Lack of association of IL-10 (rs1800896) and IL-13 (rs1800925) with non-segmental vitiligo susceptibility in South Indian population.

BACKGROUND: Vitiligo is an autoimmune depigmentation disorder caused by multiple etiologies. Genetic polymorphisms in cytokine genes influence their expression and augment disease development. Analyzing the influence of genetic polymorphisms will help in better understanding of the complex etiopathogenesis of vitiligo. AIM: To study the influence of interleukin IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms on vitiligo risk in South Indian population. METHODS: Two hundred and sixty-four vitiligo patients and 264 controls were recruited in this study. Genotyping was done by quantitative PCR and plasma cytokine levels were measured by ELISA. RESULTS: Allele frequencies of IL-10 (rs1800896) and IL-13 (rs1800925) SNPs were observed to be equal in the groups. Mutant allele G of IL-10 (rs1800896) enhanced the familial inheritance of vitiligo (P < 0.0001, OR-25.1, 95% CI-7.64-82.7) and influenced the development of vulgaris type of vitiligo (P = 0.034, OR-1.83, 95% CI-1.07-3.13). Ancestral allele A of IL-10 (rs1800896) conferred protection against development of acrofacial vitiligo (P = 0.04, OR-0.56, 95% CI-0.33-0.95). Circulatory IL-10 levels in vitiligo patients were higher than controls (P < 0.0001). Individuals with genotype GG of IL-10 (rs1800896) had the highest circulatory levels of IL-10 (P < 0.0001). Among the genotypes of IL-13 (rs1800925) variant, none influenced the phenotype of nonsegmental vitiligo such as gender, family history, age of onset and types of vitiligo (P > 0.05). In addition, no difference was noted in the circulatory levels of IL-13 between patients and controls (P = 0.48). Within patients, CC genotype of IL-13 (rs1800925) was observed to enhance the circulatory IL-13 levels (P < 0.0001). LIMITATION: Replication group analysis in a larger multicentric cohort in future would validate further understanding of vitiligo susceptibility in South Indian ethnics. CONCLUSION: IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms did not confer risk to develop vitiligo in South Indian population.

Association of PTPN22 gene polymorphism with non-segmental vitiligo in South Indian Tamils.

INTRODUCTION: Non-segmental vitiligo (NSV) is a depigmentation skin disease with loss of melanocytes in the skin. AIM: To evaluate whether the protein tyrosine phosphatase non-receptor type (PTPN22) single nucleotide polymorphism at +1858C/T had any association with non-segmental vitiligo in South Indian Tamils. MATERIAL AND METHODS: Genomic DNA was extracted using the phenol-chloroform method, and PTPN22 +1858C/T polymorphism was assayed by Taqman 5'allele discrimination assay. Protein levels were quantified by ELISA. RESULTS: We found that the allelic frequency of variants of PTPN22 (rs2476601) were significantly different between controls and cases showing a vitiligo risk in the South Indian Tamil population. PTPN22 levels were higher in the heterozygous CT genotype in NSV, when compared with that of the major variant CC genotype of rs2476601. CONCLUSIONS: This study suggests that the heterozygous CT genotype, of the PTPN22 SNP rs2476601, has a strong risk association with non-segmental vitiligo in South Indian Tamils.

Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis. OBJECTIVES: We determined the association of VEGF gene polymorphisms with risk of psoriasis in South Indian Tamils. METHODS: 300 cases of psoriasis and 300 controls were recruited in this case-control study. Genotyping of SNPs of VEGF gene was done using Taqman 5' allele discrimination assay. Estimation of VEGF levels in plasma was done by ELISA. RESULTS: VEGF (rs2010963) polymorphism and the CTC haplotype were found to confer an increased risk of psoriasis. However, two other VEGF SNPs, rs833061, and rs699947, showed no association with psoriasis susceptibility. VEGF levels were higher in patients with psoriasis, as compared with controls and significantly correlated with disease severity. CONCLUSIONS: Our results indicate that VEGF (rs2010963) polymorphism and CTC haplotype of the VEGF SNPs (rs699947, rs833061, and rs2010963) confer an increased risk of psoriasis in the South Indian Tamil population. Plasma VEGF levels are higher in patients with psoriasis, as compared with controls and are significantly correlated with disease severity.

