Search Results (34)

Morbid obesity is a chronic condition characterized by metabolic disorders and low-grade chronic inflammation, both of which are closely linked to insulin resistance and adipokine dysregulation. In addition to its systemic effects, obesity also leads to structural and functional changes in the skin, supporting its role as an active metabolic and immunological organ. This study analyzed skin lesions occurring in individuals with morbid obesity and explored their potential relevance in the context of metabolic risk and treatment response rather than establishing clinically validated tools. The focus was on how excess adipose tissue affects the skin through metabolic, hormonal and mechanical mechanisms. Although this review focuses on morbid obesity, many of the included studies examine general obesity without separating its severity. Therefore, the findings may not fully reflect patients with BMI ≥ 40 kg/m² and should be interpreted with caution. Three main areas were considered: the pathophysiological mechanisms underlying obesity-related skin lesions, selected dermatological manifestations as potential markers associated with metabolic risk, and changes in these manifestations during pharmacological, surgical, and lifestyle interventions. Available studies show that acanthosis nigricans and multiple acrochordons are consistently associated with insulin resistance, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease. An increase in BMI is also associated with impairment of the epidermal barrier, changes in the composition of skin lipids, and modifications of the skin microbiome, while biomechanical factors promote the development of chronic inflammation in the intertriginous areas. It has been shown that normalization of metabolic parameters achieved through GLP-1-based pharmacotherapy, bariatric surgery, or lifestyle changes can improve some skin manifestations, especially acanthosis nigricans. However, it should be emphasized that most available data are based on cross-sectional or observational studies, and validated composite dermatological indices are still unavailable. Skin changes in patients with morbid obesity often reflect underlying metabolic and hormonal disturbances. They may have potential as additional, non-invasive clinical clues, but they should not be treated as independent tools for risk assessment or treatment monitoring. At present, most evidence shows associations only, and it is unclear whether these findings add meaningful predictive value beyond standard metabolic markers. More prospective studies are needed to confirm their clinical usefulness and to define their role in assessing metabolic risk and monitoring treatment over time. Full article

Autosomal recessive familial partial lipodystrophy type 5 (FPLD5) due to a homozygous NP_001186481.1; p.E186* CIDEC variant has previously been reported in a 19-year-old female with diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. Now, we report an 18-year-old Hispanic female who presented with FPL, along with hirsutism, acanthosis nigricans, and marked insulin resistance, and was found to have an extremely rare homozygous variant in CIDEC (NM_001199623.2:c.224G>T; NP_001186552.1; p.Ser75Ile) by whole exome sequencing. She also harbored a novel homozygous variant in WRN (NM_000553.4:c.1856T>G; NP_000544; p.Leu619Arg). Both serine 75 of the CIDEC protein and leucine 619 of the WRN protein were well conserved across species. She developed an invasive papillary thyroid carcinoma at the age of 17 years. Our report confirms the previously reported association of the biallelic CIDEC variant with the FPL phenotype and also highlights the extremely rare possibility of co-occurrence of FPLD5 with thyroid cancer, a clinical feature of Werner syndrome. Thus, our patient may not only need surveillance for the metabolic complications of FPLD5, such as diabetes, hypertriglyceridemia, and hepatic steatosis, but also for WRN-associated neoplasms and features of premature aging. Full article

Background/Objectives: The skin is an important indicator of overall health, and its relationship with insulin resistance (IR) and metabolic syndrome (MetS) has garnered increasing attention. This review explores the connection between glucose dysregulation and various dermatological conditions, aiming to highlight integrative approaches for management. Methods: A comprehensive literature search was conducted in June and July 2024 across PubMed, Google Scholar, and Embase. Peer-reviewed studies on glucose dysregulation in dermatology were identified using terms such as “insulin,” “metabolic syndrome,” and “dermatological manifestations.” Relevant studies were selected based on their contributions to understanding these relationships. Results: The review identified significant associations between glucose dysregulation, MetS, and conditions such as psoriasis, acne, acanthosis nigricans, seborrheic dermatitis, and hidradenitis suppurativa. Key findings indicated that elevated insulin levels and inflammatory markers correlate with the severity of these skin disorders. Notably, dietary interventions and probiotics show potential in modulating inflammation and improving metabolic health. Conclusions: There is a clear link between glucose dysregulation and several dermatological conditions, underscoring the importance of a holistic treatment approach. By addressing glucose control and incorporating lifestyle modifications, clinicians can improve patient outcomes and mitigate the complications associated with IR and MetS. Further research is essential to refine these integrative strategies and assess their effectiveness in clinical practice. Full article

