group. They were observed with an improvement of between 50 and 70% (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe differences observed in the results of the previous two tables.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePercentage of improvement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreated only with phototherapy\u003c/p\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTreated with phototherapy and TCA\u003c/p\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBelow 25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (5/92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (0/65%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBetween 25% and 50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5/2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0/15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBetween 50% and 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5/2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (0/15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (5/2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0/5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the study of the therapeutic effect using the final score in the intervention group, the average score was 1.6 and in the control group was 1. In which 75% of the intervention group received less than 2 and 75% of the control group received less than 1 score. According to these results, the final scores of the intervention and control groups were compared using paired t-tests and a significant difference was found (p-value\u0026thinsp;=\u0026thinsp;0/004) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntervention (treated with phototherapy and TCA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl (treated with phototherapy only)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e* 0/004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e* Checked by paired-t-test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIt is also worth mentioning that in general, the patients' satisfaction with the treatment process on a scale of 10 had an average of 4.8 with a standard deviation of 2.1.\u003c/p\u003e \u003cp\u003eIn the study of the final score by gender in the intervention and control groups, it was observed that in both subgroups of patients, male and female, the mean final score of the intervention group was higher than the control group (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e* Checked by Mann-Whitney test\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage female score (standard deviation)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThe average score of sir (standard deviation)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntervention (treated with phototherapy and TCA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1/59 (\u0026plusmn;\u0026thinsp;0/09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1/61 (\u0026plusmn;\u0026thinsp;0/97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/949*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl (treated with phototherapy only)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1/22 (\u0026plusmn;\u0026thinsp;0/75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1/05 (\u0026plusmn;\u0026thinsp;0/23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/634*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e.\u003c/p\u003e \u003cp\u003eThen, the correlation between the final scores of the intervention and control groups with age and skin phototypes was measured. As can be seen in the table, there was a significant but weak correlation between the final score of the intervention and the skin phenotype (r\u0026thinsp;=\u0026thinsp;0.328, p\u0026thinsp;=\u0026thinsp;0.039).\u003c/p\u003e \u003cp\u003eThe skin phototypes in this study were phototypes 2, 3, and 4. Kruskal-Wallis test showed that the final score of the intervention group did not differ significantly between different skin phenotypes (p-value\u0026thinsp;=\u0026thinsp;0.4) and in the control group (p-value\u0026thinsp;=\u0026thinsp;0.4) there was a significant difference between these three groups of skin phototypes (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e\u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSkin phototype\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntervention (treated with phototherapy and TCA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe correlation coefficient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0/146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep-value *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eControl (treated with phototherapy only)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe correlation coefficient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/214\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep-value *\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/184\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e* Checked by Spearman statistical test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, the comparative effect of phototherapy alone and phototherapy with topical TCA in vitiligo in acral areas were investigated. In total, 40 patients with acral vitiligo were studied in this study, 55% of whom were female and the rest were male. About half of the patients had a positive family history of vitiligo. In the study of the frequency of different types of Fitzpatrick skin phototypes, according to this study in Iran, types 1, 5, and 6 were not found among patients and the highest frequency was related to type 3 (24 people, 60%), type 2, respectively. (11 people, 37.5%) and type 4 (5 people, 12.5%).