Pharmacogenetic markers to predict the clinical response to methotrexate in south Indian Tamil patients with psoriasis.

INTRODUCTION: Despite the advent of several new systemic therapies, methotrexate remains the gold standard for the treatment of moderate to severe psoriasis. However, there exists a significant heterogeneity in individual response to methotrexate. There are no consistently reliable markers to predict methotrexate treatment response till date. OBJECTIVES: We aimed to demonstrate the association of certain genetic variants in the HLA (HLA-A2, HLA-B17, and HLA-Cw6) and the non-HLA genes including T-helper (Th)-1, Th-2, Th-17 cytokine genes (IFN-γ, IL-2, IL-4, IL-10, IL-12B, and IL-23R), and T-regulatory gene (FOXP3) with the methotrexate treatment response in South Indian Tamil patients with psoriasis. METHODS: Of the 360 patients recruited, 189 patients with moderate to severe psoriasis were treated with methotrexate. Of the 189 patients, 132 patients responded to methotrexate and the remaining 57 patients were non-responders. We analyzed the association of aforesaid polymorphisms with the methotrexate treatment outcome using binary logistic regression. RESULTS: We observed that there were significant differences between genotype frequencies of HLA-Cw6 and FOXP3 (rs3761548) among the responders compared to non-responders, with conservative estimation. We observed that pro-inflammatory cytokines such as IFN-γ, IL-2, IL-12, and IL-23 were markedly reduced with the use of methotrexate, in comparison to the baseline levels, while the plasma IL-4 levels were increased posttreatment. CONCLUSION: Our results serve as preliminary evidence for the clinical use of genetic markers as predictors of response to methotrexate in psoriasis. This might aid in the future in the development of a point-of-care testing (POCT) gene chip, to predict optimal treatment response in patients with psoriasis, based on their individual genotypic profile.

Immunophenotyping of T cells in the peripheral circulation in psoriasis.

BACKGROUND: Psoriasis is a T-helper (Th)-1/Th17-mediated chronic inflammatory disease. Cytokine mediated interaction between T lymphocytes and keratinocytes lead to keratinocyte hyper-proliferation, which leads to further inflammation in the psoriatic plaques. There is an increased population of T-helper cells in the skin lesions as well as in the peripheral circulation in psoriasis. However, the relative percentage of each T-cell phenotype in the disease pathogenesis is understudied. Our aim was to study the immune-phenotype of the different T-helper/T-reg cell subsets in patients with psoriasis, with respect to healthy controls. MATERIALS AND METHODS: A total of 189 cases of psoriasis and 189 age- and gender-matched healthy controls were recruited in this cross-sectional study. Disease severity was determined by psoriasis area severity index (PASI) scoring. Peripheral blood mononuclear cells were isolated by Ficoll-Paque density centrifugation, and T-cell immunophenotyping was done by flow cytometric analysis. RESULTS: In psoriasis, we observed an imbalance in T-cell immunophenotype, characterised by an increase in Th1/Th17 cells and a relative decrease in Th2/T-reg cells, as compared to the healthy controls. We also found that the percentage of Th1/Th17 cells showed a linear trend, increasing with increasing disease severity (PASI). CONCLUSION: Our results suggest an immune-dysregulation in psoriasis associated with a predominance of Th1/Th17 phenotype, especially with increasing severity of the disease.

The HLA-C*06 allele as a possible genetic predisposing factor to psoriasis in South Indian Tamils.

