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.

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.

Dermatological manifestations in Costello syndrome: A prospective multicentric study of 31 HRAS-positive variant patients.

BACKGROUND: Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description. OBJECTIVES: To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations. METHODS: We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S). CONCLUSIONS AND RELEVANCE: This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.

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.

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.

Clinical factors associated with remission of obese acanthosis nigricans after laparoscopic sleeve gastrectomy: a prospective cohort study.

BACKGROUND: Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals. METHODS: The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n =178) or OB with AN (OB_AN, n =141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG. RESULTS: OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels ( P <0.01). In addition, there was a significant positive correlation between changes in AN scores and epidermal thickness and skin pigmentation scores after surgery ( P <0.01). CONCLUSION: The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.

Improved Insulin Secretion Response and Beta-cell Function Correlated with Increased Prolactin Levels After Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients with Acanthosis Nigricans.

OBJECTIVE: To explore insulin secretion patterns, ß-cell function, and serum prolactin (PRL) concentrations in Chinese morbidly obese patients with Acanthosis nigricans (AN) and their alterations after laparoscopic sleeve gastrectomy (LSG). METHODS: A total of 138 morbidly obese subjects undergoing LSG were categorized as simple obesity without AN (OB group, n = 55) and obesity with AN (AN group, n = 83). Oral glucose tolerance test (OGTT), PRL, and related metabolic indices were performed pre- and 12 months post-LSG. Insulin secretion patterns were derived from insulin secretion peak time during OGTT: type I (peak at 30 or 60 min) and type II (peak at 120 or 180 min). RESULTS: Preoperatively, AN group showed significantly higher proportions of type II insulin secretion pattern, fasting insulin (FINS), and homeostatic model assessment of insulin resistance (HOMA-IR) whereas lower oral glucose insulin sensitivity (OGIS), insulinogenic index (IGI), and disposition index (DI) than OB group, which were improved significantly at 12 months postoperatively in both groups, more pronounced in AN group. Intriguingly, serum PRL declined substantially in AN group than OB group at baseline whereas elevated only in the AN group post-LSG. After adjusting for confounding factors, elevated PRL correlated significantly with increased IGI and DI, and decreased HOMA-IR in both genders, as well as increased OGIS in females, which was detected only in the AN group CONCLUSION: Morbidly obese patients with AN presented delayed insulin secretion response, impaired insulin secretion, and ß-cell dysfunction, which were significantly improved by LSG and might benefit from elevated PRL.

Dermatoses in overweight and obese children and their relationship with insulin and skin color.

BACKGROUND/AIM: The aim of the present study was to investigate the prevalence of obesity-related dermatoses in obese children, and the association between these dermatoses and insulin resistance as well as skin color. METHODS: Obese, overweight, and normal weight children according to body mass index who were followed up and treated in the outpatient clinics were included in the study. Dermatological examinations of the participants were performed, and fasting insulin and glucose levels were checked. RESULTS: The obese and overweight children were evaluated as the patient group (70 girls, 41 boys, mean age: 12.37 ± 3.14 years). One hundred one healthy children with normal weight were determined as the control group (59 girls, 42 boys, mean age: 12.15 ± 2.43). The first five common dermatoses in the patient group when compared with the control group were keratosis pilaris (KP), striae distensae, hyperhidrosis, acanthosis nigricans (AN), and plantar hyperkeratosis. The first five dermatoses which were positively correlated with formation and insulin resistance were KP, striae distensae, AN, hyperhidrosis, and plantar hyperkeratosis. According to the Fitzpatrick skin scale, we found that the darker the skin color, the higher the probability of AN and KP (OR, 0.298; 95% CI, 0.106-0.834, p = 0.021; OR, 0.306; 95% CI, 0.117-0.796, p = 0.015, respectively). CONCLUSION: Some dermatoses associated with obesity and insulin resistance were not found in obese children, or there was no significant association. These results indicate that many skin morbidities may be prevented by preventing and treating obesity and insulin resistance in the early period.

T follicular helper phenotype mycosis fungoides associated with acanthosis nigricans.

The association between acanthosis nigricans (AN) and mycosis fungoides (MF) has rarely been described, but it is known that MF may appear as AN-like vegetating and papillomatous plaques in skin folds, or may be associated with paraneoplastic AN. There have also been recent descriptions of a form of "intertriginous MF" that is characterized by skin fold involvement and the expression of T follicular helper (TFH) markers, and that often has an aggressive course. We describe the case of a 48-year-old man affected by MF associated with AN, whose lesions were characterized by a TFH immunophenotype and the expression of the GATA-3 nuclear master regulator that may be related to a TFH-2 subpopulation or possible disease progression.

