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A multitude of factors may influence fatigue in psoriasis and psoriatic arthritis (PsA); however, their individual fatigue components have not been thoroughly examined. To explore characteristics of fatigue and its potential drivers in a cohort of patients with psoriasis with or without PsA. Adults with psoriasis and a nonpsoriasis control group completed the Multidimensional Fatigue Inventory-20 questionnaire. Patients with psoriasis also reported joint pain intensity, pruritus, skin pain, and sleep problems using a numerical rating scale. Linear regression models were applied to continuous outcomes, and beta coefficients (β) for the slopes were estimated with 95% confidence intervals (CIs). Among 2741 adults with psoriasis (of which 593 also had PsA) and 3788 controls, the impact on total fatigue was greatest for PsA (β = 5.22; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25), compared with the general population (P trend <.0001). Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23 [95% CI, 2.03-2.44] for each 1-point increase in joint pain numerical rating scale score). We lacked information on the effect of pharmacotherapy. These findings highlight the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common disease that is associated with atopic and nonatopic comorbidities. There has been a growing interest in this area of AD, because presence or risk of comorbidities can in many ways impact the management of patients with AD. Thus, some treatments for AD may improve its comorbidities as well, whereas others may increase their risk. In this review article, we discuss various comorbidities of AD mostly on the basis of the results of recent multiple systematic reviews and meta-analyses to update readers about this rapidly developing area of dermatology. We emphasize the important information provided by studies presenting both relative risk and absolute risk, and show that AD is associated with, among others, atopic comorbidities such as asthma, rhinitis, and food allergy, nonatopic comorbidities such as ocular, psychiatric, infectious, endocrine, autoimmune, and cardiovascular diseases, and certain cancers. Clinicians need to be aware of these and be cognizant about positive and negative effects of existing and new treatments for AD. [ABSTRACT FROM AUTHOR]

Upadacitinib is a selective reversible Janus kinase (JAK) inhibitor with established efficacy in moderate-to-severe atopic dermatitis (AD). We evaluated the safety of upadacitinib in patients with moderate-to-severe AD. Integrated safety data from the 16-week placebo-controlled periods of 1 phase 2b and 3 ongoing phase 3 studies (16 weeks) and longer-term safety data from patients receiving upadacitinib during the blinded extension periods of the three phase 3 studies were analyzed (all upadacitinib exposure). Treatment-emergent adverse events (TEAEs) were presented as exposure-adjusted rates per 100 patient-years (PY). Safety results were similar between the 16-week and all upadacitinib exposure groups. The latter group included 2485 patients (333 adolescents), receiving upadacitinib 15 mg (n = 1239) or 30 mg (n = 1246) for a mean duration of approximately 1 year. Upadacitinib was well tolerated by both adults and adolescents. TEAEs and discontinuation due to AEs were reported more frequently in patients receiving 30 mg upadacitinib (respectively, 311.9 and 5.7 events per 100 PY) versus 15 mg (respectively, 274.6 and 4.4 events per 100 PY). Serious adverse event rates (15/30 mg, 7.1/7.7 events per 100 PY) were similar in both groups. Acne was the most frequently reported adverse event (15/30 mg, 13.3/20.2 events per 100 PY). Serious infection rates were similar across treatment groups. Adjudicated major adverse cardiovascular event and venous thromboembolic event rates were ≤0.1 events per 100 PY. Rates of malignant neoplasms were within the expected range for the general population. Upadacitinib was well tolerated, and no new important safety risks were observed among adults and adolescents with moderate-to-severe AD treated for approximately 1 year compared to the known safety profile of upadacitinib. [ABSTRACT FROM AUTHOR]

Contact dermatitis is a common disease that is caused by repeated skin contact with contact allergens or irritants, resulting in allergic contact dermatitis (ACD) and/or irritant contact dermatitis. Attempts have been made to identify biomarkers to distinguish irritant and allergic patch test reactions, which could aid diagnosis. Some promising candidates have recently been identified, but verification and validation in clinical cases still need to be done. New causes of ACD are constantly being recognized. In this review, 10 new contact allergens from recent years, several relating to anti-aging products, have been identified. Frequent allergens causing considerable morbidity in the population, such as the preservative methylisothiazolinone, have been regulated in the European Union. A significant drop in the number of cases has been seen, whereas high rates are still occurring in other areas such as North America. Other frequent causes are fragrance allergens, especially the widely used terpenes and acrylates found in medical devices for control of diabetes. These represent unsolved problems. Recent advances in immunology have opened the way for a better understanding of the complexity of contact dermatitis, especially ACD—a disease that may be more heterogenous that previous understood, with several subtypes. With the rapidly evolving molecular understanding of ACD, the potential for development of new drugs for personalized treatment of contact dermatitis is considerable. [ABSTRACT FROM AUTHOR]

