Risks for Staphylococcus aureus colonization in patients with psoriasis: a systematic review and meta‐analysis

Evidence on whether patients with psoriasis have a higher risk for staphylococcal colonization than healthy controls remains controversial. To synthesize the current literature, we performed a systematic review on the prevalence and relative risk (RR) of Staphylococcus aureus colonization in patients with psoriasis. We modified the QUADAS‐2 instrument to assess the reporting quality of individual studies and applied random‐effects models in meta‐analysis. Overall we identified 21 eligible studies, of which 15 enrolled one or more comparison groups. The pooled prevalence of staphylococcal colonization in patients with psoriasis was 35·3% [95% confidence interval (CI) 25·0–45·6] on lesional skin and 39·2% (95% CI 33·7–44·8) in the nares. Patients with psoriasis were 4·5 times more likely to be colonized by S. aureus than healthy controls were on the skin (RR 5·54, 95% CI 3·21–9·57) and 60% more in the nares (RR 1·60, 95% CI 1·11–2·32). Cutaneous and nasal colonization by meticillin‐resistant S. aureus also appeared higher in patients with psoriasis (pooled prevalence 8·6%) than in healthy controls (2·6%), yet the difference was not statistically significant (P = 0·74). In contrast, despite of a similar risk for nasal staphylococcal colonization (RR 0·67, 95% CI 0·38–1·18), patients with psoriasis were less likely to carry S. aureus on lesional skin than atopic patients (RR 0·64, 95% CI 0·40–1·02). In summarizing the current literature, we found that patients with psoriasis were at an increased risk for staphylococcal colonization compared with healthy individuals. Prospective studies on how bacterial loads correlate with disease activity can guide the clinical management of bacterial colonization while preventing the emergence of drug‐resistant strains.     

Psoriasis and smoking: a systematic review and meta‐analysis

Psoriasis is an inflammatory skin disease associated with increased cardiovascular comorbidity. Smoking is associated with an increased risk of cardiovascular disease, and prior studies have suggested that patients with psoriasis are more likely to be active smokers. Smoking may also be a risk factor in the development of psoriasis. We conducted a systematic review and meta‐analysis to assess the prevalence of smoking among patients with psoriasis, and we reviewed the contribution of smoking to the incidence of psoriasis. A total of 25 prevalence and three incidence studies were identified. The meta‐analysis of prevalence studies included a total of 146 934 patients with psoriasis and 529 111 patients without psoriasis. Random effects meta‐analysis found an association between psoriasis and current smoking [pooled odds ratio (OR) 1·78, 95% confidence interval (CI) 1·52–2·06], as well as between psoriasis and former smoking (pooled OR 1·62, 95% CI 1·33–1·99). Meta‐regression analysis did not reveal any sources of study heterogeneity, but a funnel plot suggested possible publication bias. A subset of studies also examined the association between moderate‐to‐severe psoriasis and smoking, with a pooled OR of 1·72 (95% CI 1·33–2·22) for prevalent smoking. The three incidence studies found an association between smoking and incidence of psoriasis, with a possible dose‐effect of smoking intensity and duration on psoriasis incidence. These findings suggest that smoking is an independent risk factor for the development of psoriasis, and that patients with established psoriasis continue to smoke more than patients without psoriasis.     

Zinc and atopic dermatitis: a systematic review and meta‐analysis

Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21–1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38–1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non‐significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71–3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High‐quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.     

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.     

Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris

Background Adherence to treatment is an indicator of treatment success. Long‐term data on adherence to biologic treatment in psoriasis are lacking. Objectives To compare the tumour necrosis factor (TNF)‐α inhibitors regarding drug survival rate and safety in patients with psoriasis. Methods This study is based on data from the Danish nationwide database DERMBIO covering patients with psoriasis treated with a biologic agent. All patients who received anti‐TNF‐α treatment in academic referral centres were included. Baseline data, adverse events, time on treatment and reason for stopping treatment were recorded. Hazard ratios (HRs) for factors determining drug survival were calculated by logistic regression. Results In total, 882 treatment series with etanercept (n = 311), adalimumab (n = 427) or infliximab (n = 144) were administered to 747 patients. Significant predictors of drug survival were: sex, the anti‐TNF‐α agent and the previous response to an anti‐TNF‐α agent. In the group of anti‐TNF‐α‐naïve patients the longest drug survival was observed for infliximab, followed by adalimumab [HR vs. infliximab 3·70, 95% confidence interval (CI) 1·99–6·89] and etanercept (HR vs. infliximab 3·18, 95% CI 1·72–5·86). The 4‐year drug survival is in the range of 40% for etanercept or adalimumab vs. 70% for infliximab. There was no difference in number of adverse events. Conclusions The overall efficacy of anti‐TNF‐α drugs diminishes with time, as envisaged by the progressive loss of patient adherence to treatment. The major reasons for stopping treatment were loss of efficacy, followed by adverse events. Infliximab had the best patient retention ability, with 70% of patients still being on the drug after 4 years of treatment.     

Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta‐analysis of randomized controlled trials

Concerns have been raised regarding an increased risk of major adverse cardiovascular events (MACEs) (myocardial infarction, cerebrovascular accident or cardiovascular death) in patients treated with anti‐interleukin (IL)‐12/23 agents for moderate‐to‐severe psoriasis. We aimed to examine the risk of MACEs in adult patients with plaque psoriasis that are exposed to biologic therapies via a meta‐analysis of randomized controlled trials (RCTs). Data were obtained from systematic searches in the Cochrane Library, MEDLINE and Embase, U.S. Food and Drug Administration, European Medicines Agency, individual pharmaceutical companies online search platforms and five trials registers (up to 31 March 2016). We selected RCTs reporting adverse events in adults with plaque psoriasis receiving at least one licensed dose of biologic therapy, conventional systematic therapy or placebo. We calculated Peto odds ratios (ORs) with 95% confidence intervals (CIs) and calculated I² statistics to assess heterogeneity. Overall, 38 RCTs involving 18 024 patients were included. No MACEs were observed in 29 studies, while nine RCTs reported 10 patients experiencing MACEs. There was no statistically significant difference in risk of MACEs associated with the use of biologic therapies overall (OR 1·45, 95% CI 0·34–6·24); tumour necrosis factor‐α inhibitors (adalimumab, etanercept and infliximab) (OR 0·67, 95% CI 0·10–4·63); anti‐IL‐17A agents (secukinumab and ixekizumab) (OR 1·00, 95% CI 0·09–11·09) or ustekinumab (OR 4·48, 95% CI 0·24–84·77). No heterogeneity was observed in these comparisons. In conclusion, the limited existing evidence suggests that licensed biologic therapies are not associated with MACEs during the short randomized controlled periods in clinical trials.     

Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study

Background Psoriasis has been linked to cardiovascular comorbidities in cross‐sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease (CVD) is limited. Objectives To make a prospective evaluation of the association between psoriasis and risk of incident nonfatal CVD. Methods Participants (n = 96 008) were included from the Nurses’ Health Study II, and followed for 18 years. Information on physician‐diagnosed psoriasis was obtained by self‐report and diagnosis was confirmed by supplementary questionnaires. We included 2463 individuals with self‐reported psoriasis and a subsample of 1242 with validated psoriasis. The main outcome was incident nonfatal CVD events [nonfatal myocardial infarction (MI) and nonfatal stroke], ascertained by biennial questionnaires and confirmed. Results During 1 709 069 person‐years of follow‐up, 713 incident nonfatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate‐adjusted hazard ratio (HR) of nonfatal CVD, 1·55 [95% confidence interval (CI): 1·04–2·31]. HRs for nonfatal MI and stroke were 1·70 (95% CI: 1·01–2·84) and 1·45 (95% CI: 0·80–2·65), respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR: 2·06, 95% CI: 1·31–3·26). For individuals with concomitant psoriatic arthritis, the risk of nonfatal CVD was even higher (HR: 3·47; 95% CI: 1·85–6·51). Women diagnosed with psoriasis at < 40 years of age or with duration of psoriasis ≥ 9 years had substantial elevations in CVD risk: HR: 3·26 (95% CI: 1·21–8·75) and 3·09 (95% CI: 1·15–8·29), respectively. Conclusions Psoriasis is an independent predictor for nonfatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis.     