Generalized lipodystrophies (GLs) are rare diseases characterized by a lack of body fat. When patients with a GL phenotype are referred with a presumptive diagnosis of congenital generalized lipodystrophy (CGL) but genetic testing for known pathogenic variants is negative, the diagnosis of acquired generalized lipodystrophy (AGL) becomes a more likely diagnosis. No single test confirms such a diagnosis, and it is crucial to recognize the similarities and differences between these diseases. We review the literature and report four GL cases from our lipodystrophy outpatient clinic, highlighting the main points for an accurate diagnosis. Similarities: phlebomegaly, umbilical scar protrusion, loss of Bichat’s fat pad, muscle hypertrophy, and hepatomegaly can occur in both. Cirrhosis can also arise, but in AGL, it occurs as a consequence of hepatic steatosis and also due to autoimmune hepatitis. Insulin resistance is frequent, and patients present acanthosis nigricans and acrochordons and may develop difficult-to-control diabetes and its complications, despite very high daily doses of insulin. Low HDL and hypertriglyceridemia are frequent and may progress to acute pancreatitis. Serum leptin levels are typically low and contribute to hyperphagia. Differences: AGL patients’ body fat loss occurs gradually in childhood or adolescence, whereas CGL patients are born with the characteristic phenotype. Evaluating photographs of AGL patients in the first years of life can provide evidence of this selective and gradual fat loss. Some AGL patients may have panniculitis (inflamed and painful subcutaneous nodules), with or without autoimmune diseases. In conclusion, recognizing both similarities and differences is crucial for making an accurate diagnosis and ensuring the most appropriate treatment. Full article

In contrast to several high-income nations, childhood obesity prevalence is rising in low/middle-income countries. Our objective was to study risk factors and complications of childhood overweight/obesity in an urban lower middle-income country setting. This was an observational study. Children aged 2–18 years at a pediatric clinic in Chennai, India were enrolled over a 12-month period. The definition of overweight was >23rd and obesity >27th adult equivalent percentile Body Mass Index. Parents and children completed a risk-factor questionnaire. Children with obesity/overweight were evaluated for complications. Of 103 children enrolled, 61% were obese/overweight and 39% healthy weight. Independent predictors of absence of overweight/obesity were as follows: never/rarely consuming sugar-sweetened beverages, never/rarely eating out, and sleep duration > 11 h. Exercise performed rarely/never independently predicted overweight/obesity. No significant difference was observed with screen time or a vegetarian diet. Complications in 54 obese/overweight children included prediabetes (15%), hypertension (11%), dyslipidemia (22%), nonalcoholic fatty liver disease (22%), acanthosis nigricans (24%), and anxiety/depression (17%). In conclusion, differences were observed in behaviors associated with childhood obesity in an urban lower middle-income environment compared to those in high-income nations. Behaviors associated with childhood obesity in an urban lower middle-income environment are similar to those reported from high-income nations, with some differences. Complications of overweight/obesity are common in this setting. Full article