Psoriasis is a multi-factorial heritable prototypical immune-mediated inflammatory disease, characterized by hyperproliferation of keratinocytes in the affected skin. There are no studies till date, to the best of our knowledge, about the association of HLA-C*06, the risk variant in the PSORS 1 susceptibility locus that confers the greatest risk for early onset of psoriasis, with the disease in South Indian Tamil patients with psoriasis. The present study was performed to determine the association of HLA-C*06 with psoriasis in the South Indian Tamil ethnic population. Three hundred and fifty-five cases of psoriasis and 360 healthy controls were included in this case-control study. Severity grading according to psoriasis area severity index (PASI) scoring was done in patients with psoriasis. PCR assays with sequence-specific primers (PCR-SSP) were used for specific detection of HLA-C*06. PCR with analysis of restriction fragment length polymorphism was used to distinguish between patients homozygous and heterozygous for HLA-C*06. We observed that those with the HLA-C*06-positive allele had a 3.5 times higher odds of having psoriasis compared to those without, [p < 0.0001, OR 3.5, 95 % CI (2.59-4.79)]. Among cases of psoriasis, it was noted that there was a significant association of HLA-C*06 positivity with female psoriatics [p = 0.006; OR 2.49 (1.28-4.87)] and early age of onset of psoriasis [p = 0.002; OR 2.04 (1.29-3.20)]. Our results suggest that the HLA-C*06 allele is positively associated with susceptibility to psoriasis, female gender and early onset of psoriasis in South Indian Tamils.

Investigation of association of the IL-12B and IL-23R genetic variations with psoriatic risk in a South Indian Tamil cohort.

BACKGROUND: Psoriasis is a T-cell mediated chronic systemic inflammatory skin disease. Emerging evidences suggest the interleukin (IL)-12B and IL-23R genes encoding the common p40 subunit of IL-12 and IL-23 are the key cytokines in T-helper (Th)1 and Th17 differentiation and function. Certain allelic variants of these genes significantly influence the risk of psoriasis. Hence we undertook to study the association of IL-12B and IL-23R gene polymorphisms with disease susceptibility in South Indian Tamil patients with psoriasis. METHODS: 360 psoriatics and 360 healthy controls were included in this case control study. IL-12B gene (rs3212227) and IL-23R gene (rs2201841, rs10889677 and rs11805303) polymorphisms were typed by using TaqMan 5'allele discrimination assay and cytokine levels were assayed by ELISA. RESULTS: We observed that the patients carrying the risk genotypes of IL-12B (rs3212227) and IL-23R (rs2201841) conferred an increased susceptibility to psoriasis. We did not find any significant association between IL-23R (rs10889677 and rs11805303) gene polymorphisms and psoriasis risk in South Indian Tamil population. We did not observe any significant difference in haplotypes between the psoriasis cases and controls. We observed a significant increase in the mean IL-23 levels in psoriatics and the higher levels of IL-23 were found in the minor variant genotype CC when compared with that of heterozygous CT and major variant TT genotypes of rs2201841. Individual genotypes of rs10889677 and rs11805303 and IL-12 (rs3212227) were not significantly associated with their plasma levels. CONCLUSION: Our results suggest that IL-12B (rs3212227) and IL-23R (rs2201841) polymorphisms confer increased risk of psoriasis in our ethnic South Indian Tamils.

25-hydroxy vitamin D and ischaemia-modified albumin levels in psoriasis and their association with disease severity.

