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.

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.

Acanthosis nigricans in middle-age adults: A highly prevalent and specific clinical sign of insulin resistance.

BACKGROUND: Insulin resistance (IR) precedes the diagnosis of many metabolic and non-metabolic illnesses, including type 2 diabetes mellitus (T2DM). Acanthosis nigricans (AN) is a clinical sign associated with IR. However, AN prevalence and diagnostic accuracy in middle-age adults before or at the time of prediabetes/diabetes diagnosis remain uncertain. METHODS: With the aim to define AN prevalence and diagnostic accuracy, adults between 40 and 60 years of age were consecutively invited to participate in the study. Participants were categorised into one of two main groups: individuals with normoglycaemia (group 1) and hyperglycaemia (group 2 [ie, prediabetes/diabetes]). Demographic, clinical, anthropometric characteristics, homeostasis model assessment of IR, homeostatic model assessment of ß-cell function, as well as the presence of AN on the neck, axillae, elbows and knuckles were assessed. RESULTS: A total of 320 consecutive participants with a mean age of 49.3 years (59.4% women) were included. Overall, AN prevalence was 46.3%, while AN in group 1 and group 2 was 36.3% and 49.6%, respectively (P = .04). The most common affected sites in group 1 (n = 80) were the knuckles (21.2%) and the neck (17.5%), while in group 2 (n = 240), the neck (29.6%) followed by the knuckles (26.7%). The specificity and positive predictive value of AN for IR were 0.85 and 0.86 in group 1 and 0.90 and 0.96 in group 2, respectively. CONCLUSIONS: In middle-age adults, within the entire spectrum of carbohydrate tolerance, AN is highly prevalent and specific. This finding supports its assessment as a reliable and convenient clinical sign of IR. The understanding of AN behaviour through different carbohydrate tolerance strata, and its different locations, could lead to early detection of individuals at high metabolic risk or help direct a more pathophysiological treatment approach in patients with T2DM.

The metabolic salute: A unique presentation of transverse nasal acanthosis nigricans and allergic rhinitis in an obese pediatric patient.

Acanthosis nigricans (AN) is a well-known cutaneous condition that is most commonly associated with insulin resistance and obesity when present in a pediatric patient. We present a unique presentation of AN in an adolescent African American girl with a history of perennial allergic rhinitis. She presented with AN affecting the neck, axillae, as well as the transverse nasal crease, a consequence of habitual pushing of the nasal tip upward due to chronic obstruction and itching from allergic rhinitis known as the "allergic salute." All providers should be aware of this rare presentation, as the presence of AN should prompt additional evaluation to determine the underlying cause and effect of appropriate treatment.

Cardiometabolic profile of obese children in a sub-Saharan African setting: a cross-sectional study.

BACKGROUND: Cardiovascular and metabolic consequences of obesity in children, unlike adults, are still not well understood nor have they been subject to extensive research in Africa. We aimed to identify the cardio-metabolic complications associated with childhood obesity at the early phase of the management of obese children in a reference center in Cameroon. METHODS: In this cross-sectional study conducted from November 2013 to September 2014 and based on World Health Organization (WHO) classification of Obesity (BMI > 3SD under 5 years and BMI > 2SD from 5 and above), we included children aged 3 to 17 years who were being followed up for obesity at the pediatric endocrinology unit of the Mother and Child Center of the Chantal BIYA Foundation in Yaounde, Cameroon. A control group composed of children with normal BMI coming for a routine check up or vaccination was matched to the obese subjects. In both groups, we measured waist circumference (WC), blood pressure, fasting lipid profile and fasting glycaemia. We also considered the presence or absence of acanthosis nigricans. Data were analyzed using STATA software version 11.0, and presented as means, medians, compared with parametric and non-parametric statistical tests. RESULTS: We enrolled 38 obese children and 38 controls matched for sex and age. The majority of our participants were boys with a sex ratio of 1.24, and median age was 9.9 years. The median Z score of BMI was 3.21 in obese children. Approximately (n = 35) 90% of obese children (<6% in controls p < 0.001) presented with an abdominal obesity (WC/height ratio > 0.5) and 58% (n = 22) had acanthosis nigricans (5% (n = 2) in controls, p < 0.001). Type 2 diabetes mellitus was found in one participant, hypercholesterolemia in about 16% (n = 6) and high blood pressure in 25% (n = 8) of participants. Metabolic syndrome was present in 19% (n = 4) of obese children aged >10 years. CONCLUSIONS: Obesity in children is associated with early onset metabolic disorders such as dyslipidemia, high blood pressure and type 2 diabetes. The screening and management of these complications is therefore recommended.

Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma.