Insulin resistance (IR) plays a pivotal role in the pathogenesis of several dermatological diseases, including psoriasis, acne, acanthosis nigricans, and hidradenitis suppurativa (HS). These conditions are characterized by chronic inflammation, oxidative stress, and metabolic dysfunction, which are exacerbated by IR. This narrative review examines the emerging role of nutraceutical insulin-sensitizing agents (ISAs), including myo-inositol, alpha-lipoic acid, vitamin D, vitamin C, and folic acid, in managing IR-related dermatological disorders. A comprehensive literature search was conducted across Cochrane Library and MEDLINE (1965–May 2025), focusing on clinical trials involving nutraceutical ISAs in dermatological conditions associated with IR. Only human studies published in English were included. Evidence from randomized controlled trials (RCTs) and observational studies suggests that ISAs improve glycemic control, reduce oxidative stress, and modulate inflammatory pathways in IR-related dermatoses. Notably, myo-inositol combined with magnesium and folic acid has demonstrated significant reductions in acne severity, hirsutism, and quality-of-life impairments in women with polycystic ovary syndrome. Similar benefits have been observed in psoriasis and HS, though data remain limited. Nutraceutical ISAs offer a promising adjunctive approach for the management of IR-associated dermatological diseases, potentially addressing both metabolic dysfunction and skin inflammation. However, robust RCTs with long-term follow-up are needed to confirm these preliminary findings and to establish optimal treatment regimens. Full article

Skin paraneoplastic syndromes (SPNSs) are a group of disorders that arise as a consequence of cancer but are not directly related to the tumor mass itself. This review aims to provide a comprehensive overview of these syndromes, encompassing their pathophysiology, clinical features, diagnostic approaches, differential diagnosis, and management strategies. These syndromes, which include conditions such as Bazex syndrome, acanthosis nigricans, dermatomyositis, and necrolytic migratory erythema often manifest prior to or concurrently with a cancer diagnosis, serving as potential early warning signs of underlying malignancies. This review delves into the spectrum of SPNSs and their associations with specific cancer types. Special emphasis is placed on the critical role of dermatologists and oncologists in identifying these skin manifestations as potential markers of malignancy. By raising awareness of SPNSs, this paper highlights the pivotal importance of prompt recognition and intervention in reducing cancer-related mortality. Full article

Diabetes mellitus (DM) is a chronic metabolic disorder associated with late diagnosis due to the absence of early symptoms in patients. Cutaneous manifestations of DM often serve as indicators of insulin resistance and vary with disease progression, highlighting severity and systemic involvements. With an increasing global burden and rapidly rising prevalence, skin findings associated with DM have become more crucial for the rapid identification and treatment of underlying metabolic processes. However, current challenges in identification include inaccurate or missed detection in darker-skinned populations, which may be attributed to the lack of inclusion of diverse skin types in textbooks and research studies. This review provides clinicians with comprehensive updates on the diagnosis and treatment of cutaneous signs, complications, comorbidities, medication-associated side effects associated with DM, and the treatment of these manifestations. Full article

Background and Objectives: Gallbladder cancer (GBC) is a biologically aggressive malignancy characterised by poor survival outcomes often attributed to delayed diagnosis due to nonspecific clinical presentations. Paraneoplastic syndromes (PNSs), atypical symptoms caused by cancer itself, may serve as valuable indicators for timely diagnosis, particularly in malignancies with nonspecific features. Understanding the manifestations of PNSs in GBC is, therefore, critical. This systematic review collates case studies documenting the association of PNS with GBC, including subsequent management and clinical outcomes. Materials and Methods: A comprehensive search of PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases yielded 49 relevant articles. Upon searching other information sources, two more relevant articles were identified via citation sources. Results: The paraneoplastic syndromes were classified according to haematological (leukocytosis), dermatological (inflammatory myositis like dermatomyositis and polymyositis, acanthosis nigricans, Sweet’s syndrome, exfoliative dermatitis), neurological, metabolic (hypercalcemia, hyponatremia), and others (chorea). The analysis included the age, sex, and country of origin of the patient, as well as the time of PNS diagnosis relative to GBC diagnosis. Furthermore, common presenting complaints, investigations, and effectiveness of treatment modalities using survival time were assessed. Conclusions: While PNS management can offer some benefits, oncologic outcomes of GBC are largely poor. The majority of PNS in GBC are reported in advanced stages, and, hence, PNS has a minimal role in early diagnosis. PNS management can improve a patient’s quality of life, and thus recognition and treatment are important considerations in the holistic management of GBC patients. Full article

