Insights Into the Safety and Efficacy of Chemical Peels in Treating Acanthosis Nigricans – a Systematic Review of Clinical Studies and Randomised Controlled Trials

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It is strongly associated with insulin resistance, obesity, metabolic syndrome, and, in rare cases, malignancies. Various treatment modalities, including chemical peels, fractional CO2 laser, and microneedling, have been explored to improve the cosmetic appearance of affected skin. However, no definitive consensus on treatment exists. Objective : This systematic review aims to evaluate and compare the efficacy of chemical peels like Trichloroacetic acid (TCA), Glycolic acid (GA), Retinoic acid (RA), etc, with or without physical modalities such as fractional CO2 laser, and microneedling in managing AN, assessing their clinical outcomes, safety profiles, and long-term effectiveness. Methods : A systematic search of electronic databases was conducted to identify randomised controlled trials (RCTs), cohort studies, and comparative clinical studies evaluating the efficacy of chemical peels in AN treatment. Studies reporting objective clinical improvements, patient-reported outcomes, and adverse effects were included. The primary outcome measure was improved pigmentation and skin texture, which was assessed using validated scoring systems such as the Acanthosis Nigricans Area and Severity Index (ANASI). Results : A total of 8 eligible studies were included. TCA (15-20%) peels demonstrated significant improvement in pigmentation compared to glycolic acid (35-70%), though higher concentrations increased the risk of post-inflammatory hyperpigmentation (PIH). Microneedling, particularly when combined with TCA peels, enhanced treatment outcomes by improving agent penetration and collagen remodelling. Conclusion : Chemical peels offer varying degrees of efficacy in the treatment of AN. TCA peels remain a cost-effective first-line option, while physical modalities such as fractional CO2 laser offer superior long-term benefits for thicker lesions. Microneedling enhances the effects of peels, making combination therapies a promising approach. Future studies should focus on standardising treatment protocols, assessing long-term outcomes, and exploring newer treatment combinations to optimise AN management. Dermatology Endocrinology & Metabolism Acanthosis nigricans chemical peels trichloroacetic acid glycolic acid fractional CO2 laser microneedling post-inflammatory hyperpigmentation Figures Figure 1 Figure 2 INTRODUCTION Acanthosis nigricans (AN) is a dermatological disorder characterised by hyperpigmented, thickened, and velvety-textured skin, commonly affecting flexural areas such as the neck, axillae, groin, and inframammary folds. It is often associated with metabolic disorders, particularly insulin resistance, obesity, polycystic ovarian syndrome (PCOS), and type 2 diabetes mellitus (T2DM).[ 1 ] While benign acanthosis nigricans is frequently linked to metabolic syndromes, a rare but serious variant, malignant acanthosis nigricans, is associated with underlying malignancies, especially gastric adenocarcinoma. Acanthosis nigricans is primarily associated with elevated insulin levels that bind to insulin-like growth factor 1 receptors (IGF-1Rs) on keratinocytes and fibroblasts. This binding stimulates the proliferation of these cell types, which manifests as distinct plaques and papillomatosis.[ 2 ] Given its strong correlation with metabolic dysfunction, AN is not just a cosmetic concern but a clinical marker of systemic disease, necessitating a multidisciplinary treatment approach. The therapeutic approach includes treating the underlying disease or tumour, avoiding the inciting agent in drug-induced AN, and utilising topical creams, chemical peels, fractional CO2 lasers, and microneedling.[ 2 ] Several clinical trials and studies have been done on the effectiveness of chemical peels such as trichloroacetic acid (TCA), glycolic acid (GA), retinoic acid (RA), etc, in treating AN. Hence, it is necessary to conduct a systematic review that analyses the efficacy, safety and role of various chemical peels in managing acanthosis nigricans. We systematically reviewed clinical studies and randomised trials that used either chemical peels as monotherapy or combination therapy with procedures such as fractional CO2 laser, microneedling, etc. and comparison studies with various chemical peels in adult patients with acanthosis nigricans to elucidate their long-term efficacy and safety and provide possible recommendations for their use. METHODS Literature search In October 2025, we performed a comprehensive literature search from inception through January 2026 to study the efficacy of chemical peel treatment on patients with acanthosis nigricans. We used relevant MeSH terms such as ("acanthosis nigricans") AND ("chemical peel" OR "trichloroacetic acid" OR "TCA peel" OR "glycolic acid" OR "retinoic acid" OR "peeling" OR "chemexfoliation") to search the PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and SCOPUS databases. The systematic review was registered in PROSPERO (CRD42024616894) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting systematic reviews. Eligibility criteria and selection of studies Studies were included following the PICOS principles (Population, Intervention, Comparison, Outcome, and Study design). The inclusion criteria for selecting the articles were English and published from inception to January 2026. Only randomised controlled trials (RCTs), quasi-randomised trials, split-lesion studies, pilot studies, and prospective cohort studies reporting outcomes of chemical peels in patients with AN, either alone or in combination with other interventions for treating acanthosis nigricans in human subjects, were selected for the review. There were no restrictions on country, gender, or age. We excluded preclinical studies, case reports, posters, conference abstracts, editorials, letters and case series. The primary outcome measure was efficacy, and the secondary outcome was safety. Four reviewers selected the articles independently (S.G., D.A., S.R., and N.J.). The final selection was based on a full-text assessment. Reference lists of selected articles were screened for additional relevant studies. Data extraction A standardised template for data extraction was built, and four reviewers (S.G., D.A., S.R., and N.J.) independently extracted the baseline and outcome data from all included studies. Discrepancies between the authors were resolved through discussion. Studies published by the same author and in the same year have been checked for possible overlap and data duplication. Risk of bias assessment The revised Cochrane Risk of Bias tool for Randomised Controlled Trials (Cochrane Rob 2.0) was utilised by four reviewers (S.G., D.A., S.R., and N.J.) to evaluate the risk of bias in each study.[ 3 ] This assessment considered factors such as random sequence generation, allocation concealment, blinding of participants and trial personnel, deviations from anticipated interventions, absence of outcome data, and selection of reported outcomes. RESULTS Eligible Studies The systematic data search returned 847 reference articles, of which 147 duplicates were removed. The remaining 694 references were screened based on title and abstract, and 651 were excluded. Full texts of 43 articles were obtained and assessed for eligibility. The inclusion criteria and data completeness were used to select the final 8 articles for this review, as shown in the PRISMA Flow Diagram. [ Fig. 1 ] Study Characteristics: The characteristics of patients in the included studies are shown in Table 1 . The review included eight clinical studies and controlled trials published until January 2026, comprising 216 patients. All patients included in this review were aged 10–45 years. Most of the included studies reported a male predominance, and the mean duration of AN ranged from 1 to 20 years. The studies included in this systematic review were conducted in patients with acanthosis nigricans and pseudoacanthosis nigricans, with or without comorbidities such as diabetes, dyslipidemia, etc., at the time of enrollment. Different chemical peels with varying depths of penetration were investigated for their safety and efficacy as monotherapy in Zayed et al.'s study [ 4 ], compared with other peels in Bharti et al.'s study [ 5 ], and with other skin rejuvenation procedures such as microneedling and lasers in other research. Table 1 Characteristics of included studies Name of the Study Country Study type Study population Age group/ Mean age (years) Mean duration of disease Associated systemic diseases Sites of skin involvement Treatment protocol Abu Oun et al. Egypt Split neck Comparative study 20 Egyptian patients with neck AN 18–44 2–20 years; Median 5.5 Not detailed, likely excluded Neck Right: CO2 laser; Left: 5% Retinoic acid; 4 sessions with 2- week interval Bharati et al. India Randomized open- label study 40 patients with AN 18 (mean) GA: 2.64 ± 2.06 TCA: 3.64 ± 4.50 Majority were obese or overweight. Face, neck, elbow Group A: 15% TCA; Group B: 35% GA; 3 sessions, 2-week intervals Eldeeb et al. Egypt Randomized comparative clinical trial 40 patients with pseudo-AN 20–45 2 ± 0.8 years Excluded such as diabetes, hormonal disorders, and malignancy Neck and axilla Group A: TCA 20% (4 sessions, 4-week interval); Group B: CO2 laser (4 sessions, 4–6week interval) Fouda et al. Egypt Split neck comparative study 20 patients 14–33 Median − 4.5 years, ranging from 2 to 10 years 5% patients have associated systemic diseases. Neck Fractional CO2 laser (Right side) Vs TCA 20% peel (Left side) Ghiasi et al. Iran