Appearances may be deceptive: florid cutaneous and mucosal papillomatosis.

We present a case in which a patient presented with widespread cutaneous warty lesions misdiagnosed as warts 3 months before the diagnosis of his advanced gastric adenocarcinoma. Florid cutaneous and mucosal papillomatosis is a paraneoplastic dermatosis, following a parallel course with the underlying malignancy, which is most often gastric adenocarcinoma.

Evaluation of androgen-dependent skin findings of polycystic ovary syndrome (PCOS).

AIM: The purpose of the study was to investigate the biochemical and metabolic abnormalities related to the cutaneous characteristics of PCOS. MATERIAL­METHODS: Patients diagnosed with PCOS were included in the study. Demographic data and accompanying androgen-dependent skin findings (acne, seborrhea, androgenic alopecia, acanthosis nigricans, skin tag, and hirsutism) were recorded. The free testosterone, total testosterone, dehydroepiandrosterone sulfate, androstenedione,17-Hidroksi progesterone, sex hormone binding globulin, prolactin, fasting glucose, fasting insulin, HbA1C, HDL, and triglycerides, follicle-stimulating hormone, luteinized hormone, free androgen index, and HOMA-IR levels of the patients were measured. The hormonal values of the patients with PCOS with and without skin findings were compared. RESULTS: The HOMA-IR values of the acanthosis nigricans (+) PCOS group were significantly higher than the acanthosis nigricans (-) PCOS group (p < .001). The DHEA-SO4, FAI, and FI values of patients with hirsutism (HR) (+) PCOS were found to be statistically higher than patients with HR (-) PCOS (p = .006, p = .015, p = .004). CONCLUSION: PCOS is among the most common endocrine disorders of women of reproductive age and was associated with some hormonal, metabolic, and skin findings. Certain androgenic and metabolic variables developing in PCOS might correlate with cutaneous symptoms.

Two Cases of Insulin-Derived Amyloidosis With Acanthosis Nigricans-Like Changes.

ABSTRACT: Insulin-derived amyloidosis (AIns) is a rare iatrogenic subtype of cutaneous amyloidosis occurring at frequent insulin injection sites. Here, we describe 2 cases of AIns accompanied by acanthosis nigricans (AN)-like changes, a rare finding which has been reported fewer than 5 times in the literature. We also report the first case of an AIns nodule being misdiagnosed as a keloid. Both of our patients presented with asymptomatic, hyperkeratotic, pigmented plaques at frequent insulin injection sites, and histopathologic examination showed (1) nodular aggregates of amyloid demonstrating apple-green birefringence with Congo red staining and (2) AN-like features, such as epidermal papillomatosis, hyperkeratosis, and hyperpigmentation. Accurate diagnosis of AIns is crucial, because repeated insulin injection into a nodule can impair glycemic control. However, misdiagnosis is common, as observed with our second patient, whose AIns nodule was misdiagnosed by an outside provider as a keloid, perhaps because of the presence of AN-like features. Our case report adds to the limited but growing body of literature on AIns and significantly increases the number of reported cases of AIns with AN-like features, an even rarer phenomenon.

[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.

Berardinelli-Seip Congenital Lipodystrophy - A Case Report and Review of Literature.

Berardinelli-Seip Congenital Lipodystrophy (BSCL), also known as congenital generalised lipodystrophy, is a genetic disorder where there is an absolute deficiency of adipose tissue. It affects the development of adipocytes and ultimately leads to an inability to store fat in adipocytes. It is extremely rare. Most of the cases reported are from Africa and North America. Only a handful of cases have been reported in the world. The aim of this case report is to highlight the significance of this rare metabolic disorder, which should be considered whilst managing young patients with severe insulin resistance. We present a case of a young Asian child with an increasing need for insulin for his diabetes. He was previously managed on the lines of type 1 diabetes mellitus and his insulin requirements kept on increasing. Diagnosis on the basis of genetic studies was not possible due to the non-availability of the test in Pakistan. BSCL is an infrequent condition leading to several cardiometabolic complications. Timely diagnosis can lead to better management and prevention of complications. Keywords: Insulin resistance, Lipodystrophy, Acanthosis nigricans, Hypertriglyceridemia, Genetic disease.