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Enhanced expression of angiotensin-converting enzyme 2 in psoriatic skin and its upregulation in keratinocytes by interferon- : implication of inflammatory milieu in skin tropism of SARS-CoV-2 (c) Protein expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) was determined in skin homogenates of patients with psoriasis (n = 40) and controls (n = 30) in triplicate (Student's t-test). Dear Editor, The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a challenging situation globally due to its contagious nature. [Extracted from the article]

Dear Editor, Nonsegmental generalized vitiligo (NSGV) is the most common and progressive clinical form of vitiligo[1] and narrowband ultraviolet B (NB-UVB) is the preferred and most effective treatment modality in active NSGV (aNSGV).[2] The effect of NB-UVB treatment on microRNA (miRNA) expression and its association with clinical outcome in aNSGV is unknown. miRNA are noncoding oligonucleotides that are known to regulate various biological processes and are implicated in a variety of diseases.[3] Limited studies are available regarding the role of miRNA in vitiligo pathogenesis, but the precise mechanism of action is unknown.[4] This study aimed to investigate the expression of miRNA (peripheral blood, serum, lesional and nonlesional skin) and pigmentation-associated genes (lesional vs. nonlesional) in untreated aNSGV and NB-UVB-treated aNSGV (tNSGV). GLO:F03/01jul20:bjd18890-fig-0001.jpg PHOTO (COLOR): microRNA (miRNA) expression profile in peripheral blood mononuclear cells (PBMCs) of (a) active nonsegmental generalized vitiligo (aNSGV) (n = 26) and healthy controls (n = 20); (b) aNSGV(n = 26) and narrowband ultraviolet-B-treated aNSGV (tNSGV) (n = 21); (c) lesional and nonlesional skin in aNSGV (n = 26) and tNSGV (n = 21); and (d) miRNA expression levels of skin pigmentation-associated genes in lesional and nonlesional skin in aNSGV (n = 8), tNSGV (n = 8) and healthy controls (n = 6). The present study indicated that NB-UVB-induced repigmentation may occur by modulation of miRNA expression and enhanced expression of pigmentation-associated genes at a molecular level in aNSGV. [Extracted from the article]

Background Accurately diagnosing the subtype of epidermolysis bullosa ( EB) is critical for management and genetic counselling. Modern laboratory techniques are largely inaccessible in developing countries, where the diagnosis remains clinical and often inaccurate. Objectives To develop a simple clinical diagnostic tool to aid in the diagnosis and subtyping of EB. Methods We developed a matrix indicating presence or absence of a set of distinctive clinical features (as rows) for the nine most prevalent EB subtypes (as columns). To test an individual patient, presence or absence of these features was compared with the findings expected in each of the nine subtypes to see which corresponded best. If two or more diagnoses scored equally, the diagnosis with the greatest number of specific features was selected. The matrix was tested using findings from 74 genetically characterized patients with EB aged > 6 months by an investigator blinded to molecular diagnosis. For concordance, matrix diagnoses were compared with molecular diagnoses. Results Overall, concordance between the matrix and molecular diagnoses for the four major types of EB was 91·9%, with a kappa coefficient of 0·88 [95% confidence interval ( CI) 0·81-0·95; P < 0·001]. The matrix achieved a 75·7% agreement in classifying EB into its nine subtypes, with a kappa coefficient of 0·73 (95% CI 0·69-0·77; P < 0·001). Conclusions The matrix appears to be simple, valid and useful in predicting the type and subtype of EB. An electronic version will facilitate further testing. [ABSTRACT FROM AUTHOR]

Background Vitiligo is an autoimmune depigmentation disease, and defects in regulatory T cells (Tregs) have been proposed in the pathogenesis of generalized vitiligo ( GV). However, the role of programmed cell death ( PD)1+ Tregs has not been studied. Objectives To investigate the status of Tregs, PD1+ Tregs and associated parameters in active GV ( aGV) during the first episode of disease attack and to establish the clinical correlation. Methods The percentages of circulating Tregs, PD1+ Tregs and CD3+ CD4+ PD1+ T cells were evaluated in 50 patients with aGV and 51 controls. Expression levels of FOXP3, TGFB1, CTLA4 and genes for chemokine receptors ( CCR4, CCR7) and their ligands ( CCL21, CCL22) were quantified in peripheral blood and in lesional, perilesional, nonlesional and normal skin sections. The corresponding proteins were immunolocalized in tissue of a GV. Results The percentage of Tregs was decreased ( P = 0·001) and that of PD1+ Tregs increased ( P = 0·001) in peripheral blood of patients with a GV compared with controls. The abundance of TGFB1 and CCL21 m RNA was significantly decreased in the peripheral blood of patients with a GV. Significant differences in forkhead box P3, transforming growth factor-β and CCL21 protein expression were found in skin sections. Conclusions Deficiency in Treg frequency and decreased expression of Treg-associated parameters ( TGFB and CCL21) suggested a possible defect in Tregs that may alter their suppression function and skin homing in a GV. The increased PD1+ Tregs suggests that the PD1/ PD ligand pathway may be involved in a GV and may have a role in Treg exhaustion. Further study is required to delineate the effect of PD1 in regulating Treg function in a GV. [ABSTRACT FROM AUTHOR]

