Systematic review of topical, laser, and oral treatments in acanthosis nigricans clinical trials.

Acanthosis nigricans (AN), with an estimated prevalence of 19.4% in the U.S., presents as hyperpigmented, velvety plaques in intertriginous regions. Acanthosis Nigricans negatively affects psychological well-being and particularly impacts skin of color individuals. Addressing the underlying cause of acanthosis nigricans, as current guidelines recommend, is often challenging. This highlights the importance of skin directed treatment for acanthosis nigricans. This systematic review evaluated topical, laser, and oral treatments for acanthosis nigricans and provides evidence-based recommendations for clinical use. Adhering to PRISMA guidelines, we evaluated 19 clinical trials investigating topical, oral, and laser interventions for acanthosis nigricans. Oxford Centre for Evidence-Based Medicine guidelines were used to make clinical recommendations. We strongly recommend topical tretinoin (grade A) and endorse the appropriate use of adapalene gel, urea cream, and fractional carbon dioxide laser therapy (grade B). Further research is essential to enhance our understanding of alternative treatments to determine additional evidence-based recommendations. This review aims to guide clinicians in managing acanthosis nigricans, especially when direct treatment of underlying conditions is impractical.

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.

BACKGROUND: Acanthosis nigricans is a non-inflammatory skin pigmentary disorder characterized by a dark, velvety appearance, primarily observed in the neck and axillary areas. It is commonly associated with obesity, diabetes, and insulin resistance. Although the primary treatment is correcting the underlying disorders, many aesthetic modalities have been established to improve appearance owing to cosmetic concerns. AIMS: We aimed to compare and investigate the effectiveness and side effects of tretinoin 0.05% and glycolic acid 70% in treating acanthosis nigricans lesions of the axillary and neck area. METHODS: This single-blinded, randomized trial recruited patients with neck or axillary involvement. Each patient was randomized to use cream tretinoin 0.05% every other night on one side, while the other side was treated with glycolic acid 70%, which was applied every 2 weeks at the clinic for four consecutive sessions. The study duration was 8 weeks, and patients were evaluated every 2 weeks based on their response to treatment, satisfaction, and side effects. RESULTS: Thirty patients, including 14 with neck lesions and 16 with axillary lesions, were included. Tretinoin was significantly more effective for axillary lesions in terms of treatment response and patient satisfaction (p = 0.02 and p = 0.008, respectively). It was also shown that as the severity of the lesions increased, the response to treatment and patient satisfaction decreased, specifically when treating axillary lesions with glycolic acid (p = 0.02 and p = 0.03, respectively). CONCLUSION: Neither method was significantly effective for neck lesions. However, tretinoin 0.05% was shown to be more efficacious in treating axillary lesions of acanthosis nigricans, despite causing minimal side effects.

Comparing the efficacy and safety profiles of 0.025% and 0.05% tretinoin creams in treating acanthosis nigricans: a randomized double-blinded study.

Acanthosis nigricans (AN) is a skin disorder with hyperpigmented and velvety plaques without a standardized treatment regimen. We aimed to compare the efficacy and safety profile of 0.025% and 0.05% tretinoin creams in managing AN. An 8-week, randomized double-blinded study was conducted in adults with AN. Participants were instructed to apply tretinoin cream on their posterior neck. Narrowband reflectance spectrophotometry was used to measure skin improvement through melanin (M) and erythema (E) indices at each follow-up visits at weeks 2, 4, and 8. Improvements in Acanthosis nigricans scoring chart (ANSC), investigator- and patient-global evaluation (IGE and PGE) and adverse cutaneous irritations were also scored. Both the 0.025% and 0.05% tretinoin creams were efficacious in acanthosis nigricans treatment with 17.1 ± 8.0% improvement and 18.4 ± 9.8% improvement after 8 weeks treatment by reflectance spectrophotometry measurement, respectively. There were generally no significant differences in efficacy, improvements in ANSC, IGE, and PGE scores, and local cutaneous irritations between the two groups. The 0.025% and 0.05% tretinoin demonstrate similar efficacy and safety profiles in the management of AN. Both concentrations are well tolerated with mild degree of local cutaneous irritation.

