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 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.

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.

Comparison of the efficacy and safety of 0.1% adapalene gel and 0.025% tretinoin cream in the treatment of childhood acanthosis nigricans.

BACKGROUND: There have been few published randomized controlled trials for the treatment of childhood acanthosis nigricans (AN) to date. OBJECTIVE: To assess the efficacy of topical 0.1% adapalene gel compared to 0.025% tretinoin cream in the treatment of childhood AN. METHODS: An 8-week, randomized, split-neck, comparative study between topical 0.1% adapalene gel and 0.025% tretinoin cream for the treatment of neck hyperpigmentation associated with AN was performed. M index measured by a narrowband reflectance spectrophotometer and both investigator's global evaluation (IGE) and parent's global evaluation (PGE) scales were used to evaluate efficacy. RESULTS: There was no statistically significant difference between 0.1% adapalene gel and 0.025% tretinoin cream in the treatment of AN-associated hyperpigmentation (P = 0.56). Mean differences in M indices between week 0 and week 8 of 0.1% adapalene and 0.025% tretinoin treatment were 24.2 ± 7.9% and 23.8 ± 8.3% improvement, respectively. Regarding treatment efficacy, 90.0% and 85.0% of participants had more than 75% improvement in IGE in 0.1% adapalene and 0.025% tretinoin treatment sides, respectively. In addition, 75.0% and 65.0% of participants had more than 75.0% improvement in PGE in 0.1% adapalene and 0.025% tretinoin treatment sides, respectively. LIMITATIONS: Lack of histopathological evaluations. CONCLUSIONS: We found no significant difference between topical 0.1% adapalene gel and 0.025% tretinoin in the treatment of AN.

Acanthosis Nigricans and Its Response to Metformin.

Acanthosis nigricans (AN) is the most common cutaneous manifestation of insulin resistance (IR) and is commonly seen in non-Caucasian populations. Variable benefits of metformin in the treatment of AN have been reported in the literature. We report an adolescent Caucasian boy with IR and extensive AN who showed complete resolution of AN after 2 years of metformin, despite persistence of IR.

Effective treatment by glycolic acid peeling for cutaneous manifestation of familial generalized acanthosis nigricans caused by FGFR3 mutation.

BACKGROUND: Acanthosis nigricans (AN) can occur as a cutaneous manifestation of genetic diseases, one of which is associated with activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3). OBJECTIVE: We explored familial AN patients with FGFR3 mutations and examined the effectiveness of glycolic acid (GA) peeling in improving their skin manifestations. METHODS: Sanger sequencing was performed for the genomic DNA extracted from leucocytes of the family members involving familial AN. GA peeling was carried out for the two patients of familial AN once every 2 weeks. RESULTS: Heterozygous c.1949A>C (p.K650T) mutation in FGFR3 was identified for the affected family members examined, whereas the wild-type sequence was found for two unaffected individuals. Hyperpigmentation and coarseness of the skin were improved by GA peeling at regular intervals with few adverse effects. CONCLUSION: We diagnosed our cases as familial generalized AN caused by heterozygous c.1949A>C (p.K650T) mutation of FGFR3. We propose that GA peeling is a useful and safe therapeutic option to treat familial AN.

[Woman 19-old with hirsutism, obesity and acanthosis nigricans]. / Chora lat 19 z hirsutyzmem, otyloscia i zmianami skórnymi o typie rogowacenia ciemnego.

19-year-old hirsute woman with obesity, skin lesions with features of acanthosis nigricans around neck, armpits, thoracic cage and wrists escalating for couple of months, elevated testosterone and insulin plasma levels was admitted to hospital to perform diagnostic approach. The final diagnosis was hyperandrogenism-insulin resistance-acanthosis nigricans syndrome (HAIR-AN syndrome), considered as a subtype of policystic ovary syndrome (PCOS) and impaired glucose tolerance. HAIR-AN is characterized by coexistence of: hyperandrogenism (HA), insulin resistance (IR) and acanthosis nigricans (AN). These symptoms are result of increased insulin and androgens levels. Due to accompanying complications (obesity, hyperglycemia, hyperlipidemia, infertility) patients with HAIR-AN syndrome should be monitored and treated. Rarely acanthosis nigricans, especially when occurs rapidly and extensively, may be a paraneoplastic disorder. Life style modification with BMI reduction was recommended and metformin, a drug improving sensitivity to insulin, was administered. Patient should be monitored due to possible complications of obesity, diabetes and hyperinsulinemia.

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.