Single-blinded, randomized trial 30 patients (neck or axillary AN) 12–45 yrs Mean: 25.27 ± 10.74 Most < 7 years (70%), others 7– 20 years 17 (56.7%) had obesity, diabetes, PCO and others. Neck and axilla One side: Tretinoin 0.05% every other night; other side: GA 70% every 2 weeks; 8 weeks total Khashaba et al. Egypt Randomized clinical trial 40 patients 10–45 1–2 years Some patients had associated medical conditions. Neck, axillae, ante cubital fossa Right side: 15% TCA; Left side: Microneedling + 15% TCA; monthly for 3 months Zaki et al. Egypt Prospective randomized comparative study 20 patients with pseudo-acanthosis nigricans 18–40 Not specified Excluded systemic diseases such as diabetes, etc. Neck Right side: Fractional CO2 laser (3 sessions, 2-week intervals); Left side: Glycolic acid 70% peel (3 sessions, 2-week intervals) Zayed et al. Egypt Pilot study 6 females with 10 lesions of AN. 31.5 years (21–43) 9.4 years Not mentioned Neck, cheeks, axilla TCA 15%, weekly sessions for 4 weeks Risk of bias assessment among included trials All studies reported a random allocation of study participants. Four trials adequately reported allocation concealment, all trials performed blinding of participants and researchers, and reported blinding of outcome assessment. [ 4 – 11 ] One study had a low risk of bias concerning selective outcomes reporting, randomisation process and missing outcome data. The methodological quality and risk of bias of the included trials are summarised in Fig. 2 a and 2 b. TREATMENT PROTOCOLS: Various chemical peels were used in the above-finalised studies, administered at distinct intervals and sessions. Few studies used them as monotherapy, and others used them to compare with other peels and procedures to determine their safety and efficacy. The efficacy and safety outcomes of the included studies have been summarised in Table 2 . Table 2 Safety and Efficacy outcomes of the included studies: Study Treatment Intervention Duration of Treatment (weeks) Baseline assessment Efficacy Outcomes Safety and Tolerability Abu Oun et al. 2021 Fractional CO2 laser vs. Retinoic Acid 5% 8 weeks (4 sessions, biweekly) ANASI score, dermatologist assessment, dermoscopic evaluation ANASI Score: Highly significant reduction in the score on both halves after therapy. Dermoscopic Score: Improvement seen in dermoscopic features of AN. like sulci cutis, cristae cutis, pigmentation, milia-like cysts, etc. on both halves. Mild erythema and peeling with RA, no serious events Bharati et al. 2024 15% TCA vs. 35% GA 6 weeks (3 sessions, biweekly) ANASI score, PAS, PSS ANASI Scores: TCA group: Decrease from 22.33 to 13.26; GA group: Decrease from 17.07 to 12.49. Both improvements were statistically significant (p 2. Patient Satisfaction Score (PSS): Higher satisfaction in the TCA group (45% excellent) than GA group (15% excellent) . Mild irritation and PIH noted in both groups Eldeeb et al. 2021 Fractional CO2 laser vs. TCA 20% 16–24 weeks (up to 4 sessions) Percentage improvement, dermatologic assessment TCA had a higher frequency of excellent or marked improvement over laser in blinded physician assessment after treatment Higher adverse effects in TCA group (erythema, PIH, burning) Fouda et al. Fractional CO2 Laser (right side) vs TCA 20% (left side) 12 weeks (4 sessions every three weeks) ANASI score, dermatologist assessment Fractional CO2 laser side: Excellent improvement – 20%, Marked improvement − 45%, moderate improvement − 35%. TCA 20% peel side: moderate improvement – 50%, mild improvement – 40%, and marked improvement – 2%. ANASI: Greater % of reduction in fractional CO2 laser (from 20 to 6) compared to the TCA 20% peel (from 20 to 8) Pain and erythema noted in 13 (65%) patients in Fractional CO2 laser treatment as compared to none with TCA peel. Ghiasi et al. 2024 Tretinoin 0.05% vs. GA 70% 8 weeks Treatment response, patient satisfaction, photographic evaluation Tretinoin more effective than glycolic acid (p = 0.02 for treatment response, p = 0.008 for patient satisfaction) in treating axillary lesions. However, there was no significant difference in efficacy between the tw treatments in neck treatment. Minimal side effects; some burning and irritation reported Khashaba et al. 2024 15% TCA vs. 15% TCA + Microneedling 12 weeks (3 monthly sessions) Improvement in pigmentation, texture, SCANS score Excellent improvement in pigmentation and texture was more common with the TCA + microneedling arm. Statistically significant (P-values < 0.001) improvement seen in both arms. No serious side effects reported Zaki et al. 2018 Fractional CO2 laser vs. GA 70% 6 weeks (3 sessions, biweekly) ANASI score, dermatologist assessment, photographs ANASI Score: GA side: Decrease from 23.55 to 13.50 (p = 0.001). In CO₂ laser group, minimal improvement seen (23.50 to 19.10), not statistically significant (p = 0.1) Physician assessment: Significantly greater improvement with GA peel > CO₂ laser on a 0–4 scale. Mild transient erythema and burning with GA, no major side effects Zayed et al. 2014 TCA 15% 4 weeks (weekly sessions) Investigator and patient assessment, clinical response All six patients showed improvement in hyperpigmentation and skin texture. Investigator-graded responses: excellent in 3 lesions, moderate in 5, mild in 2. No side effects reported. EFFICACY OF CHEMICAL PEELS AS MONOTHERAPY: Trichloroacetic Acid (TCA) 15–20% Peels 15% TCA peel consistently showed moderate to good improvement across multiple studies. In Bharati et al., 15% TCA was more effective than 35% GA, with a greater ANASI score reduction (baseline: 22.33 → 13.26 at 8 weeks, P < 0.001) across three sessions. In Khashaba et al., TCA plus microneedling showed significantly greater improvement in both pigmentation and texture than TCA alone [ 6 ]. In a small Egyptian pilot cohort conducted by Zayed et al., six women with about 10 AN lesions in total (neck, face, axilla) underwent weekly 15% TCA for 4 weeks; all lesions improved in pigmentation, thickness, and overall appearance, with no side effects.[ 4 ] Fouda et al. (2023) reported moderate improvement with 20% TCA in 50% of patients, but inferior to fractional CO₂ laser (20% marked improvement).[ 7 ] Eldeeb et al. (2021) noted a marked improvement in only 10% of patients after four weekly sessions with 20% TCA.[ 8 ] Safety & Tolerability : Mild and transient burning and erythema were the most common side effects; PIH was more prevalent with TCA, especially in darker skin types​​. As reported by Bharati et al., typical side effects with 15% TCA included peeling (70%), burning (45%), and transient PIH.(5) Higher PIH rates (20%) and persistent erythema were seen with 20% TCA in the study by Eldeeb et al., 2021.[ 8 ] Combination with microneedling increased discomfort (pain, erythema, etc.), but did not significantly increase complication rates. Glycolic Acid (GA) 35–70% Peels Efficacy : GA peel at 70% concentration demonstrated moderate clinical improvement (43%) in pseudo-AN and was more effective than fractional CO₂ in Zaki et al.'s study.[ 9 ] ​However, Bharati et al. (2024) found a modest ANASI reduction with GA 35% (17.07 → 12.49 at 8 weeks, P < 0.001), with only 5% of patients achieving more than 50% improvement.[ 5 ] However, Ghiasi et al. (2024) noted GA’s inferiority to tretinoin for axillary AN (P = 0.02).[ 10 ] Taken together, GA peels appear capable of achieving moderate reductions in pigmentation and thickness, with GA 70% sometimes outperforming fractionated laser for neck pseudo‑AN but not consistently surpassing retinoids or TCA in other settings. Safety & Tolerability : GA peels were generally better tolerated with fewer and milder adverse effects than TCA, making them favourable for sensitive skin and as a first-line agent​. [ 4 , 5 ] COMPARATIVE EFFICACY VERSUS OTHER PEELS AND NON‑PEEL THERAPIES: Retinoic Acid Peel and Topical Retinoids Efficacy : Retinoic acid 5% was less effective than the fractional CO₂ laser in Abu Oun et al.’s trial, though it showed significant improvement​.[ 11 ] Tretinoin 0.05% was more effective than GA 70% for axillary lesions, but peels offered faster results than topical agents in Ghiasi et al.’s study​.[ 10 ] Safety & Tolerability : Tretinoin was generally well-tolerated and suitable for long-term use. Side effects were minimal and localised (dryness, irritation)​. Chemical Peels vs Fractional CO₂ Laser Efficacy Superior outcomes were observed with the fractional CO₂ laser in comparison to 20% TCA in studies by Fouda et al., with significantly larger reductions in ANASI scores, and Eldeeb et al., with 85% of patients in the laser group achieving a marked to excellent response, versus only 10% in the TCA group​​.[ 7 , 8 ] In contrast, 70% GA peel showed slightly better immediate efficacy than fractional CO₂ in Zaki et al.'s split-neck study (43% vs 19% improvement), possibly due to rapid exfoliation effects.[ 9 ] Compared with retinoic acid, fractional CO₂ again showed superior efficacy in clinical and dermoscopic assessments​. Thus, fractional CO₂ appears substantially more efficacious than TCA 20%, but its advantage over GA 70% is inconsistent and may be negligible for pure AN of the neck. Safety & Tolerability : The fractional CO₂ laser had fewer side effects like PIH (5% vs 20% in the TCA group),​ as seen in a study by Eldeeb et al.[ 8 ] However, cases of PIH and folliculitis were reported with CO₂ treatment in Zaki et al.'s study, highlighting possible variation based on skin type or the treatment site.[ 9 ] Pain and erythema were more frequent than with peels, as shown by the Fouda et al. study.