Comparative study between fractional carbon dioxide laser versus retinoic acid chemical peel in the treatment of acanthosis nigricans.

BACKGROUND: Acanthosis nigricans (AN) is a common dermatological issue with several therapeutic modalities to treat. Despite retinoid is the first drug of choice in the treatment, the fractional-ablative carbon dioxide (CO2 ) laser has revealed as a promising procedure for the management of neck-AN, outstanding to its ability for superficial ablation of the skin surface, with trans-epidermal melanin elimination. OBJECTIVES: To decide whether fractional-ablative CO2 laser or retinoic acid (5%) peel is the more effective and safe choice for AN treatment. METHODS: In this study, twenty Egyptian cases with neck-AN were enrolled, where each case was exposed to four sessions with 2 weeks apart of both fractional CO2  laser on the right half of the neck and retinoic acid peel on the left half of the neck. Cases were assessed by a scoring system: Acanthosis Nigricans Area and Severity Index (ANASI) score, two blinded dermatologists, and dermoscopically before and one month after treatment. RESULTS: We found a highly statistically significant improvement among both treated groups regarding (ANASI) score and dermatologist's assessments. Bedside, the degree of sulci cutis, cristae cutis, brown-to-dark brown dots, and milia-like cysts, dermoscopic sign improvement was evident in both treated groups. However, fractional CO2 laser shows the superior result to retinoic acid peel in the treatment. CONCLUSION: Fractional CO2 laser and retinoic acid peel are considered effective modalities for neck-AN treatment. However, fractional CO2 laser was more effective.

The efficacy and safety of 20% urea cream and 10% urea cream in the treatment of acanthosis nigricans in adolescents, a randomized comparative double-blind study.

BACKGROUND: Acanthosis nigricans is commonly associated with obesity. It is characterized by brown-black skin thickening on the neck and the flexural areas. This study aimed to assess the efficacy of topical 20% urea cream compared to 10% urea cream in the treatment of acanthosis nigricans in adolescents. MATERIAL AND METHODS: A randomized comparative, double-blind study was conducted on participants aged 12-18 years with acanthosis nigricans of the neck. Treatment efficacy was assessed via narrowband reflectance spectrophotometer, while the overall success rates at weeks 2, 4, and 8 were evaluated by the investigator- and participant-assessed global evaluation scales. RESULTS: A total of 40 participants with acanthosis nigricans were enrolled and completed the study. Throughout the period of 8 weeks of treatment, 20% urea showed greater improvement of hyperpigmentation compared to 10% urea (p = 0.001), with 22.5 ± 11.9% and 10.7 ± 8.1% improvements, respectively. Findings from the overall global evaluation scales were consistent with the results from the narrowband reflectance spectrophotometer. Treatment with 10% urea and 20% urea was well-tolerated without any local serious adverse reactions. CONCLUSION: Urea cream improves neck hyperpigmentation associated with acanthosis nigricans in adolescents, in which the 20% concentration shows superior efficacy to the 10% concentration.

A Case of Nevoid Acanthosis Nigricans Successfully Treated with Topical Ketoconazole Plus Urea.

