Mapping of PARK2 and PACRG overlapping regulatory region reveals LD structure and functional variants in association with leprosy in unrelated indian population groups.

Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations.

Can We Predict the Effectiveness of Intralesional Immunotherapy in Recalcitrant Warts?

Immunotherapy has been used for recalcitrant, large, and multiple warts, although it is difficult to predict which patient will respond. An open interventional cohort trial was conducted in 50 adult patients with recalcitrant multiple, nongenital warts in whom intralesional immunotherapy was given using the Mycobacterium welchii vaccine. The authors determined whether the wart resolution was dependent on the immune response. The response of various types of warts was also compared with the initial immune response. Complete cure was used as a treatment endpoint, which was defined as a lack of recurrence at follow-up of at least 6 months. The majority of patients had palmoplantar warts (54%). A total of 26 patients achieved a clinical cure. The high immune group achieved a higher complete cure rate (60%) as compared with the low immune group (20%) (P=.008; absolute risk reduction=.44; number needed to treat=3) with a fewer number of sessions (P=.004). This difference was most marked in palmoplantar warts (P=.04). Immunotherapy using M welchii is a useful modality in recalcitrant warts in patients who have a test site induration of ≥10 mm, but this does not affect the recurrence rates.

A rapid tattoo removal technique using a combination of pulsed Er:YAG and Q-Switched Nd:YAG in a split lesion protocol.

BACKGROUND: Tattoo removal has evolved over the years and though Q-switched laser is the 'workhorse' laser, it invariably requires multiple sittings, which are dependent on numerous factors, including the skin colour, location of the tattoo, age of the tattoo, colour of pigment used, associated fibrosis and the kind of tattoo treated. Though ablative lasers, both pulsed CO2 and Er:YAG, have been used for recalcitrant tattoos, very few studies have been done comparing them with pigment-specific lasers. Our study was based on the premise that ablating the epidermis overlying the tattoo pigment with Er:YAG could help in gaining better access to the pigment which would enable the Q-switched laser to work effectively with less beam scattering. OBJECTIVE: A study of rapid tattoo removal (RTR) technique using a combination of pulsed Er:YAG and Q-Switched Nd:YAG in a split lesion protocol. MATERIALS AND METHODS: This prospective study was undertaken during 2010-13 at a laser Clinic in the Maulana Azad Medical College, New Delhi. A total of 10 patients were recruited, 5 of amateur tattoo and 5 of professional tattoo. After informed consent each tattoo was arbitrarily 'split' into two parts. One part was treated with QS Nd:YAG laser(1064 nm) and the other part with Er:YAG laser immediately followed by the QS Nd:YAG. The laser treatments were repeated at 6-week intervals until the tattoo pigment had cleared. On the combination side in subsequent sittings only the QS Nd:YAG was used, to minimize repetitive ablation. To ensure consistency in the intervention methods a trained dermatologist who was independent of the treatment delivery randomly rated 10% of the procedures. RESULTS: The mean improvement achieved by the Q-switched laser (2.93) was less than the combination laser (3.85) side (p = 0.001) and needed more sessions (3.8 vs. 1.6; p = 0.001). There was a statistically significant difference in the improvement on the combination side till the second session. On the combination side patients required a maximum of 2 sessions, while the Q-switched laser required 3-5 sessions for appreciable lightening. CONCLUSION: From our study it was concluded that use of a pulsed ablative laser may help in rapid removal of tattoos in conjunction with QS lasers with minimal side effects and can be used as a RTR.

Which type of atrophic acne scar (ice-pick, boxcar, or rolling) responds to nonablative fractional laser therapy?