Background: Patients with psoriasis have an impaired quality of life and higher use of analgesics than the general population. Whether such use is due to skin pain or a consequence of joint pain resulting from psoriatic arthritis (PsA) is not clear.Objectives: To assess symptoms, disease burden, and use of analgesics in patients with psoriasis with and without PsA.Method: Symptoms, general health (EurQol 5-dimension and 5-levels), and use of analgesics were assessed in patients with psoriasis and the general population from the Danish Skin Cohort.Results: We included 4016 patients with psoriasis (847 with concomitant PsA) and 3490 reference individuals. For patients with psoriasis having PsA, itch, skin pain, and/or joint pain was associated with worse general health. Use of opioids within 12 months was observed among 9.0% of the general population, 14.2% of patients with psoriasis without PsA, and 22.7% of patients with concomitant PsA. Of the symptoms, only joint pain was associated with use of analgesics (odds ratio, 3.72 (2.69-5.14); P < .0001).Limitations: Cross-sectional design.Conclusion: Patients with psoriasis (especially concomitant PsA) have a higher use of analgesics compared with the general population, which appears to be a result of increased joint pain. [ABSTRACT FROM AUTHOR]

Background: Conjunctivitis and several other ocular surface diseases (OSDs) have been linked to atopic dermatitis (AD) and its treatment.Objectives: To examine the association between AD, conjunctivitis, and other OSDs.Methods: A systematic review and meta-analysis was performed. Two authors independently searched EMBASE, PubMed, SCOPUS, and Web of Science and performed title/abstract and full-text review and data abstraction. Pooled random-effects prevalence and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated.Results: The search yielded 5719 nonduplicate articles; 134 were included in the quantitative analysis. AD was associated with conjunctivitis compared to reference individuals (OR, 2.78; 95% CI, 2.33-3.32); the prevalences of conjunctivitis in patients with AD and reference individuals were 31.7% (95% CI, 27.7-35.9) and 13.3% (95% CI, 11.0-15.7), respectively. Keratoconus (OR, 3.71; 95% CI, 1.99-6.94) and ocular herpes simplex (OR, 3.65; 95% CI 2.04-6.51) were also associated with AD.Limitations: Disease definitions differed and often relied on self-reports. Few studies provided data concerning AD phenotype or OSDs other than conjunctivitis.Conclusions: Conjunctivitis is the most common ocular comorbidity in AD. Signs and symptoms of conjunctivitis and other OSDs in AD may be underreported, making proactive inquiry and examination by physicians treating patients with AD important. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) has been linked to systemic infections in adulthood, but large-scale studies are few, and potential associations are unclear.Objective: To examine whether adults with AD have increased risk of developing systemic infections leading to hospital-based management.Methods: Nationwide register-based cohort study including all Danish adults from 1995 through 2017. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by using Cox models.Results: A total of 10,602 adults with AD (median age, 29.8 y; interquartile range, 22.6-44.8) and 106,020 reference individuals were included. The overall incidence rate per 10,000 person-years of systemic infections was 180.6 (95% CI, 172.6-189.0) among adults with AD compared with 120.4 (95% CI, 118.3-122.5) among reference adults. The association between AD and systemic infections was observed for musculoskeletal (adjusted HR [aHR], 1.81; 95% CI, 1.42-2.31), heart (aHR, 1.75; 95% CI, 1.21-2.53), and upper (aHR, 1.42; 95% CI, 1.15-1.73) and lower respiratory tract infections (aHR, 1.21; 95% CI, 1.10-1.33). The risk of sepsis (aHR, 1.19; 95% CI, 1.01-1.44) and skin infections (aHR, 2.30; 95% CI, 2.01-2.62) was also increased.Limitations: The findings cannot be generalized to adults with milder AD seen outside the hospital system.Conclusion: We found an increased risk of systemic infections among adults with hospital managed AD. [ABSTRACT FROM AUTHOR]