Dear Editor, Nevoid acanthosis nigricans (AN) is a rare form of benign AN that can be mostly found as a solitary lesion distributed along Blaschko's lines (1). It is not associated with any known syndrome, endocrinopathy, drugs, or internal malignancy. Treatments include retinoid, calcipotriol, and laser treatments (2). Herein we report a case of nevoid AN successfully treated with topical ketoconazole plus urea. A 15-year-old woman presented with a 3-year history of asymptomatic plaques on her abdomen that were increasing in size. She had no medical history and no family history and was not obese. Physical examination revealed dark-brownish pigmented plaques on the midline and right side of her abdomen (Figure 1, a). Potassium hydroxide test was negative. Thyroid function test, antinuclear antibody test, and liver and renal function tests were within normal limits. Histological examination of skin biopsy showed hyperkeratosis and papillomatosis with minimal acanthosis and a mild perivascular lymphocytic infiltration in the superficial dermis (Figure 1, b). Some melanophages were observed in the superficial dermis. Based on the clinical features and these histological findings, a diagnosis of nevoid AN was established. Additionally, there were numerous hyphae and spores in the stratum corneum that were confirmed by Grocott staining (Figure 1, c) and periodic acid-Schiff staining (Figure 1, d). Fungal infection was suggested, and the result of a potassium hydroxide test was considered to be pseudo-negative. Topical ketoconazole cream was initially administrated for one month, and the rough surface was markedly improved (Figure 1, e). Subsequently, topical 20 % urea cream was used and the area of skin lesion decreased in size after 6 months (Figure 1, f). We discontinued ketoconazole cream after 2 months. To the best of our knowledge, this is the first case of nevoid AN successfully treated with topical ketoconazole plus urea. Some cases of AN appear to have an associated endocrinopathy (1). However, genetic factors may also play a role in the pathogenesis of AN. It has been reported that mosaic mutation in fibroblast growth factor 3 (FGFR3) is associated with nevoid AN (3). All known mutations in FGFR3 are gain-of-function mutations, and the activity of the FGFR3 signal correlates with the severity of AN. Involvement of fungal infection has not been reported in the pathogenesis of nevoid AN. We did not identify the fungal species in our patient, but Malassezia infection was suggested. In general, potassium hydroxide test can reveal only yeast forms of Malassezia, and pseudo-negative results may often occur. The abundant hyphae and spores in the stratum corneum are a characteristic pathological feature of Malassezia infection, and the obvious effects of ketoconazole may support the Malassezia infection. Since Malassezia is known to promote cytokine production in human keratinocytes (4), an autocrine FGFR3 signal might accelerate the proliferation of keratinocytes such as myeloma cells (5). Urea is the most widely used moisturizer and keratolytic agent, and has been utilized for the treatment of various hyperkeratotic cutaneous diseases. We successfully treated nevoid AN with the combination of topical ketoconazole and urea. This combination therapy may have fewer side-effects than previous reported treatments and could be considered as an optional treatment. Acknowledgment: The patients in this manuscript have given written informed consent to publication of their case details.

The randomized trials of 10% urea cream and 0.025% tretinoin cream in the treatment of acanthosis nigricans.

BACKGROUND: Acanthosis nigricans is characterized as hyperpigmented skin and velvety surface on posterior and lateral folds of the neck and the intertriginous areas. This study aimed to assess the efficacy of topical 10% urea cream compared to 0.025% tretinoin cream in the treatment of acanthosis nigricans. MATERIAL AND METHODS: This was an 8-week trial, double-blind, randomized, comparative study of topical 10% urea and 0.025% tretinoin for the treatment of the neck hyperpigmentation. The Mexameter MX18 was used for assessing treatment efficacy. The global evaluation scale was also used to evaluate the overall success rate at weeks 2, 4, and 8 of the study. RESULTS: There was a statistically significant difference between 10% urea and 0.025% tretinoin in the treatment of acanthosis nigricans (p < 0.01). The efficacy of 10% urea and 0.025% tretinoin treatment shows 11.4 ± 5.7% and 20.1 ± 9.7% improvement, respectively. The treatment efficacy using the investigator's global evaluation found that 36.8% of participants treated with 10% urea and 63.2% of participants treated with 0.025% tretinoin had more than 75% skin improvement. CONCLUSION: Both medications significantly improved neck hyperpigmentation. However, the efficacy of 0.025% tretinoin was significantly better than 10% urea in the treatment of acanthosis nigricans. CLINICAL TRIALS REGISTRY: TCTR20180703003.

Tripe palms and Malignant Acanthosis Nigricans: More than a diagnostic pointer.