Elevated serum levels of interleukin 21 are associated with disease severity in patients with psoriasis

Background  Psoriasis is an immune disorder involving numerous cytokines. Recent studies have shown that interleukin (IL)‐21 plays an important role in a variety of inflammatory and autoimmune diseases. It is highly expressed in psoriatic plaques and promotes the proliferation of epidermis in mice. It seems that IL‐21 plays an important role in the pathogenesis of psoriasis. However, whether or not it is elevated in the peripheral blood of patients with psoriasis and is associated with disease severity is unclear. Therefore, our study focuses on serum IL‐21 levels and their correlation with disease severity. Objectives  To detect serum IL‐21 levels in patients with psoriasis and investigate the correlation between these and the Psoriasis Area and Severity Index (PASI) scores. Methods  Blood samples were collected from patients with plaque psoriasis and from healthy control subjects. Serum IL‐21 levels were measured by enzyme‐linked immunosorbent assay in 37 patients with psoriasis and 37 healthy controls. The PASI scores of patients with psoriasis and their correlation with serum IL‐21 levels were evaluated. Results  Serum IL‐21 levels were higher in patients with psoriasis than in healthy controls (P < 0·01). Serum IL‐21 levels were positively correlated with PASI scores in the patients with psoriasis (r = 0·471, P < 0·01). Conclusions  Serum IL‐21 levels in patients with psoriasis are elevated and positively correlate with PASI scores. These results indicate that IL‐21 may play an important role in the pathogenesis of psoriasis.     

Does early life exposure to antibiotics increase the risk of eczema? A systematic review

A number of studies have suggested that early life exposure to antibiotics can lead to an increased risk of developing eczema. This systematic review and meta‐analysis of observational studies, involving children or young adults aged 0–25 years, assessed the impact of antibiotic exposure either in utero or during the first 12 months of life on subsequent eczema risk. Twenty studies examined the association between prenatal and/or postnatal exposure to antibiotics and development of eczema. The pooled odds ratio (OR) for the 17 studies examining postnatal antibiotic exposure was 1·41 [95% confidence interval (CI) 1·30–1·53]. The pooled OR for the 10 longitudinal studies was 1·40 (95% CI 1·19–1·64), compared with a pooled OR of 1·43 (95% CI 1·36–1·51) for the seven cross‐sectional studies. There was a significant dose–response association, suggesting a 7% increase in the risk of eczema for each additional antibiotic course received during the first year of life [pooled OR 1·07 (95% CI 1·02–1·11)]. Finally, the pooled OR for the four studies relating to antenatal exposure was 1·30 (95% CI 0·86–1·95). We conclude that exposure to antibiotics in the first year of life, but not prenatally, is more common in children with eczema.     

Psoriasis and melanocytic naevi: does the first confer a protective role against melanocyte progression to naevi?

Background Some of the cytokines that have effects on melanogenesis are also reported to be involved in psoriasis. Objectives We therefore studied the relationship between psoriasis and melanocytic naevi. In particular, the aim of our study was to investigate the number of melanocytic naevi in patients with psoriasis vs. controls. Methods We performed a prospective case–control study, analysing 93 adult patients with psoriasis and 174 adult aged‐matched controls. For each participant a questionnaire was completed to establish personal data, personal medical history, and personal and familial history of skin cancer and psoriasis. We analysed interleukin (IL)‐1α, IL‐6 and tumour necrosis factor (TNF)‐α gene expression at the peripheral blood mononuclear cell level in patients with psoriasis and in controls. Results In our study, patients with psoriasis presented a lower number of areas with naevi in comparison with controls (P < 0·0001). Nobody had ever had squamous cell carcinoma or melanoma in the psoriatic group; moreover, there was a significant difference in familial history of melanoma between the two groups (none in the psoriatic group vs. 8% in the control group; P < 0·05). IL‐1α, IL‐6 and TNF‐α expression levels were higher in patients with psoriasis. Conclusions People with psoriasis had fewer melanocytic naevi. This suggests that the proinflammatory cytokine network in psoriasis skin might inhibit melanogenesis, melanocyte growth and/or progression to naevi.     

Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility

NACHT leucine‐rich repeat‐ and PYD‐containing (NLRP)3 protein controls the inflammasome by regulating caspase‐1 activity and interleukin (IL)‐1β processing. The contribution of IL‐1β in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domain–containing protein (CARD)8, a negative regulator of caspase‐1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single‐nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan^® Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211 genotype was significantly different in cases and controls in overall terms [OR 1.3 (1.1–1.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.     

