An Indian Expert Group Review of Acanthosis Nigricans with Recommendations for Early Detection and Timely Management.

INTRODUCTION: Acanthosis nigricans (AN) is a visible cutaneous manifestation of several underlying systemic conditions, such as prediabetes, diabetes mellitus (DM), polycystic ovarian syndrome (PCOS), metabolic syndrome (MS), and malignancy. AN is commonly seen in obese individuals and is a proven skin marker of insulin resistance (IR). Its typical clinical presentation and location, especially on the nape of the neck, allows for easy visual identification. Obesity, IR, and other noncommunicable diseases (NCD) are on the rise in India, with many cases being undiagnosed or missed. Every sixth diabetic in the world is Indian. AN can thus play a vital role in screening, early identification, and reduction of morbidity, especially of IR-related disorders. Currently, there are no national or international multidisciplinary guidelines or recommendations for AN. OBJECTIVE: To review published current literature and evidence on AN, its associations, and management. To recommend an approach to clinical identification of AN, associated/underlying disorders, investigations, and management, including lifestyle modifications. To sensitize and familiarize clinicians and healthcare workers across India with AN presentations. This will enable early detection of conditions such as IR, prediabetes, DM, PCOS, malignancy, etc., in practice and in the community. MATERIALS AND METHODS: The PCOS Society of India constituted a multispecialty Expert Working Group with representation from various national societies to review all published scientific evidence. Expert group meetings were conducted to provide recommendations. CONCLUSION: Acanthosis nigricans is a simple, non-invasive, cost-effective screening tool for early identification of IR. It is important to integrate and disseminate information and training on AN across medical specialties. The government of India has launched several National Health Programmes to help address the rising burden of NCD in the population. AN would provide a simple screening tool to pick up undiagnosed or missed cases.

Gender, racial, ethnic, and Fitzpatrick skin type representation in Acanthosis nigricans clinical trials.

Acanthosis nigricans (AN) is characterized by dark, velvety patches and thin plaques primarily in the body folds. AN is more prevalent in skin of color populations, including Black/African American, Native American, and Hispanic patients. As the U.S. population becomes increasingly diverse, the need for inclusive dermatologic research becomes more pressing. Given the increased prevalence of AN in skin of color patients, there is a need to evaluate representation in AN clinical trials. This study aims to uncover gender, race, ethnicity, and Fitzpatrick skin type (FST) representation in AN clinical trials. A systematic literature search was performed across PubMed, Embase, and Cochrane databases to identify participant characteristics in clinical trials focused on AN treatment. Our review yielded 21 clinical trials, totaling 575 participants, with an identified predominance of female participants (69.0%) and a surprising absence of race or ethnicity data. Out of the 11 studies that included FST data, 1.2% of participants were type II, 20.6% were type III, 50.0% were type IV, and 28.2% were type V. None of the participants were FST I or VI. Herein, we highlight a predominate inclusion of female and FST III-V patients in AN clinical trials, the populations most impacted by this condition. We also highlight the need for improved race and ethnicity reporting and the importance of including all FSTs in clinical studies. Addressing this gap is critical for developing safe, efficacious, patient-centered, and equitable treatments for all AN patients. Future research should prioritize comprehensive inclusion of race, ethnicity, and the full spectrum of FSTs.

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.

Utility of "Acanthosis Nigricans" and "Skin Tags" as a screening tool for risk of developing noncommunicable diseases: A cross-sectional study at a health facility in Lucknow (India).