BACKGROUND: Few studies have examined the role of fractional lasers in individual acne scars (ice-pick, box car, rolling) using objective assessment tools in darkly pigmented skin. OBJECTIVE: To evaluate the effect of 1,540-nm fractional lasers on individual acne scars. METHODS AND MATERIALS: A prospective interventional study was conducted in 35 patients using a 1,540-nm fractional laser. Six sessions were performed with four passes per session and a dose varying from 70 to 100 mJ to maximize the DWR. A self-devised objective assessment tool with dose settings to optimize the depth-to-width ratio (DWR) and a visual analog scale (VAS) were used to count individual atrophic scars. Final results were assessed 6 months after final laser treatment. RESULTS: Acne scar reduction efficiency was used to validate the improvement of individual scars, a meaningful difference was considered as 51% or greater improvement. The boxcar scars (52.9%) responded better than the rolling (43.1%) and ice-pick scars (25.9%), with statistically significant improvement (p < .05) seen in boxcar scars after four sessions. Overall VAS scores revealed significant improvement (p < .001). CONCLUSION: Using an objective evaluation tool, an erbium-doped glass laser was found to improve atrophic acne scars, markedly so for boxcar and rolling scars. The VAS score overestimated improvement because of its subjective nature.

Comparative study of flip-top transplantation and punch grafting in stable vitiligo.

BACKGROUND: Because of limitations of medical treatment in vitiligo, various surgical techniques have been devised. There is a scarcity of comparative studies of surgical techniques in vitiligo. OBJECTIVE: To compare the effectiveness and side-effect profile of flip-top transplantation (FTT) and punch grafting (PG) in patients with stable vitiligo. MATERIALS AND METHODS: Twenty patients with stable vitiligo were treated using PG and FTT on 26 lesions; 156 grafts were taken (78 PG, 78 flip-top grafts). They were graded for response in the form of repigmentation as excellent (91-100%), very good (76-90%), good (51-75%), fair (31-50%), poor (<30%). Onset and maximum pigment spread were observed. RESULTS: Sixty-five percent of our patients showed excellent repigmentation with FTT, versus 50% with PG (p = .44). Thirty percent of patients with FTT and 40% with PG had side effects. The differences in onset of repigmentation, completion, and pigment spread between the two techniques were statistically significant (p < .001). CONCLUSIONS: Flip-top transplantation was equally effective as PG for treating vitiligo, although graft uptake rate was higher with FTT, with more pigment spread, and cost less.

Association of variants in BAT1-LTA-TNF-BTNL2 genes within 6p21.3 region show graded risk to leprosy in unrelated cohorts of Indian population.

Host immune response against Mycobacterium leprae plays an important role in providing resistance to infection and disease progression. Genome-wide linkage and association studies suggest the possibility of multiple risk loci within HLA (6p21.3) region. Any systematic study of relevance within the histocompatibility complex of importance in host immune response would be pertinent because of non-replication of the known loci and unavailable information on some of the unexplored genes and regions. A systematic scan was performed of the selected region involving LTA-TNF-LTB genes within 6p21.3 with a resolution of 1SNP/127 bp; and the SNPs in flanking BAT1, NFKBIL and BTNL2-DRA genes on the basis of their tag status or their presence in promoter/exonic regions with MAF of >5%. Nine SNPs located in BAT1, LTA, TNF genes and BTNL2-DRA interval showed strong association with leprosy susceptibility in two independent sets of North Indian population which was replicated in a geographically distinct East Indian population. Conditional logistic regression showed at least one functional SNP remaining significant in each gene, suggesting an independent role of each of the disease associated SNPs. In vitro reporter assay revealed that two SNPs located at BAT1 promoter and 13 kb upstream to LTA gene affected the transcription factor binding site, hence the gene expression. We unravel the role of unexplored immunologically important genes, BAT1 and BTNL2, in addition to known LTA and TNF genes, and the haplotypes of the significantly associated SNPs therein, to understand susceptibility to the disease, leprosy and its differential severity.

Leprosy and the adaptation of human toll-like receptor 1.

Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world. Despite several major studies on susceptibility to leprosy, few genomic loci have been replicated independently. We have conducted an association analysis of more than 1,500 individuals from different case-control and family studies, and observed consistent associations between genetic variants in both TLR1 and the HLA-DRB1/DQA1 regions with susceptibility to leprosy (TLR1 I602S, case-control P = 5.7 x 10(-8), OR = 0.31, 95% CI = 0.20-0.48, and HLA-DQA1 rs1071630, case-control P = 4.9 x 10(-14), OR = 0.43, 95% CI = 0.35-0.54). The effect sizes of these associations suggest that TLR1 and HLA-DRB1/DQA1 are major susceptibility genes in susceptibility to leprosy. Further population differentiation analysis shows that the TLR1 locus is extremely differentiated. The protective dysfunctional 602S allele is rare in Africa but expands to become the dominant allele among individuals of European descent. This supports the hypothesis that this locus may be under selection from mycobacteria or other pathogens that are recognized by TLR1 and its co-receptors. These observations provide insight into the long standing host-pathogen relationship between human and mycobacteria and highlight the key role of the TLR pathway in infectious diseases.