[ 7 ] TCA alone vs TCA plus microneedling Khashaba et al. randomised 40 patients with AN to split‑lesion treatment with TCA 15% peel alone versus microneedling followed by a single coat of TCA 15% every 2 weeks for four sessions. Both sides demonstrated significant improvement in overall AN grade (SCANS) after treatment, but the combination side showed greater gains in pigmentation and texture, and higher patient satisfaction, despite increased procedural pain. [ 6 ] This trial suggests that combining low‑strength TCA with microneedling‑enhanced delivery enhances efficacy over peel alone without introducing serious safety concerns, and may be an additional option where facilities and patient tolerance permit. Discussion Current treatment paradigms for acanthosis nigricans (AN) are evolving to encompass the management of cutaneous pathology, the underlying condition, and pharmacological agents. Non-pharmacological approaches include weight management and increased physical activity, aimed at improving insulin sensitivity in individuals with insulin-resistant AN. The treatment approach for AN is multifaceted, as dermatological manifestations frequently coexist with underlying medical conditions. Preliminary investigations for the workup of AN should involve evaluating patients for insulin resistance syndrome, characterised by obesity, dyslipidemia, hypertension, and type II diabetes mellitus.[ 12 ] Health care providers should procure a fasting lipid panel, glucose, and insulin levels, and complete blood count and liver function tests. In instances where malignancy-associated AN is suspected, imaging modalities such as plain radiography, computed tomography, or magnetic resonance imaging may yield pertinent insights. Using oral metformin and other insulin-sensitising medications is beneficial, as these therapeutic strategies target the underlying etiological factors contributing to AN.[ 2 ] Topical retinoids are regarded as the primary treatment for insulin-resistant acanthosis nigricans (AN) because they modify the keratinisation rate. However, topical tretinoin requires prolonged periods of application and predominantly targets hyperkeratosis, without markedly enhancing hyperpigmentation. Other topical agents, including vitamin D3 analogues such as calcipotriol, salicylic acid, urea, and podophyllin, require frequent applications. The modified triple combination regime (tretinoin 0.05%, hydroquinone 4%, fluocinolone acetonide 0.01%) has reportedly helped improve the lesions when used at night.[ 13 ] Chemical peels have emerged as the primary treatment for various pigmented dermatoses, including acanthosis nigricans affecting the face, neck, and axillae. From the synthesised data, it has been found that the chemical peels consistently yield clinically meaningful but rarely complete improvement in AN, with typical responses falling in the mild‑to‑moderate (1–50% clearance) range after 3–4 sessions, and excellent responses (≥ 76% clearance) seen in a minority of patients, across controlled and uncontrolled trials. TCA 15% and GA 35–70% both substantially reduce AN severity score (ANASI or equivalent) over 6–8 weeks compared with baseline, but neither can currently be considered a definitive stand‑alone cure. [ 4 – 11 ] Topical tretinoin remains at least as effective, and often more so, than peels in axillary and possibly truncal AN, but requires longer continuous use and is more irritating; peels may therefore be best positioned as adjunctive or “boosting” procedures for cosmetic debulking of pigmentation and hyperkeratosis in selected patients already undergoing systemic and topical measures for the underlying metabolic milieu. [ 6 – 10 ] Considering the site of treatment and the treatment modality that were used, neck pseudo‑AN appears particularly amenable to GA 70% peels and fractional CO₂, with GA sometimes outperforming laser in short‑term pigmentation reduction and fractional CO₂ clearly surpassing TCA 20% in both neck and axillae. Axillary lesions, by contrast, responded better to topical tretinoin than to 70% GA in Ghiasi et al., suggesting that site‑specific occlusion dynamics, skin thickness, and sweat may modulate peel efficacy. [ 4 , 6 , 8 , 11 ] Combination approaches such as microneedling plus 15% TCA provide enhanced textural and pigment improvement over peel alone and may point the way toward lower‑strength peels delivered via energy‑ or device‑assisted methods to maximise efficacy while minimising depth‑related complications.[ 6 ] TCA 15–20% (superficial) is a safe, inexpensive option that produces mild to moderate improvement in most patients with AN after 3–4 sessions; however, this approach carries a higher risk of post-inflammatory hypopigmentation (PIH) compared with other interventions. It may be preferable to GA 35% for general AN severity reduction, but it is less effective than fractional CO₂ and often slightly inferior to topical tretinoin in head‑to‑head trials.[ 4 , 5 , 8 ] GA 70% is particularly effective for neck pseudo‑AN, sometimes outperforming fractional CO₂ and offering faster pigment shedding due to accelerated exfoliation, though its advantage diminishes in axillae, and it is not clearly superior to topical retinoids.[ 9 , 10 ] Fractional CO₂ laser is superior to TCA 20% for pseudo‑AN and at least comparable to GA 70%, but peels remain attractive where lasers are unavailable or unaffordable.[ 7 – 9 ] Topical tretinoin (0.025–0.05%) often matches or exceeds peel efficacy, especially in axillary lesions, but at the cost of more irritation and a need for prolonged application; peels are best viewed as adjuncts or accelerators of cosmetic improvement in motivated patients.[ 8 , 10 ] Adjunctive microneedling enhances TCA 15% outcomes, improving pigmentation and texture at the expense of greater procedural pain but without added serious AEs, and may be a highly effective and practical alternative, especially in resource-limited environments. [ 7 ] Among the modalities evaluated, fractional CO₂ laser demonstrated superior efficacy and optimal cosmetic outcomes, albeit with moderate tolerability. However, it is imperative to consider the associated costs of these treatments and the potential risk of post-inflammatory hyperpigmentation. Limitations and Future Directions: Nevertheless, chemical peels have emerged as the primary treatment alongside other topical agents for all pigmentary disorders, including acanthosis nigricans. Both chemical peels and fractional CO₂ lasers are effective for acanthosis nigricans, but each offers trade-offs between efficacy and tolerability. Enhancing patients' comprehension of AN and its aetiology should be a cornerstone of effective clinical management. While aesthetic outcomes are indeed significant in the context of AN, it is imperative to identify and address the underlying pathophysiology to ensure comprehensive care. The evidence base is limited by small sample sizes (often n = 20–40), short follow-up periods (usually ≤ 3 months), single-centre study designs, and a heterogeneous scoring system, which together limit generalisability and preclude robust pooled estimates. Many comparisons are open-label or split-site without controls, raising the possibility of expectation and assessor bias; however, the use of blinded dermatologists and standardised indices (ANASI, SCANS) in several trials partially mitigates this. [ 4 – 10 ] Notably, most trials focus on obesity‑associated pseudo‑AN in young adults of darker phototypes; extrapolation to syndromic, malignant or drug‑induced AN, to lighter skin types, or to pediatric populations should be cautious. Furthermore, nearly all studies continued or recommended lifestyle modification and weight reduction, so the pure incremental benefit of peels over optimised systemic management remains incompletely defined. [ 5 – 8 ] Declarations Acknowledgements: I would like to acknowledge and sincerely thank Dr K. Naveenkumar , M.S., DNB, FISS (Orthopaedic Spine Surgeon), SMVMCH, Puducherry, for providing the technical support and guidance in the preparation of this manuscript. Statement of Ethics: This study does not contain any studies with human or animal subjects performed by any of the authors. Conflict of Interest: The authors have no conflicts of interest to declare. Funding Sources: This study was not supported by any sponsor or funder. Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by S.G., D.A., S.R., and N.J. The first draft of the manuscript was written by S.G., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability: All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author. References Patel NU, Roach C, Alinia H, Huang W, Feldman S. Current treatment options for acanthosis nigricans. Clin Cosmet Investig Dermatol. 2018 Aug;Volume 11:407–13. Phiske M. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239. McGuinness LA, Higgins JP. Risk‐of‐bias VISualization (robvis): an R package and Shiny web app for visualizing risk‐of‐bias assessments. Res Synth Methods. 2021;12(1):55–61. Zayed A, Sobhi RM, Abdel Halim DM. Using trichloroacetic acid in the treatment of acanthosis nigricans: a pilot study. J Dermatol Treat. 2014 Jun 1;25(3):223–5. Bharati B, Sarkar R, Garg T, Goyal R, Mendiratta V. Efficacy of 15% trichloroacetic acid peel versus 35% glycolic acid peel in acanthosis Nigricans: A randomized open-label study. J Cutan Aesthetic Surg. 2024 Apr;17(2):94–9. Khashaba SA, Alaa S, Eldeeb F. 15% Trichloroacetic Acid Peel Alone versus in Combination with Microneedling in Acanthosis Nigricans Patients. J Clin Aesthetic Dermatol. 2024;17(4):28–32. Fouda I, Shatta AS, Obaid ZM. Fractional Carbon Dioxide Laser versus Trichloroacetic Acid 20% Peel in the Treatment of Acanthosis Nigricans: A Split Neck Comparative Study. J Clin Aesthetic Dermatol. 