Assessment of Patients with Periorbital Melanosis for Hyperinsulinemia and Insulin Resistance.

BACKGROUND: Periorbital melanosis (PM) is one of the most common dermatological condition seen in routine practice. Several cutaneous markers such as acanthosis nigricans have been associated with insulin resistance (IR). However, the association of PM with IR needs to be substantiated. OBJECTIVE: The objective of the study is to evaluate the association of circulating adipokines and IR with PM. MATERIALS AND METHODS: In this cross-sectional study, we recruited 100 patients with PM and 100 age- and gender-matched healthy controls. The serum levels of leptin, adiponectin, fasting glucose, fasting insulin, insulin-like growth factor-1 (IGF-1), homeostatic model assessment of insulin resistance (HOMA-IR), and leptin: adiponectin ratio (L/A ratio) were assayed. RESULTS: The serum levels of leptin, fasting glucose, fasting insulin, HOMA-IR, L/A ratio were significantly higher in patients with PM as compared to controls. The serum levels of adiponectin were significantly lower in cases as compared to controls. On multivariate regression analysis, leptin, adiponectin, and HOMA-IR were found to be significant, even after adjusting for BMI, blood pressure and LDL and HDL cholesterol. CONCLUSION: Our findings suggest that patients with PM have hyperinsulinemia, IR, and elevated L/A ratio. PM as a marker of IR in adults may help in identifying patients early and thus aid in the early prevention and management of the disease.

Immunophenotype of circulatory T-helper cells in patients with non-segmental vitiligo.

INTRODUCTION: Non-segmental vitiligo (NSV) is an immune-mediated skin depigmentation disease. Cytokine-mediated interaction between T lymphocytes and melanocytes leads to death of melanocytes, causing a defect in melanin synthesis and thereby depigmentation. There is an increased population of T-helper cells in the skin lesions as well as in the peripheral circulation in NSV. However, the relative percentage of each T-cell phenotype in the disease pathogenesis is rarely studied. AIM: To study the immunophenotype of the different T-helper/Treg cell subsets in patients with NSV, in comparison to healthy controls. MATERIAL AND METHODS: A total of 80 patients with NSV and eighty age- and gender-matched healthy controls were recruited in this cross-sectional study. Disease activity was determined by vitiligo index of disease activity (VIDA) scoring. Peripheral blood mononuclear cells were separated by Ficoll-Paque density centrifugation, and T-cell immunophenotyping was done by flow cytometric analysis. RESULTS: In patients with NSV, we observed an imbalance in T-cell immunophenotype, characterized by an increase in Th1 (p < 0.0001) and Th17 cells (p = 0.01). There is no difference in relative percentage of Th2/Treg cells, as compared to the healthy controls (p > 0.05). CONCLUSIONS: There is a significant immune-dysregulation with a preponderance of circulatory Th1/Th17 phenotype in NSV patients.

Cutaneous manifestations in disorders of hepatobiliary system.

BACKGROUND: Hepatobiliary diseases are associated with various mucocutaneous changes that are directly and indirectly associated with these diseases. There is a dearth of studies from India dealing with cutaneous manifestations in liver disorders. AIM: This study was conducted to know the spectrum of cutaneous changes and their correlation with liver function tests in patients with disorders of hepatobiliary system. METHODS: This was a descriptive study conducted among in patients and outpatients with primary hepatobiliary disorders at a tertiary care center in South India. Detailed history taking and examination was done. Visual analog score (VAS) and 5D itch score was employed to quantify pruritus. Correlation of liver function tests with pruritus and comparison of skin changes in the major disease groups was attempted. RESULTS: A total of 303 patients were recruited. Hepatic mass/malignancy followed by nonalcoholic liver disease were the most common diagnoses. Icterus followed by pruritus were the most common cutaneous complaints. The mean VAS and 5D itch scores among the patients with pruritus were 4.7 ± 1.9 and 13.6 ± 4.9. The most common mucocutaneous findings observed were icterus (241 patients; 79.5%), ichthyosis/xerosis (172 patients; 56.7%), pallor (131 patients; 43.2%), excoriations (118 patients; 38.9%), hyperpigmented palmar creases (118 patients; 38.9%), clubbing (113 patients; 37.2%), and pedal edema (85 patients; 28%). There was statistically significant correlation between serum bilirubin levels and pruritus. CONCLUSION: The common mucocutaneous manifestations associated with primary hepatobiliary disorders were icterus, ichthyosis/xerosis, pallor, excoriations, hyperpigmented palmar creases, clubbing, and pedal edema.

Familial gastrointestinal stromal tumors, lentigines, and café-au-lait macules associated with germline c-kit mutation treated with imatinib.

BACKGROUND: Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (GISTs) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c-kit (most commonly), platelet-derived growth factor receptor A, neurofibromatosis-1, and succinate dehydrogenase genes. MATERIALS AND METHODS: We report on molecular characterization and tumor histopathology of two siblings in whom lentigines and café-au-lait macules were present along with multifocal GIST. Immuhistochemical analysis of CD34 and CD117 was performed on GIST biopsy samples from both siblings, while c-kit mutational analysis was done by PCR and direct sequencing on DNA from peripheral blood leukocytes of all family members and from paraffin-embedded gastric biopsy specimens of affected siblings. RESULTS: Histopathology revealed positive expression of CD117 and CD34. Mutational analysis showed the germline c.1676T>C mutation in c-kit exon 11, (p.(Val559Ala)), in the peripheral blood of both siblings and a second exon 11 mutation, c.1669T>A (p.(Trp557Arg)) in the tumor biopsy of one of them. Initiation of imatinib treatment resulted in striking resolution of their hyperpigmentation and a stable gastrointestinal disease in one of them. CONCLUSIONS: A c-kit mutational test in familial GISTs is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment.