Consistent responses with guselkumab treatment in Asian and non‐Asian patients with psoriasis: An analysis from VOYAGE 1 and VOYAGE 2

Guselkumab, an interleukin‐23 blocker, was superior to placebo and adalimumab and well‐tolerated in phase 3 psoriasis studies (VOYAGE 1 and VOYAGE 2). This analysis evaluated the consistency of response in the Asian subpopulation in VOYAGE 1 and VOYAGE 2. Study designs were identical through week 24; patients were randomized to guselkumab, placebo, or adalimumab. Investigator's Global Assessment (IGA), Psoriasis Area and Severity Index (PASI), safety, and pharmacokinetic and immunogenicity data from VOYAGE 1 and VOYAGE 2 were pooled and compared by race (Asian, n = 199; non‐Asian, n = 1630). At week 16, treatment differences between guselkumab and placebo were 78.2 (95% confidence interval [CI], 66.9–89.6) and 76.4 (95% CI, 72.7–80.2) percentage points for IGA 0/1 (score of 0 or 1) and 70.1 (95% CI, 60.0–80.1) and 68.5 (95% CI, 64.9–72.2) percentage points for PASI 90 (≥90% improvement) in the Asian and non‐Asian populations, respectively. Treatment differences between guselkumab and adalimumab were 31.1 (95% CI, 17.7–44.6) and 16.1 (95% CI, 11.2–21.0) percentage points for IGA 0/1 and 24.9 (95% CI, 9.4–40.5) and 23.2 (95% CI, 17.7–28.6) percentage points for PASI 90 in the Asian and non‐Asian populations, respectively. Similar results were observed at week 24. Safety was generally similar between populations and among treatment groups. Median serum guselkumab concentrations over time were comparable between the populations. Comparable responses between the Asian and non‐Asian populations in this analysis suggest that the overall efficacy, safety, and the resulting benefit/risk analyses from VOYAGE 1 and VOYAGE 2 are applicable to Asian populations.     

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.     

Glutathione S-transferase genotype is associated with sensitivity to psoralen-ultraviolet A photochemotherapy

Background There is marked interpatient variation in responses to psoralen–ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of PUVA sensitivity may facilitate treatment predictability. The glutathione S‐transferases (GSTs) influence cutaneous defence against UV radiation‐induced oxidative stress and are therefore candidate biomarkers of PUVA sensitivity. Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null polymorphisms have been associated with increased UVB erythemal sensitivity and skin cancer risk. PUVA also increases skin cancer risk. Objectives To investigate the effect of GST genotype on PUVA sensitivity. Methods We investigated GST genotype in patients starting PUVA (n = 111) and the effects of 8‐methoxypsoralen (8‐MOP) on antioxidant response element (ARE)‐regulated gene expression in mammalian cells. Results Lower minimal phototoxic doses (MPD) (P = 0·022) and higher serum 8‐MOP concentrations (P = 0·052) were seen in GSTM1‐null allele homozygotes compared with patients with one or two active alleles. In a subset of patients with psoriasis (n = 50), the GSTM1 genotype was not associated with PUVA outcomes, although MPD [hazard ratio (HR) 1·37; 95% confidence interval (CI) for HR 1·15–1·64] and GSTT1‐null (HR 2·39; 95% CI for HR 1·31–4·35) and GSTP1b (HR 1·96; 95% CI for HR 1·10–3·51) genotypes were associated with clearance of psoriasis in this patient group. Exposure of mammalian cells to 8‐MOP induced gene expression via the ARE, a regulatory sequence in promoters of cytoprotective genes including GSTs, suggesting that these genes may be implicated in 8‐MOP metabolism. Conclusion The polymorphic human GSTs are associated with PUVA sensitivity. Further studies are required to examine the clinical relevance of these preliminary findings.     

Benefit‐risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis

Background Safety of tumour necrosis factor (TNF) antagonists is a primary concern for clinicians prescribing them to patients with psoriasis. Objectives To determine the benefit‐risk balance of TNF antagonists in psoriasis. Methods Through integrated analyses of published literature, we calculated the number needed to treat (NNT) for various efficacy measures and the number needed to harm (NNH) for various adverse events for approved dosing regimens of adalimumab, etanercept and infliximab. Integrated analyses that included open‐label safety data from TNF‐antagonist clinical trials were also conducted. Results PASI 75 treatment effect data from the literature result in NNT values of 1·6 (95% confidence interval, CI 1·5–1·7) for adalimumab 40 mg every other week; 3·2 (95% CI 2·8–3·7) for etanercept 50 mg weekly or 25 mg twice weekly, and 2·3 (95% CI 2·1–2·5) for etanercept 50 mg twice weekly; and 1·4 (95% CI 1·3–1·5) for infliximab 5 mg kg^?1 dosing. For serious noninfectious, serious infectious and malignant adverse events, point estimates of the NNHs are generally at least two orders of magnitude larger than the NNTs, and the 95% CIs for the NNHs for adalimumab, etanercept and infliximab overlap. Analyses that included open‐label data corroborated, with increased exposure to study agents, the low risk of adverse events observed in placebo‐controlled periods. Conclusions These analyses demonstrated that, during the initial year of treatment, the likelihood of success with anti‐TNF therapy for psoriasis was several orders of magnitude greater than the likelihood of serious toxicity.     