Context: Over the past three decades, there has been a significant rise in the prevalence of noncommunicable diseases (NCDs) globally, accompanied by a relative decline in communicable diseases. Aims: With this background, the research was planned to determine the prevalence of acanthosis nigricans (AN) or skin tags (STs) in the study population and to examine the relationship between the presence of AN and ST with commonly used indicators such as waist-to-height ratio (W/Ht.), Indian Diabetes Risk Score (IDRS), and body mass index for predicting the risk of NCDs. Settings and Design: This cross-sectional study was done at a health facility in Lucknow (India). Methodology: Consecutive sampling was employed to select 152 apparently healthy adults as the participants. Data collection involved administering a questionnaire and conducting anthropometry using standardized methods. Visual inspection was conducted to identify AN or ST on the common sites. Statistical Analysis Used: Data entry was done in Microsoft Office Excel, followed by data analysis using SPSS. To test the association between variables "significance of difference of mean," Chi-square test, logistic regression analysis, and estimation of Kohen's kappa were used. A "P" value was considered statistically significant at <0.05 level. The sensitivity and specificity of AN and ST were also estimated in predicting the risk of NCDs. Results: The prevalence of AN was 19.08% (95% confidence interval [CI] = 12.76%-25.40%), while the prevalence of STs was 28.29% (95% CI = 21.05%-35.53%). AN showed a sensitivity of 22.4% and specificity of 96.3% with W/Ht. ratio as the standard, and a sensitivity of 26.44% and specificity of 90.77% with IDRS as the standard. ST exhibited a sensitivity of 32.0% and specificity of 88.89% with W/Ht. ratio as the standard, and a sensitivity of 37.93% and specificity of 84.62% with IDRS as the standard. Conclusion: AN and ST can be used as simple and time-saving tools in screening protocols for (NCDs). Further research is desirable to validate the findings.

Résumé Contexte: Au cours des trois dernières décennies, il y a eu une augmentation significative de la prévalence des maladies non transmissibles (MNT) à l'échelle mondiale, accompagnée d'un déclin relatif des maladies transmissibles. Objectifs: Dans ce contexte, la recherche était prévue pour déterminer la prévalence de l'acanthose nigricans (AN) ou des acrochordons (ST) dans la population étudiée et pour examiner la relation entre la présence d'AN et de ST avec des indicateurs couramment utilisés tels que la taille. rapport taille (W/Ht.), score de risque de diabète indien (IDRS) et indice de masse corporelle pour prédire le risque de MNT. Paramètres et conception: cette étude transversale a été réalisée dans un établissement de santé à Lucknow (Inde). Méthodologie: Un échantillonnage consécutif a été utilisé pour sélectionner 152 adultes apparemment en bonne santé comme participants. La collecte de données impliquait l'administration d'un questionnaire et la réalisation d'anthropométries à l'aide de méthodes standardisées. Une inspection visuelle a été réalisée pour identifier AN ou ST sur les sites communs. Analyse statistique utilisée: La saisie des données a été effectuée dans Microsoft Office Excel, suivie d'une analyse des données à l'aide de SPSS. Pour tester l'association entre les variables " signification de la différence de moyenne ", le test du chi carré, l'analyse de régression logistique et l'estimation du kappa de Kohen ont été utilisés. Une valeur " P " a été considérée comme statistiquement significative au niveau < 0,05. La sensibilité et la spécificité de l'AN et du ST ont également été estimées pour prédire le risque de MNT. Résultats: La prévalence de l'AN était de 19,08 % (intervalle de confiance à 95 % [IC] = 12,76 % à 25,40 %), tandis que la prévalence des ST était de 28,29 % (IC à 95 % = 21,05 % à 35,53 %). AN a montré une sensibilité de 22,4 % et une spécificité de 96,3 % avec W/Ht. ratio comme standard, et une sensibilité de 26,44 % et une spécificité de 90,77 % avec IDRS comme standard. ST présentait une sensibilité de 32,0 % et une spécificité de 88,89 % avec W/Ht. ratio comme standard, et une sensibilité de 37,93 % et une spécificité de 84,62 % avec IDRS comme standard. Conclusion: AN et ST peuvent être utilisés comme des outils simples et permettant de gagner du temps dans les protocoles de dépistage des (MNT). Des recherches plus approfondies sont souhaitables pour valider les résultats. Mots-clés: diagnostic d'Acanthosis nigricans, dépistage des maladies non transmissibles, diagnostic des acrochordons.

Acanthosis nigricans independently predicts hepatic fibrosis in people with type 2 diabetes in North India.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. METHODOLOGY: We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. RESULTS: Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91-3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93-61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50-4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235-0.76420). CONCLUSION: Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies.