Coexistence of two atypical variants of pityriasis rosea: a case report and review of literature.

We report the case of a 16-year-old Indian girl who presented with multiple small papular lesions and larger erythema multiforme-like plaques in a Christmas tree pattern over her body for 3 weeks. Histopathologic examination was performed, and she was diagnosed with pityriasis rosea presenting with two atypical morphological variants-generalized papular and erythema multiforme-like. A brief review of literature of these two rare types is also presented.

Genetic variations and interactions in anti-inflammatory cytokine pathway genes in the outcome of leprosy: a study conducted on a MassARRAY platform.

BACKGROUND: Mycobacterium leprae is the etiologic pathogen that causes leprosy. The outcome of disease is dependent on the host genetic background. METHODS: We investigated the association of 51 single-nucelotide polymorphisms (SNPs) in anti-inflammatory cytokines (IL-10, TGFB1, IL-6, IL-4, and IL-13) and receptors (IL-10RA, IL-10RB, TGFBR1, TGFBR2, IL-6R, IL-4R, IL-5RA, IL-5RB, and IL-13RA1) with susceptibility to leprosy in a case-control study from New Delhi in northern India. This was followed by replication testing of associated SNPs in a geographically distinct and unrelated population from Orissa in eastern India. The functional potential of SNPs was established with in vitro reporter assays. RESULTS: Significant associations (P < .05) were observed for 8 polymorphisms (rs1800871, rs1800872, and rs1554286 of IL-10; rs3171425 and rs7281762 of IL-10RB; rs2228048 and rs744751 of TGFBR2; and rs1800797 of IL-6) with leprosy. This association was replicated for 4 SNPs (rs1554286 of IL-10, rs7281762 of IL-10RB, rs2228048 of TGFBR2, and rs1800797 of IL-6). The interaction study revealed a significantly greater association with leprosy risk than was obtained for any SNP individually. CONCLUSIONS: This study provides an interesting insight on the cumulative polygenic host component that regulates leprosy pathogenesis.

An observational study of methionine-bound zinc with antioxidants for mild to moderate acne vulgaris.

APC is a novel methionine-based zinc complex with antioxidants that has been used in acne as a nutritional supplement. This is based on the proven role of zinc and antioxidants in improving acne, specially the inflammatory lesions. The objectives of this study are to explore the efficacy, safety, and tolerability of APC in acne patients with mild to moderate facial acne vulgaris. In this exploratory trial, 48 patients were treated with oral APC thrice a day for 3 months followed by a 4-week treatment-free period. At the end of treatment (Week 12), there was a statistically significant improvement in the global acne count (p < 0.05), which began after 8 weeks (p < 0.05). Almost 79% (38/48) of the patients had 80-100% improvement. There was a significant reduction in pustules (8 weeks (p < 0.05) and 12 weeks (p < 0.001)), and papules and closed comedones (8 weeks (p < 0.05) and 12 weeks (p < 0.001)). Only two patients had side effects. The current data indicate that treatment with oral APC thrice daily for 12 weeks in patients with mild to moderate facial acne vulgaris is efficacious and well tolerated. As the onset of action is late, concomitant topical therapy can enhance the results.

Linear nodular collagenoma--successful treatment with intralesional triamcinolone acetonide.

A 17-year-old boy presented with papules and nodules arranged linearly on the neck and on the forehead. A diagnosis of collagenoma was made. Intralesional injection of triamcinolone acetonide resulted in marked effacement of the lesions.

The spectrum of skin disease among Indian children.