Background Patients with congenital ichthyosis, especially those with darker skin types, are at increased risk of developing vitamin D deficiency and rickets. The relationships between 25-hydroxyvitamin D [25( OH)D], parathyroid hormone ( PTH) and bone health have not been studied previously, in ichthyosis. Objectives To determine the threshold levels of 25( OH)D and PTH for impaired bone health in children with congenital ichthyosis. Methods In this cross-sectional study, 119 children with ichthyosis and 168 controls were recruited. Serum 25( OH)D, PTH, calcium, phosphate and alkaline phosphatase ( ALP) were measured. Radiological screening for rickets was carried out only in children with ichthyosis. Results Forty-seven children with ichthyosis had either clinical or radiological evidence of rickets. The correlation between serum 25( OH)D and PTH showed that a serum level of 25( OH)D 8 ng mL−1 was associated with a significant increase in PTH. The correlation between PTH and ALP showed that a serum PTH level of 75 pg mL−1 was associated with a significant increase in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal recessive congenital ichthyosis ( ARCI) and epidermolytic ichthyosis ( EI) were found to have significantly increased PTH, ALP and radiological rickets scores compared with common ichthyosis. Conclusions Serum levels of 25( OH)D ≤ 8 ng mL−1 and PTH ≥ 75 pg mL−1 significantly increases the risk for development of rickets [odds ratio ( OR) 2·8; 95% confidence interval ( CI) 1·05-7·40; P = 0·04] in ichthyosis. Among the different types, patients with ARCI ( OR 4·83; 95% CI 1·74-13·45; P < 0·01) and EI ( OR 5·71; 95% CI 1·74-18·79; P < 0·01) are at an increased risk of developing rickets. [ABSTRACT FROM AUTHOR]

Background Alteration in T-lymphocyte function and cytokines secreted by T-cell subsets has been proposed in the immunopathogenesis of alopecia areata ( AA). The role of T-helper and regulatory T-cell cytokines in the pathogenesis of active AA has not been established. Objectives To assess the role of hallmark cytokines of T-helper cells (Th1, Th2 and Th17) and regulatory T cells (Tregs) in the pathogenesis of AA, and its clinical correlation. Methods Fifty-one patients with AA and 45 age- and sex-matched healthy control subjects were included in the study. Serum interleukin ( IL)-2, interferon ( IFN)-γ, IL-10, IL-13, IL-17A and transforming growth factor ( TGF)-β1 were measured by enzyme-linked immunosorbent assay in both groups. Correlation of serum cytokine levels with age, sex, disease subtype and duration, number of patches on the scalp, associated autoimmune disorders and atopy was studied. Results The serum cytokine levels of IL-2, IFN-γ, IL-13 and IL-17A were significantly increased, and serum TGF-β1 levels were significantly decreased ( P < 0·05) in patients with AA compared with controls. Serum IL-2 levels were significantly different among AA subgroups ( P < 0·05). IL-2 levels were positively correlated with the total disease duration and the number of patches on the scalp. Conclusions The increased levels of serum IL-2, IFN-γ, IL-13 and IL-17A suggested altered T-helper cell function, and reduced serum TGF-β1 levels suggested a defect in Treg function. Therefore, enhanced T-cell-mediated immunity and breakdown of immune tolerance due to deficiency in Tregs may facilitate the occurrence of AA. [ABSTRACT FROM AUTHOR]

