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Background: Psoriasis is associated with high alcohol consumption, but the causality of this relationship is unclear. Objective: We aimed to use a Mendelian randomization approach to investigate the causal effects of alcohol on incident psoriasis. Methods: We included 102,655 adults from the prospective Copenhagen studies. All participants filled out a questionnaire on alcohol consumption, were physically examined, and had blood drawn for biochemical and genetic analyses. We created a genetic instrument based on the number of fast-metabolizing alleles in alcohol dehydrogenase 1B and alcohol dehydrogenase 1C, known to be associated with alcohol consumption, to test whether alcohol consumption was causally associated with psoriasis. Results: Observationally, we found an increased risk of incident psoriasis among individuals with high alcohol consumption compared to those with low alcohol consumption with a hazard ratio of 1.30 (95% confidence interval 1.05-1.60) in the fully adjusted model. Using genetic data to predict alcohol consumption to avoid confounding and reverse causation, we found no association between number of fast-metabolizing alleles and risk of psoriasis. Limitations: Alcohol consumption was self-reported and psoriasis was defined using the International Classification of Diseases 10th revision and 8th revision codes. Conclusion: Alcohol consumption is observationally but not causally associated with incident psoriasis.
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BACKGROUND: Living with hand eczema (HE) has been associated with impaired quality of life (QoL), having anxiety and depression but the magnitude of association is not clear. OBJECTIVES: The aim of this systematic review and meta-analysis was to determine the psychological burden in terms of anxiety, depression and quality of life in patients with HE. METHODS: Several databases were systematically searched. Weighted means with standard deviation (SD) were calculated for disease severity, QoL, depression and/or anxiety scores among patients with HE. For studies presenting QoL, depression and/or anxiety scores in patients with HE and in controls the weighted means were compared with an unpaired t-test. In studies reporting Hand Eczema Severity Index (HECSI) and Dermatology Life Quality Index (DLQI), the correlation between HECSI and DLQI was estimated using Spearman's rank correlation (rs). RESULTS: In total, 81 studies encompassing 17,835 patients with HE and 31,541 controls were included. The weighted mean DLQI was 10.66 (SD 8.93) corresponding to a moderate-to-large effect on QoL and a strong correlation (rs: 0.76, 95% CI:0.56-0.87) between DLQI and HECSI was observed. The mean EQ-5D-VAS was significantly lower in patients with HE compared with controls (68.03 (SD 10.52) vs. 80.63 (SD 1.17), p < 0.00001). Patients with HE had higher mean HADS (Hospital Anxiety and Depression Scale) anxiety score (7.4 vs. 5.8, p = 0.0008) than controls but not higher HADS depression score (6.5 vs. 5.7, p = 0.32). Only one study assessed risk of anxiety, depression and suicidal ideation showing an increased odds of all diseases among patients with HE compared with controls. CONCLUSION: Hand eczema has a moderate-to-severe impact on quality of life with a strong correlation between disease severity and impact on quality of life. Patients with hand eczema have an impact on QoL comparable to other chronic diseases when measured with generic QoL scoring systems.
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BACKGROUND: It is unknown if an unhealthy diet can affect the risk of developing psoriasis. OBJECTIVES: We hypothesised that individuals with an unhealthy diet have increased risk of prevalent and incident psoriasis. METHODS: We included 105,332 adults from the Copenhagen General Population Study, who were invited between 2003 and 2015. Response-rate was 43%. An unhealthy versus healthy diet was defined according to adherence to general national dietary guidelines. The participants were grouped into low, intermediate, and high adherence to general national dietary guidelines based on information from a food frequency questionnaire. Identification of psoriasis was made using ICD codes. RESULTS: Of the 105,332 individuals, 580 had a diagnosis of psoriasis at the time of enrolment and 640 received a diagnosis during the median follow-up of 9 years. Risk of prevalent psoriasis increased according to non-adherence to general national dietary guidelines in a stepwise manner with an age and sex adjusted odds ratio of 1.70 (95% confidence interval 1.26-2.30) in individuals with low vs. high adherence to dietary guidelines. Results were similar in a multivariable adjusted model. Prospective analyses adjusted for age and sex showed a weak association between non-adherence to dietary guidelines and risk of incident psoriasis (P for trend 0.04). This association disappeared, when adjusting for multiple confounders (P for trend 0.50). CONCLUSIONS: Although individuals with psoriasis have an unhealthier diet, diet alone does not appear to independently increase the risk of developing psoriasis.
