Copy number variations of the human histamine H4 receptor gene are associated with systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a complex genetic disease; the histamine H4 receptor (HRH4) has been shown to be related to different kinds of autoimmune disorders; and copy number variations (CNVs) have been found to be associated with various types of diseases. Objectives To explore a possible association between HRH4 (formerly H4R) CNVs and the risk of SLE. Methods Genomic DNA and RNA from 340 patients with SLE and 392 healthy controls were extracted, and CNVs and mRNA levels of HRH4 were examined. Results The expression of HRH4 mRNA was significantly increased in patients with SLE compared with controls. Amplification of HRH4 copy numbers significantly increased the risk of SLE [P < 0·001, odds ratio (OR) 2·26, 95% confidence interval (CI) 1·50–3·40]. HRH4 amplifications also positively correlated with the incidence of arthritis (P = 0·019, OR 1·96, 95% CI 1·11–3·47), and proteinuria (P < 0·001, OR 2·95, 95% CI 1·73–5·00) and antinuclear antibody abnormalities (P < 0·001, OR 2·97, 95% CI 1·66–5·33). Deletions of HRH4 copy numbers were protective against proteinuria (P = 0·03, OR 0·50, 95% CI 0·26–0·94). Conclusion CNVs of the HRH4 gene are associated with SLE.     

Genetic association of HLA-DQB1 and HLA-DRB1 polymorphisms with alopecia areata in the Italian population

Background Alopecia areata (AA) is a multifactorial disease characterized by hair loss especially from the scalp. As for other autoimmune conditions, the major histocompatibility complex (HLA) region is associated with AA susceptibility. Objective To provide evidence for the association of specific HLA‐DQB1 and HLA‐DRB1 alleles with AA in an Italian population, using a case–control approach. Methods We performed a case–control study to investigate whether HLA‐DQB1 and ‐DRB1 alleles predispose to AA in the Italian population. HLA class II typing was performed in 85 patients with AA and 210 healthy controls from the same ethnic group. Results An increased frequency of DQB1*03, coding for DQ7 heterodimers, and a decreased rate of the DQB1*06 allele were observed in patients when compared with controls; the greatest and significant difference was in the group of cases with a more severe phenotype [AA > 50% patients (more than 50% hair loss) vs. controls, P = 4·5 × 10^?3, P_c = 0·031, odds ratio (OR) 2·01, 95% confidence interval (CI) 1·22–3·31 and P = 2·5 × 10^?3, P_c = 0·017, OR 0·22, 95% CI 0·07–0·72, respectively]. DQB1*03, serologically related to DQ8 or coding for DQ9 molecules, was not associated with AA susceptibility. Out of all patients, 65·9% carried DQ7 heterodimers compared with 49·5% of the controls (P = 7·3 × 10^?3, OR 1·97, 95% CI 1·17–3·32) and DQ7 prevalence rose to 76·3% in patients with AA > 50% (P = 1·7 × 10^?3, OR 3·28, 95% CI 1·48–7·27). No significant difference was found in the distribution of DRB1 variants or phenotypes among cases and controls. Conclusion Our data show a correlation between the HLA‐DQB1 locus and the occurrence of AA in Italy supporting DQB1*03(DQ7) as a predisposing allele for the disease and the relevance of the HLA genetic test in the clinical management of AA.     

Filaggrin polymorphism P478S, IgE level, and atopic phenotypes

Background Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. Objectives To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. Methods In total, 116 children aged 2–5 years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. Results A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4·60, 95% confidence interval (CI) 1·88–11·24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4·68, 95% CI 1·37–16·03). Further, a similar result was obtained for allergic rhinitis (OR 3·23, 95% CI 1·01–10·30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5·67, 95% CI 1·93–16·60) in children with IgE level ≥ 100 kU L^?1. However, the association was not evident when IgE level was < 100 kU L^?1. Conclusions Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.     