BACKGROUND: Tripe palms (TP) is one of the rare cutaneous paraneoplastic manifestations of various intra-abdominal malignancies. TP and malignant acanthosis nigricans (MAN) occur together and may precede even years before the index cancer. Though rare, the clinical significance of TP and MAN holds significance as an indicator of internal malignancy. CASE: Here, we describe 71-year, postmenopausal female with ovarian cancer who presented to us with a history of dyspepsia, abdominal distension, and weight loss. On detailed history and evaluation, it was found that she had TP and MAN 4 years before diagnosis. CONCLUSION: The unique presentation preceding the primary illness necessitates extensive early work-up to look for malignancy and the initial consideration for surgery due to the tumor biology in such patients.

Nevoid acanthosis nigricans: Report of four cases localized to the umbilicus.

Nevoid acanthosis nigricans is a rare, benign form of acanthosis nigricans. Of the 24 cases documented in the literature, only two are exclusively localized to the umbilicus. We present four cases of nevoid acanthosis nigricans localized to the umbilicus; in patients less than 25 years of age, with no known co-morbidities, three of whom were females. Two of the cases received, with good response, treatment based on topical calcipotriol, a medication not previously reported to be used for this indication. Contrary to other types of acanthosis nigricans, the nevoid acanthosis nigricans is not associated with any syndrome, endocrinopathy, obesity, medication, or neoplasia and it can be confused with other pathologies such as epidermal nevus or dermatosis neglecta.

Paraneoplastic Conjunctival Acanthosis Nigricans: A Case Report.

PURPOSE: To report a patient who presented with red eye and diffuse palpebral conjunctival thickening and papillary growth bilaterally. METHODS: A 63-year-old woman with a medical history of stage IV adenocarcinoma of the lung with metastasis to the bone, the lung, and the lymph nodes presented with redness and irritation of both eyes for 3 months. The patient has been treated with topical corticosteroids for 3 weeks with no relief of symptoms. RESULTS: Clinical examination and pathology report of conjunctival biopsy confirmed the diagnosis of conjunctival acanthosis nigricans. CONCLUSIONS: Conjunctival acanthosis nigricans is a rare paraneoplastic condition that resembles papilloma and can present a challenge in diagnosis. When acanthosis nigricans occurs after the diagnosis of malignancy, it can be an indicator of progression of the underlying condition. The diagnosis of conjunctival acanthosis nigricans in a patient with no history of cancer should prompt clinicians for further malignancy workup.

Resolution of confluent and reticulated papillomatosis after bariatric surgery.

Confluent and reticulated papillomatosis (CARP), a rare dermatologic disorder characterized by hyperpigmented papules that subsequently develop into plaques with reticulated margins, is frequently confused with acanthosis nigricans. The aetiology and pathogenesis of CARP is not yet fully understood, but it is often present in individuals with obesity and PCOS. This case report describes an African American adolescent female with obesity with a rash diagnosed as CARP after unsuccessful treatment with antifungals and corticosteroids. Her dermatosis proved recalcitrant to antibiotics and metformin but started to resolve immediately after bariatric surgery. This case report supports insulin resistance as a contributor to CARP's pathogenesis and as well as its association with obesity. Clinically significant weight reduction should be considered in the management of this challenging skin condition.

Topical rapamycin for acanthosis nigricans in the Fitzpatrick IV/V adolescent population.

Dermatologically, FGFR3 mutations can lead to acanthosis nigricans (AN), epidermal nevi, and seborrheic keratosis. A recent case report found that topical rapamycin (sirolimus) can improve FGFR3-induced epidermal nevi with AN features in children, specifically with Fitzpatrick skin type (FST) I/II, and we would like to expand these findings to skin plaques with extensive AN-like features in the FST IV/V adolescent population. An 18-year-old female with FST IV/V and FGFR3-induced hypochondroplasia presented to our clinic with extensive AN-like plaques. Significant improvement with lightening and thinning of the plaques was observed after applying 1% topical rapamycin cream twice daily. Topical rapamycin should be considered as a treatment option for AN, particularly in FST IV/V adolescents with FGFR3-induced AN.

