Nonsegmental vitiligo follows Blaschko's lines and embryonic pigmentary segments.

BACKGROUND: Pathogenic mechanism that determines the localization of vitiligo patches and thus a patterned distribution in patients with nonsegmental vitiligo has remained poorly elucidated. A distributional similarity of the vitiligo patches with Blaschko's lines has been documented in patients with segmental vitiligo, both isolated segmental vitiligo and mixed vitiligo but never in cases of nonsegmental vitiligo. METHODS: Distribution of nonsegmental vitiligo patches on face and neck regions was assessed and compared with Blaschko's lines and also with embryonic pigmentary segments on the face. RESULTS: This study has documented distributional similarity of the nonsegmental vitiligo patches on face and neck with Blaschko's lines and the "embryonic pigmentary segments" among 154 (58.6%) cases. Patches around the palpebral and other fissures like periorbital, perinasal, perioral, and periaural were more common. In addition to the vitiligo patches, the spared areas were also found to respect the embryonic segmental outlines and follow the Blaschko's lines. CONCLUSION: Distributional pattern of the individual nonsegmental vitiligo patches along the Blaschko's lines and embryonic pigmentary segments suggests that mosaicism might control the susceptibility to the disease process in a patterned manner. LIMITATION: No genetic testing could be performed to confirm the hypothesis. Evaluation of nonsegmental vitiligo was done only on the face and neck areas.

A Nationwide, Multicentric Case-Control Study on Vitiligo (MEDEC-V) to Elicit the Magnitude and Correlates.

BACKGROUND: Vitiligo is an acquired, idiopathic, and common depigmentation disorder. The values of various epidemiologic parameters are often doubtful due to the methodological weaknesses of the studies. AIMS: To elicit the magnitude of various epidemiological parameters and important correlates of vitiligo. MATERIALS AND METHODS: Every vitiligo patient attending the outpatient department of medical colleges spread over most of the Indian states were examined over a period of 1 year. Various epidemiological and clinical variables were examined and compared with age and sex-matched controls (registered in the Clinical Trial Registry of India CTRI/2017/06/008854). RESULTS: A total of 4,43,275 patients were assessed in 30 medical colleges from 21 Indian states. Institutional prevalence of vitiligo was 0.89% (0.86% in males and 0.93% in females, P < 0.001). The mean age at presentation and mean age at onset were 30.12 ± 17.97 years and 25.14 ± 7.48 years, respectively. Head-neck was the most common primary site (n = 1648, 41.6%) and most commonly affected site (n = 2186, 55.17%). Most cases had nonsegmental vitiligo (n = 2690, 67.89%). The disease started before 20 years of age in more than 46% of cases. About 77% of all cases had signs of instability during the last 1 year. The family history, consanguinity, hypothyroid disorders, and depressed mood were significantly (P < 0.001) higher among the cases. First, second, and third-degree family members were affected in 269 (60.04%), 111 (24.78%), and 68 (15.18%) cases, respectively. Work-related exposure to chemicals was significantly higher among cases (P < 0.008). Obesity was less common among vitiligo cases [P < 0.001, odds ratio (OR) 0.78, 95% confidence interval (CI): 0.71-0.86]. CONCLUSION: This is one of the largest studies done on vitiligo in India. The prevalence of vitiligo was found to be 0.89% among hospital attendees. Prevalence of vitiligo was higher among females than in males and prevalence of family history, consanguinity, hypothyroid disorders were higher in vitiligo than among controls.

MicroRNAs play an important role in contributing to arsenic susceptibility in the chronically exposed individuals of West Bengal, India.

Arsenic exposure by groundwater contamination is a menace which threatens more than 26 million individuals of West Bengal. Interestingly, with similar levels of arsenic exposure, only 15-20% of the population show arsenic-induced skin lesions, the hallmarks of chronic arsenic toxicity, but the rest do not. In this study, our aim was to identify whether microRNAs (miRNA) have any role to play in causing such arsenic susceptibility. Global plasma miRNA profiling was done in 12 arsenic-exposed individuals with skin lesions and 12 exposed individuals without skin lesions. Two hundred two miRNAs were found to be differentially regulated between the two study groups. Results were validated by quantitative real-time PCR in 30 exposed subjects from each of the groups, which showed that among others miR-21, miR-23a, miR-27a, miR-122, miR-124, miR-126, miR-619, and miR-3613 were significantly upregulated and miR-1282 and miR-4530 were downregulated in the skin lesion group compared with the no skin lesion group. Bioinformatic analyses predicted that these altered miRNAs have targets in 7 different biochemical pathways, including glycerophospholipid metabolism, colorectal cancer, glycosphingolipid biosynthesis, T cell receptor signaling, and neurotrophin signaling pathways; glycerophospholipid metabolism pathway being the most enriched pathway. Association study show that these microRNAs contribute significantly to the increased prevalence of other non-dermatological health effects like conjunctival irritations of the eyes and respiratory distress in the study subjects. To our knowledge, this is the first study of its kind involving miRNA expressions contributing to arsenic susceptibility in the exposed population of West Bengal.