Histological regression in primary melanoma: not a predictor of sentinel lymph node metastasis in a cohort of 397 patients

Background Regression has been proposed as a potential marker of dissemination in thin melanomas. Previous studies have shown conflicting results. Objective To determine if regression in melanoma is associated with an increased risk of sentinel lymph node (SLN) metastasis. Methods A cohort analysis was conducted. Data on all patients were collected on a standardized case report form during 10 years. A total of 397 consecutive patients with melanoma who underwent a SLN biopsy were analysed. All cases of melanoma and SLN biopsies were examined by the same two pathologists. Differences between melanomas with and without SLN metastasis were compared using Fisher’s exact test or the two‐sample t‐test and the χ² test. Multivariable logistic regression was used to adjust for possible confounding factors. Results We analysed 397 patients (411 melanomas) who underwent a SLN biopsy. The median Breslow index was 1·8 mm (interquartile range 1·1–3). Regression was observed in 23% (n = 94). SLN metastases were observed in 26% (n = 106). The frequency of SLN metastasis was 16% in melanomas with regression and 29% without regression (P = 0·012). The adjusted odds ratio (OR) for regressive melanoma was 0·9 [95% confidence interval (CI) 0·4–1·9; P = 0·777]. The risk of SLN metastasis was increased in melanoma cases with a Breslow index from 1·5 to < 2·0 mm (adjusted OR 3·1; 95% CI 1·4–7·1; P = 0·006) and ≥ 2·0 mm (adjusted OR 3·5; 95% CI 1·7–7·4; P = 0·001) and ulceration of the melanoma (adjusted OR 1·8; 95% CI 1·1–3·2; P = 0·03). Conclusion Regression is not an independent predictor of the risk of SLN metastasis in melanoma.     

Wide spectrum of filaggrin-null mutations in atopic dermatitis highlights differences between Singaporean Chinese and European populations

Background  Null mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and predispose to atopic dermatitis (AD). Cohort studies in Europe and Japan have reported an FLG mutation carrier frequency of between 14% and 56%, but the prevalent European FLG mutations are rare or absent in Chinese patients with IV and AD. Objectives  To investigate further the spectrum of FLG‐null mutations in Chinese patients and to compare it with that in other populations. Methods  We conducted comprehensive FLG genetic analysis in a discovery cohort of 92 Singaporean Chinese individuals with IV and/or moderate‐to‐severe AD. All detected FLG mutations were then screened in a cohort of 425 patients with AD and 440 normal controls. Results  In total, 22 FLG‐null mutations, of which 14 are novel, were identified in this study; the combined null FLG genotype of 17 mutations detected in cases and controls showed strong association with AD [Fisher’s exact test; P = 5·3 × 10^?9; odds ratio (OR) 3·3], palmar hyperlinearity (Fisher’s exact test; P = 9·0 × 10^?15; OR 5·8), keratosis pilaris (Fisher’s exact test; P = 0·001; OR 4·7) and with increased severity of AD (permutation test; P = 0·0063). Conclusions  This study emphasizes the wider genetic landscape of FLG‐null mutations in Asia that is slowly emerging.     

Association between atopic dermatitis and obesity in adulthood

Background Obesity in early childhood is associated with increased risk for and severity of atopic dermatitis (AD). Objective  To determine whether obesity in adulthood is associated with risk of AD. Methods This was a retrospective case–control study of 2090 adults using questionnaire, height and weight, and skin‐prick testing between January 1994 and December 2003. Results  Obesity in adults was associated with increased AD [multinomial logistic regression: adjusted odds ratio (aOR) 1·43, 95% confidence interval (CI) 1·08–1·89; P = 0·01], but not nonatopic dermatitis (aOR 0·59, 95% CI 0·21–1·68; P = 0·32). Obesity was also associated with increased atopic asthma (aOR 1·98, 95% CI 1·47–2·66, P < 0·0001), but not associated with nonatopic asthma (P = 0·20), atopic or nonatopic rhinoconjunctivitis (P = 0·08 and 0·31, respectively), food allergies (P = 0·67 and 0·35, respectively) or atopy (P = 0·40). The association between obesity and AD remained significant even when controlling for history of asthma, rhinoconjunctivitis and food allergies (aOR 1·40, 95% CI 1·05–1·86; P = 0·02) or in subset analyses of subjects with AD alone (aOR 1·96, 95% CI 1·02–3·75; P = 0·04) and with comorbid asthma, rhinoconjunctivitis and/or food allergies (aOR 1·40, 95% CI 1·03–1·91; P = 0·03). Conclusion Obesity in adulthood is associated with AD. Further studies are warranted to determine if weight loss may prevent or mitigate AD in adults.     