Psoriasis is a T-helper-1 (Th1)/Th17-mediated chronic inflammatory skin disease, characterised by hyperproliferation of keratinocytes. Psoriasis and cardiovascular disease share similar pathogenic mechanisms such as vascular endothelial cell dysfunction, oxidative stress and metabolic syndrome. 25-hydroxy vitamin D is an immune-regulatory hormone, with the ability to reduce cellular proliferation in psoriasis. Ischaemia-modified albumin (IMA) is a marker of oxidative stress. This study examined 25-hydroxy vitamin D, IMA and high-sensitivity C-reactive protein (hs-CRP) levels in patients with psoriasis, in comparison with healthy controls and their possible association with disease severity. A total of 43 cases of psoriasis and 43 controls were included in this cross-sectional study, and severity grading was performed according to psoriasis area severity index (PASI) scoring. Serum 25-hydroxy vitamin D, IMA and hs-CRP were evaluated in all study subjects. In psoriasis, 25-hydroxy vitamin D showed a significant decline, while hs-CRP and IMA levels were significantly elevated, as compared with controls. Serum 25-hydroxy vitamin D showed a significant negative correlation with PASI score. hs-CRP and IMA showed a significant positive correlation with PASI score. Significant negative correlation was observed between 25-hydroxy vitamin D and hs-CRP; 25-hydroxy vitamin D and IMA levels in psoriasis. The results indicate that psoriasis is associated with significantly lowered 25-hydroxy vitamin D levels, along with increased systemic inflammation and oxidative stress, especially in severe disease. Thus, vitamin D supplementation might reduce systemic inflammation and oxidative stress and help in delaying the pathogenesis of co-morbidities associated with psoriasis.

TNFAIP3 and TNIP1 polymorphisms confer psoriasis risk in South Indian Tamils.

Psoriasis is a chronic inflammatory skin disease with genetic and environmental factors having an important role in its aetiology. Several genome-wide association studies have reported the association of the genes of the TNFα signalling, tumour necrosis factor alpha-induced protein 3 (TNFAIP3), TNFAIP3-interacting protein 1 (TNIP1) with psoriasis in Western and Chinese populations. The aim of this study is to demonstrate whether the TNFAIP3 and TNIP1 genes contribute to the risk of psoriasis in the ethnically distinct South Indian population. 360 psoriatic subjects and 360 healthy controls were recruited in this case control study. TNFAIP3 (rs610604) and TNIP1 (rs17728338) polymorphisms were typed by using TaqMan 5 allele discrimination assay. The results demonstrated that the SNPs rs610604 and rs17728338 of the TNFAIP3 and TNIP1 genes, respectively, were associated with psoriasis in our population at both allelic and genotypic levels. Thus, our results suggest that TNFAIP3 (rs610604) and TNIP1 (rs17728338) polymorphisms confer increased risk of psoriasis and may play a vital role in its pathogenesis in our ethnic South Indian Tamils.

Effect of treatment with methotrexate and coal tar on adipokine levels and indices of insulin resistance and sensitivity in patients with psoriasis vulgaris.

BACKGROUND AND OBJECTIVES: Recent studies have implicated adipokines in the pathogenesis of the immune-mediated inflammatory disease, psoriasis and its associated comorbidities. Hence, we undertook to study adipokine levels and indices of insulin resistance and sensitivity in patients with psoriasis vulgaris, in comparison with controls and their association with disease severity and response to therapy. METHODS: Sixty cases of psoriasis vulgaris and 60 age- and gender-matched healthy controls were included in this study. Severity grading according to psoriasis area severity index scoring was done in all psoriatics. Serum levels of adipokines [leptin, adiponectin, resistin and interleukin-6 (IL-6)] and insulin were estimated in all psoriatics at baseline and at 12 weeks on follow-up and in controls. RESULTS: Baseline levels of the inflammatory adipokines (leptin, resistin and IL-6) and insulin resistance indices were significantly higher in psoriatics, as compared to controls, while that of the anti-inflammatory adipokine, adiponectin and insulin sensitivity indices were significantly lower in psoriatics, as compared with controls. Baseline inflammatory adipokines, serum insulin level and insulin resistance indices demonstrated a significant positive correlation with the severity of psoriasis, while the anti-inflammatory adipokine, adiponectin and insulin sensitivity indices demonstrated a significant negative correlation with the disease severity. After 12 weeks of therapy (both topical and systemic), there was a significant reduction in the levels of inflammatory adipokines and a significant increase in the levels of anti-inflammatory adipokine-adiponectin. However, a significant decrease in insulin levels and insulin resistance indices were observed only with systemic therapy with methotrexate. CONCLUSION: The present results implicate that adipokines are significantly associated with pathogenesis of psoriasis and hence adequate and early control of psoriasis may contribute to the decreased development of metabolic syndrome, including the risk of cardiovascular disease.