Combination of metformin with liraglutide in treating HAIR-AN syndrome in children: A case report and literature review. / 二甲双胍联合利拉鲁肽治疗儿童HAIR-AN综合征1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndrome is a special and rare subtype of polycystic ovarian syndrome. It can lead to hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) accompanied by acne, hirutism, irregular menstruation, and other androgen excess symptoms. A case of pediatric HAIR-AN syndrome with severe AN was admitted to the Department of Endocrinology, China-Japan Friendship Hospital. The patient's clinical manifestations, laboratory data, imaging features, and gene sequencing were analyzed, and the patient was diagnosed with pediatric HAIR-AN syndrome. Obesity, IR, hyperglycemia, menstrual disorder, and AN were significantly improved after treating with metformin and liraglutide. HAIR-AN syndrome occurs in various forms. When the patient appears unexplained acanthosis nigricans and menstrual disorders, the disease should be considered possible. Early diagnosis and symptomatic supportive treatment can improve the quality of life.

Correlation between Acanthosis Nigricans Scoring Chart (ANSC) and narrowband reflectance spectrophotometer in assessing severity of acanthosis nigricans.

INTRODUCTION: There is a lack of standardized tool to monitor treatment outcome of acanthosis nigricans. To meet this end, we developed the Acanthosis Nigricans Scoring Chart (ANSC) that evaluates skin color (score range of 1-8) and skin texture (score range of 1-6), which adds up to a total ANSC score (score range of 2-14). We aimed to determine the correlation of ANSC to narrowband reflectance spectrophotometry and to evaluate its reliability. METHODS: A cross-sectional study was conducted in adult acanthosis nigricans patients. Two raters independently graded participants using ANSC twice, in which scores were correlated to readings from Mexameter MX18. Intra- and interrater reliability were also evaluated via intraclass correlation coefficient (ICC). RESULTS: Participants had mean (sd) melanin and erythema indices of 615.8 (176.2) and 451.4 (53.4), respectively. Mean (sd) total ANSC score was 9.43 (2.43). The total ANSC score and skin color subdomain demonstrated strong correlations (r > 0.6) with spectrophotometric results, whereas skin texture showed a moderate correlation (r = 0.4-0.6). Total ANSC score generally had excellent intra- and interrater reliabilities (ICC > 0.85). CONCLUSION: The total ANSC score and its subdomains strongly correlate with spectrophotometer and demonstrate excellent reliability in assessing acanthosis nigricans.

Insulin resistance in various grades of acanthosis nigricans.

INTRODUCTION: Insulin resistance (IR) is a metabolism disorder that contributes to the pathophysiology of acanthosis nigricans (AN). In turn, AN is a self-determining risk factor and cutaneous marker of IR. However, conflicting evidence makes the AN-IR relationship debatable and open to exploration. If established, it could provide opportunities for early diagnosis and management of IR before the onset of diabetes mellitus and its complications by screening AN patients. This study investigates the prevalence of IR among AN patients and evaluates the association between IR and AN severity. METHODS: Eighty-seven patients, 18 to 60 years old, with untreated AN and absence of diabetes mellitus, underwent detailed history, systemic, and cutaneous examinations, as well as measurement of their body mass index (BMI), waist and hip circumference and their ratio (WHR), fasting blood glucose (FBG) and lipid profile, fasting serum insulin levels, and quantitative insulin-sensitivity check index (QUICKI). Severity of the neck lesions was graded according to Burke et al.'s grading system. RESULTS: AN was noted most commonly in younger age groups with 93.1% of the cases younger than 45. All patients had lesions on the neck, and 63.3% of the cases had multiple site involvement. Nearly 84% of the cases were overweight or obese. AN grades exhibited a significant positive association with BMI (p = 0.002) and WHR (p = 0.016). High IR (< 0.35 QUICKI) was seen in 55 (63.2%) AN patients. IR, QUICKI, and triglyceride levels showed no significant association with AN severity and the number of AN lesion sites (p > 0.05). LDL levels (p = 0.02) and WHR (p = 0.049) showed a significant positive association with the number of AN lesion sites, but not with AN severity grading (p > 0.05). CONCLUSIONS: IR is present in AN patients, but the association between IR and AN severity is not significant enough to qualify AN as a screening tool for IR.

Acanthosis Nigricans Is a Strong Predictor of Low Blood Calcidiol Levels in Children and Adolescents.