Probiotics in pregnant women to prevent allergic disease: a randomized,double‐blind trial

Background Previous reports have suggested that certain probiotics given to mothers and children at risk of atopy halves the incidence of atopic dermatitis (AD) at 2 years of age. Objectives To examine if probiotics given to pregnant women in a nonselected population could prevent atopic sensitization or allergic diseases during the child’s first 2 years. Methods In a randomized, double‐blind trial of children from a nonselected maternal population (ClinicalTrials.gov identifier: NCT00159523), women received probiotic milk or placebo from 36 weeks of gestation to 3 months postnatally during breastfeeding. The probiotic milk contained Lactobacillus rhamnosus GG, L. acidophilus La‐5 and Bifidobacterium animalis subsp. lactis Bb‐12. Children with an itchy rash for more than 4 weeks were assessed for AD. At 2 years of age, all children were assessed for atopic sensitization, AD, asthma and allergic rhinoconjunctivitis. The intention‐to‐treat (ITT) analysis was enabled by multiple imputations. Results Four hundred and fifteen pregnant women were computer randomized. At 2 years, 138 and 140 children in the probiotic and the placebo groups, respectively, were assessed. In the ITT analysis, the odds ratio (OR) for the cumulative incidence of AD was 0·51 in the probiotic group compared with the placebo [95% confidence interval (CI) 0·30–0·87; P = 0·013]. There were no significant effects on asthma (OR 0·68, 95% CI 0·26–1·80; P = 0·437) or atopic sensitization (OR 1·52, 95% CI 0·74–3·14; P = 0·254). Conclusions Probiotics given to nonselected mothers reduced the cumulative incidence of AD, but had no effect on atopic sensitization.     

Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta‐analysis of observational studies

Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of the study was to systematically review the literature and critically answer the question: In patients with HS, do cardiovascular risk factors appear at a significantly higher rate compared with controls? The main search was conducted in Medline, Embase and the Cochrane Central Register. Studies eligible for inclusion were of case–control, cross‐sectional and cohort design, and included comparison of any cardiovascular risk factor(s) in patients with HS with those of control groups. An I² value > 50% was considered to show substantial heterogeneity. In this case, DerSimonian and Laird random‐effect models were considered to compute pooled odds ratios (OR). Otherwise, a fixed‐effects model was suitable. Nine studies, with 6174 patients with HS and 24 993 controls, were included. Significant association of HS with obesity [OR 3·45, 95% confidence interval (CI) 2·20–5·38, P < 0·001], central obesity (OR 2·97, 95% CI 1·41–6·25, P = 0·004), active smoking (OR 4·34, 95% CI 2·48–7·60, P < 0·001), history of smoking (OR 6·34, 95% CI 2·41–16·68, P < 0·001), hypertriglyceridemia (OR 1·67, 95% CI 1·14–2·47, P = 0·009), low high‐density lipoprotein (HDL) (OR 2·48, 95% CI 1·49–4·16, P < 0·001), diabetes (OR 2·85, 95% CI 1·34–6·08, P = 0·007) and metabolic syndrome (OR 2·22, 95% CI 1·62–3·06, P < 0·001) was detected. Associations were significant both in population and hospital patients with HS, with hospital HS groups having uniformly higher ORs than the population HS groups. Causality could not be assessed. Heterogeneity was substantial in all analyses. This systematic review indicated that cardiovascular risk factors appear at a significantly higher rate in patients with HS compared with controls. The need for screening of patients with HS for modifiable cardiovascular risks is emphasized.     