2023 Nov;16(11):36–41. Eldeeb F, Wahid RM, Alakad R. Fractional carbon dioxide laser versus trichloroacetic acid peel in the treatment of pseudo‐acanthosis nigricans. J Cosmet Dermatol. 2022 Jan;21(1):247–53. Zaki NS, Hilal RF, Essam RM. Comparative study using fractional carbon dioxide laser versus glycolic acid peel in treatment of pseudo-acanthosis nigricans. Lasers Med Sci. 2018 Sep;33(7):1485–91. Ghiasi M, Samii R, Tootoonchi N, Balighi K, Heidari S. Comparison of efficacy and safety of tretinoin 0.05% and glycolic acid peeling 70% in axillary and neck lesions of acanthosis nigricans: A single‐blinded, randomized trial. J Cosmet Dermatol. 2024 Jun;23(6):2090–6. Abu Oun AA, Ahmed NA, Hafiz HSA. Comparative study between fractional carbon dioxide laser versus retinoic acid chemical peel in the treatment of acanthosis nigricans. J Cosmet Dermatol. 2022 Mar;21(3):1023–30. Patel NU, Roach C, Alinia H, Huang W, Feldman S. Current treatment options for acanthosis nigricans. Clin Cosmet Investig Dermatol. 2018 Aug;Volume 11:407–13. Das A, Datta D, Kassir M, Wollina U, Galadari H, Lotti T, et al. Acanthosis nigricans: A review. J Cosmet Dermatol. 2020;19(8):1857–65. Additional Declarations The authors declare no competing interests. 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Gautam","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYDCCAwwMjA0MDAlQrg0QMzYeIFYLiE4D0yRpOQwTxA34bh9/Jjmjoi5P3v2M+YOfOeft1rYfBtpSYxONS4vkuRwzyQ1nDhcbnskxbOzddjt525lEoJZjabkNOLQYnOFhk3zYdiBxY0OOYQMvUIvZAaAWxobDeLSwP5N8+K8ucWP/G8PGv9vOJZudf0hIC4OZ5MYG5sT5EjmGzbzbDtiZ3SBgi+QZHmPLGccOJ26QeFY4W3ZbcoLZDaAtCXj8wneG/eHNnpq6xPn9yRs+vt1mZ292Pv3hgw81Nji1IFx4AEInglUmEFIOAvJQQ+2JUTwKRsEoGAUjCwAAHedu3ZcH3kkAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3824-9800","institution":"Saveetha Institute of Medical and Technical Sciences, Chennai","correspondingAuthor":true,"prefix":"","firstName":"S","middleName":"Sukesh","lastName":"Gautam","suffix":""},{"id":626690318,"identity":"6da39e5f-4aed-4271-9119-882165facf84","order_by":1,"name":"Darshini Adhinathan","email":"","orcid":"","institution":"Saveetha Institute of Medical and Technical Sciences, Chennai","correspondingAuthor":false,"prefix":"","firstName":"Darshini","middleName":"","lastName":"Adhinathan","suffix":""},{"id":626690319,"identity":"526cb66c-917e-4c63-9421-da9a1b945bae","order_by":2,"name":"Sai Rithika Reddy","email":"","orcid":"https://orcid.org/0009-0002-0235-7591","institution":"Saveetha Institute of Medical and Technical Sciences, Chennai","correspondingAuthor":false,"prefix":"","firstName":"Sai","middleName":"Rithika","lastName":"Reddy","suffix":""},{"id":626690320,"identity":"33962149-ad20-47c3-84dc-1d330559c10c","order_by":3,"name":"Namrita Jeyaraj","email":"","orcid":"https://orcid.org/0000-0001-9487-6406","institution":"Armoraa Skin, Hair \u0026 Laser Clinic, Chennai","correspondingAuthor":false,"prefix":"","firstName":"Namrita","middleName":"","lastName":"Jeyaraj","suffix":""}],"badges":[],"createdAt":"2026-04-21 01:06:34","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-9477098/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9477098/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107453377,"identity":"eeec2e1a-989f-47de-87b3-e2f8d479aec8","added_by":"auto","created_at":"2026-04-21 15:32:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":446849,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Flow Diagram\u003c/p\u003e","description":"","filename":"Fig1PRISMAFlowDiagram.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9477098/v1/c089e726416d630f8e257368.jpg"},{"id":107453378,"identity":"c0c2ee11-20de-43b4-aa7f-4fbbcdec46a6","added_by":"auto","created_at":"2026-04-21 15:32:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":109863,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea. \u003c/strong\u003eThe methodological quality of the included randomised trials was categorised as ‘high’, ‘low’, ‘some concerns’, \u0026nbsp;or ‘no information’ risk of bias according to the Cochrane risk-of-bias assessment tool.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig. 2b. \u003c/strong\u003eGraph summarising the risk of bias of all included randomised trials.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9477098/v1/d0a8c057996982d9716cba81.jpg"},{"id":107490478,"identity":"3bb87dc4-83ce-4818-804f-7d93cb965b87","added_by":"auto","created_at":"2026-04-22 02:52:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1054945,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9477098/v1/8416d0ef-3730-4f34-a587-74ad6d1f0161.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eInsights Into the Safety and Efficacy of Chemical Peels in Treating Acanthosis Nigricans – a Systematic Review of Clinical Studies and Randomised Controlled Trials\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcanthosis nigricans (AN) is a dermatological disorder characterised by hyperpigmented, thickened, and velvety-textured skin, commonly affecting flexural areas such as the neck, axillae, groin, and inframammary folds. It is often associated with metabolic disorders, particularly insulin resistance, obesity, polycystic ovarian syndrome (PCOS), and type 2 diabetes mellitus (T2DM).[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] While benign acanthosis nigricans is frequently linked to metabolic syndromes, a rare but serious variant, malignant acanthosis nigricans, is associated with underlying malignancies, especially gastric adenocarcinoma.\u003c/p\u003e \u003cp\u003eAcanthosis nigricans is primarily associated with elevated insulin levels that bind to insulin-like growth factor 1 receptors (IGF-1Rs) on keratinocytes and fibroblasts. This binding stimulates the proliferation of these cell types, which manifests as distinct plaques and papillomatosis.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Given its strong correlation with metabolic dysfunction, AN is not just a cosmetic concern but a clinical marker of systemic disease, necessitating a multidisciplinary treatment approach. The therapeutic approach includes treating the underlying disease or tumour, avoiding the inciting agent in drug-induced AN, and utilising topical creams, chemical peels, fractional CO2 lasers, and microneedling.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Several clinical trials and studies have been done on the effectiveness of chemical peels such as trichloroacetic acid (TCA), glycolic acid (GA), retinoic acid (RA), etc, in treating AN. Hence, it is necessary to conduct a systematic review that analyses the efficacy, safety and role of various chemical peels in managing acanthosis nigricans. We systematically reviewed clinical studies and randomised trials that used either chemical peels as monotherapy or combination therapy with procedures such as fractional CO2 laser, microneedling, etc. and comparison studies with various chemical peels in adult patients with acanthosis nigricans to elucidate their long-term efficacy and safety and provide possible recommendations for their use.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eLiterature search\u003c/h2\u003e \u003cp\u003eIn October 2025, we performed a comprehensive literature search from inception through January 2026 to study the efficacy of chemical peel treatment on patients with acanthosis nigricans. We used relevant MeSH terms such as (\"acanthosis nigricans\") AND (\"chemical peel\" OR \"trichloroacetic acid\" OR \"TCA peel\" OR \"glycolic acid\" OR \"retinoic acid\" OR \"peeling\" OR \"chemexfoliation\") to search the PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and SCOPUS databases. The systematic review was registered in PROSPERO (CRD42024616894) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for reporting systematic reviews.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEligibility criteria and selection of studies\u003c/h3\u003e\n\u003cp\u003eStudies were included following the PICOS principles (Population, Intervention, Comparison, Outcome, and Study design). The inclusion criteria for selecting the articles were English and published from inception to January 2026. Only randomised controlled trials (RCTs), quasi-randomised trials, split-lesion studies, pilot studies, and prospective cohort studies reporting outcomes of chemical peels in patients with AN, either alone or in combination with other interventions for treating acanthosis nigricans in human subjects, were selected for the review. There were no restrictions on country, gender, or age. We excluded preclinical studies, case reports, posters, conference abstracts, editorials, letters and case series. The primary outcome measure was efficacy, and the secondary outcome was safety. Four reviewers selected the articles independently (S.G., D.A., S.R., and N.J.). The final selection was based on a full-text assessment. Reference lists of selected articles were screened for additional relevant studies.\u003c/p\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003e A standardised template for data extraction was built, and four reviewers (S.G., D.A., S.R., and N.J.) independently extracted the baseline and outcome data from all included studies. Discrepancies between the authors were resolved through discussion. Studies published by the same author and in the same year have been checked for possible overlap and data duplication.\u003c/p\u003e\n\u003ch3\u003eRisk of bias assessment\u003c/h3\u003e\n\u003cp\u003e The revised Cochrane Risk of Bias tool for Randomised Controlled Trials (Cochrane Rob 2.0) was utilised by four reviewers (S.G., D.A., S.R., and N.J.) to evaluate the risk of bias in each study.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] This assessment considered factors such as random sequence generation, allocation concealment, blinding of participants and trial personnel, deviations from anticipated interventions, absence of outcome data, and selection of reported outcomes.