Background/Objectives: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age. It is associated with glucose intolerance, insulin resistance and diabetes mellitus. The oral glucose tolerance test (OGTT) is commonly employed to detect glucose intolerance, but it can be inconvenient and time-consuming. We aimed to evaluate the precision of haemoglobin A1c (HbA1c) and other serum markers in predicting abnormal glucose tolerance (AGT). Methods: This diagnostic study involved 121 PCOS women who attended the Gynaecologic Endocrinology Unit at Siriraj Hospital. Patients underwent assessments for weight, height, waist circumference, modified Ferriman–Gallwey score and acanthosis nigricans. Blood samples were collected to measure fasting glucose and insulin levels after a 75-gram oral OGTT, fasting insulin level, HbA1c, lipid profile, androgen profile and complete blood count. Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of beta-cell function (HOMA-β), quantitative insulin sensitivity check index (QUICKI) and fasting glucose-to-insulin ratio (G/I ratio) were calculated. The sensitivity, specificity and accuracy of these serum markers were compared. Results: The prevalence of AGT was 24.8%. The area under the receiver operating characteristic curve for HbA1c in detecting AGT was 0.656, while HOMA-IR, HOMA-β, QUICKI and the G/I ratio had values of 0.817, 0.737, 0.817 and 0.77, respectively. The G/I ratio cut-off point of 6% demonstrated a sensitivity of 73.3%, specificity of 74.7%, positive predictive value of 48.9%, negative predictive value of 89.5% and accuracy of 74.4%. Conclusions: The G/I ratio is the most accurate compared to other serum markers in detecting AGT among Thai women with PCOS. Full article

Background: Acne is a pathology of the pilosebaceous unit. It is characterized by a highly complex etiopathology which includes inflammation, hyperkeratinization, increased sebum production, colonization of Cutibacterium acne, hyperandrogenemia, and hyperinsulinemia. This condition, together with hirsutism, androgenic alopecia, and acanthosis nigricans, are highly prevalent cutaneous manifestations of the polycystic ovary syndrome (PCOS). While conventional therapies represent effective treatment options, they are not free from side effects which may reduce compliance. In this context, considerable attention has been directed toward nutraceutical supplements, which include different molecules with great potential to reduce inflammation, hyperkeratinization, hyperseborrhea, and hyperinsulinemia. Myo-inositol has been shown to be effective in improving some of the signs and symptoms of patients with microcystic ovaries: reducing body mass index (BMI), testosterone free levels, dehydroepiandrosterone sulfate (DHEAS) levels, and improving ovarian function and insulin sensitivity. Methods: The authors conducted a retrospective study that included 200 patients suffering from PCOS. Over 6 months, they analyzed the effects of the supplementation of LEVIGON™ (Sanitpharma; Milan, Italy)—a specific nutraceutical formulation containing myo-inositol, microlipodispersed magnesium, and folic acid—on the clinical picture of acne and hirsutism. Results: The supplementation of LEVIGON™ showed a significant reduction of BMI, testosterone, testosterone free, and DHEAS levels, thus improving the clinical picture of acne and hirsutism. Moreover, the impact of acne on the quality of life, assessed using the Cardiff Acne Disability Index (CADI) and Dermatology Life Quality Index (DLQI) scale, improved significantly after 3 and 6 months. Women with hirsutism benefited also from a significant improvement of the Ferriman-Gallwey score after both 3 and 6 months (p < 0.0001; p < 0.0001 respectively compared to the baseline). Conclusions: Myo-inositol supplementation, associated with microlipodispersed magnesium in a bioaccessible form, proved to be extremely useful in reducing acne and hirsutism in patients suffering from microcystic ovaries. In addition, there were no side effects, thus confirming excellent compliance. Further long-term randomized clinical trials are needed to confirm this preliminary evidence. Full article