Skin diseases in children are encountered frequently and their characterization is essential for the preparation of academic, research and health plans. A retrospective study was designed to evaluate the epidemiologic features of pediatric dermatoses in India. The setting was a tertiary care referral center in India (Kalawati Saran Children's Hospital, New Delhi) during January 1997 to December 2003. A total of 30,078 children less than 12 years of age with 32,341 new dermatoses were recorded, with a male to female ratio of 1.07:1. Most of the disease was seen in the 1- to 5-year age group (44.94%). The most common skin diseases were infections and infestations (47.15%) consisting of bacterial infections (58.09%) and scabies (21.54%), followed by eczemas (26.95%), infantile seborrheic dermatitis, scabies, and pityriasis alba. Other unique dermatoses in our settings were papular uticaria (3.59%), miliaria (5.46%), postinflammatory pigmentary abnormalities (1.68%), and nutritional deficiency dermatoses (0.45%). A majority of patients were diagnosed clinically and special diagnostic tests were conducted in 2.6% of patients. The most common diagnostic test used was KOH mount (59.2%), followed by skin biopsy (39%). Nearly 90% of patients were seen without any referral and in the remaining, a majority were referred by pediatricians (75%). A majority of patients were diagnosed to have infection followed by dermatitis in our setting.

A prospective study of cutaneous manifestations of spinal dysraphism from India.

Recognition of cutaneous markers of spinal dysraphism is important to prevent the morbidity associated with underlying spinal anomalies. To investigate the frequency and type of cutaneous stigmata in different forms of spinal dysraphism and to assess the role of ultrasonography and/or magnetic resonance imaging in diagnosing spinal dysraphism at two pediatric dermatology tertiary care centers. Over a 4-year period, all pediatric patients presenting to the dermatology clinic with dorsal midline cutaneous stigmata were evaluated clinically and with imaging studies (radiography, ultrasonographic examination and magnetic resonance imaging/Doppler). Surgical interventions were planned in conjunction with neurosurgery and orthopedic specialists. On examination, 245 (4.2%) had 285 cutaneous stigmata. Of the 180 patients evaluated with radiography, ultrasonographic examination and magnetic resonance imaging, 50 patients (28%) had spinal dysraphism (with 64 cutaneous stigmata). The most common stigmata associated with occult spinal dysraphism were lipoma (10) and dimples (12) and in open spinal dysraphism lipomeningomyelocoele (10) and meningomyelocoele (10). Statistically, lipomeningomyelocoele/myelomeningocoele, atypical dimples and port-wine stains were most associated with spinal dysraphism (p < 0.001). In 80 children less than 6 months of age, radiography with ultrasonographic examination revealed an SD in 16, while magnetic resonance imaging was diagnostic in four cases. Ultrasonographic examination performed fairly well in children less than 6 months and in cases of flat cutaneous stigmata it missed only 5% of cases, but in cases with bulky overlying masses (lipoma, hemangioma) it missed 15% of cases.

An array of unusual clinical features in a woman with amlodipine-induced linear immunoglobulin A disease.

Linear immunoglobulin A disease (LAD) is a rare, autoimmune, vesicular-bullous disease that is either idiopathic or drug-induced, most commonly by vancomycin and in rare instances by amlodipine. In drug-induced LAD, certain uncommon and atypical clinical features can occur. In our patient, a 49-year-old woman with amlodipine-induced LAD, atypical features such as koebnerization and palmo-plantar involvement occurred. She presented with tense, clear fluid-filled vesicles, bullae, and erosions all over her body, especially on the palms and soles, with some lesions showing a string-of-pearls appearance. The lesions were preceded by pruritus, and the patient had changed her anti-hypertensive medication from telmisartan to telmisartan-amlodipine for previous 10 days. Skin biopsy and direct immunofluorescence testing confirmed LAD. During the hospital stay, along with new crops of lesions, a few vesicles were present along the lines where she had scratched and the band of tight elastic sleeves of the sterile gown she wore, which is suggestive of koebnerization. Knowing the atypical manifestations of drug-induced LAD may aid clinicians in determining an early diagnosis, and LAD should be an important consideration in the differential diagnosis of vesiculobullous disease with palmar-plantar involvement. Amlodipine is a commonly used anti-hypertensive drug, so knowledge of its potential to cause this disease is important. Furthermore, knowing the potential for koebnerization, avoidance of trauma and the gentle handling of these patients can lead to early recovery from this self-limiting disease.

Seasonal aggravation of acne in summers and the effect of temperature and humidity in a study in a tropical setting.