Background Stability is considered the most important parameter before performing any melanocyte transplantation procedure in vitiligo; however, current criteria rely on the history given by the patients. Objective This study was undertaken to determine the clinical, biochemical and immunological factors determining stability of disease in patients with generalized vitiligo to facilitate better patient selection for melanocyte transplantation and to understand immunological mechanisms for disease activity. Methods Thirty-three patients with generalized vitiligo with < 10% body surface area involved were allocated to three clinical stability groups: Group 1 (stability > 3 months but < 1 year), Group 2 (≥ 1 year but < 2 years) and Group 3 (≥ 2 years). Melanocyte transplantation was done using suction blister epidermal grafting (SBEG) on a single patch. Blood was drawn for catalase estimation from all patients and from 10 healthy control subjects. A 3-mm punch biopsy was taken on the day of transplantation from the margin of the macule in the first five patients in each group for the immunohistochemistry of CD4, CD8, CD45RO, CD45RA and FoxP3. Those with ≥ 75% repigmentation at 6 months were labelled as responders. Results The success rate was 0% in Group 1, 37·5% in Group 2 and 77·8% in Group 3. The difference in the success rate between the groups was statistically significant ( P = 0·005). The median period of stability was significantly higher in the responders compared with that in the nonresponders ( P = 0·001). Catalase levels were not significantly different between patients in the three groups of cases and in controls, or between responders and nonresponders. Lesional CD8 cells were significantly higher in Group 1 compared with Group 3. The percentages of CD8 and CD45RO cells were significantly higher in the nonresponders compared with the responders. Conclusion Along with clinical stability, the proportion of CD8 and CD45RO cells in skin biopsies might help to determine the stability of the disease and thereby predict the success of transplantation. [ABSTRACT FROM AUTHOR]

This paper demonstrates the analysis of levetiracetam, a new chiral antiepileptic drug, at ng/mL levels using an ultra-high-performance liquid chromatography (UHPLC)–photodiode absorbance (PDA) method. Three different sample preparation methods, liquid–liquid extraction with Extrelut, solid phase extraction (SPE) with Oasis HLB and Oasis MAX SPE cartridges, and protein precipitation with organic solvents were carried out. The last preparatory method is the simplest and provides the best recoveries: between 97.1% and 100.4% with RSD value below 5%. The column for separation is BEH C18 column (1.7 µm particle size and 100 × 2.1 mm i.d.) and acetonitrile-phosphate buffer (pH = 6.6; 0.01 M) (10/90 v/v) is the mobile phase. The results obtained are compared to analysis conducted by the HPLC method. The UHPLC method was validated in the range of 2–100 µg/mL levetiracetam concentration (R2 = 0.9997). LOD and LOQ are 10 ng/mL and 33 ng/mL, respectively. The developed UHPLC method was applied to plasma samples of patient with epilepsy. [ABSTRACT FROM PUBLISHER]

Summary Background Ichthyosiform erythroderma due to keratinizing disorders may suppress cutaneous vitamin D synthesis, leading to vitamin D deficiency and rickets. Objectives To determine the prevalence of vitamin D deficiency and rickets in children and adolescents with congenital ichthyosis and other keratinizing disorders with erythroderma and scaling. Patients and methods In this cross-sectional study, 45 children and adolescents with ichthyosiform erythroderma due to keratinizing disorders, and 66 controls (group 1: age and sex matched, with skin diseases other than keratinizing disorders; group 2: age and sex matched, healthy volunteers) were included. Evidence of rickets was determined clinically (physical examination and radiographs) and biochemically {serum calcium, phosphorus, alkaline phosphatase, 25-hydroxy vitamin D [25(OH)D] and parathyroid hormone (PTH)}. Results All patients in the disease group had clinical, radiological or biochemical evidence of rickets [25(OH)D < 20 ng mL−1], and analysis was done for all subjects with the available biochemical reports. The mean serum 25(OH)D levels of the disease group was 8·38 ± 5·23 ng mL−1 and was significantly lower than in control group 1 (11·1 ± 5·8 ng mL−1) ( P < 0·01) and control group 2 (13·5 ± 6·9 ng mL−1) ( P < 0·001). The prevalence of vitamin D deficiency [25(OH)D < 20 ng mL−1] was significantly higher in the disease group ( n = 38 of 39, 97·4%) than in control group 2 ( n = 12, 70·6%) ( P < 0·01), and total controls ( n = 56, 84·8%) ( P = 0·04). The frequency of hyperparathyroidism (PTH > 65 pg mL−1) was also significantly higher in the disease group than in controls ( P < 0·01). Conclusions Children and adolescents with various forms of ichthyosiform erythroderma, especially those with pigmented skin (types IV-VI), are at increased risk of developing vitamin D deficiency and clinical rickets. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated how solar ultraviolet B (UVB) radiation influences vitamin D synthesis in pediatric patients with Fitzpatrick skin phototypes IV and V. Topics explored include the measurement of sunlight exposure and vitamin D concentration in study participants, the recorded biochemical parameters following solar UVB exposure, and the observed post-treatment increase in baseline melanin index.

Seventeen patients with the type II (erythema nodosum leprosum) (ENL) reaction were studied. They received multidrug therapy and also the anti-reactional drugs prednisolone clofazimine or chloroquin, and we measured serum levels of complement components before treatment and after the reaction had subsided. Factor B was significantly elevated after treatment with each of the three drugs. C3 levels were significantly increased after treatment, the largest change being in patients treated with clofazimine. In these patients there was also a concomitant decrease in C3d levels. This suggests that clofazimine has complement modulating activity and we would recommend it as the drug of choice in treatment of the ENL reaction. [ABSTRACT FROM AUTHOR]

The article discusses the systematic review and meta-analysis of depression in patient with vitiligo. It mentions that vitiligo can have a profound psychological impact in more than half of the affected individuals. It notes that the social stigma associated with vitiligo has significant impact on social interaction, job and marriage prospects, and sexual relationships.