\u003c/p\u003e \u003cp\u003eData were evaluated by the opinions of 3 specialist physicians about the percentage of healing of skin lesions in the control and interventionc groups. According to the results, the highest number of lesions, 37 lesions from the control group and 26 lesions from the intervention group had a recovery percentage of less than 25%, followed by 6 lesions from the intervention group with an improvement of 25 to 50% and again 6 lesions from this group. They were observed with an improvement of between 50 and 70%.\u003c/p\u003e \u003cp\u003eIn the study of the therapeutic effect using the final score in the intervention group, the mean score was 1.6 and in the control group was 1. In which 75% of the intervention group received less than 2 and 75% of the control group received less than 1 score. According to these results, the final scores of the intervention and control groups were compared using paired t-tests and a significant difference was found.\u003c/p\u003e \u003cp\u003eIn a 2016 study by Hunter et al in Cairo, 10 patients with stable vitiligo of segmental bread and acral bread received two TCA-treated lesions per patient (one with 15% TCA and the other with 25% TCA). Patients then underwent phototherapy with NBUVB. TCA-treated lesions had a significant improvement in 70%, moderate improvement in 10%, and minimal improvement in 20%, while TCA-treated lesions had a significant improvement in 25% in 20%, moderate improvement in 40%, and 10%. They had a slight improvement and concluded that a TCA of 15% would increase the clinical response with phototherapy\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, the aim was to compare 2 different concentrations of TCA (15% and 25%) which resulted in the improvement of some lesions with complications and improvement of TCA 15, and the treatment of BASE was phototherapy. It was performed on acral lesions that are more resistant to various treatments and if the response is more likely to respond to other areas. And in our study, there was no comparison of different percentages of TCA, and vice versa, the comparison of the effect of phototherapy alone and TCA was that we could distinguish the effect of phototherapy as a separate variable in response and add the effect of TCA separately to the response of lesions with more confidence. Also, due to the increase of local complications in TCA with a higher percentage, we used 15% TCA to reduce complications and reduce systemic absorption. With the same percentage, fewer results were obtained.\u003c/p\u003e \u003cp\u003eIn a 2016 study by Mofty et al. In Egypt on 30 patients with stable vitiligo, patients were divided into three groups: a chemical peel group with 25% TCA, another group treated with dermapen, and a third group treated with fractional CO2 laser. The effects of these therapies on the serum levels of IL-17 and MMP-9 were evaluated\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, to be effective, instead of clinical response, the immune response was used in response to treatments such as TCA, which was the highest response with TCA among other recombinant methods such as dermapen and CO2 laser, and we also used the clinical response of this substance in the study, we used it ourselves and examined it.\u003c/p\u003e \u003cp\u003eIn another study by Puri et al. In India in 2012, 30 patients with vitiligo stable who had not previously responded or had little response to topical or oral steroid therapy were divided into two groups of 15. With 100% TCA and the other group treated with Phenol 88%. Significant pigmentation was observed in 66.6% of the TCA group in 80% of the phenol group. Moderate pigmentation was seen in 13.3% of both groups and mild pigmentation was seen in 20% of the TCA group and 6.6% of the phenol group\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, the aim was to compare the effects and side effects of TCA and phenol, both of which were used with high percentages, which due to the significant response in both groups indicated the relative effectiveness of both substances, but in the study, We observed lower excellent response and relatively moderate response, which could be due to the use of lower concentrations of the solution, but these studies also had higher side effects due to the use of high concentrations of high substances, which in our study had no skin side effects. No response was observed. Also, another reason for more response to solutions such as TCA in the study than can be used in acral areas that have a lower resistance response than acral areas in our study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this study support the effectiveness of TCA in causing repigmentation in acral vitiligo patches. Further studies are needed on this matter.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval\u003c/h2\u003e\n\u003cp\u003eThe study protocol was approved by the Regional Medical Ethics Committee at MUMS (IR.MUMS.MEDICAL.REC.1399.622) conducted according to the Declaration of Helsinki principles. All participants provided written informed consent before participating in this investigation.