BACKGROUND: Malignant acanthosis nigricans (MAN), characterized by the presence of a hyperpigmented, velvety cutaneous thickening, is recognized as a cutaneous sign of internal malignancy. Few MAN has been reported in the Asian race ever before. CASE PRESENTATION: Here, we report a rare case of MAN with severe mucosa and soles and extraordinary facial involvement in the Asian race. A 74-year-old man presented with hyperkeratotic eruption for 7 months. Physical examination revealed hyperkeratotic plaques on the face, dorsal skin of fingers and heels, and papillomatosis of buccal mucosa. Biopsy findings from skin lesion revealed hyperkeratosis, papillomatosis, and hyperpigmentation of the basal layer. The endoscopic ultrasound with biopsy of the gastric tissue revealed gastric cardia tubular adenocarcinoma. The patient was diagnosed with MAN associated with gastric adenocarcinoma, immediately following tumor resection and lymphadenectomy. A slight improvement was seen in the skin condition but died of cancer cachexia 3 months later. CONCLUSIONS: We report our typical patient to highlight the importance of MAN, which was an early clue to the discovery of gastric adenocarcinoma.

Dermatologic manifestations of acromegaly: A case in point and a focused review.

Acromegaly is a systemic syndrome caused by overproduction of growth hormone. Cutaneous, endocrine, cardiovascular, skeletal, and respiratory systems are affected. Cutaneous changes in acromegaly relate to overexpression of growth hormone and insulin-like growth factor 1 on skin cells and adnexa. Dermal glycosaminoglycan accumulation and edema cause skin distention that is most prominent in the face, hands, and feet. Oily skin with large pores, hypertrichosis, and excessive sweating are common features. Pigmented skin tags, acanthosis nigricans, and psoriasis are also encountered. Cutaneous manifestations of acromegaly are various and prominent, and are an important clue for the early diagnosis and treatment of this high-morbidity disorder.

Characterization of membrane protein interactions in plasma membrane derived vesicles with quantitative imaging Förster resonance energy transfer.

Here we describe an experimental tool, termed quantitative imaging Förster resonance energy transfer (QI-FRET), that enables the quantitative characterization of membrane protein interactions. The QI-FRET methodology allows us to acquire binding curves and calculate association constants for complex membrane proteins in the native plasma membrane environment. The method utilizes FRET detection, and thus requires that the proteins of interest are labeled with florescent proteins, either FRET donors or FRET acceptors. Since plasma membranes of cells have complex topologies precluding the acquisition of two-dimensional binding curves, the FRET measurements are performed in plasma membrane derived vesicles that bud off cells as a result of chemical or osmotic stress. The results overviewed here are acquired in vesicles produced with an osmotic vesiculation buffer developed in our laboratory, which does not utilize harsh chemicals. The concentrations of the donor-labeled and the acceptor-labeled proteins are determined, along with the FRET efficiencies, in each vesicle. The experiments utilize transient transfection, such that a wide variety of concentrations is sampled. Then, data from hundreds of vesicles are combined to yield dimerization curves. Here we discuss recent findings about the dimerization of receptor tyrosine kinases (RTKs), membrane proteins that control cell growth and differentiation via lateral dimerization in the plasma membrane. We focus on the dimerization of fibroblast growth factor receptor 3 (FGFR3), a RTK that plays a critically important role in skeletal development. We study the role of different FGFR3 domains in FGFR3 dimerization in the absence of ligand, and we show that FGFR3 extracellular domains inhibit unliganded dimerization, while contacts between the juxtamembrane domains, which connect the transmembrane domains to the kinase domains, stabilize the unliganded FGFR3 dimers. Since FGFR3 has been documented to harbor many pathogenic single amino acid mutations that cause skeletal and cranial dysplasias, as well as cancer, we also study the effects of these mutations on dimerization. First, we show that the A391E mutation, linked to Crouzon syndrome with acanthosis nigricans and to bladder cancer, significantly enhances FGFR3 dimerization in the absence of ligand and thus induces aberrant receptor interactions. Second, we present results about the effect of three cysteine mutations that cause thanatophoric dysplasia, a lethal phenotype. Such cysteine mutations have been hypothesized previously to cause constitutive dimerization, but we find instead that they have a surprisingly modest effect on dimerization. Most of the studied pathogenic mutations also altered FGFR3 dimer structure, suggesting that both increases in dimerization propensities and changes in dimer structure contribute to the pathological phenotypes. The results acquired with the QI-FRET method further our understanding of the interactions between FGFR3 molecules and RTK molecules in general. Since RTK dimerization regulates RTK signaling, our findings advance our knowledge of RTK activity in health and disease. The utility of the QI-FRET method is not restricted to RTKs, and we thus hope that in the future the QI-FRET method will be applied to other classes of membrane proteins, such as channels and G protein-coupled receptors.

The Castleman's Disease and Related Disorders--A Case Report.