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e \u003cb\u003eEligible Studies\u003c/b\u003e The systematic data search returned 847 reference articles, of which 147 duplicates were removed. The remaining 694 references were screened based on title and abstract, and 651 were excluded. Full texts of 43 articles were obtained and assessed for eligibility. The inclusion criteria and data completeness were used to select the final 8 articles for this review, as shown in the PRISMA Flow Diagram. \u003cb\u003e[\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e]\u003c/b\u003e\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy Characteristics:\u003c/h2\u003e \u003cp\u003eThe characteristics of patients in the included studies are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The review included eight clinical studies and controlled trials published until January 2026, comprising 216 patients. All patients included in this review were aged 10\u0026ndash;45 years. Most of the included studies reported a male predominance, and the mean duration of AN ranged from 1 to 20 years. The studies included in this systematic review were conducted in patients with acanthosis nigricans and pseudoacanthosis nigricans, with or without comorbidities such as diabetes, dyslipidemia, etc., at the time of enrollment. Different chemical peels with varying depths of penetration were investigated for their safety and efficacy as monotherapy in Zayed et al.'s study [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], compared with other peels in Bharti et al.'s study [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and with other skin rejuvenation procedures such as microneedling and lasers in other research.\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\u003eCharacteristics of included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eName of the Study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStudy population\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAge group/ Mean age (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean duration of disease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAssociated systemic diseases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eSites of skin involvement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTreatment protocol\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbu Oun et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEgypt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSplit neck Comparative study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 Egyptian patients with neck AN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u0026ndash;44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u0026ndash;20 years;\u003c/p\u003e \u003cp\u003eMedian 5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNot detailed, likely excluded\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNeck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eRight: CO2 laser; Left: 5% Retinoic acid; 4 sessions with 2- week interval\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBharati et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRandomized open- label study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 patients with AN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGA: 2.64\u0026thinsp;\u0026plusmn;\u0026thinsp;2.06 TCA: 3.64\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMajority were obese or overweight.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eFace, neck, elbow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eGroup A: 15% TCA; Group B: 35% GA; 3 sessions, 2-week intervals\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEldeeb et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEgypt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRandomized comparative clinical trial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 patients with pseudo-AN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eExcluded such as diabetes, hormonal disorders, and malignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNeck and axilla\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eGroup A: TCA 20% (4 sessions, 4-week interval); Group B: CO2 laser (4 sessions, 4\u0026ndash;6week interval)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFouda et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEgypt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSplit neck comparative study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMedian\u0026thinsp;\u0026minus;\u0026thinsp;4.5 years, ranging from 2 to 10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5% patients have associated systemic diseases.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNeck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFractional CO2 laser (Right side) Vs TCA 20% peel (Left side)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGhiasi et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSingle-blinded, randomized trial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 patients (neck or axillary AN)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u0026ndash;45 yrs Mean: 25.27\u003c/p\u003e \u003cp\u003e\u0026plusmn;\u0026thinsp;10.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMost\u0026thinsp;\u0026lt;\u0026thinsp;7 years (70%), others 7\u0026ndash; 20 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17 (56.7%) had obesity, diabetes, PCO and others.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNeck and axilla\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eOne side: Tretinoin 0.05% every other night; other side: GA 70% every 2 weeks; 8 weeks total\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKhashaba et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEgypt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRandomized clinical trial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;2 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSome patients had associated medical conditions.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNeck, axillae, ante cubital fossa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eRight side: 15% TCA; Left side: Microneedling\u0026thinsp;+\u0026thinsp;15% TCA; monthly for 3 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZaki et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEgypt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProspective randomized comparative study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 patients with pseudo-acanthosis nigricans\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNot specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eExcluded systemic diseases such as diabetes, etc.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNeck\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eRight side: Fractional CO2 laser (3 sessions, 2-week intervals); Left side: Glycolic acid 70% peel (3 sessions, 2-week intervals)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZayed et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEgypt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePilot study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 females with 10 lesions of AN.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.5 years (21\u0026ndash;43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.4 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNot mentioned\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNeck, cheeks, axilla\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTCA 15%, weekly sessions for 4 weeks\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRisk of bias assessment among included trials\u003c/h3\u003e\n\u003cp\u003eAll studies reported a random allocation of study participants. Four trials adequately reported allocation concealment, all trials performed blinding of participants and researchers, and reported blinding of outcome assessment. [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] One study had a low risk of bias concerning selective outcomes reporting, randomisation process and missing outcome data. The methodological quality and risk of bias of the included trials are summarised in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003ea and \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003eb.\u003c/p\u003e\n\u003ch3\u003eTREATMENT PROTOCOLS:\u003c/h3\u003e\n\u003cp\u003eVarious chemical peels were used in the above-finalised studies, administered at distinct intervals and sessions. Few studies used them as monotherapy, and others used them to compare with other peels and procedures to determine their safety and efficacy. The efficacy and safety outcomes of the included studies have been summarised in 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\u003eSafety and Efficacy outcomes of the included studies:\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTreatment Intervention\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDuration of Treatment\u003c/p\u003e \u003cp\u003e(weeks)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBaseline assessment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEfficacy Outcomes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSafety and Tolerability\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbu Oun et al. 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFractional CO2 laser vs. Retinoic Acid 5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 weeks\u003c/p\u003e \u003cp\u003e(4 sessions, biweekly)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANASI score, dermatologist assessment, dermoscopic evaluation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eANASI Score: Highly significant reduction in the score on both halves after therapy.