\u003c/p\u003e\n\u003ch2\u003eAuthor Contributions Statement\u003c/h2\u003e\n\u003cp\u003eYasaman Rastegar: Data collection and writing the manuscript text.\u003c/p\u003e\n\u003cp\u003eMaryam Emadzadeh: Statistical analysis of data.\u003c/p\u003e\n\u003cp\u003eSeyede Zahra Ghasemi: English editing of the manuscript text.\u003c/p\u003e\n\u003cp\u003eMasoumeh Hosseininezhad and Shatila Torabi: Data collection and cooperation in writing the manuscript text.\u003c/p\u003e\n\u003cp\u003eYalda Nahidi: Study designer, supervisor, and reviser of the manuscript text.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eYasaman Rastegar: Data collection, writing the manuscript text, prepared figures and tables. Maryam Emadzadeh: Statistical analysis of data. Seyede Zahra Ghasemi: English editing of the manuscript text. Masoumeh Hosseininezhad and Shatila Torabi: Data collection and cooperation in writing the manuscript text. Yalda Nahidi: Study designer, supervisor, and reviser of the manuscript text.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors would like to express their sincere gratitude to all the Colleagues and patients for their participation in this study. This research was supported by the Mashhad University of Medical Sciences (code number: 990674).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEzzedine K, Eleftheriadou V, Whitton M, van Geel N (2015) Vitiligo Lancet 386:74\u0026ndash;84\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrimes PE, Hensin T, Rosamaria C, Vitiligo (2017) Pathogenesis, clinical features, and diagnosis. UpToDate Accedido Marzo 19:2019\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBacigalupi RM, Postolova A, Davis RS (2012) Evidence-based, non-surgical treatments for vitiligo. Am J Clin Dermatol 13:217\u0026ndash;237\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHowitz J, Brodthagen H, Schwartz M, Thomsen K (1977) Prevalence of vitiligo: epidemiological survey on the Isle of Bornholm, Denmark. Arch Dermatol 113:47\u0026ndash;52\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoisseau-Garsaud AM, Garsaud P, Cal\u0026egrave;s‐Quist D, H\u0026eacute;l\u0026eacute;non R, Qu\u0026eacute;n\u0026eacute;herv\u0026eacute; C, Claire RCS (2000) Epidemiology of vitiligo in the French West Indies (Isle of Martinique). Int J Dermatol 39:18\u0026ndash;20\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlikhan A, Felsten LM, Daly M, Petronic-Rosic V (2011) Vitiligo: a comprehensive overview: part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. JAAD 65:473\u0026ndash;491\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKr\u0026uuml;ger C, Schallreuter KU (2012) A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol 51:1206\u0026ndash;1212\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDas SK, Majumder PP, Chakrabotry R, Majumdar TK, Haldar B, Rao DC (1985) Studies on vitiligo I. Epidemiological profile in Calcutta, India. Genet Epidemiol 2:71\u0026ndash;78\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE (2017) New discoveries in the pathogenesis and classification of vitiligo. J Am Acad Dermatol 77:1\u0026ndash;13\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThurmon TF, Jackson J, Fowler CG (1976) Deafness and vitiligo. Birth Defects Orig Artic Ser 12:315\u0026ndash;320\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA (2003) Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 16:208\u0026ndash;214\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePasseron T, Ortonne J-P (2005) Physiopathology and genetics of vitiligo. J Autoimmun 25:63\u0026ndash;68\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Den Boorn JG, Konijnenberg D, Dellemijn TAM, Van Der Veen JPW, Bos JD, Melief CJM et al (2009) Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. JID 129:2220\u0026ndash;2232\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA (2012) A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8\u0026thinsp;+\u0026thinsp;T-cell accumulation in the skin. JID 132:1869\u0026ndash;1876\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su M-W et al (2014) CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med 6:223ra23\u0026ndash;ra23\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBertolotti A, Boniface K, Vergier B, Mossalayi D, Taieb A, Ezzedine K et al (2014) Type I interferon signature in the initiation of the immune response in vitiligo. PCMR 27:398\u0026ndash;407\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKotb El-Sayed M-I, Abd El-Ghany AA, Mohamed RR (2018) Neural and Endocrinal Pathobiochemistry of Vitiligo: Comparative Study for a Hypothesized Mechanism. Front Endocrinol (Lausanne) 9:197\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEnkhtaivan E, Lee CH (2021) Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication. Int J Mol Sci 22:8071\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMajumder PP, Nordlund JJ, Nath SK (1993) Pattern of familial aggregation of vitiligo. Arch Dermatol 129:994\u0026ndash;998\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNath SK, Majumder PP, Nordlund JJ (1994) Genetic epidemiology of vitiligo: multilocus recessivity cross-validated. AJHG 55:981\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilva SAME, Michniak-Kohn