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Background Narrowband ultraviolet B (NB‐UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. Objectives To examine whether NB‐UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB‐UVB on antimicrobial peptide and cytokine expression in the skin. Methods Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB‐UVB exposures on the whole body, given three times a week. Serum calcidiol (25‐hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real‐time quantitative polymerase chain reaction. Results At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L^?1). NB‐UVB treatment significantly increased (P < 0·001) serum calcidiol. The increase was 59·9 nmol L^?1 (95% confidence interval, CI 53·5–66·9) in psoriasis, 68·2 nmol L^?1 (95% CI 55·4–80·1) in AD and 90·7 nmol L^?1 (95% CI 63·8–123·4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0·001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human β‐defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB‐UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB‐UVB caused a marked but nonsignificant decrease of interleukin (IL)‐1β and IL‐17 in psoriasis lesions. Conclusions The present study shows that in addition to a significant improvement of psoriasis and AD, NB‐UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.     

A randomized controlled trial in children with eczema: nurse practitioner vs. dermatologist

Background We hypothesized that a nurse practitioner would improve the quality of life of a child with eczema more than a dermatologist because of a structured intervention and more consultation time. Objectives To compare the level of care by nurse practitioners with that by dermatologists in children with eczema. Methods New referrals aged ≤ 16 years with a diagnosis of eczema were recruited. In a randomized, parallel‐group study with a follow‐up period of 1 year, 160 participants were randomized either to conventional care from a dermatologist or to care from a nurse practitioner. The primary outcome measure was change in quality of life at 12 months, as assessed by the Infants’ Dermatitis Quality of Life Index (IDQOL) for children aged ≤ 4 years, and by the illustrated version of the Children’s Dermatology Life Quality Index (CDLQI) for children aged 4–16 years. Secondary outcomes were changes in IDQOL and CDLQI at 4 and 8 months, family impact of childhood atopic dermatitis (Dermatitis Family Impact Questionnaire, DFI), eczema severity (objective SCORAD) and patient satisfaction (Client Satisfaction Questionnaire‐8, CSQ‐8) at 4, 8 and 12 months. Results The mean IDQOL in the dermatologist group improved significantly from 11·6 [SD 8·1; 95% confidence interval (CI) 9·0–14·2] at the baseline to 5·6 (SD 3·9; 95% CI 4·3–7·0) at 12 months with a mean change from the baseline of ?6·5 (SD 6·6; 95% CI ?14·2 to ?8·9; P < 0·001). The mean IDQOL in the nurse practitioner group improved significantly from 10·7 (SD 4·9; 95% CI 9·1–12·3) at baseline to 5·7 (SD 5·4; 95% CI 4·0–7·5) at 12 months with a mean change from the baseline of ?4·9 (SD 5·5; 95% CI ?6·8 to ?3·0; P < 0·001). The between‐groups difference was (?)1·7 (95% CI ?4·6 to 1·2; P = 0·26). The mean CDLQI in the dermatologist group improved significantly from 12·1 (SD 6·3; 95% CI 9·9–14·2) at baseline to 5·6 (SD 4·2; 95% CI 4·2–7·1) at 12 months with a mean change from the baseline of ?5·9 (SD 6·0; 95% CI ?8·0 to ?3·9; P < 0·001). The mean CDLQI in the nurse practitioner group improved significantly from 10·0 (SD 4·4; 95% CI 8·5–11·4) at the baseline to 4·9 (SD 3·5; 95% CI 3·7–6·1) at 12 months with a mean change from the baseline of ?5·2 (SD 4·0; 95% CI ?6·6 to ?3·8; P < 0·001). The between‐groups difference was (?)0·7 (95% CI ?3·3 to 1·7; P = 0·55). The between‐groups comparison was not significant for the IDQOL and the CDLQI at baseline or 4, 8 and 12 months. Both treatment groups showed significant improvement in DFI and objective SCORAD at 12 months. The between‐groups comparison was not significant at baseline or 4, 8 and 12 months. Significantly higher satisfaction levels were observed at 4, 8 and 12 months in the nurse practitioner group. Conclusions The level of care provided by a nurse practitioner in terms of the improvement in the eczema severity and the quality of life outcomes was comparable with that provided by a dermatologist. In addition, the parents were more satisfied with the care that was provided by a nurse practitioner.     