Psoriasis and chronic obstructive pulmonary disease: a case-control study

Background Previous reports have demonstrated an association between psoriasis and the metabolic syndrome. Chronic obstructive pulmonary disease (COPD) has also been associated with the metabolic syndrome. Objectives To assess the association between psoriasis and COPD in a population‐based case–control study. Methods A case–control study was performed utilizing the database of Clalit Health Services, a large healthcare provider organization in Israel. Patients over the age of 20 years who were diagnosed with psoriasis (‘cases’) were compared with a sample of age‐ and gender‐matched enrollees without psoriasis (‘controls’) regarding the prevalence of COPD. Group matching was performed. Data on health‐related lifestyles and other comorbidities were collected. χ² tests, t‐tests and logistic regression models were used to compare between study groups. Results The study included 12 502 psoriasis cases and 24 287 controls. The prevalence of COPD was significantly higher in patients with psoriasis [5·7% vs. 3·6%, P < 0·001, odds ratio (OR) 1·63, 95% confidence interval (CI) 1·47–1·81]. A multivariate logistic regression model demonstrated that psoriasis was significantly associated with COPD, after controlling for confounders, including age, sex, socioeconomic status, smoking and obesity (adjusted OR 1·27, 95% CI 1·13–1·42, P < 0·001). Conclusions In this large, population‐based case–control study, psoriasis was found to be associated with COPD. Dermatologists caring for patients with psoriasis should be aware of this association, consult an internist or pulmonologist, and advise the patients to stop smoking and reduce additional risk factors for COPD.     

Increased risk of psoriasis following chronic rhinosinusitis without nasal polyps: a population‐based matched‐cohort study

Background Although chronic rhinosinusitis without nasal polyps (CRSsNP) and psoriasis both share immunological disturbances as pathological factors, no prior study has investigated the risk for psoriasis among patients with CRSsNP. Objectives To investigate the subsequent risk for psoriasis following a diagnosis of CRSsNP by utilizing a cohort study design and a population‐based dataset in Taiwan. Methods In total, 13 242 subjects with CRSsNP were included in the study cohort and 39 726 subjects were randomly extracted for the comparison cohort. We individually tracked each individual in this study (n = 52 968) for a 5‐year period following their index date to identify those subjects who received a subsequent diagnosis of psoriasis. Cox proportional hazards regression analysis was conducted to calculate the 5‐year risk of subsequent psoriasis following a diagnosis of CRS among the sampled subjects. Results The incidence rate of psoriasis during the 5‐year follow‐up period was 1·41 [95% confidence interval (CI) 1·14–1·71] per 1000 person‐years and 0·69 (95% CI 0·59–0·81) per 1000 person‐years for the study and comparison cohort, respectively. Stratified Cox proportional hazards regression revealed that the hazard ratio for psoriasis during the 5‐year follow‐up period for subjects with CRSsNP compared with the control group was 2·01 (95% CI 1·54–2·62) after adjusting for monthly income, geographical region, hypertension, diabetes, coronary heart disease and hyperlipidaemia, and censoring the cases who died during the 5‐year follow‐up period. Conclusion This study detected an increased risk for psoriasis among patients with CRSsNP.     

Cause‐specific mortality in patients with severe psoriasis: a population‐based cohort study in the U.K.