Background: Clinical consensus differs as to when blood vitamin D (VD) levels should be measured in children. Obesity and metabolic syndrome are risk factors for low VD levels and are also associated with acanthosis nigricans (AN). Objectives: To test whether the clinical diagnosis of AN is a strong predictor for vitamin D deficiency (VDD) in children. Methods: Within the study period (2015-2020), we identified 677 consecutive individuals (age <18 years) with available calcidiol measurements and compared those with (n = 273) and without (n = 404) AN. Bivariate associations and the occurrence of AN were tested using the chi-squared test. Multivariate logistic regression was performed to control for confounding variables, and adjusted odds ratios with 95% confidence intervals (CI) were reported. Multiple regression analysis was performed, and unstandardized beta coefficients, standard errors, and standardized beta coefficients were reported. Results: Individuals with AN had 3.6 times higher odds of VDD than those without (95% CI: 1.38-9.51, P = 0.009). Males had 0.41 times lower odds of having AN than females (95% CI: 0.21-0.79, P = 0.008). Individuals with vitamin D sufficiency (VDS) were much less likely to be diagnosed with metabolic syndrome compared with those who were vitamin D deficient (P = 0.011), even after adjusting for body mass index z-scores. Conclusion: Children and adolescents with AN are at a higher risk of VDD and should likely be tested for low calcidiol levels.

[The 495th case: young female-hyperandrogenemia-severe insulin resistance].

A 22-year-old female has complained of hirsutism, acanthosis nigricans, enlarged clitoris, and menstrual disorders since puberty. Laboratory examinations revealed hyperandrogenemia. Severe insulin resistance and diabetes were found during hospitalization in our hospital. She was diagnosed with type A insulin resistance syndrome finally. After treatment with metformin, the acanthosis nigricans was significantly relieved, blood glucose was controlled satisfactorily, and the menstrual cycle was restored.

Acanthosis Nigricans: An Updated Review.

BACKGROUND: Early recognition of acanthosis nigricans is important because acanthosis nigricans can be a cutaneous manifestation of a variety of systemic disorders and, rarely, as a sign of internal malignancy. OBJECTIVE: The purpose of this article is to familiarize pediatricians with the clinical manifestations, evaluation, diagnosis, and management of acanthosis nigricans. METHODS: A search was conducted in November 2021in PubMed Clinical Queries using the key term "acanthosis nigricans". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. RESULTS: Acanthosis nigricans is characterized by symmetric, hyperpigmented, and velvety plaques with ill-defined borders, typically involving intertriginous areas. Obesity is the most common cause of acanthosis nigricans which is increasingly observed in obese children and adolescents and can serve as a cutaneous marker of insulin resistance. Early recognition of acanthosis nigricans is important because acanthosis nigricans can also be a cutaneous manifestation of a variety of systemic disorders and, rarely, as a sign of internal malignancy. This may consist of weight reduction, discontinuation of causative drugs, treatment of underlying endocrinopathy, or treatment of an underlying malignancy. For patients with isolated acanthosis nigricans and for those whose underlying cause is not amenable to treatment, treatment of the lesion may be considered for cosmetic reasons. Topical retinoids, vitamin D analogs, chemical peels, and other keratolytics are often used for the treatment of localized lesions. Seldom, systemic therapy such as oral retinoids may be considered for extensive or generalized acanthosis nigricans and acanthosis nigricans unresponsive to topical therapy. Other uncommon treatment modalities include dermabrasion, laser therapy, and surgical removal. CONCLUSION: Although acanthosis nigricans is treatable, a complete cure is difficult to achieve. The underlying cause should be treated, if possible, to resolve and prevent the recurrence of acanthosis nigricans. The diagnosis is mainly clinical, based on the characteristic appearance (symmetrically distributed, hyperpigmented, velvety, papillomatous, hyperkeratotic plaques with ill-defined borders) and the typical sites (intertriginous areas, flexural area, and skin folds) of the lesions. The diagnosis might be difficult for lesions that have atypical morphology or are in an unusual location. Clinicians should be familiar with the clinical signs, evaluation, diagnosis, and therapy of acanthosis nigricans because of the link between it and underlying diseases.

Malignant acanthosis nigricans and diseases with extensive oral papillary hyperplasia.