Evolving role of immunotherapy in the treatment of refractory warts.

Cutaneous and genital warts are common dermatological conditions caused by the human papilloma virus (HPV). Although it is a benign condition, it causes disfigurement, has a tendency to koebnerize, and can be transmitted to others. This makes adequate and timely treatment important. There are several conventional treatments available with variable response. Topical and systemic immunotherapy has now found a significant place in the treatment of warts because of its nondestructive action, ease of use, and promising results. Through this review, we would like to present a brief overview of the various immunotherapeutic agents used. These include more established agents such as imiquimod, Mycobacterium w vaccine, bacillus Calmette-Guérin vaccine, measles, mumps, and rubella vaccine, Candida antigen, trichophyton antigen, tuberculin, zinc, cimetidine, levamisole, HPV vaccine, and autoimplantation therapy. Other agents such as contact immunotherapy which is sparsely used now than before and newer agents such as Corynebacterium parvum, sinecatechins, echinacea, propolis, glycyrrizinic acid, and Vitamin D have also been discussed. The mechanism of action of these agents, along with their dosage, mode of administration, duration of use, expected outcomes and comparative efficacy, evidence for their use, and expected side effects, if any, are reviewed.

Extensive nevus comedonicus involving the palm: questionable role of the pilosebaceous unit in pathogenesis.

A 10-year-old boy had multiple grouped pits with black plugs arranged along the lines of Blaschko on his left chest, arm, and palm. Involvement of the palms is rarely reported in the literature. Recent reports have described mosaic acneiform conditions that could share pathogenetic mechanisms with nevus comedonicus. We briefly review the literature on mosaic conditions with acneiform lesions including nevus comedonicus.

Multiple hair whorls in a child with normal cranial and neurologic development.

Hair whorls are a normal characteristic of the human scalp and abnormally placed or absent whorls have been associated with cranial or neurologic abnormalities. We report a case of multiple whorls in a child with normal neurologic development. We also include a brief review of the literature on the development of hair whorls and their associations.

Mongolian spots--a prospective study.

To determine the frequency and clinical presentation of Mongolian spots (MS) and assess their evolution with age, this study was conducted in three phases. The first phase examined 2,313 babies born at Jawaharlal Institute of Postgraduate Medical Education and Research between October and December 2010 for the number, size, shape, color, and distribution of MS. Babies with MS were followed up at 6 months and 1 year, in the second and third phases, respectively, to note the evolution of the patches. Of 2,313 babies, 1,524 (65.9%) had MS. The majority had a single patch (n = 790), measuring less than 5 cm (n = 932), with an irregular shape (n = 981) and a blue-green color (n = 577). The most common site was sacral (n = 1,203), and the most common extrasacral site was a lower extremity (n = 156). A single case of superimposed MS was recorded. Male sex and prematurity were significantly associated with MS (p < 0.05). At 6 months, 73 of 634 babies (11.5%) showed fading and 83 (13.1%) showed complete disappearance. At 1 year, 90 (14.2%) showed fading and 268 (42.3%) showed complete disappearance. Multiple MS (p < 0.05), extrasacral position (p < 0.05), size larger than 10 cm (p < 0.05), and dark-colored lesions (blue/blue-black) (p < 0.05) were significantly associated with persistence beyond 1 year. Seven hundred ninety babies (51.8%) had a single MS. More than 40% of MS disappeared by 1 year. Multiple patches, extrasacral position, size larger than 10 cm, and dark-colored lesions were markers of persistence beyond 1 year.

Is it Lucio Phenomenon or Necrotic Erythema Nodosum Leprosum?

Lucio phenomenon (LP) or erythema necroticans is a relatively rare, peculiar reaction pattern occurring in untreated lepromatous (LL) or borderline lepromatous (BL) leprosy cases. A 38-year-old male, a cook by occupation, was referred to the dermatology clinic from otolaryngology department with blistering over both the hands and feet of 2 days duration. He had been admitted 1 week back with epistaxis and nasopharyngeal myiasis in otolaryngology department. He was started on systemic antibiotics gentamycin, crystalline penicillin, and metronidazole with nasal instillation of turpentine oil 2 drops 6 times a day. Two days later, he had developed edema with painless hemorrhagic blistering over the dorsum of left hand followed by involvement of the right hand, dorsa of both feet, and both the earlobes within a day. Histopathology of the blister showed sub-epidermal blister, with necrotizing leukocytoclastic vasculitis of papillary dermal vessels with thrombosis, numerous acid-fast bacilli in macrophages, and macrophage granulomas extending up to subcutis. In view of the absent fever or constitutional symptoms, and the classical angular infarcts and hemorrhagic blisters evolving into ulcers with angulated margins, we considered LP as the most likely diagnosis. The patient was started on a combination of WHO recommended multibacillary anti-leprosy therapy and prednisolone (40 mg/day).

Rabson-Mendenhall syndrome with recurrent cerebral infarcts caused by a novel INSR mutation.

Rabson-Mendenhall syndrome (RMS) is an autosomal recessive disorder characterized by extreme insulin resistance and certain characteristic phenotypic features. The primary defect lies in the insulin receptor and involves biallelic mutations that lead to a loss of function through various postulated defects. We present a 9-year-old female patient with RMS complicated by multiple cerebral infarcts, in whom genetic analysis revealed a novel insulin receptor mutation.