Association between HLA-DRB1 polymorphisms and pemphigus vulgaris: a meta-analysis

Background Several studies have reported that HLA‐DRB1 may be correlated with pemphigus vulgaris (PV), but most have been based on small samples and the results remain inconsistent and unclear. Objectives To investigate the correlation between DRB1 and PV by a meta‐analysis of case–control/nonfamily studies. Methods PubMed, Wiley Online Library, ScienceDirect, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were searched for studies including: (i) ‘pemphigus’; and (ii) ‘human leukocyte antigen’, ‘HLA’, ‘major histocompatibility complex’, ‘MHC’ or ‘DRB1’. Eighteen selected studies were used in meta‐analyses to evaluate DRB1 alleles and phenotypes by calculating the respective odds ratios (ORs) and 95% confidence intervals (CIs). Stratified meta‐analyses and meta‐regression analysis were also conducted. Results The frequencies of three genotypes (allele and phenotype, respectively) were significantly increased in PV: DRB1*04 [P‐value for comparability (Pc) < 0·00001, OR 3·61, 95% CI 2·28–5·71; Pc = 0·0002, OR 4·14, 95% CI 1·98–8·65], DRB1*08 (Pc = 0·03, OR 2·25, 95% CI 1·07–4·70; Pc = 0·0003, OR 2·46, 95% CI 1·51–4·01) and DRB1*14 (Pc < 0·00001, OR 6·47, 95% CI 4·52–9·26; Pc < 0·00001, OR 9·68, 95% CI 4·47–20·98). Three others (allele and phenotype, respectively) were significantly decreased in PV: DRB1*03 (Pc < 0·00001, OR 0·28, 95% CI 0·19–0·41; Pc = 0·0001, OR 0·25, 95% CI 0·12–0·51), DRB1*07 (Pc = 0·004, OR 0·45, 95% CI 0·26–0·78; Pc = 0·0002, OR 0·27, 95% CI 0·14–0·54) and DRB1*15 (Pc = 0·001, OR 0·35, 95% CI 0·18–0·66; Pc = 0·002, OR 0·32, 95% CI 0·16–0·65). Ethnicity partially explained the heterogeneity of DRB1*07, DRB1*08 and DRB1*14 phenotypes. Conclusions Our findings suggest that DRB1*04, DRB1*08 and DRB1*14 are statistically significant susceptibility factors for PV. Conversely, DRB1*03, DRB1*07 and DRB1*15 may be negatively associated with PV. Specific HLA‐DRB1 types may influence the susceptibility or resistance to PV, which needs further investigations.     

Impact of glucocorticoid‐induced adverse events on adherence in patients receiving long‐term systemic glucocorticoid therapy

Summary Background Factors influencing adherence to long‐term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood. Objective To evaluate the relationship between glucocorticoid‐induced adverse events and therapeutic adherence in patients on long‐term glucocorticoid treatment. Methods A cross‐sectional survey was conducted in three departments of dermatology/internal medicine between April and September 2008. Patients were asked to provide data regarding symptoms they attributed to glucocorticoids, and adherence to treatment was measured using the four‐item Morisky–Green adherence scale. Logistic regression analyses were used to assess the association between reported adverse events and adherence to glucocorticoids. Results A total of 255 questionnaires were completed and analysed [women 78%; median age 48 years (interquartile range (IQR) 34–65); connective tissue diseases 59%; median duration of treatment 24 months (IQR 8–72); median daily dose 10 mg (IQR 6–20)]. Among these 255 patients, 199 (78%) reported themselves as ‘good adherents’ and 56 (22%) as ‘poor adherents’ to treatment. Poor adherence was associated with younger age [odds ratio (OR) 0·97, 95% confidence interval (CI) 0·95–0·99, per increasing year; P < 0·01], presence of glucocorticoid‐induced epigastralgia (OR 4·02, 95% CI 2·00–8·09; P < 0·01) and presence of glucocorticoid‐induced morphological changes (OR 2·49, 95% CI 1·19–5·21; P = 0·02). Moreover, patients with poor adherence were likely to report concomitantly poor adherence to dietary advice associated with glucocorticoid therapy (OR 2·44, 95% CI 1·12–5·26; P = 0·02). Conclusions As with other chronic therapies, the presence of glucocorticoid‐induced adverse events is associated with an altered self‐reported adherence to glucocorticoids. Patients who report epigastric pain or morphological changes that they associate with glucocorticoid therapy are particularly at risk of poor adherence. Adherence to dietary advice associated with glucocorticoid therapy may be an indirect measure of treatment adherence.     