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Psoriasis is an immune-mediated inflammatory disease associated with an increased risk of cardiovascular disease (CVD). The risk of CVD increases with the severity of psoriasis, and exposure to systemic inflammation may partly explain the increased risk of CVD in these patients. This raises the question of whether anti-psoriatic treatment, in addition to treating the skin lesions, also lowers the risk of developing CVD. Different types of studies have examined the impact of systemic anti-psoriatic treatments on the risk of CVD in patients with psoriasis and epidemiological observational studies with, e.g., myocardial infarction and stroke as outcomes, and clinical studies investigating circulating inflammatory biomarkers in the blood indicate that anti-psoriatic therapy has a protective effect; however, no randomized controlled trial (RCT) has examined the impact of systemic anti-psoriatic treatment on future hard cardiovascular endpoints. This narrative review provides an overview of the clinical cardiovascular imaging studies examining the effect of systemic anti-psoriatic treatment on the risk of subclinical CVD in patients with psoriasis. We found a total of 24 clinical imaging studies, where 16 of these were observational cohort studies and eight were RCTs. The observational studies suggest an improvement in the risk of subclinical CVD based on different cardiovascular imaging biomarkers; however, the RCTs showed inconsistent results and mainly included vascular inflammation as the outcome. Future RCTs including other imaging biomarkers as surrogates for subclinical CVD, with longer follow-up and with hard cardiovascular endpoints are warranted to address whether systemic anti-psoriatic treatments reduce the risk of CVD.
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Psoríase , Vitamina D , Vitamina D/análogos & derivados , Humanos , Estudos Transversais , Vitamina D/sangue , Vitaminas , Psoríase/sangue , Calcifediol , ObesidadeRESUMO
The impact of diet on psoriasis is not well studied but it is of interest to many patients. A hypocaloric diet with corresponding weight loss can reduce psoriasis severity in overweight or obese patients and should be considered an important supplement to conventional therapy, as argued in this review. Gluten-free diet might improve severity of psoriasis in patients with coeliac disease or merely presence of coeliac-specific antibodies. Mediterranean diet might also be beneficial. Overall, studies do not support a beneficial effect of micronutrient supplements (i.e., vitamin D, selenium, vitamin B12) in patients with normal serum levels.
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Doença Celíaca , Psoríase , Humanos , Dieta Redutora , Obesidade/complicações , Obesidade/terapia , Dieta , Vitaminas , Psoríase/terapia , Suplementos Nutricionais , Doença Celíaca/complicações , Doença Celíaca/terapiaRESUMO
Background: Smoking is strongly associated with higher risk of psoriasis in several observational studies; however, whether this association is causal or can be explained by confounding or reverse causation is not fully understood. Randomized controlled trials are the gold standard when examining causality; however, when this method is not feasible, the Mendelian randomization design is an alternative. Herein genetic variants can be used as robust proxies for modifiable exposures and thereby avoiding confounding and reverse causation.In this study, we hypothesized that smoking is an independent and causal risk factor for psoriasis and tested this using a Mendelian randomization design. Methods: We used data from the Copenhagen General Population Study including 105,912 individuals with full information on lifestyle factors, biochemistry, and genotype data. In total, 1,240 cases of moderate to severe psoriasis were included to investigate the association between smoking and psoriasis. To assess causality of the association, we used the genetic variant CHRNA3 rs1051730, where the T-allele is strongly associated with high lifelong cumulative smoking, as a proxy for smoking. Results: In observational analyses, the multivariable adjusted hazard ratio of developing moderate to severe psoriasis was 1.64 (95% confidence interval: 1.35-2.00) in ever smokers with ≤ 20 pack-years and 2.23 (1.82-2.73) in ever smokers with > 20 pack-years compared to never smokers. In genetic analyses, the odds ratio of developing moderate to severe psoriasis was 1.05 (0.95-1.16) per CHRNA3 rs10511730 T-allele in ever smokers. Conclusion: Smoking was an independent risk factor for moderate to severe psoriasis in observational analyses. However, using a genetic variant as a robust proxy for smoking, we did not find this association to be causal.