Castleman's disease is a rare primary disease of the lymph nodes. Little is known about the management of the disease. Surgical treatment gives a very good result. What other modalities of treatment could be done is not yet established. The role of surgery gives good result and follow up evaluation is satisfactory. We found a solitary intra-abdominal mass of lymphoid hyperplasia with a histological diagnosis of Castlemans disease identified in the pathological data base. Unicentric disease was defined as it was a solitary mass. Clinical, Radiological and Laboratory data were analysed to evaluate treatment response. The patient also has related disorders as Acanthosis nigricans, Myoneuronal disorder as-MG and bronchiolitis. The patient diagnosed as angiofollicular hyperplasia (Castleman's disease). After evaluation patient under went surgical treatment, partial excision of tumor mass due to morbid adhesion with inferior vena cava. The patient becomes symptom free and lump disappears within 60 days of treatment. There was no recurrence of the disease after further evaluation. The author recommends that in Unicentric variant of Castlemans disease surgical resection of the tumor is curative. The unicentric tumour may be hyaline-vascular or hyaline-vascular/ plasma cell type. Partial resection, Radiotherapy or observation alone may avoid excessive aggressive therapy.

Cutaneous manifestations of the subtypes of polycystic ovary syndrome in Korean patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of childbearing-age. Although PCOS has common dermatological manifestations, including hirsutism, acne and androgenetic alopecia, little is known about the dermatological characteristics of PCOS patients in Asia. OBJECTIVE: The goal of this study is to elucidate the dermatological characteristics and metabolic and hormonal parameters of Korean PCOS patients classified by the three ASRM/ESHERE criteria. METHODS: We investigated 40 untreated PCOS patients who were newly diagnosed in the Department of Obstetrics & Gynecology of Seoul National University Hospital. Patients were classified according to the presence of irregular menstruation (IM), polycystic ovary morphology (PCOM) and hyperandrogenism (HA). Acne specific questionnaire, physical examination, and blood sampling were thoroughly conducted. RESULTS: Twenty four patients (60.0%) met the criteria for the IM/HA/PCOM group and sixteen (40.0%) belonged to the IM/PCOM group. Acne was the most commonly observed dermatological manifestation (95.0%) followed by hirsutism (60.0%), seoborrhea (47.5%), acanthosis nigricans (20.0%) and androgenetic alopecia (12.5%). Hirsutism was more frequently observed in the IM/HA/PCOM group; the prevalence of other cutaneous manifestations did not differ significantly. Acne was most often observed on the face and most acne lesions were distributed on the forehead and cheek. Serum dehydroepiandrosterone sulphate level was higher in IM/HA/PCOM group, while serum cholesterol and high density lipoprotein concentrations were higher in the IM/PCOM group. CONCLUSION: We described several dermatological manifestations and serum hormonal and metabolic parameters in Korean PCOS patients. Cutaneous manifestations might be the first signs of PCOS; therefore, dermatologists should be more aware of cutaneous manifestations of various ethnicities.

[Association between acanthosis nigricans and metabolic syndrome in children with obesity].

OBJECTIVE: To investigate adipokines levels in obese children with acanthosis nigricans (AN) and to explore the relationship between AN and metabolic syndrome (MS). METHODS: A cross-sectional study was performed on 109 obese children and 47 age- and gender-matched normal controls. The obese children were divided into two groups with AN and without AN. Serum levels of adiponectin, leptin, TNF-α and retinol-binding protein 4 (RBP4) were measured using ELISA. Multiple logistic regression analysis was performed to estimate the association of clinical parameters with MS. RESULTS: Waist-hip ratio, systolic blood pressure, triglyceride, fasting insulin and insulin resistance index (HOMA-IR) were significantly higher in obese children with AN than in those without AN and normal controls (P<0.05). The obese children with AN and without AN had lower adiponectin levels than normal controls (P<0.05), on the contrary, the obese children with AN had higher leptin levels than those without AN and normal controls (P<0.05). Multiple logistic regression analysis revealed that AN (OR=3.469, 95%CI: 1.518-7.929) and BMI (OR=7.108, 95%CI: 2.359-21.416) were independent risk factors for MS. CONCLUSIONS: As a visible marker of insulin resistance, AN is associated with abnormal adipokines secretion. Reducing the incidence of AN and losing weight may prevent obesity associated MS.

Polycystic ovary syndrome: a review for dermatologists: Part I. Diagnosis and manifestations.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women who are of reproductive age. The pathogenesis involves several associated hormonal pathways that culminate in metabolic, reproductive, and cardiovascular effects. The hallmark features of hyperandrogenism and hyperinsulinemia have systemic long-term implications. Dermatologists frequently evaluate and manage the cutaneous manifestations of PCOS (ie, acanthosis nigricans, hirsutism, acne, and alopecia), and therefore play a key role in its diagnosis and management. In part I of this continuing medical education article, we review the definition, etiology, pathogenesis, and clinical features of PCOS.