Background Severe psoriasis is associated with excess mortality and increased risk of cardiovascular death. Population‐based data evaluating cause‐specific mortality in patients with psoriasis are limited. Objectives To describe cause‐specific mortality in patients with severe psoriasis. Methods We performed a cohort study from 1987 to 2002 of patients ≥ 18 years using the General Practice Research Database. We compared patients with a psoriasis code and a history of systemic therapy consistent with severe psoriasis (n = 3603) with patients with no history of psoriasis (n =14 330). Age‐ and sex‐adjusted Cox models were created for each of the leading causes of death defined by the Centers for Disease Control. Results Patients with severe psoriasis were at increased risk of death from cardiovascular disease [hazard ratio (HR) 1·57, 95% confidence interval (CI) 1·26–1·96], malignancies (HR 1·41, 95% CI 1·07–1·86), chronic lower respiratory disease (HR 2·08, 95% CI 1·24–3·48), diabetes (HR 2·86, 95% CI 1·08–7·59), dementia (HR 3·64, 95% CI 1·36–9·72), infection (HR 1·65, 95% CI 1·26–2·18), kidney disease (HR 4·37, 95% CI 2·24–8·53) and unknown/missing causes (HR 1·43, 95% CI 1·09–1·89). The absolute and excess risk of death was highest for cardiovascular disease (61·9 and 3·5 deaths per 1000 patient‐years, respectively). Conclusions Severe psoriasis is associated with an increased risk of death from a variety of causes, with cardiovascular death being the most common aetiology. These patients were also at increased risk of death from causes not previously reported, such as infection, kidney disease and dementia. Additional studies are necessary to determine the degree to which excess causes of death are due to psoriasis, its treatments, associated behaviours, or other factors.     

Paediatric-onset psoriasis is associated with ERAP1 and IL23R loci, LCE3C_LCE3B deletion and HLA-C*06

Summary Background Recent genome‐wide association studies have identified several genetic risk factors for psoriasis, but data on their association with age at onset are lacking. Objectives To compare the association between known risk alleles and psoriasis in well‐defined cohorts with paediatric‐ and adult‐onset psoriasis. Methods Based on previous studies we selected seven genes and loci associated with psoriasis. Patients with paediatric‐onset (< 18 years) and adult‐onset psoriasis (≥ 18 years) and controls were genotyped. Genotype frequencies were compared between controls (n = 450) and all cases (n = 217), and between controls and cases stratified for confirmed age at onset (paediatric onset n = 80, adult onset n = 85). Results Paediatric‐onset psoriasis showed a significant association with single nucleotide polymorphisms in the ERAP1 (P = 0·042) and IL23R loci (P = 0·042), LCE3C_LCE3B‐del (P = 0·003) and HLA‐C*06 (P = 1·72 × 10^?19) when compared with the control group. A significant association of these four genes was also demonstrated when all psoriasis cases were compared with controls. In adult‐onset psoriasis a significant association was found for HLA‐C*06 (P = 5·11 × 10^?6) and for LCE3C_LCE3B‐del (P = 0·042). No associations were found for the IFIH1, IL12B and TRAF3IP2 loci. Conclusions Notwithstanding the small cohort sizes, we demonstrated an association with established and recently discovered genetic risk factors in paediatric‐onset psoriasis including genes involved in epidermal barrier function and adaptive immunity. Our data suggest that heritable factors may play a more important role in paediatric‐onset psoriasis than in adult‐onset psoriasis.     

Elevation of serum epidermal growth factor and interleukin 1 receptor antagonist in active psoriasis vulgaris

Background Psoriatic plaques present a complex expression profile, including high levels of cytokines, chemokines and growth factors. Circulating cytokines have been suggested to reflect the activation status of the inflammatory process. Objectives To analyse 20 cytokines, chemokines and growth factors in 14 patients with psoriasis vulgaris at the start and during the course of ultraviolet B treatment. Methods A multiplex cytokine assay was used. Results We identified increased serum levels of epidermal growth factor (EGF) (mean 323 vs. 36·6 pg mL^?1, P =0·0001), interleukin (IL)‐1 receptor antagonist (mean 39·1 vs. 14·6 pg mL^?1, P =0·02) and tumour necrosis factor‐α (mean 7·5 vs. 4·5 pg mL^?1, P =0·04) at baseline in patients with psoriasis compared with matched controls. None of these cytokines was correlated to the severity of the disease (Psoriasis Area and Severity Index) or decreased with phototherapy, suggesting that sources other than lesional skin contribute to the production of these cytokines. Using cluster analysis, we observed coordinate upregulation of EGF, IL‐6, macrophage inflammatory protein‐1β and vascular endothelial growth factor. Conclusions The sustained high expression of inflammatory circulating cytokines is a potential mechanism linking psoriasis with its extracutaneous comorbidities.