Epidermolysis bullosa pruriginosa showing good response to low-dose thalidomide - a report of two cases.

Epidermolysis bullosa pruriginosa is a rare distinctive variant of dystrophic epidermolysis bullosa characterized by intense pruritus, lichenified plaques in linear distribution, and anonychia. It is a difficult condition to treat and causes a great deal of distress. The present authors report two cases showing good response to low-dose thalidomide, with clinical and symptomatic improvement. The exact mechanism of action is not yet clear.

A case to illustrate the role of ophthalmologist in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) affects the eye as part of the disease or due to the drugs used in therapy. Ocular involvement is seen in one third of the patients with SLE. SLE is rare in India and found less frequently in males and children. SLE retinopathy is usually bilateral. We report an unusual case of unilateral macular infarction in a boy caused by systemic lupus erythematosus. A fourteen year old boy was presented with skin rashes and loss of vision in left eye. Posterior segment examination showed hyperemic edematous disc, arteriolar attenuation, venous dilatation, multiple cotton wool spots around the disc and macula in the left eye. There was no improvement in vision with pulse steroids and cyclophosphamide. The clinical implication of SLE retinopathy is that the disease is severe and warrants systemic immunosuppressive therapy. SLE-induced macular infarction is rare and has poor visual prognosis. As serious ocular complications of SLE can be silent, routine ophthalmological evaluation is warranted in all patients.

How best to halt and/or revert UV-induced skin ageing: strategies, facts and fiction.

Once considered mainly a cosmetic issue, photoageing research has long moved to the forefront of investigative dermatology. Besides obvious market pressures, increasing insight into the mechanistic overlap between UV-induced skin cancer and UV-induced skin ageing has contributed to this development. Also, as strategies that work to antagonize intrinsic skin ageing/senescence may also be exploited against photoageing (and vice versa!), it has become an important skin research challenge to dissect both the differences and the overlap mechanisms between these interwined, yet distinct phenomena. Finally, the current surge in putative 'antiageing' products, devices, and strategies - too many of which boldly promise to fight and/or repair the perils that come along with a lifetime spent in the sun in the absence of convincing evidence of efficacy - makes it particularly pertinent to critically review the available evidence to support often made antiageing claims. The current CONTROVERSIES feature, therefore, aimed to provide both guidance through, and critical voices in, the antiageing circus. Here, a panel of experts defines relevant key problems, points the uninaugurated to intriguing aspects of photoageing that one may not have considered before, highlights promising strategies for how best to halt and/or revert it, and spiritedly debates some controversially discussed approaches.

Kumkum-induced dermatitis: an analysis of 46 cases.

Kumkum is a commonly used cosmetic in India, traditionally based on turmeric powder, and its ingredients can cause various types of dermatosis. We undertook a study to characterize kumkum-induced dermatitis clinically and to identify by patch testing the allergens involved. In total, 46 patients with kumkum-induced dermatitis (mean age of these cases 46.5 years; female : male ratio 1.8 : 1) were investigated. The forehead was the most commonly involved site (31/46), followed by the glabellar area (16/46), hair parting (6/46), abdomen (5/46), and neck (3/46). Pigmented contact dermatitis was seen in 35 patients (76.1%), and allergic contact dermatitis in 11 patients (23.9%). In total, 25 patients were patch tested. The commonest positive allergic reaction was to thimerosal (18/25, 72%), followed by gallate mix (12/25, 48%). Para-phenylenediamine, Kathon CG, benzotriazol, tert-butyl hydroquinone and parabens gave a reaction for one patient each (1/25, 4%). Patch testing with kumkum was positive in 7 of 13 patients tested.