\u003c/p\u003e \u003cp\u003eDermoscopic Score: Improvement seen in dermoscopic features of AN.\u003c/p\u003e \u003cp\u003elike sulci cutis, cristae cutis, pigmentation, milia-like cysts, etc. on both halves.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild erythema and peeling with RA, no serious events\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBharati et al. 2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15% TCA vs. 35% GA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 weeks\u003c/p\u003e \u003cp\u003e(3 sessions, biweekly)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANASI score, PAS, PSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eANASI Scores:\u003c/p\u003e \u003cp\u003eTCA group: Decrease from 22.33 to 13.26; GA group: Decrease\u003c/p\u003e \u003cp\u003efrom 17.07 to 12.49. Both improvements were statistically significant (p\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003ePhysician Assessment Score (PAS):\u003c/p\u003e \u003cp\u003eGreater proportion of TCA group participants achieved PAS\u0026thinsp;\u0026gt;\u0026thinsp;2. Patient Satisfaction Score (PSS): Higher satisfaction in the TCA group (45% excellent) than GA group (15% excellent) .\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild irritation and PIH noted in both groups\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEldeeb et al. 2021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFractional CO2 laser vs. TCA 20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u0026ndash;24 weeks\u003c/p\u003e \u003cp\u003e(up to 4 sessions)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage improvement, dermatologic assessment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTCA had a higher frequency of excellent or marked improvement over laser in blinded physician assessment after treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigher adverse effects in TCA group (erythema, PIH, burning)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFouda et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFractional CO2 Laser (right side) vs TCA 20% (left side)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003cp\u003e(4 sessions\u003c/p\u003e \u003cp\u003eevery three weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANASI score, dermatologist assessment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFractional CO2 laser side: Excellent improvement \u0026ndash; 20%, Marked improvement\u0026thinsp;\u0026minus;\u0026thinsp;45%, moderate improvement\u0026thinsp;\u0026minus;\u0026thinsp;35%.\u003c/p\u003e \u003cp\u003eTCA 20% peel side: moderate improvement \u0026ndash; 50%,\u003c/p\u003e \u003cp\u003emild improvement \u0026ndash; 40%, and marked improvement \u0026ndash; 2%.\u003c/p\u003e \u003cp\u003eANASI: Greater % of reduction in fractional CO2 laser (from 20 to 6) compared to the TCA 20% peel (from 20 to 8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePain and erythema noted in 13 (65%) patients in Fractional CO2 laser treatment as compared to none with TCA peel.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGhiasi et al. 2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTretinoin 0.05%\u003c/p\u003e \u003cp\u003evs. GA 70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTreatment response, patient satisfaction, photographic evaluation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTretinoin more effective than glycolic acid (p\u0026thinsp;=\u0026thinsp;0.02 for treatment response, p\u0026thinsp;=\u0026thinsp;0.008 for patient satisfaction) in treating axillary lesions. However, there was no significant difference in efficacy between the tw treatments in neck treatment.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMinimal side effects; some burning and irritation reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKhashaba et al. 2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15% TCA vs. 15% TCA +\u003c/p\u003e \u003cp\u003eMicroneedling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 weeks\u003c/p\u003e \u003cp\u003e(3 monthly sessions)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eImprovement in pigmentation, texture, SCANS score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eExcellent improvement in pigmentation and texture was more common with the TCA\u0026thinsp;+\u0026thinsp;microneedling arm. Statistically significant (P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.001) improvement seen in both arms.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo serious side effects reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZaki et al. 2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFractional CO2 laser vs. GA 70%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 weeks\u003c/p\u003e \u003cp\u003e(3 sessions, biweekly)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eANASI score, dermatologist assessment, photographs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eANASI Score: GA side: Decrease from 23.55 to 13.50 (p\u0026thinsp;=\u0026thinsp;0.001). In CO₂ laser group, minimal improvement seen (23.50 to 19.10), not statistically significant (p\u0026thinsp;=\u0026thinsp;0.1)\u003c/p\u003e \u003cp\u003ePhysician assessment: Significantly greater improvement with GA peel\u003c/p\u003e \u003cp\u003e\u0026gt; CO₂ laser on a 0\u0026ndash;4 scale.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild transient erythema and burning with GA, no major side effects\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZayed et al. 2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTCA 15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 weeks\u003c/p\u003e \u003cp\u003e(weekly sessions)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eInvestigator and patient assessment, clinical response\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAll six patients showed improvement in hyperpigmentation and skin texture.\u003c/p\u003e \u003cp\u003eInvestigator-graded responses: excellent in 3 lesions, moderate in 5, mild in 2.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo side effects reported.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eEFFICACY OF CHEMICAL PEELS AS MONOTHERAPY:\u003c/h2\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003eTrichloroacetic Acid (TCA) 15\u0026ndash;20% Peels\u003c/h2\u003e \u003cp\u003e15% TCA peel consistently showed moderate to good improvement across multiple studies. In Bharati et al., 15% TCA was more effective than 35% GA, with a greater ANASI score reduction (baseline: 22.33 \u0026rarr; 13.26 at 8 weeks, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) across three sessions. In Khashaba et al., TCA plus microneedling showed significantly greater improvement in both pigmentation and texture than TCA alone [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In a small Egyptian pilot cohort conducted by Zayed et al., six women with about 10 AN lesions in total (neck, face, axilla) underwent weekly 15% TCA for 4 weeks; all lesions improved in pigmentation, thickness, and overall appearance, with no side effects.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Fouda et al. (2023) reported moderate improvement with 20% TCA in 50% of patients, but inferior to fractional CO₂ laser (20% marked improvement).[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Eldeeb et al. (2021) noted a marked improvement in only 10% of patients after four weekly sessions with 20% TCA.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eSafety \u0026amp; Tolerability\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eMild and transient burning and erythema were the most common side effects; PIH was more prevalent with TCA, especially in darker skin types​​. As reported by Bharati et al., typical side effects with 15% TCA included peeling (70%), burning (45%), and transient PIH.(5) Higher PIH rates (20%) and persistent erythema were seen with 20% TCA in the study by Eldeeb et al., 2021.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Combination with microneedling increased discomfort (pain, erythema, etc.), but did not significantly increase complication rates.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eGlycolic Acid (GA) 35\u0026ndash;70% Peels\u003c/h2\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e\u003cb\u003eEfficacy\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eGA peel at 70% concentration demonstrated moderate clinical improvement (43%) in pseudo-AN and was more effective than fractional CO₂ in Zaki et al.'s study.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] ​However, Bharati et al. (2024) found a modest ANASI reduction with GA 35% (17.07 \u0026rarr; 12.49 at 8 weeks, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with only 5% of patients achieving more than 50% improvement.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] However, Ghiasi et al. (2024) noted GA\u0026rsquo;s inferiority to tretinoin for axillary AN (P\u0026thinsp;=\u0026thinsp;0.02).[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Taken together, GA peels appear capable of achieving moderate reductions in pigmentation and thickness, with GA 70% sometimes outperforming fractionated laser for neck pseudo‑AN but not consistently surpassing retinoids or TCA in other settings.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eSafety \u0026amp; Tolerability\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eGA peels were generally better tolerated with fewer and milder adverse effects than TCA, making them favourable for sensitive skin and as a first-line agent​. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eCOMPARATIVE EFFICACY VERSUS OTHER PEELS AND NON‑PEEL THERAPIES:\u003c/h2\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003eRetinoic Acid Peel and Topical Retinoids\u003c/h2\u003e \u003cdiv id=\"Sec19\" class=\"Section4\"\u003e \u003ch2\u003e\u003cb\u003eEfficacy\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eRetinoic acid 5% was less effective than the fractional CO₂ laser in Abu Oun et al.\u0026rsquo;s trial, though it showed significant improvement​.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Tretinoin 0.05% was more effective than GA 70% for axillary lesions, but peels offered faster results than topical agents in Ghiasi et al.\u0026rsquo;s study​.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eSafety \u0026amp; Tolerability\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eTretinoin was generally well-tolerated and suitable for long-term use. Side effects were minimal and localised (dryness, irritation)​.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eChemical Peels vs Fractional CO₂ Laser\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eEfficacy\u003c/strong\u003e \u003cp\u003eSuperior outcomes were observed with the fractional CO₂ laser in comparison to 20% TCA in studies by Fouda et al., with significantly larger reductions in ANASI scores, and Eldeeb et al., with 85% of patients in the laser group achieving a marked to excellent response, versus only 10% in the TCA group​​.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/p\u003e \u003cp\u003eIn contrast, 70% GA peel showed slightly better immediate efficacy than fractional CO₂ in Zaki et al.'s split-neck study (43% vs 19% improvement), possibly due to rapid exfoliation effects.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Compared with retinoic acid, fractional CO₂ again showed superior efficacy in clinical and dermoscopic assessments​. Thus, fractional CO₂ appears substantially more efficacious than TCA 20%, but its advantage over GA 70% is inconsistent and may be negligible for pure AN of the neck.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eSafety \u0026amp; Tolerability\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eThe fractional CO₂ laser had fewer side effects like PIH (5% vs 20% in the TCA group),​ as seen in a study by Eldeeb et al.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] However, cases of PIH and folliculitis were reported with CO₂ treatment in Zaki et al.'s study, highlighting possible variation based on skin type or the treatment site.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Pain and erythema were more frequent than with peels, as shown by the Fouda et al. study.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eTCA alone vs TCA plus microneedling\u003c/h2\u003e \u003cp\u003eKhashaba et al. randomised 40 patients with AN to split‑lesion treatment with TCA 15% peel alone versus microneedling followed by a single coat of TCA 15% every 2 weeks for four sessions. Both sides demonstrated significant improvement in overall AN grade (SCANS) after treatment, but the combination side showed greater gains in pigmentation and texture, and higher patient satisfaction, despite increased procedural pain. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] This trial suggests that combining low‑strength TCA with microneedling‑enhanced delivery enhances efficacy over peel alone without introducing serious safety concerns, and may be an additional option where facilities and patient tolerance permit.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCurrent treatment paradigms for acanthosis nigricans (AN) are evolving to encompass the management of cutaneous pathology, the underlying condition, and pharmacological agents. Non-pharmacological approaches include weight management and increased physical activity, aimed at improving insulin sensitivity in individuals with insulin-resistant AN. The treatment approach for AN is multifaceted, as dermatological manifestations frequently coexist with underlying medical conditions. Preliminary investigations for the workup of AN should involve evaluating patients for insulin resistance syndrome, characterised by obesity, dyslipidemia, hypertension, and type II diabetes mellitus.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Health care providers should procure a fasting lipid panel, glucose, and insulin levels, and complete blood count and liver function tests. In instances where malignancy-associated AN is suspected, imaging modalities such as plain radiography, computed tomography, or magnetic resonance imaging may yield pertinent insights. Using oral metformin and other insulin-sensitising medications is beneficial, as these therapeutic strategies target the underlying etiological factors contributing to AN.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Topical retinoids are regarded as the primary treatment for insulin-resistant acanthosis nigricans (AN) because they modify the keratinisation rate. However, topical tretinoin requires prolonged periods of application and predominantly targets hyperkeratosis, without markedly enhancing hyperpigmentation. Other topical agents, including vitamin D3 analogues such as calcipotriol, salicylic acid, urea, and podophyllin, require frequent applications.\u003c/p\u003e \u003cp\u003eThe modified triple combination regime (tretinoin 0.05%, hydroquinone 4%, fluocinolone acetonide 0.01%) has reportedly helped improve the lesions when used at night.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Chemical peels have emerged as the primary treatment for various pigmented dermatoses, including acanthosis nigricans affecting the face, neck, and axillae.\u003c/p\u003e \u003cp\u003eFrom the synthesised data, it has been found that the chemical peels consistently yield clinically meaningful but rarely complete improvement in AN, with typical responses falling in the mild‑to‑moderate (1\u0026ndash;50% clearance) range after 3\u0026ndash;4 sessions, and excellent responses (\u0026ge;\u0026thinsp;76% clearance) seen in a minority of patients, across controlled and uncontrolled trials. TCA 15% and GA 35\u0026ndash;70% both substantially reduce AN severity score (ANASI or equivalent) over 6\u0026ndash;8 weeks compared with baseline, but neither can currently be considered a definitive stand‑alone cure. [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9 CR10\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTopical tretinoin remains at least as effective, and often more so, than peels in axillary and possibly truncal AN, but requires longer continuous use and is more irritating; peels may therefore be best positioned as adjunctive or \u0026ldquo;boosting\u0026rdquo; procedures for cosmetic debulking of pigmentation and hyperkeratosis in selected patients already undergoing systemic and topical measures for the underlying metabolic milieu. [\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eConsidering the site of treatment and the treatment modality that were used, neck pseudo‑AN appears particularly amenable to GA 70% peels and fractional CO₂, with GA sometimes outperforming laser in short‑term pigmentation reduction and fractional CO₂ clearly surpassing TCA 20% in both neck and axillae. Axillary lesions, by contrast, responded better to topical tretinoin than to 70% GA in Ghiasi et al., suggesting that site‑specific occlusion dynamics, skin thickness, and sweat may modulate peel efficacy. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eCombination approaches such as microneedling plus 15% TCA provide enhanced textural and pigment improvement over peel alone and may point the way toward lower‑strength peels delivered via energy‑ or device‑assisted methods to maximise efficacy while minimising depth‑related complications.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTCA 15\u0026ndash;20% (superficial) is a safe, inexpensive option that produces mild to moderate improvement in most patients with AN after 3\u0026ndash;4 sessions; however, this approach carries a higher risk of post-inflammatory hypopigmentation (PIH) compared with other interventions. It may be preferable to GA 35% for general AN severity reduction, but it is less effective than fractional CO₂ and often slightly inferior to topical tretinoin in head‑to‑head trials.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] GA 70% is particularly effective for neck pseudo‑AN, sometimes outperforming fractional CO₂ and offering faster pigment shedding due to accelerated exfoliation, though its advantage diminishes in axillae, and it is not clearly superior to topical retinoids.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Fractional CO₂ laser is superior to TCA 20% for pseudo‑AN and at least comparable to GA 70%, but peels remain attractive where lasers are unavailable or unaffordable.[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Topical tretinoin (0.025\u0026ndash;0.05%) often matches or exceeds peel efficacy, especially in axillary lesions, but at the cost of more irritation and a need for prolonged application; peels are best viewed as adjuncts or accelerators of cosmetic improvement in motivated patients.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Adjunctive microneedling enhances TCA 15% outcomes, improving pigmentation and texture at the expense of greater procedural pain but without added serious AEs, and may be a highly effective and practical alternative, especially in resource-limited environments. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAmong the modalities evaluated, fractional CO₂ laser demonstrated superior efficacy and optimal cosmetic outcomes, albeit with moderate tolerability. However, it is imperative to consider the associated costs of these treatments and the potential risk of post-inflammatory hyperpigmentation.\u003c/p\u003e \u003cdiv id=\"Sec25\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and Future Directions:\u003c/h2\u003e \u003cp\u003eNevertheless, chemical peels have emerged as the primary treatment alongside other topical agents for all pigmentary disorders, including acanthosis nigricans. Both chemical peels and fractional CO₂ lasers are effective for acanthosis nigricans, but each offers trade-offs between efficacy and tolerability. Enhancing patients' comprehension of AN and its aetiology should be a cornerstone of effective clinical management. While aesthetic outcomes are indeed significant in the context of AN, it is imperative to identify and address the underlying pathophysiology to ensure comprehensive care.\u003c/p\u003e \u003cp\u003eThe evidence base is limited by small sample sizes (often n\u0026thinsp;=\u0026thinsp;20\u0026ndash;40), short follow-up periods (usually\u0026thinsp;\u0026le;\u0026thinsp;3 months), single-centre study designs, and a heterogeneous scoring system, which together limit generalisability and preclude robust pooled estimates. Many comparisons are open-label or split-site without controls, raising the possibility of expectation and assessor bias; however, the use of blinded dermatologists and standardised indices (ANASI, SCANS) in several trials partially mitigates this. [\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8 CR9\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eNotably, most trials focus on obesity‑associated pseudo‑AN in young adults of darker phototypes; extrapolation to syndromic, malignant or drug‑induced AN, to lighter skin types, or to pediatric populations should be cautious. Furthermore, nearly all studies continued or recommended lifestyle modification and weight reduction, so the pure incremental benefit of peels over optimised systemic management remains incompletely defined. [\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e I would like to acknowledge and sincerely thank \u003cem\u003eDr\u0026nbsp;K.\u0026nbsp;Naveenkumar\u003c/em\u003e, M.S., DNB, FISS (Orthopaedic Spine Surgeon), SMVMCH, Puducherry,\u0026nbsp;for providing the technical support and guidance in the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of Ethics:\u0026nbsp;\u003c/strong\u003eThis study does not contain any studies with human or animal subjects\u003c/p\u003e\n\u003cp\u003eperformed by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u0026nbsp;\u003c/strong\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Sources:\u0026nbsp;\u003c/strong\u003eThis study was not supported by any sponsor or funder.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by S.G., D.A., S.R., and N.J. The first draft of the manuscript was written by S.G., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePatel NU, Roach C, Alinia H, Huang W, Feldman S. Current treatment options for acanthosis nigricans. Clin Cosmet Investig Dermatol. 2018 Aug;Volume 11:407\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003ePhiske M. An approach to acanthosis nigricans. Indian Dermatol Online J. 2014;5(3):239. \u003c/li\u003e\n\u003cli\u003eMcGuinness LA, Higgins JP. Risk‐of‐bias VISualization (robvis): an R package and Shiny web app for visualizing risk‐of‐bias assessments. Res Synth Methods. 2021;12(1):55\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eZayed A, Sobhi RM, Abdel Halim DM. Using trichloroacetic acid in the treatment of acanthosis nigricans: a pilot study. J Dermatol Treat. 2014 Jun 1;25(3):223\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eBharati B, Sarkar R, Garg T, Goyal R, Mendiratta V. Efficacy of 15% trichloroacetic acid peel versus 35% glycolic acid peel in acanthosis Nigricans: A randomized open-label study. J Cutan Aesthetic Surg. 2024 Apr;17(2):94\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eKhashaba SA, Alaa S, Eldeeb F. 15% Trichloroacetic Acid Peel Alone versus in Combination with Microneedling in Acanthosis Nigricans Patients. J Clin Aesthetic Dermatol. 2024;17(4):28\u0026ndash;32. \u003c/li\u003e\n\u003cli\u003eFouda I, Shatta AS, Obaid ZM. Fractional Carbon Dioxide Laser versus Trichloroacetic Acid 20% Peel in the Treatment of Acanthosis Nigricans: A Split Neck Comparative Study. J Clin Aesthetic Dermatol. 2023 Nov;16(11):36\u0026ndash;41. \u003c/li\u003e\n\u003cli\u003eEldeeb F, Wahid RM, Alakad R. Fractional carbon dioxide laser versus trichloroacetic acid peel in the treatment of pseudo‐acanthosis nigricans. J Cosmet Dermatol. 2022 Jan;21(1):247\u0026ndash;53. \u003c/li\u003e\n\u003cli\u003eZaki NS, Hilal RF, Essam RM. Comparative study using fractional carbon dioxide laser versus glycolic acid peel in treatment of pseudo-acanthosis nigricans. Lasers Med Sci. 2018 Sep;33(7):1485\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eGhiasi M, Samii R, Tootoonchi N, Balighi K, Heidari S. Comparison of efficacy and safety of tretinoin 0.05% and glycolic acid peeling 70% in axillary and neck lesions of acanthosis nigricans: A single‐blinded, randomized trial. J Cosmet Dermatol. 2024 Jun;23(6):2090\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eAbu Oun AA, Ahmed NA, Hafiz HSA. Comparative study between fractional carbon dioxide laser versus retinoic acid chemical peel in the treatment of acanthosis nigricans. J Cosmet Dermatol. 2022 Mar;21(3):1023\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003ePatel NU, Roach C, Alinia H, Huang W, Feldman S. Current treatment options for acanthosis nigricans. Clin Cosmet Investig Dermatol. 2018 Aug;Volume 11:407\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eDas A, Datta D, Kassir M, Wollina U, Galadari H, Lotti T, et al. Acanthosis nigricans: A review. J Cosmet Dermatol. 2020;19(8):1857\u0026ndash;65. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Saveetha University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acanthosis nigricans, chemical peels, trichloroacetic acid, glycolic acid, fractional CO2 laser, microneedling, post-inflammatory hyperpigmentation","lastPublishedDoi":"10.21203/rs.3.rs-9477098/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9477098/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Acanthosis nigricans (AN) is a dermatological condition characterised by hyperpigmented, velvety, thickened skin, primarily affecting intertriginous areas such as the neck, axillae, and groin. It is strongly associated with insulin resistance, obesity, metabolic syndrome, and, in rare cases, malignancies. Various treatment modalities, including chemical peels, fractional CO2 laser, and microneedling, have been explored to improve the cosmetic appearance of affected skin. However, no definitive consensus on treatment exists.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: This systematic review aims to evaluate and compare the efficacy of chemical peels like Trichloroacetic acid (TCA), Glycolic acid (GA), Retinoic acid (RA), etc, with or without physical modalities such as fractional CO2 laser, and microneedling in managing AN, assessing their clinical outcomes, safety profiles, and long-term effectiveness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A systematic search of electronic databases was conducted to identify randomised controlled trials (RCTs), cohort studies, and comparative clinical studies evaluating the efficacy of chemical peels in AN treatment. Studies reporting objective clinical improvements, patient-reported outcomes, and adverse effects were included. The primary outcome measure was improved pigmentation and skin texture, which was assessed using validated scoring systems such as the Acanthosis Nigricans Area and Severity Index (ANASI).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: A total of 8 eligible studies were included. TCA (15-20%) peels demonstrated significant improvement in pigmentation compared to glycolic acid (35-70%), though higher concentrations increased the risk of post-inflammatory hyperpigmentation (PIH). Microneedling, particularly when combined with TCA peels, enhanced treatment outcomes by improving agent penetration and collagen remodelling.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Chemical peels offer varying degrees of efficacy in the treatment of AN. TCA peels remain a cost-effective first-line option, while physical modalities such as fractional CO2 laser offer superior long-term benefits for thicker lesions. Microneedling enhances the effects of peels, making combination therapies a promising approach. Future studies should focus on standardising treatment protocols, assessing long-term outcomes, and exploring newer treatment combinations to optimise AN management.\u003c/p\u003e","manuscriptTitle":"Insights Into the Safety and Efficacy of Chemical Peels in Treating Acanthosis Nigricans – a Systematic Review of Clinical Studies and Randomised Controlled Trials","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-21 15:32:15","doi":"10.21203/rs.3.rs-9477098/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"39358e27-aa29-4d6d-b82e-c0312f730c71","owner":[],"postedDate":"April 21st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66744339,"name":"Dermatology"},{"id":66744340,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"2026-04-21T15:32:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-21 15:32:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9477098","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9477098","identity":"rs-9477098","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}