Does insulin resistance co-exist with glucocorticoid resistance in the metabolic syndrome? Studies comparing skin sensitivity to glucocorticoids in individuals with and without acanthosis nigricans.

BACKGROUND: The metabolic syndrome is associated with increased risk for both diabetes and coronary artery disease, which insulin resistance alone does not satisfactorily explain. We propose an additional and complementary underlying mechanism of glucocorticoid resistance. RESULTS: Using acanthosis nigricans (AN) and skin vasoconstrictor (SVC) response to topically applied beclomethasone dipropionate as markers of insulin and glucocorticoid resistance, respectively, we compared anthropometric, biochemical, pro-inflammatory markers and the SVC response in subjects with AN in two studies: STUDY 1 was used to compare subjects with AN (Grade 4, n = 32), with those without AN (n = 68) while STUDY 2 compared these responses among a cross-section of diabetic patients (n = 109) with varying grades of AN (grade 0, n = 30; grade 1, n = 24; grade 2, n = 18; grade 3, n = 25; grade 4, n = 12). FINDINGS: In both studies there was an inverse relationship between AN Grade 4 and the SVC response, (P < 0.001). In STUDY 1, AN Grade 4 was associated with age, waist circumference, BMI, fasting blood glucose, plasma lipids and hs-CRP (P < 0.05). SVC was an independent predictor of CRP and those with combined AN and a negative SVC response, CRP levels were highest. In Study 2 when the SVC response in subjects with type 2 diabetes mellitus with varying degrees of AN was studied, it showed that for any degree of AN, the SVC response is more likely to be negative and was independent of gender and ethnicity. CONCLUSION: An absent SVC response represents a new biomarker for the metabolic syndrome and the exaggerated inflammatory response, which characterizes the metabolic syndrome, may be an outcome of deficient glucocorticoid action in vascular tissue.

[Paraneoplastic acanthosis nigricans of the esophagus: a case report]. / Acanthosis nigricans als paraneoplastische Erkrankung des Ösophagus: ein Fallbericht.

A 69-year-old man presented for endoscopic examination of the upper gastrointestinal tract because of dysphagia for solid food and unintended weight loss. Several months before, he had noticed brownish-gray skin lesions in the neck, in the thorax and in both axillae. A dermatological consultant expressed the suspicion of a paraneoplastic disease. Endoscopic examination revealed an adenocarcinoma of the esophagogastric junction as well as multiple small polyps in the middle and the lower thirds of the esophagus. Histological examination showed papilloma-like proliferations without atypia, which were diagnosed as acanthosis nigricans of the esophagus. After completion of the staging investigation regarding the cardiac carcinoma, combination chemotherapy was started because of the presence of liver metastases. Subsequently, partial regression of the carcinoma as well as of the dermal and esophageal lesions was noted. Acanthosis nigricans is a rare paraneoplastic disease of the esophagus. As an indicator lesion, its detection should prompt a search for a malignant tumor in the gastrointestinal tract.

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.

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.

Risk factors for medication-induced diabetes and type 2 diabetes.

OBJECTIVE: To compare the prevalence of risk factors in children aged <18 years diagnosed with medication-induced diabetes mellitus versus those diagnosed with type 2 diabetes. STUDY DESIGN: This retrospective observational study used data from a Canadian prospective surveillance study in which clinical features of new cases of type 2 diabetes (n = 225) and medication-induced diabetes (n = 58) were reported over a 2-year period. The presence of risk factors for type 2 diabetes (eg, obesity, family history of type 2 diabetes, ethnicity, acanthosis nigricans, hypertension, polycystic ovarian syndrome) was compared in the 2 groups using descriptive statistics and logistic regression. RESULTS: Compared with the children with type 2 diabetes, the children with medication-induced diabetes were more likely to be Caucasian (P < .0001) and less likely to be obese (P < .0001), to have a positive family history of type 2 diabetes (P = .0001), to have acanthosis nigricans (P < .0001) on clinical examination, and to have an obesity-related comorbidity, such as polycystic ovarian syndrome (P = .04), dyslipidemia (P = .02), hypertension (P = .04), or an elevated alanine aminotransferase level (P = .05). CONCLUSIONS: Evaluating for the typical risk factors for type 2 diabetes is not sufficient to identify all children at risk for developing medication-induced diabetes. Further studies are needed to help inform guidelines on screening for and prevention of medication-induced diabetes in children.

Acne-associated syndromes: models for better understanding of acne pathogenesis.

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea-acne-hirsutism-androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) and pyogenic arthritis-pyoderma gangrenosum-acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.