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Análise da Randomização Mendeliana , Fumar , Humanos , Análise da Randomização Mendeliana/métodos , Fatores de Risco , Fumar Tabaco , CausalidadeRESUMO
Background: Psoriasis is observationally associated with a higher risk of non-alcoholic fatty liver disease (NAFLD); however, the causal relationship between the two diseases remains unclear. Objective: We hypothesized that individuals with NAFLD or elevated liver fat content have higher risk of psoriasis and that NAFLD is a causal risk factor for psoriasis. We tested this using a Mendelian randomization approach. Methods: We included 108,835 individuals from the Danish general population, including 1,277 individuals with psoriasis and 802 individuals with NAFLD according to ICD codes. To estimate liver fat content, a subset of the participants (N = 7,416) also had a CT scan performed. First, we tested whether a diagnosis of NAFLD or elevated liver fat content was observationally associated with risk of psoriasis. Subsequently, we used the genetic variants PNPLA3 and TM6SF2, both strongly associated with NAFLD and high liver fat content, to test whether NAFLD was causally associated with increased risk of psoriasis. Results: Observationally, individuals with vs. without a diagnosis of NAFLD had higher risk of psoriasis with an odds ratio of 2.03 (95% confidence interval 1.28-3.21). The risk of psoriasis increased in a stepwise manner with increasing liver fat content with an odds ratio of 5.00 (2.63-9.46) in individuals in the highest quartile of liver fat content compared to individuals in the lowest quartile. In genetic analyses, PNPLA3 and TM6SF2 were both associated with increased risk of NAFLD but not with increased risk of psoriasis. Conclusion: Observationally, a diagnosis of NAFLD or elevated liver fat content was associated with higher risk of psoriasis. However, using genetic variants as a proxy for NAFLD, we did not find evidence of a causal relationship between NAFLD and psoriasis. Thus, the observational association between NAFLD and psoriasis is presumably a result of shared confounding factors or reverse causation.
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Hepatopatia Gordurosa não Alcoólica , Psoríase , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Análise da Randomização Mendeliana , Fatores de Risco , Psoríase/epidemiologia , Psoríase/genéticaRESUMO
Women with cardiovascular disease are underdiagnos-ed, undertreated and under-represented in research. Even though the increased risk of cardiovascular disease among patients with psoriasis is well establi-shed, only a few studies have examined women with psoriasis. This study examined the prevalence of cardio-vascular risk factors and cardiovascular disease among women with psoriasis. Using the Copenhagen City Heart Study and the Copenhagen General Population Study, 66,420 women were included in a cross-sectional design. Of these, 374 (0.56%) women had hospital-diagnosed psoriasis. Women with vs with-out hospital-diagnosed psoriasis had higher odds ratios of having traditional cardiovascular risk factors, including hypertriglyceridaemia, smoking, obesity, type 2 diabetes, and low physical activity, and of having non-traditional cardiovascular risk factors, including low level of education, high level of psycho-social stress, and low-grade inflammation. Compared with women from the general population, the multi-variable adjusted odds ratio of heart failure and ischaemic cerebrovascular disease in women with hospital-diagnosed psoriasis was 2.51 (95% confidence interval 1.33-4.73) and 2.06 (1.27-3.35). In conclusion, women with hospital-diagnosed psoriasis have a higher prevalence of traditional and non- traditional cardiovascular risk factors, and increased risk of heart failure and ischaemic cerebrovascular disease, even after adjusting for these cardiovascular risk factors.
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Doenças Cardiovasculares , Transtornos Cerebrovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Psoríase , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Prevalência , Psoríase/diagnóstico , Psoríase/epidemiologia , Fatores de RiscoRESUMO
During recent years, we have observed an increasing occurrence of cercarial dermatitis in Denmark. We here describe 5 new cases from 2019 to 2020 associated with bathing in lakes Esrum sø, Furesø, and Ringen with emphasis on clinical symptoms and their relation to previous exposure to bird schistosome cercariae. In 2020, 2 patients from Furesø suffered from different severity of clinical symptoms after morning bathing in the same lake. We suggest that the differential symptoms may be explained by primary versus secondary exposure to the immunogenic pathogen.
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In this review, we discuss mucoid cysts, which are common benign cysts, most often located dorsally or laterally to the distal interphalangeal joint. The origin of the cyst is suggested to be similar to that of a ganglion, or to be a degeneration of dermis, and it is often linked to osteoarthritis. Two types of mucoid cysts seem to exist, probably needing different treatment. A cyst is usually asymptomatic and needs no treatment, but limited joint movement, pain and nail deformity may occur. In the latter case, conservative or surgical treatment is asked for. If a cyst is atypical, pathology is needed.