Contact sensitivity in patients with venous leg ulcer: A multi-centric Indian study.

Venous leg ulcers are the most common form of non-healing leg ulcers. They are subjected to treatments such as topical medications, dressings, and compression therapies. This can lead to exposure to a number of allergens with subsequent sensitisation and contact dermatitis of the regional skin. This may contribute to the poor ulcer healing. To detect the various contact sensitisers in patients with venous leg ulcers through patch testing, patients from 6 centres across India with venous leg ulcers of longer than 6 weeks duration were enrolled for the study. They were patch tested using a special parch test kit with 27 antigens. A total of 172 patients were included in the study; 82 (48.2%) tested positive for at least 1 antigen. Among them, polyvalent sensitisation was noted in 71% of patients. Wood tar mix (10.4%) and the framycetin (8.7%) were the most common allergens. There is a high frequency of allergic sensitisation to various ingredients of topical therapies used in the venous ulcer management, which may interfere with wound healing. Avoiding them can help obtain a better therapeutic outcome.

Role of microRNAs in senescence and its contribution to peripheral neuropathy in the arsenic exposed population of West Bengal, India.

Arsenic induced senescence (AIS) has been identified in the population of West Bengal, India very recently. Also there is a high incidence of arsenic induced peripheral neuropathy (PN) throughout India. However, the epigenetic regulation of AIS and its contribution in arsenic induced PN remains unexplored. We recruited seventy two arsenic exposed and forty unexposed individuals from West Bengal to evaluate the role of senescence associated miRNAs (SA-miRs) in AIS and their involvement if any, in PN. The downstream molecules of the miRNA associated with the disease outcome, was also checked by immuoblotting. In vitro studies were conducted with HEK 293 cells and sodium arsenite exposure. Our results show that all the SA-miRs were upregulated in comparison to unexposed controls. miR-29a was the most significantly altered, highest expression being in the arsenic exposed group with PN, suggesting its association with the occurrence of PN. We looked for the expression of peripheral myelin protein 22 (PMP22), a specific target of miR-29a associated with myelination and found that both in vitro and in vivo results showed over-expression of the protein. Since this was quite contrary to miRNA regulation, we checked for intermediate players ß-catenin and GSK-3ß upon arsenic exposure which affects PMP22 expression. We found that ß-catenin was upregulated in vitro and was also highest in the arsenic exposed group with PN while GSK-3ß followed the reverse pattern. Our findings suggest that arsenic exposure alters the expression of SA-miRs and the mir-29a/beta catenin/PMP22 axis might be responsible for arsenic induced PN.

Evidence-based Review, Grade of Recommendation, and Suggested Treatment Recommendations for Melasma.

Treatment of melasma is known to be less satisfactory, often incomplete, and relapse is frequent. Although many treatment options are available, they are either known to be unsafe on long-term use or their long-term safety profile is unknown. Patients often use various drugs, even topical steroid-based preparation without any medical supervision for long period of time, making the skin unsuitable for many of the drugs available. Thus, there has been gross disparity among the treating physician about what drugs and what regimen are best suitable for various categories of melasma patients and in different situations. With this background, numerous newer drugs, mostly combinations of some proprietary molecules or even unknown plant extracts, have flooded the market for the management of melasma. Information on efficacy or safety of these products are almost unknown. Studies on Asian people, especially Indian population, are far less commonly available. Therapeutic guideline for use on Indian patients with melasma is almost missing. Extrapolation of data from Caucasian people for use on Asian people may not be scientifically justifiable because Caucasian and Asian people are known to have inherent difference in their response as well as tolerance to the drugs used for melasma. With this background, we have extensively evaluated, following a strict, scientifically designed protocol, all the available studies on melasma management till May 2016 and prepared this document on level of evidence, grade of recommendation and suggested therapeutic guideline for melasma as per the method proposed by Oxford Centre of Evidence-Based Medicine. Various ethical, social, logical, regional, and economic issues in the context of Indian and similar populations were given due importance while preparing the suggested therapeutic recommendation.

Medical Management of Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

Melasma is one of the most common hyperpigmentary disorders found mainly in women and dark-skinned patients. Sunlight, hormones, pregnancy, and genetics remain the most implicated in the causation of melasma. Although rather recalcitrant to treatment, topical agents such as hydroquinone, modified Kligman's Regime, azelaic acid, kojic acid, Vitamin C, and arbutin still remain the mainstay of therapy with sun protection being a cornerstone of therapy. There are several new botanical and non botanical agents and upcoming oral therapies for the future. There is a lack of therapeutic guidelines, more so in the Indian setup. The article discusses available evidence and brings forward a suggested treatment algorithm by experts from Pigmentary Disorders Society (PDS) in a collaborative discussion called South Asian Pigmentary Forum (SPF).