Oral papillary lesions represent a variety of developmental and neoplastic conditions. Early diagnoses of different papillary lesions are challenging for oral medicine specialists. Malignant acanthosis nigricans (MAN) is a rare cutaneous disorder and a potential marker of underlying hidden tumours. It is characterized by papillary lesions that always involve the oral mucosa. In oral medicine specialities, MAN is not well understood. When the early signs of MAN are extensive oral lesions and slight cutaneous pigmentation without obvious florid cutaneous papillomatosis, the diagnosis can be incorrect or delayed. Oral medicine specialists should ask affected patients to provide details of their medical history and conduct a timely systemic examination.

[How to explore... hyperandrogenism associated with insulin resistance ? An example based on the HAIR-AN syndrome.] / Comment j'explore une hyperandrogénie dans un contexte d'insulinorésistance. Un exemple basé sur le syndrome HAIR-AN.

HAIR-AN, a syndrome associating hyperandrogenism, insulin resistance and acanthosis nigricans, is currently considered as a severe form of polycystic ovary syndrome. The physiopathology of this syndrome relies on the insulin resistance which is the basis of a vicious circle : the resulting hyperinsulinism leads to an excessive production of androgens. The latter increases abdominal fat deposition which in turn worsens the insulin resistance. Hyperinsulinism is also responsible for the acanthosis nigricans by stimulating the IGF-1 receptors on keratinocytes and fibroblasts. Hyperandrogenism is clinically translated into hirsutism that can be severe. Frequently, menstrual irregularity and obesity are part of the syndrome. HAIR-AN syndrome begins soon after puberty and is currently under-diagnosed. Treatment relies on an improvement in insulin-resistance by a loss of body weight and the use of insulin sensitizers. Moreover, anti-androgenic drugs will help improving hirsutism. Although more invasive, bariatric surgery has shown a great efficacy in this syndrome : by permitting a substantial loss of weight, it often normalizes insulin-sensitivity, allowing for improvements in hyperandrogenism and acanthosis nigricans.

Considéré comme une forme sévère du syndrome des ovaires micropolykystiques, le syndrome de HAIR-AN associe une hyperandrogénie, une résistance à l'insuline et un acanthosis nigricans. La base physiopathologique du syndrome HAIR-AN est un cercle vicieux ayant pour point de départ la résistance à l'insuline : l'hyperinsulinisme qui en résulte entraîne une production excessive d'androgènes. Ces derniers, en aggravant le dépôt de graisse abdominale, majorent la résistance à l'insuline. Il s'agit donc d'un phénomène auto-entretenu. En stimulant le récepteur à l'IGF-1 des kératinocytes et des fibroblastes, l'hyperinsulinisme est également responsable de l'acanthosis nigricans. L'hyperandrogénie se traduit cliniquement par un hirsutisme pouvant être sévère. On notera fréquemment aussi une irrégularité menstruelle et une obésité. Le syndrome HAIR-AN débute tôt après la puberté et est actuellement sous-diagnostiqué. Le traitement est, avant tout, celui de la résistance à l'insuline et nécessite donc une perte de poids associée à l'utilisation de molécules insulino-sensibilisatrices. De plus, des traitements hormonaux anti-androgéniques aideront également à diminuer le hirsutisme. Plus invasive, la chirurgie bariatrique a cependant démontré une grande efficacité chez ces patientes : en permettant une perte de poids conséquente, elle normalise souvent la sensibilité à l'insuline, ce qui améliore significativement l'hyperandrogénie et l'acanthosis nigricans.

Paraneoplastic Dermatoses in Breast Cancer: Malignant Acanthosis Nigricans with Tripe Palm.

Our patient was a 43-year-old, single black woman, born and living in Paracambi, State of Rio de Janeiro, who worked as a surgical instrumentalist. She was sent to our sector of dermatology due to hypochromia and diffuse skin roughness that had first appeared 8 years previously. She had been diagnosed 6 months before admission with ductal infiltrating metastatic carcinoma in the right breast, with therapeutic failure of chemotherapy and radiotherapy. Her menarche had occurred at age 13 years, she reported normal menstrual cycles from there on, and she had never been pregnant. She denied neoplasias and other comorbidities in her family history.