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Cistos Glanglionares , Doenças da Unha , Osteoartrite , Dedos/diagnóstico por imagem , Dedos/cirurgia , Cistos Glanglionares/diagnóstico por imagem , Cistos Glanglionares/cirurgia , HumanosRESUMO
Psoriasis is a common immune-mediated chronic inflammatory disease, and observations have pointed toward the IL-23/Th17 cell axis as having a key role in the pathogenesis of psoriasis. This new immunological understanding of the pathogenesis has been translated into targeted and highly effective biologic therapies. Tildrakizumab is a humanized IgG1/k monoclonal antibody targeting the p19 unit of IL-23 and has been registered for the treatment of patients with moderate-to-severe chronic plaque psoriasis in adults since 2018. This review provides an overview of the efficacy and safety of tildrakizumab, focusing on the results from clinical trials. In both Phase II and III trials, tildrakizumab 100 and 200 mg was significantly more efficacious than both placebo and etanercept at week 12. The effect of tildrakizumab continued to increase until week 28. Long-term follow-up showed high levels of efficacy for up to 3 years. Despite no difference between 100 and 200 mg in Phase III studies, subgroup analyses showed better efficacy when treated with 200 mg in patients with bodyweight ≥90 kg. The overall drug safety was good, and besides discrete higher incidence of nasopharyngitis, the conducted clinical trials show that tildrakizumab was very well tolerated without any safety concerns. Compared to other IL-23p19 inhibitors, tildrakizumab seemed to have slightly lower efficacy. However, to determine its position in the treatment algorithm of psoriasis, head-to-head trials with other IL-17, IL-12/23, and IL-23 inhibitors and long-term real-world data are required.
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T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Herein, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class-II-restricted epitopes, we found that myosin heavy chain alpha (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in mice. Transferred MYHCA614-629-specific CD4+ T (TCR-M) cells selectively accumulated in the myocardium and mediastinal lymph nodes (med-LN) of infarcted mice, acquired a Treg phenotype with a distinct pro-healing gene expression profile, and mediated cardioprotection. Myocardial Treg cells were also detected in autopsies from patients who suffered a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in MI-patients. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence showing that MI-context induces pro-healing T cell autoimmunity in mice and confirms the existence of an analogous heart/med-LN/T cell axis in MI patients.
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Antígenos/imunologia , Infarto do Miocárdio/imunologia , Miocárdio/imunologia , Cadeias Pesadas de Miosina/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígenos/genética , Camundongos , Camundongos Transgênicos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/patologia , Cadeias Pesadas de Miosina/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Linfócitos T Reguladores/patologiaRESUMO
PURPOSE: CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population. PATIENTS AND METHODS: We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests. RESULTS: Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer. CONCLUSION: CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation.
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Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Quinase do Ponto de Checagem 2/genética , Mutação em Linhagem Germinativa , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/genética , Idoso , Dinamarca/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Heterozigoto , Humanos , Incidência , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Inquéritos e QuestionáriosAssuntos
Azatioprina/uso terapêutico , Eosinofilia/tratamento farmacológico , Eosinófilos/patologia , Miocardite/tratamento farmacológico , Miocárdio/patologia , Prednisolona/uso terapêutico , Biópsia , Quimioterapia Combinada , Eosinofilia/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Contagem de Leucócitos , Pessoa de Meia-Idade , Miocardite/patologiaRESUMO
BACKGROUND: In patients presenting with an acute coronary syndrome, left over right coronary dominance appears to be independently associated with increased long-term mortality. This could lead to decreasing numbers of patients with a left dominant coronary artery system in older age groups. METHODS: We assessed the type of coronary dominance in different age groups in postmortem angiograms that were routinely performed at autopsy between 1993 and 2007. Coronary dominance was determined by identifying the origin of the posterior descending artery and posterolateral branches on postmortem angiography. Age, gender, and cause of death were recorded from the autopsy database. The prevalence of left dominant, right dominant, and codominant systems was determined in three increasing age categories, with cutoffs based on tertiles. RESULTS: A total 1620 coronary angiograms were assessed; 167 were excluded because it was not possible to determine coronary dominance. The median age of all patients was 71 years; 56% were male. Of all deaths, 40% were classified as cardiac. Regarding coronary dominance, 81.2% was right, 9.1% was left, and 9.7% was codominant. Overall, a decrease in prevalence of left and codominant coronary systems was observed with increasing age in the three age cohorts (≤ 63 years, 64-75 years, and ≥ 76 years) (P=.001 for overall comparison). CONCLUSIONS: In this large autopsy cohort, the prevalence of a left dominant or codominant coronary system decreased with increasing age. These findings could relate to a slightly higher risk of mortality in case of left versus right coronary artery occlusion.