B, Leonardi GR (2017) An overview about oxidation in clinical practice of skin aging. Bras Dermatol 92:367\u0026ndash;374\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaddha NC, Dwivedi M, Mansuri MS, Gani AR, Ansarullah M, Ramachandran AV et al (2013) Vitiligo: interplay between oxidative stress and immune system. Exp Dermatol 22:245\u0026ndash;250\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpeeckaert R, Dugardin J, Lambert J, Lapeere H, Verhaeghe E, Speeckaert MM et al (2018) Critical appraisal of the oxidative stress pathway in vitiligo: a systematic review and meta-analysis. JEADV 32:1089\u0026ndash;1098\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuri N, Mojamdar M, Ramaiah A (1987) In vitro growth characteristics of melanocytes obtained from adult normal and vitiligo subjects. J Invest Dermatol 88:434\u0026ndash;438\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWesterhof W, d'Ischia M (2007) Vitiligo puzzle: the pieces fall in place. Pigment Cell Res 20:345\u0026ndash;359\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUeki H (2005) Koebner phenomenon in lupus erythematosus with special consideration of clinical findings. Autoimmun Rev 4:219\u0026ndash;223\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Geel N, Speeckaert R, Taieb A, Picardo M, B\u0026ouml;hm M, Gawkrodger DJ et al (2011) Koebner's phenomenon in vitiligo: European position paper. Pigment Cell Melanoma Res 24:564\u0026ndash;573\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEyre RW, Krueger GG (1982) Response to injury of skin involved and uninvolved with psoriasis, and its relation to disease activity: Koebner and 'reverse' Koebner reactions. Br J Dermatol 106:153\u0026ndash;159\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLahiri K, Malakar S, Sarma N, Banerjee U (2006) Repigmentation of vitiligo with punch grafting and narrow-band UV-B (311 nm)--a prospective study. Int J Dermatol 45:649\u0026ndash;655\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal US, Gulati R, Shukla SR, Mathur N (2004) Satellite repigmentation after punch grafting. Int J Dermatol 43:273\u0026ndash;274\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEzzedine K, Sheth V, Rodrigues M, Eleftheriadou V, Harris JE, Hamzavi IH et al (2015) Vitiligo is not a cosmetic disease. J Am Acad Dermatol 73:883\u0026ndash;885\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEzzedine K, Whitton M, Pinart M (2016) Interventions for Vitiligo. JAMA 316:1708\u0026ndash;1709\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMajid I, Imran S (2012) Ultrathin split-thickness skin grafting followed by narrowband UVB therapy for stable vitiligo: an effective and cosmetically satisfying treatment option. Indian J Dermatol Venereol Leprol 78:159\u0026ndash;164\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu N, Xu A, Wu X (2014) Follow-up study of vitiligo patients treated with autologous epidermal sheet transplants. J Dermatolog Treat 25:200\u0026ndash;204\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeetham HJ, Chan JL, Pandya AG (2012) Characterization of clinical response in patients with vitiligo undergoing autologous epidermal punch grafting. Dermatol Surg 38:14\u0026ndash;19\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCortelazzi C, Pellacani G, Raposio E, Di Nuzzo S (2020) Vitiligo management: combination of surgical treatment and phototherapy under reflectance confocal microscopy monitoring. Eur Rev Med Pharmacol Sci 24:7366\u0026ndash;7371\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArora S, Gupta P (2012) Automated microneedling device - A new tool in dermatologist's kit -. Rev JPAD 22:354\u0026ndash;357\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShin J, Lee JS, Hann SK, Oh SH (2012) Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study. Br J Dermatol 166:658\u0026ndash;661\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYuan J, Chen H, Yan R, Cui S, Li Y-H, Wu Y et al (2016) Fractional CO2 lasers contribute to the treatment of stable non-segmental vitiligo. Eur J Dermatol 26:592\u0026ndash;598\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl Mofty M, Esmat S, Hunter N, Mashaly HM, Dorgham D, Shaker O et al (2017) Effect of different types of therapeutic trauma on vitiligo lesions. Dermatol Ther 30:e12447\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalloum A, Bazzi N, Maalouf D, Habre M (2020) Microneedling in vitiligo: A systematic review. Dermatol Ther 33:e14297\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLotti T, Gori A, Zanieri F, Colucci R, Moretti S (2008) Vitiligo: new and emerging treatments. Dermatol Ther 21:110\u0026ndash;117\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMigayron L, Boniface K, Seneschal J, Vitiligo (2020) From Physiopathology to Emerging Treatments: A Review. Dermatol Ther (Heidelb) 10:1185\u0026ndash;1198\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNahhas AF, Braunberger TL, Hamzavi IH (2019) Update on the Management of Vitiligo. Skin Therapy Lett 24:1\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdel-Malek ZA, Jordan C, Ho T, Upadhyay PR, Fleischer A, Hamzavi I (2020) The enigma and challenges of vitiligo pathophysiology and treatment. Pigment Cell Melanoma Res 33:778\u0026ndash;787\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDayal S, Sahu P, Yadav M, Jain VK (2017) Clinical efficacy and safety on combining 20% trichloroacetic acid peel with topical 5% ascorbic acid for melasma. JCDR 11:WC08\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Mofty M, Mostafa WZ, Esmat S, Zayed A, Mashaly H, Hussien MF et al (2019) Site‐oriented depigmentation in vitiligo patients using Q‐switched Nd: YAG laser (1,064/532 nm), cryotherapy and chemical peels: A comparative study. Dermatol Ther 32:e13052\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuri N, Puri A (2012) A comparative study on 100% tca versus 88% phenol for the treatment of vitiligo. Our Dermatology Online 3:184\u0026ndash;186\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHunter N, Mashaly H, Dorgham D, Ismail S (2016) Trichloroacetic acid peel 15%+ NB-UVB versus trichloroacetic acid peel 25%+ NB-UVB for stable non-segmental vitiligo. Med J Cairo Univ 84:1959\u0026ndash;1963\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl Mofty M, Essmat S, Youssef R, Sobeih S, Mahgoub D, Ossama S et al (2016) The role of systemic steroids and phototherapy in the treatment of stable vitiligo: a randomized controlled trial. Dermatol Ther 29:406\u0026ndash;412\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Footnotes","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e bathwater Psoralen\u0026thinsp;+\u0026thinsp;ultraviolet light A\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Vitiligo, phototherapy, 15% trichloroacetic acid solution, chronic skin disease, chemical peeling","lastPublishedDoi":"10.21203/rs.3.rs-6689842/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6689842/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground;\u003c/h2\u003e \u003cp\u003eVitiligo is a chronic skin disease with pigmentation disorder resulting in excessive psychological stress for patients with discolored spots. Despite methods including phototherapy, local and systemic immunosuppressants, and surgical techniques, the treatment of vitiligo is still one of the most difficult dermatology challenges. This study aimed to evaluate the additive effect of peeling with 15% TCA trichloroacetic acid solution on the response to phototherapy in patients with acral vitiligo.\u003c/p\u003e\u003ch2\u003eMethods;\u003c/h2\u003e \u003cp\u003ePatients with vitiligo referred to Imam Reza Hospital in Mashhad were examined for the extent of organ involvement by the disease using photography. Phototherapy was performed as a standard treatment and one limb was treated with chemical peeling with 15% TCA for 4 sessions once a week before receiving phototherapy. Then, the rate of repigmentation of the patient's limbs after treatment with phototherapy along with chemical peeling was measured with 15% TCA and compared with the side that received only phototherapy treatment.\u003c/p\u003e\u003ch2\u003eResults;\u003c/h2\u003e \u003cp\u003e40 patients with acral vitiligo were studied, 55% of whom were female. Data regarding the percentage of healing of skin lesions in the intervention and control groups were evaluated by specialists. According to the results, the highest number of lesions, 37 from the control group and 26 from the intervention group, had a recovery percentage of less than 25%, followed by 6 lesions from the intervention group with an improvement of 25 to 50%. Assessing the therapeutic effect using the final score the mean score was 1.6 in the intervention, and 1 in the control group. The final scores of the intervention and control groups were compared using paired t-tests and a significant difference was found.\u003c/p\u003e\u003ch2\u003eConclusions;\u003c/h2\u003e \u003cp\u003eThe results of this study support the effectiveness of TCA in causing repigmentation in acral vitiligo patches.\u003c/p\u003e","manuscriptTitle":"Evaluation of the additive effect of peeling with 15% TCA on the response to phototherapy in patients with acral vitiligo referred to dermatology clinics of Mashhad University of Medical Sciences, Iran","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-13 06:16:01","doi":"10.21203/rs.3.rs-6689842/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-17T19:52:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-02T09:42:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"59701770871697001507859156760166018368","date":"2025-07-01T09:13:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"163300039947847325719391604579275867676","date":"2025-06-29T16:35:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"213940358126571979156568525507062375912","date":"2025-06-24T20:37:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276877264640786481292194063218208065224","date":"2025-06-11T03:04:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-10T20:29:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-19T12:22:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-19T12:17:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2025-05-18T04:59:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0b3cdd4b-0dad-4e2a-a886-59b1a19f0ee3","owner":[],"postedDate":"June 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:11:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-13 06:16:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6689842","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6689842","identity":"rs-6689842","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}