Water-filtered infrared A for the treatment of chronic venous stasis ulcers of the lower legs at home: a randomized controlled blinded study

Background Water‐filtered infrared A (wIRA) radiation can improve the healing of acute and chronic wounds both by thermal and thermic as well as by nonthermal and nonthermic effects. wIRA increases tissue temperature, oxygen partial pressure and perfusion. Objectives Investigation of the influence of wIRA on chronic venous stasis ulcers in an investigator‐initiated, randomized, controlled, blinded study. Methods Fifty‐one patients with nonhealing chronic venous stasis ulcers of the lower legs were treated with compression therapy, wound cleansing, nonadhesive wound dressings and 30 min irradiation [wIRA + visible light (VIS) or VIS alone], predominantly at home, five times per week over 9 weeks and an additional 4 weeks without irradiation. Results Compared with the control group with VIS alone, the group with wIRA + VIS showed better wound healing [after 9 weeks 85 vs. 67·5 on a 0–100 visual analogue scale (VAS), median difference 15, 95% confidence interval (CI) 3–30, P = 0·012], a higher percentage of patients with a healing trend [after 9 weeks 21 of 25 (84%) vs. 13 of 26 (50%), P = 0·023], better granulation (after 9 weeks 90 vs. 80 on a 0–100 VAS, median difference 10, 95% CI 0–30, P = 0·036), a trend to less exudation (after 5 weeks 30 vs. 55 on a 0–100 VAS, P = 0·075) and to faster reduction of the wound area (after 7 weeks 39% vs. 19·5% reduction of wound area, median difference 20·5%, 95% CI ?4–49%, P = 0·10; for wounds with an initial area < 10 cm²: after 13 weeks 92% vs. 47% reduction of wound area, median difference 30%, 95% CI 0–68%, P = 0·11). The main variable ‘Integral of relative ulcer area for each individual patient over time, standardized to an initial size of 1′ did not reach significance. The application of wIRA at home was easily manageable. Conclusions For the treatment of chronic venous stasis ulcers, the application of wIRA combined with phlebological therapy, compression therapy and wound dressing can be useful and can be recommended.     

Association of KIF3A,but not OVOL1 and ACTL9, with atopic eczema in Italian patients

Background Atopic eczema (AE) (OMIM %603165) is the most common chronic inflammatory skin disease characterized by xerosis, pruritus, and erythematous lesions with increased transepidermal water loss. It’s a complex disease due to the interaction between environmental and genetics factors. To date, different loci have been related to the disease. Objectives To verify the association, between AE and rs479844, rs2164983, and rs2897442, target for OVOLI (11q13), ACTL9 (19p13.2), and in KIF3A (5q31) genes in the Italian population. Recently, these SNPs have been validated as associated to the disease. Methods A case‐control study testing a cohort of 359 AE cases and 778 controls. Results  We confirmed the association between rs2897442 in KIF3A gene and the disease at both allele and genotype level (P‐value: 4·8 × 10^?4 and P‐value: 6·3 × 10^?4, respectively). The C allele of the SNP showed an Odds Ratio (OR) of 1·46 (95% CI 1·18–1·82), moreover the CC genotype achieved an OR of 2·77 (95% CI 1·66–4·61). We failed to reveal association between AE and the other two SNPs tested. Conclusions Our study indicated KIF3A as a novel gene implicated in the development of AE in the Italian population.     

