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.

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.

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.

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.

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.

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.

Disseminated cutaneous rhinosporidiosis.

Rhinosporidiosis is a chronic granulomatous disorder caused by Rhinosporidium seeberi. It frequently involves the nasopharynx and occasionally affects the skin. We herewith report a 55-year-old man who has disseminated cutaneous rhinosporidiosis. He presents with multiple reddish lesions over the nose of 10 year's duration. In the past year, he develops skin lesions over the right arm and over back. Histopathological examination of the skin biopsy specimen from the representative cutaneous lesions shows hyperplastic epithelium with numerous globular cysts of varying shape, representing sporangia in different stages of development. His serology for HIV infection by ELISA is negative. On the basis of these clinical and histopathological findings, a diagnosis of nasal rhinosporidiosis with cutaneous dissemination is made.

Segmental neurofibromatosis of face.

A 38-year-old man presented with asymptomatic skin lesions over the left side of the face of 5-years duration. He had multiple discrete soft-to-firm papules and nodules on the left side of the face along the distribution of the mandibular division of the trigeminal nerve. Histopathology examination of one of the nodules (face) showed a non-encapsulated tumor of the dermis with normal overlying epidermis. The tumor consisted of loosely spaced spindle cells and wavy collagenous strands in a clear matrix. These features were consistent with our clinical diagnosis of segmental neurofibromatosis. This case is reported for its rarity and typical manifestations.

Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotype-phenotype correlation.

The autosomal recessive disorder lipoid proteinosis results from mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in several tissues (including skin) and composed of two alternatively spliced isoforms, ECM1a and ECM1b, the latter lacking exon 7 of this 10-exon gene (ECM1). To date, mutations that either affect ECM1a alone or perturb both ECM1 transcripts have been demonstrated in six cases. However, lipoid proteinosis is clinically heterogeneous with affected individuals displaying differing degrees of skin scarring and infiltration, variable signs of hoarseness and respiratory distress, and in some cases neurological abnormalities such as temporal lobe epilepsy. In this study, we sequenced ECM1 in 10 further unrelated patients with lipoid proteinosis to extend genotype-phenotype correlation and to add to the mutation database. We identified seven new homozygous nonsense or frameshift mutations: R53X (exon 3); 243delG (exon 4); 507delT (exon 6); 735delTG (exon 7); 785delA (exon 7); 892delC (exon 7) and 1190insC (exon 8), as well as two new compound heterozygous mutations: W160X/F167I (exon 6) and 542insAA/R243X (exons 6/7), none of which were found in controls. The mutation 507delT occurred in two unrelated subjects on different ECM1 haplotypes and may therefore represent a recurrent mutation in lipoid proteinosis. Taken with the previously documented mutations in ECM1, this study supports the view that exons 6 and 7 are the most common sites for ECM1 mutations in lipoid proteinosis. Clinically, it appears that mutations outside exon 7 are usually associated with a slightly more severe mucocutaneous lipoid proteinosis phenotype, but neurological features do not show any specific genotype-phenotype correlation.

Peculiar pattern of nail pigmentation following cyclophosphamide therapy.

Cyclophosphamide is one of several cancer chemotherapy agents that can cause nail hyperpigmentation. We report a patient who began to have an unusual form of nail pigmentation after 8 months of receiving monthly pulses of dexamethasone-cyclophosphamide. The patient developed nail pigmentation that started proximally and spread distally but involved only the nails of the thumb, index finger, and half the middle finger of both hands.

Cutaneous variant of angiokeratoma corporis diffusum.

A case of angiokeratoma corporis diffusum (ACD) involving the skin of a 22-year-old patient presenting with normal physical and mental development is reported. ACD presenting with skin lesions alone is a rare but specific clinical entity, which differs from hereditary sphingolipidoses such as Fabry's disease.

Clinical profile of molluscum contagiosum in children versus adults.

Molluscum contagiosum mainly affects children, but in adults the advent of HIV has modified its clinical spectrum. Our study is designed to ascertain the clinical profile of molluscum contagiosum in children and adults and to discover the effects of underlying HIV infection. During the study period of September 2000 to June 2002, 150 cases of molluscum contagiosum are screened and recruited at the Department of Dermatology and STD, JIPMER, Pondicherry. These include 137 children (85 male, 52 female) and 13 adults (10 male, 3 female). In children molluscum contagiosum is most commonly seen in the 5-10-year age group (58 cases), followed by the 1-5-year age group (53 cases), the 10-14-year age group (23 cases), and the younger-than-1-year age group (3 cases). In adults molluscum contagiosum is most commonly seen in the 14-20-year age group, followed by 2 cases each in the age groups 20-26 years, 26-34 years, and 34-40 years. The male-to-female sex ratio was 1.6:1 in children and 3.3:1 in adults. In both children and adults the most common sites affected are the head and neck, followed by trunk, upper extremity, genitalia, and lower extremity. It appears that the distribution of molluscum in our patients is significantly affected by the high proportion of HIV-positive adults in our sample. Seropositivity for HIV by ELISA is found in 1 of 137 children and 8 of 13 adults. In these HIV-positive patients, 2 cases of giant molluscum and one furuncle-like presentation are seen.

Nodular secondary syphilis.

Secondary syphilis can have protean clinical manifestations and may present with unusual lesions, which may go unrecognized. We report a case of secondary syphilis with nodular lesions. A 22 year old male presented with nodular and annular skin lesions over the face, back and limbs and condylomata lata lesion at the penoscrotal junction associated with generalized lymphadenopathy, fever and malaise. Prior to onset of these lesions the patient also had history of a painless genital sore, which healed within two weeks. The serology revealed a reactive VDRL(1:64) and positive TPHA. The HIV serology was non-reactive. The patient responded to a single dose of benzathine penicillin, 2.4 million units, given intramuscularly. This case highlights that secondary syphilis may present with nodular lesions and should be suspected in the appropriate clinical setting.

A rare variant of erythema nodosum leprosum: a case report.

We report a patient with lepromatous leprosy who developed a rare variant of type-2 lepra reaction, characterized by pustular lesions, on switching from WHO multi drug therapy (MDT) to ofloxacin-aided MDT.

Lipoid proteinosis in two siblings: a report from south India.

A 6-year-old girl and her 9-year-old brother, born of nonconsanguineous parents, had hoarseness and multiple, asymptomatic, raised skin lesions present since childhood. On examination, both siblings had hoarseness and numerous skin-colored, waxy papules distributed over the forehead, face, neck, axilla, groin, and extremities. Acneiform (pocklike) scars were present on the face, trunk, and extremities. Eyelid beading (moniliform blepharosis) was present over bilateral upper and lower eyelids. The tongue, lips, and frenulum were thickened and infiltrated, and the patients were unable to protrude the tongue out of the mouth. The scalp had patchy alopecia. Histological examination of representative skin specimens (from both siblings) showed deposition of pink, amorphous material in the papillary dermis, around blood vessels, and around appendages. These deposits stained positive with Periodic Acid-Schiff stain, were diastase resistant, and were negative for Congo red, confirming our clinical diagnosis of lipoid proteinosis. Over 250 cases of this rare disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is rare.