Lasers in Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

Lasers have come up as the newest therapeutic modality in dermatological conditions including melasma. In this article, as a group of experts from Pigmentary Disorders Society in collaboration with South Asian Pigmentary Disorders Forum (SPF), we have tried to discuss the lasers which have been used in melasma and formulate simple consensus guidelines. Following thorough literature search, we have summarised the rationale of using the lasers and the supporting evidences have also been provided. It is clear that laser cannot be the first line treatment for melasma. However, it can be used as an adjuvant therapy in resistant cases, provided the selection of patient and counselling has been done properly.

Facial Acanthosis Nigricans: A Morphological Marker of Metabolic Syndrome.

INTRODUCTION: Acanthosis nigricans (AN) is a frequently encountered entity. Facial AN (FAN) is a subset of AN which is being increasingly recognized. Recently, reports hypothesizing the association of FAN with features of metabolic syndrome have been published. AIMS AND OBJECTIVES: The aim of this study was to study the clinicodemographic profile of patients with FAN, and to assess the correlation of hypertension, increased waist-hip ratio (WHR), increased body mass index (BMI), type 2 diabetes mellitus, deranged lipid profile, serum insulin, and impaired oral glucose tolerance test (OGTT) (parameters of metabolic syndrome) in these patients, as well as to determine the most significant predictor (highest relative risk) of development of FAN. METHODS: A multicentric case-control study was conducted (123 cases in each group) over a period of 2 years. Data were obtained on the basis of history, examination, and relevant laboratory investigations. Statistical analysis was done using Statistica version 6 (StatSoft Inc., 2001, Tulsa, Oklahoma, USA), SPSS statistics version 17 (SPSS Inc., 2008, Illinois, Chicago, USA), and GraphPad Prism version 5 (GraphPad Software Inc., 2007, San Diego, California, USA). RESULTS: Mean age of the patients with FAN was 38.83 ± 8.62 years. Mean age of onset of the disease was 30.93 ± 8.18 years. The most common site of face involved was the forehead and temporal region. The most common pigmentation was brown-black. Male sex, positive OGTT, increased WHR, and increased BMI were most significantly related to FAN. Smoking was found to have a protective effect against the development of FAN. CONCLUSION: Here, we document a significant association between male patients with positive OGTT, increased WHR, and BMI and FAN. Thus, we propose that FAN could be considered a morphological marker of metabolic syndrome.

Scrub Typhus: An Emerging Threat.

Scrub typhus is caused by Orientia tsutsugamushi (formerly Rickettsia) and is transmitted to humans by an arthropod vector of the Trombiculidae family (Leptotrombidium deliense and L. akamushi). It is the most common re-emerging Rickettsial infection in India and many other South East Asian countries. In fact, scrub typhus is confined geographically to the Asia Pacific region, a billion people are at risk and nearly a million cases are reported every year. Scrub typhus appears particularly to be distributed in the tsutsugamushi triangle which is distributed over a very wide area of 13 million km2 bound by Japan in the east, through China, the Philippines, tropical Australia in the south, and west through India, Pakistan, possibly to Tibet to Afghanistan, and southern parts of the USSR in the north. Eschar is the characteristic lesion that starts as a vesicular lesion at the site of mite feeding. Later, an ulcer forms with black necrotic center and an erythematous border along with regional lymphadenopathy. Other features are fever, maculopapular rash starting from the trunk, and spreading to the limbs. It may affect the central nervous system, cardiovascular system, renal, respiratory, and gastrointestinal systems. Serious complication in the form of myocarditis, pneumonia, meningoencephalitis, acute renal failure, gastrointestinal bleeding, and even acute respiratory distress syndrome may develop. Tetracycline or chloramphenicol remains the main stay of therapy.

Hand, Foot and Mouth Disease in West Bengal, India: A Preliminary Report on Clinicovirological Trend over 3 Successive Years (2013-2015).

INTRODUCTION: Hand, foot, and mouth disease (HFMD), an enteroviral disease has emerged as a major emerging infection in India. This is caused most commonly by enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) but can also be due to CVA4-10, CVA24, CVB2-5, and echovirus 18 (Echo18). Virological analysis of the cases of HFMD has been infrequently done in India. West Bengal is one of the worst affected states in India. OBJECTIVE: To document the clinical and etiological aspect, the changing patterns and clinic-virological correlation. Method: a total of 62 samples of throat swab were collected from affected children over 3 successive years in Kolkata, West Bengal, India. RESULT: Five cases had a previous history of HFMD during the last 1-5 years. Fever was usually of mild degree (highest 102°C). There was no apparent correlation between fever of >100°C and a positive test. There was no correlation of viral strain and clinical severity. A test positive for the Viral RNA was noted among 64.51% (40/62) cases. Multiple strains were characteristically present in each year. CVA6, EV71 were found in 2013, CVA6, EV71 in 2014, and CVA6, CVA16 in 2015. CONCLUSION: Presence of multiple strains explained the frequent occurrence of relapses. We expect this small study will serve as an important document for all future studies on HFMD.