The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis

Background Quantitative analysis of intravenous immunoglobulin (IVIg) treatment against toxic epidermal necrolysis (TEN) is lacking. Objectives To provide a meta‐analysis evidence‐based examination of IVIg efficacy against TEN. Methods A systematic review and meta‐analysis of literature published before 31 July 2011 was conducted. In observational controlled studies with at least eight patients with TEN receiving IVIg treatment, a pooled estimate of mortality risk was determined, comparing IVIg and supportive care. Statistical analyses were performed on raw data to compare the clinical differences between (i) high‐dose and low‐dose IVIg treatment in adult patients and (ii) paediatric and adult patients treated with IVIg. Results Seventeen studies met inclusion criteria. Overall mortality rate of patients with TEN treated with IVIg was 19·9%. The pooled odds ratio (OR) for mortality from six observational controlled studies comparing IVIg and supportive care was 1·00 [95% confidence interval (CI) 0·58–1·75; P = 0·99]. The pooled OR for mortality in patients treated with high‐dose IVIg vs. supportive care was 0·63 (95% CI 0·27–1·44; P = 0·27). Adults treated with high‐dose IVIg exhibited significantly lower mortality than those treated with low‐dose IVIg (18·9% vs. 50%, respectively; P = 0·022); however, multivariate logistic regression model adjustment indicated that IVIg dose does not correlate with mortality (high vs. low dose: OR 0·494; 95% CI 0·106–2·300; P = 0·369). Paediatric patients treated with IVIg had significantly lower mortality than adults (0% vs. 21·6%; P = 0·001). Conclusions Although high‐dose IVIg exhibited a trend towards improved mortality and children treated with IVIg had a good prognosis, the evidence does not support a clinical benefit of IVIg. Randomized controlled trials are necessary.     

Risk factors for nonpurulent leg cellulitis: a systematic review and meta‐analysis

Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The objectives of this systematic review and meta‐analysis were to identify and appraise all controlled observational studies that have examined risk factors for the development of nonpurulent cellulitis of the leg (NPLC). A systematic literature search of electronic databases and grey literature sources was performed in July 2015. The Newcastle–Ottawa Scale (NOS) was used to assess methodological quality of included studies. Of 3059 potentially eligible studies retrieved and screened, six case–control studies were included. An increased risk of developing NPLC was associated with previous cellulitis [odds ratio (OR) 40·3, 95% confidence interval (CI) 22·6–72·0], wound (OR 19·1, 95% CI 9·1–40·0), current leg ulcers (OR 13·7, 95% CI 7·9–23·6), lymphoedema/chronic leg oedema (OR 6·8, 95% CI 3·5–13·3), excoriating skin diseases (OR 4·4, 95% CI 2·7–7·1), tinea pedis (OR 3·2, 95% CI 1·9–5·3) and body mass index > 30 kg m⁻² (OR 2·4, 95% CI 1·4–4·0). Diabetes, smoking and alcohol consumption were not associated with NPLC. Although diabetics may have been underrepresented in the included studies, local risk factors appear to play a more significant role in the development of NPLC than do systemic risk factors. Clinicians should consider the treatment of modifiable risk factors including leg oedema, wounds, ulcers, areas of skin breakdown and toe‐web intertrigo while administering antibiotic treatment for NPLC.     

Drug-induced subacute cutaneous lupus erythematosus: evidence for differences from its idiopathic counterpart

Background Drug‐induced subacute cutaneous lupus erythematosus (DI‐SCLE) is a lupus variant with predominant skin involvement temporally related to drug exposure and resolving after drug discontinuation. It usually presents with annular polycyclic or papulosquamous eruptions on sun‐exposed skin and shows serum anti‐Ro/SSA antibodies. Objectives To address the question whether DI‐SCLE differs significantly from idiopathic SCLE by virtue of clinical features. Methods Ninety patients with SCLE seen in our departments from 2001 to 2010 were reviewed. Eleven of them diagnosed as having DI‐SCLE were evaluated for type of skin lesions, systemic involvement, clinical course, and histopathological, direct immunofluorescence and laboratory findings. The cutaneous features were compared with those of the 79 patients with idiopathic SCLE. Results The cutaneous picture was widespread in 82% of patients with DI‐SCLE and in 6% of those with idiopathic SCLE [odds ratio (OR) 66·6, 95% confidence interval (CI) 11·2–394·9; P = 0·0001]. Bullous and erythema multiforme (EM)‐like lesions were present in 45% of patients with DI‐SCLE and in 1% of those with idiopathic SCLE (OR 65·0, 95% CI 6·5–649·6; P = 0·0001). Vasculitic lesions were observed in 45% of patients with DI‐SCLE and in 3% of those with idiopathic SCLE (OR 32·1, 95% CI 5·1–201·7; P = 0·0001). Malar rash occurred in 45% of patients with DI‐SCLE and in 6% of those with idiopathic SCLE (OR 12·3, 95% CI 2·8–54·9; P = 0·001). Visceral manifestations were excluded in all patients with DI‐SCLE. Anti‐Ro/SSA antibodies were found in all but one patient with DI‐SCLE and disappeared after resolution in 73% of cases. Conclusions DI‐SCLE differs from idiopathic SCLE by virtue of distinctive cutaneous features, particularly the widespread presentation and the frequent occurrence of malar rash and bullous, EM‐like and vasculitic manifestations.     

Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age

Background Filaggrin loss‐of‐function (FLG) mutations are associated with eczema and skin barrier impairment, but it is unclear whether skin barrier impairment precedes phenotypic eczema in FLG mutation carriers. Objectives To study the association between FLG mutations, skin barrier impairment and clinical eczema at 3 months of age. Methods A total of 88 infants were examined for eczema. Disease severity was determined by the SCORAD eczema severity score. Transepidermal water loss (TEWL) was measured on unaffected forearm skin. Venous blood samples were screened for the four most common FLG mutations found in the U.K. white population (R501X, 2282del4, R2447X and S3247X). Median SCORAD and TEWL measurements in children with and without eczema and FLG mutations were compared. Results Thirty‐three per cent (29/88) of children had clinical eczema. Median SCORAD was 10·6 (range 3·5–31·0). TEWL (g m^?2 h^?1) was higher in children with eczema compared with unaffected infants (median TEWL 14·24 vs. 11·24, P < 0·001). Higher TEWL was associated with more severe disease (r = 0·59, P < 0·001, median TEWL, SCORAD < 15, 13·1 vs. 29·6, SCORAD ≥ 15, P = 0·029). Clinically dry skin was associated with higher TEWL, even in the absence of eczema (median TEWL 17·55 vs. 11·08, P = 0·008). Seventeen per cent (15/88) of children carried at least one FLG mutation. FLG mutation carriers were significantly more likely to have clinically dry skin, even in the absence of eczema [odds ratio (OR) 8·50, 95% confidence interval (CI) 1·09–66·58, P = 0·042]. FLG mutation carriers were also more likely to have eczema by 3 months of age (OR 4·26, 95% CI 1·34–13·57, P = 0·014). FLG mutations were significantly associated with higher median TEWL (all children, FLG‘yes’ 21·59 vs. FLG‘no’ 11·24, P < 0·001), even without clinical eczema (FLG‘yes’ 15·99 vs. FLG‘no’ 10·82, P = 0·01). Conclusions By the age of 3 months, FLG mutations are associated with an eczema phenotype, dry skin and TEWL. The observation that TEWL is elevated in unaffected FLG mutation carriers suggests that skin barrier impairment precedes clinical eczema.     

Impact of atopic dermatitis and loss‐of‐function mutations in the filaggrin gene on the development of occupational irritant contact dermatitis

Background Atopic dermatitis (AD) and loss‐of‐function mutations in the filaggrin gene (FLG) are both associated with chronic irritant contact dermatitis (ICD). As FLG mutations also are a major risk factor for AD, it is not clear whether FLG mutations are an independent risk factor for ICD or whether the risk is mediated by AD. Objectives To investigate the relative contribution and interaction of FLG mutations and AD in German patients with occupational ICD and controls (vocational school apprentices). Methods A total of 634 patients and 393 controls were genotyped for R501X, 2282del4, R2447X and S3247X. Current or past flexural eczema was used as an indicator of AD. Results FLG mutations were found in 15·9% of the patients with ICD and 8·3% of the controls, with a crude odds ratio (OR) of 2·09 [95% confidence interval (CI) 1·33–3·28] for the combined genotype. The adjusted OR for FLG mutations, corrected for AD, was 1·62 (95% CI 1·01–2·58). Subjects with AD were at approximately three times higher risk of developing ICD than controls (OR 2·89; 95% CI 2·09–3·99). There was no evidence of an interaction between these two risk factors. Conclusions Our results indicate that both FLG mutations and AD increase the risk of ICD. Individuals with concurrent FLG mutations and AD are at the highest risk of developing ICD.