A Molecular Perspective on the Potential Benefits of Metformin for the Treatment of Inflammatory Skin Disorders.

Due to its anti-hyperglycemic effect, metformin is the first-line medication for the treatment of type 2 diabetes, particularly in people who are obese. However, metformin is a drug with a very wide range of pharmacological properties and reports of its therapeutic effect on diseases including inflammation and cancer are increasing. Numerous research groups have reported that metformin has beneficial effects on a variety of inflammatory skin disorders including psoriasis, acanthosis nigricans, acne, hidradenitis suppurativa, and allergic contact dermatitis. According to these reports, in addition to the well-known action of metformin, that is, its anti-hyperglycemic effect, NF-kB inhibition and the resulting alteration to the cytokine network may be the potential targets of metformin. Its anti-hyperandrogenism effect has also been confirmed as the major action of metformin in some inflammatory skin diseases. Moreover, novel regulatory mechanisms, including autophagy and antioxidant processes, have been suggested as promising mechanisms of action for metformin in inflammatory skin disorders.

A case of acanthosis nigricans in a HIV-infected patient.

BACKGROUND: To date, very little information is available concerning the relationship between acanthosis nigricans (AN) and infection with human immunodeficiency virus type 1 (HIV-1). CASE PRESENTATION: Herein, we report the case of a middle-aged man admitted for fever and progressively worsening dyspnea in the context of an opportunistic pneumonia and firstly diagnosed with acquired immunodeficiency syndrome (AIDS). At the time of diagnosis, physical examination revealed the presence of a palpable, hyperpigmented skin lesion on the left areola with surface desquamation and velvety texture consistent with AN. Of note, the most common primary etiologies related to AN were excluded and the complete regression of the skin lesion was observed once antiretroviral therapy was started. CONCLUSION: This is the second report of AN found in patients with AIDS and apparently responsive to prolonged antiretroviral treatment. Possible explanations of this association are still not completely understood, probably related to virus-induced changes in lipid metabolism. Our experience suggests that HIV testing should always be considered in the setting of apparently idiopathic AN.

Comparison of the effectiveness of fractional 1550-nm erbium fiber laser and 0.05% tretinoin cream in the treatment of acanthosis nigricans: a prospective, randomized, controlled trial.

Acanthosis nigricans is a common dermatological problem. There are currently limited clinical trials to determine the efficacy and safety of laser treatments. To compare the efficacy of fractional 1550-nm erbium fiber laser versus 0.05% tretinoin cream for the treatment of acanthosis nigricans at neck, a randomized, controlled, assessor-blinded study was conducted in 18 subjects with acanthosis nigricans at the neck. All patients were treated with both fractional 1550-nm erbium fiber laser and 0.05% tretinoin cream on each side of the neck. The laser side was treated with three treatment sessions, with a 4-week interval of 1550-nm fractional erbium laser. Another side was treated with 0.05% tretinoin cream daily at bedtime for 12 weeks. We evaluated at baseline, with a 4-week interval until 4 weeks after the last treatment. The efficacy was assessed by skin color ratio, melanin index, average roughness, photographic evaluation, patients' satisfaction, and the adverse effects. At the study endpoint, week 12, the mean Visiometer-average roughness showed greater reduction in laser-treated side (24.65%) than tretinoin side (22.94%) (p = 0.004). Laser-treated side also showed greater percentage of skin color ratio reduction, melanin index reduction, and better mean of photographic-based evaluation percentage change from the baseline than tretinoin side with no significant different (p = 0.331, p = 0.116, p = 0.327, respectively). The study showed one post-inflammatory hyperpigmentation in tretinoin side. Regarding to the average roughness, fractional 1550-nm erbium fiber laser was superior to 0.05% tretinoin cream for treatment of neck-acanthosis nigricans with less side effect. Fractional 1550-nm erbium fiber laser could be considered as an alternative treatment for acanthosis nigricans.