Tropical Diseases on Insurgence: Clinician's Perspective.

Many known and unknown factors play a synergistic role in the emergence or re-emergence of some infections in a particular area or country. In recent years, India has seen a significant increase in the prevalence of many viral or bacterial diseases. Many are vector borne and are zoonotic disease while others have different source and mode of transmission. These diseases are often associated with high morbidity and mortality. Five important diseases such as leptospirosis, dengue, chikungunya, Japanese encephalitis, and leishmaniasis have been discussed in this article.

Scrub Typhus in Southern Districts of West Bengal.

Scrub typhus has been previously reported from north and eastern Indian states and areas such as Kashmir, Himachal Pradesh, Assam, Sikkim, and Darjeeling district of West Bengal. It has also been known to be endemic in some parts of South India (Eastern and Western Ghats). However, no cases have ever been reported from the southern districts of West Bengal. Here, we report five cases of scrub typhus from South 24 Parganas and Kolkata, two districts in the southern part of West Bengal, India.

Evidence and Suggested Therapeutic Approach in Psoriasis of Difficult-to-treat Areas: Palmoplantar Psoriasis, Nail Psoriasis, Scalp Psoriasis, and Intertriginous Psoriasis.

Psoriasis is resistant to treatment and it shows frequent relapse; systemic treatment is often associated with toxicities, and long-term safety data are lacking for most of the newer drugs like biologics. Moreover, some body areas such as hands, feet, intertriginous areas, scalp, and nails are even more resistant. Frequently, systemic treatments are necessary considering the higher psychological impact on the patient. There is a lack of agreement on the best therapeutic modalities in the management of psoriasis involving difficult-to-treat locations. At present, there are no Indian guidelines for these conditions. Available literature has been reviewed extensively on the treatment of psoriasis involving difficult-to-treat locations; level of evidence has been evaluated as per the Oxford Centre for Evidence-Based Medicine 2011 guideline, and therapeutic suggestions have been developed. Best care has been employed to consider socioeconomic, cultural, genetic, and ethnic factors to prepare a therapeutic suggestion that is appropriate and logical to be used among Indian population and people of similar ethnic and socioeconomic background.

A Pilot Study Evaluating Therapeutic Response of Different Dosage of Oral Glucocorticoid in Two Children with Familial Glucocorticoid Deficiency Presenting with Diffuse Mucocutaneous Hyperpigmentation.

INTRODUCTION: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive potentially life-threatening condition, characterized by glucocorticoid deficiency, preserved aldosterone/renin secretion, and secondary rise in plasma adrenocorticotropic hormone level. This occurs due to either mutation in adrenocorticotropic receptor (25%, FGD Type-1) or in the MC2 receptor accessory protein (15%-20%). However, in about 50% patients, no identifiable mutations have been identified. Clinically, it manifests with weakness, fatigue, weight loss, anorexia, nausea, vomiting, diarrhea, abdominal pain, hypoglycemia, and hypothermia. Progressive mucocutaneous pigmentation is a conspicuous presentation. Repeated hypoglycemia may result in seizure, persistent neurological, severe mental disability, and even sudden death. Standard therapy is oral glucocorticoids (10-15 mg/m2). PATIENTS AND RESULTS: Two familial cases of FGD were put on progressively increasing doses of oral glucocorticoids (10 mg, 15 mg, and 20 mg/m2/day, each for 6 weeks) to achieve the best response without any adverse effects. One patient had excellent improvement with 15 mg/m2/day, and another required 20 mg/m2/day. The latter patient had excellent overall improvement with only moderate improvement in pigmentation. CONCLUSION: Glucocorticoids replacement with optimum dose is necessary in FGD to promote physical and neurological growth and to prevent adrenal crises, hypotension, hypoglycemia, and sudden death. Higher dose than mentioned in literature (15 mg/m2/day) may be required in selected cases. Mucocutaneous pigmentation may require even higher dose than we used. More studies are required.

A Florid Case of Iatrogenic Cushing's Syndrome Induced by Topical Steroid with Osteoporosis and Hypogonadism.

Here we report a case of a young male who developed full blown iatrogenic Cushing's syndrome after use of superpotent clobetasol propionate cream 0.05% for long duration to suppress psoriatic skin lesions. He also developed osteoporosis and hypogonadism. This case demonstrates that injudicious use of topical steroids can have disastrous consequences.