BACKGROUND: Effect of seasonality on acne and acne flare has varied interpretations depending on the geographical area of study. In tropical areas, factors like high temperature and humidity may cause acne flares. AIMS: To assess the seasonal variation of acne in patients and to correlate it with the monthly temperature and humidity over a period of 1 year. METHODS: A cross-sectional study of acne patients was conducted for one year. The patient's acne was graded. Patients were specifically questioned about aggravation, improvement, or no change in their acne with respect to the seasons. The mean temperature and humidity of each month in Delhi were compared with grade of acne. This variation in acne was correlated with the temperature and humidity. A P-value < 0.05 was considered as statistically significant. RESULTS: Out of 171 patients, 82 (47.95%) patients reported seasonal variation in their acne. Among them, 69 patients (40.4%) reported aggravation in summer. Eleven (6.42%) and 2 (1.16%) patients reported aggravation in winter and rainy season, respectively. The aggravation in summer as compared to rainy and winter season was statistically significant. The mean temperature and mean humidity significantly varied with seasonal aggravation of acne. CONCLUSIONS: Both temperature and humidity have a contributing role in pathogenesis of acne and are causes of acne flare. In our study, aggravation of acne was more in summer and rainy season.

Malignant transformation of donovanosis (granuloma inguinale) in a HIV-positive patient.

Donovanosis is endemic in various parts of the world. Although donovanosis has been reported to co-exist with the human immunodeficiency virus (HIV) infection, to our knowledge there have been no reports of co-existent squamous cell carcinoma (SCC) in an HIV positive patient. In our case the patient did not respond to treatment for donovanosis and on biopsy we realized that the patient had coexistent SCC, which is hitherto unreported with granuloma inguinale.

A case of bullous Darier's disease histologically mimicking Hailey-Hailey disease.

The bullous variant of Darier's disease is a rare type and the exact nosological position relative to Hailey Hailey disease has been doubtful. We report a case of bullous Darier's disease with histological picture suggestive of Hailey-Hailey disease. We have also reviewed and summarized the differences between Darier's disease and Hailey-Hailey disease.

Treatment of Nevus lipomatosus cutaneous superficialis with CO2 laser.

Nevus lipomatosus cutaneous superficialis (NLCS) is an uncommon lesion characterized by ectopic adipose tissue in the dermis and can be generalized or localized. It presents as a soft skin colored to yellowish papules or cerebriform plaques occurring usually on the buttock or thigh in a segment distribution. We report a case of NLCS in 38-year-old female, which was treated using the ultrapulse mode CO2 Laser. We describe the scientific logic and clinical results of using the ultrapulse mode in relation to the pathology of NLCS.

Use of vegetable oils in dermatology: an overview.

Vegetable oils have been used for a wide variety of purposes since time immemorial; however, their principle use remains as skin moisturizers, especially in neonates and children. Because of their considerable efficacy and a low side effect profile and bearable cost, these oils are hugely popular as moisturizers among the common people in countries such as India. A wide variety of oils have been used, and newer ones are coming up with each passing day. This article focuses on the different types of vegetable oils and their varied uses in dermatology.

Acute Generalized Exanthematous Pustulosis Induced by Fexofenadine.

Acute generalized exanthematous pustulosis (AGEP) is a skin eruption, frequently drug induced and characterized by the acute development of multiple sterile minute pustules on an erythematous base. There is no case of fexofenadine-induced AGEP in literature (PubMed search). A 40-year-old female presented to us with fever and sudden onset development of multiple discrete to coalescent 1-2 mm nonfollicular pustules on an erythematous base present mainly on her trunk and upper extremities for past 2 days. She had a history of use of fexofenadine 180 mg OD for rhinitis for 2 days. Gram's stain showed no organism and pus culture showed no growth. Histopathological examination revealed subcorneal pustules with epidermal spongiosis. Scattered neutrophils and eosinophils were noted in the dermis. During this period, she took fexofenadine 180 mg unknowingly once following which she developed similar episode within 24-48 h. After withdrawal of the drug, the lesions subsided with scaling in 8-10 days. To the best of our knowledge, this is the first reported case of AGEP induced by fexofenadine. Recognition of such a rare entity is important given the frequent usage of fexofenadine for allergic disorders.