Paraneoplastic dermatoses (PDs) belong to a group of rare and polymorphous dermatoses, and they can often be the first sign of underlying malignancies. Therefore, dermatologists should be able to identify skin features to identify earlier underlying neoplasms. Indeed, lack of familiarity with cutaneous clues of internal malignancies can lead to a delay in the diagnosis and an impairment of the prognosis of the patients. In this review, we described several PDs, including more common and rarer PD. Indeed, while malignant acanthosis nigricans, characterized by velvety, verrucous, hyperpigmented plaques that usually affect intertriginous areas, is a well-known PD, necrolytic migratory erythema is usually misdiagnosed because its clinical features can be similar to seborrheic dermatitis. Furthermore, we focused on two paradigmatic PDs, namely paraneoplastic autoimmune multiorgan syndrome (PAMS) and paraneoplastic dermatomyositis. Indeed, PAMS represents a paradigmatic form of obligate PD, which is always associated with an underlying neoplasm, while paraneoplastic dermatomyositis belongs to the facultative PD, which can be associated with neoplasia in a variable percentage of cases. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) share several pathophysiological mechanisms. While the prevalence of MASLD has been extensively studied in PCOS populations, the occurrence of PCOS among female adolescents with transient elastography (TE)-confirmed MASLD in pediatric hepatology settings remains poorly characterized. This cross-sectional study aims to address this knowledge gap and elucidate potential clinical and biochemical differences between female adolescents with MASLD and comorbid PCOS compared to those without PCOS. Methods: The study cohort included 45 female adolescents with TE-diagnosed MASLD. Comparative analyses of clinical and laboratory parameters were performed between those with (n = 19) and those without (n = 26) comorbid PCOS, diagnosed according to the Rotterdam criteria. Results: Adolescents with MASLD and comorbid PCOS exhibited significantly higher weight, lower height, and increased waist circumference compared to those without PCOS. Additionally, the prevalence of acanthosis nigricans was significantly higher in the PCOS group (68.4% versus 34.6%, p = 0.025). Regarding laboratory parameters, serum phosphorus levels and liver enzymes—including aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase—were significantly lower in adolescents with comorbid PCOS. However, no significant differences were observed in lipid profiles, glucose metabolism, or novel non-invasive biomarkers of MASLD. Conclusions: This study reveals distinct clinical and biochemical profiles in female adolescents with MASLD and comorbid PCOS compared to those without PCOS. These findings have the potential to inform and refine future screening protocols and diagnostic algorithms for these interrelated conditions, specifically tailored to pediatric hepatology settings. Full article

Acculturation/enculturation has been found to impact childhood health and obesity status. The objective of this study is to use cross-sectional data to examine the association between proxies of adult/caregiver acculturation/enculturation and child health status (Body Mass Index [BMI], waist circumference [WC], and acanthosis nigricans [AN]) in the U.S.-Affiliated Pacific Islands (USAPI), Alaska, and Hawaiʻi. Study participants were from the Children’s Healthy Living (CHL) Program, an environmental intervention trial and obesity prevalence survey. Anthropometric data from 2–8 year olds and parent/caregiver questionnaires were used in this analysis. The results of this study (n = 4121) saw that those parents/caregivers who identified as traditional had children who were protected against overweight/obesity (OWOB) status and WC > 75th percentile (compared to the integrated culture identity) when adjusted for significant variables from the descriptive analysis. AN did not have a significant association with cultural classification. Future interventions in the USAPI, Alaska, and Hawaiʻi may want to focus efforts on parents/caregivers who associated with an integrated cultural group as an opportunity to improve health and reduce child OWOB prevalence. Full article

Rabson–Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We report the first case of RMS in a Paraguayan patient. The patient is a 6-year-old girl who presented with hypertrichosis, acanthosis nigricans, nephrocalcinosis, and elevated levels of glucose and insulin that served as diagnostic indicators for RMS. Genetic testing by next-generation sequencing (NGS) revealed two pathogenic variants in exons 2 and 19 of the INSR gene: c.332G>T (p.Gly111Val) and c.3485C>T (p.Ala1162Val), in combined heterozygosis. The novel INSR c. 332G>T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software programs predicted it as pathogenic. The c.3485C>T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and RMS. The management of RMS is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of RMS to the Paraguayan population and adds a novel pathogenic variant to the existing literature. Full article