The article discusses research being done on hypochromic vitiligo and its comparison with post-inflammatory hypopigmentation (PIH), pityriasis alba and progressive macular hypopigmentation (PMH). It references the study "Hypochromic Vitiligo: Delineation of a New Entity," by K. Ezzedine et al. published in the 2015 issue. Several issues are noted in this study including types of vitiligo, vitiligo minor in dark-skinned individuals and clinical description of vitiligo.

Summary We describe an Indian man with the unusual association of classical cutaneous features of Ehlers-Danlos syndrome, a marfanoid habitus, bladder diverticula and multiple emphysematous bullae. [ABSTRACT FROM AUTHOR]

Background Vitiligo is an acquired pigmentary disorder resulting from loss of melanocytes. Interleukin (IL)-4 has been shown to stimulate B-cell proliferation, to regulate immunoglobulin class switching (IgG1 and IgE) and to promote T-cell development. Polymorphisms in the IL4 gene are known to increase its expression, thereby implicating its role in vitiligo susceptibility. Objectives To explore intron 3 VNTR (IVS3) and -590 C/T (rs2243250) promoter polymorphisms in the IL4 gene and to correlate them with the IL4 transcript, serum IL-4 and IgE levels to achieve genotype-phenotype correlation in patients with vitiligo from Gujarat. A replication study was done in a North Indian population. Methods The case-control study was performed to investigate these polymorphisms in 505 patients and 744 controls in Gujarat, and 596 patients and 397 controls in North India by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis. IL4 transcript levels were monitored by real-time PCR. Serum IL-4 and IgE levels were measured by enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, respectively. Results The genotype frequencies differed significantly between patients with generalized vitiligo and controls for both the polymorphisms in both populations. Allele frequencies significantly differed between patients with generalized vitiligo and controls for both the polymorphisms in the population from Gujarat. Interestingly, genotype and allele frequencies for -590 C/T single nucleotide polymorphism were significantly different between patients with localized vitiligo and controls in both the populations. The study revealed significantly increased IL4 mRNA, serum IL-4 and IgE levels in patients from Gujarat. Age of onset analysis of disease in patients suggested that the TTR2R2, TTR1R2 and CTR2R2 haplotypes had a profound effect in the early onset of the disease. Conclusions Our results suggest that these polymorphisms of the IL4 gene may be genetic risk factors for susceptibility towards vitiligo and the upregulation of the IL4 transcript, protein and IgE levels in individuals with susceptible haplotypes reveal the crucial role of IL -4 in the pathogenesis of vitiligo. [ABSTRACT FROM AUTHOR]

Objective: Metabolic diseases have a profound effect on the structure and function of the retinal circulation. The aim of the study was to find out the influence of metabolic syndrome (MS) and its individual components on retinal microvascular complications and its association with serum uric acid level. Method: An observational cross sectional study was performed. 150 subjects were selected in the study.50 cases were of MS based on modified national cholesterol program adult treatment panel III (NCEP ATP III) criteria (the cut off for the waist circumference was taken as per international diabetes federation for southeast asians), 50 cases were having less than three components of MS and 50 were age and sex matched healthy controls. Serum uric acid level was measured by uricase method. Hyperuricemia was defined as ≥7 mg/dl for males and ≥6 mg/dl for females. Indirect ophthalmoscopy was performed to find out retinal microvascular complications. Result: Cases with MS had more prevalence of retinal microvascular complications and retinopathy than hypertension and diabetes alone (p < 0.000). Cotton wool spots, flame shaped hemorrhages, dot and blot hemorrhages, microaneurysms and av nicking were common findings. Retinopathy was present in 42% cases in MS group and 8% cases in less than three components group. 65.62% of cases with hyperuricemia had retinopathy. Cases with retinopathy had significantly higher uric acid levels than controls (7.0647 ± 0.4675 vs. 2.7966 ± 0.5843). 76.19% of cases with retinopathy had hyperuricemia in MS group. Prevalence of retinopathy was higher in males (68.42%) as compared to females (25.80%). Conclusion: It is concluded that there is a direct association of MS components with retinal microvascular complications. There was synergistic effect of MS on retinal microvascular changes beyond its individual components. Incidence of retinopathy was higher in patients with hyperuricemia than normouricemic patients. [ABSTRACT FROM PUBLISHER]