Background: It is well established that asthma is common in patients with atopic dermatitis (AD).Objectives: We performed a systematic review and meta-analysis to determine the prevalence of asthma and respiratory symptoms in individuals with AD as well as the association between AD and asthma.Methods: At least 2 authors independently searched the medical databases PubMed, EMBASE, LILACS, and SCOPUS for all English-language studies with data on asthma prevalence among patients with AD or the association between AD and asthma. Pooled odds ratios with 95% confidence intervals (CIs) and pooled proportions were estimated with random-effects models. The Newcastle-Ottawa scale was used to assess study quality.Results: The search yielded 39,503 articles. Of these, 213 studies were included in a quantitative analysis. The overall pooled prevalence of asthma was 25.7% (95% CI, 23.7-27.7) in patients with AD and 8.1% (95% CI, 7.0-9.4) among reference individuals. There was a significant association between AD and asthma when compared with reference individuals (odds ratio, 3.03; 95% CI, 2.64-3.47).Limitations: The definitions of AD and asthma differed across the included studies and varied from self-report to physician diagnosed.Conclusions: Asthma is a common comorbidity of AD. Physicians should be cognizant of this relationship and address asthma symptoms in their patients. [ABSTRACT FROM AUTHOR]

Background: Dupilumab, the first biological drug to be approved for the treatment of moderate to severe atopic dermatitis in adolescents and adults, has shown good efficacy and safety in clinical trials.Objective: To evaluate real-world data on the efficacy and safety of dupilumab in atopic dermatitis.Methods: PubMed and EMBASE were searched for observational studies with data on efficacy, drug survival, and safety of dupilumab for the treatment of atopic dermatitis. Primary outcomes were mean percentage change in Eczema Area and Severity Index (EASI) score and proportion of atopic dermatitis patients achieving 50%, 75%, and 90% improvement in EASI score after dupilumab therapy.Results: Twenty-two unique studies encompassing 3303 atopic dermatitis patients were included. After 16 weeks of dupilumab therapy, the pooled proportion of patients achieving 50%, 75%, and 90% EASI score improvement was 85.1%, 59.8%, and 26.8%, respectively, and the weighted mean reduction in EASI score was 69.6%. Conjunctivitis was the most common adverse event, reported in a pooled proportion of 26.1%.Limitations: Limited data in terms of size and follow-up time were available.Conclusion: Real-world data show that dupilumab is a successful and well-tolerated therapy for atopic dermatitis, but ocular adverse events commonly occur. Registries are needed to monitor for adverse events. [ABSTRACT FROM AUTHOR]

Parental history of atopic disease is a well-established risk factor for the development of atopic dermatitis (AD), but several aspects of this association remain unclear. We sought to determine the association of parental history of atopic disease with AD in offspring. We searched PubMed and EMBASE through June 2018 for relevant records and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled odds ratios (ORs) with 95% CI were calculated using random-effects models. A total of 163 records covering 149 unique studies were included. Of these, 119 studies were included in the meta-analysis. Individuals with parental history of atopic disease had increased odds of AD (OR, 1.81; 95% CI, 1.65-1.99). Parental asthma (OR, 1.56; 95% CI, 1.18-2.05) and allergic rhinitis (OR, 1.68; 95% CI, 1.34-2.11) had a smaller effect than AD (OR, 3.30; 95% CI, 2.46-4.42). The effect of maternal and paternal history was comparable for all atopic diseases. An increase in odds was observed when comparing the effect of having 1 (OR, 1.30; 95% CI, 1.15-1.47) or 2 atopic parents (OR, 2.08; 95% CI, 1.83-2.36), as well as having a parent with 1 (OR, 1.49; 95% CI, 1.28-1.74) or more atopic diseases (OR, 2.32; 95% CI, 1.92-2.81). This study provides evidence-based risk estimates that may guide physicians who counsel parents with a history of atopic disease about their children's risk of AD. This information is of particular importance for future efforts toward establishing prophylactic interventions for AD on a general population level. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common inflammatory skin disease associated with several immune-mediated inflammatory diseases (IMIDs); however, little is known of the chronology of disease development.Objective: To investigate the chronology of IMIDs relative to psoriasis.Methods: We utilized routinely collected data from Danish nationwide administrative registries to examine the occurrence of IMIDs in patients with psoriasis (n = 10,923) and general population controls (n = 109,230).Results: Approximately 20% of patients with psoriasis developed ≥1 IMID, with a 5-fold increased risk compared with the general population. Most IMIDs were diagnosed before psoriasis, except for psoriatic arthritis. Psoriasis was significantly associated with having multiple IMIDs (odds ratio 15.2, 95% confidence interval 11.6-20.0). Human leukocyte antigen B27 positivity was significantly more frequent among psoriasis patients.Limitations: Clinical measurements were unavailable.Conclusion: IMIDs occur frequently in patients with psoriasis and most are diagnosed before psoriasis. The observed chronology might represent important mechanisms of disease development. [ABSTRACT FROM AUTHOR]

Background: Factors that are associated with patient-reported importance of obtaining complete or almost complete clearance of psoriasis and atopic dermatitis (AD) are unknown.Objectives: To investigate the importance of and factors associated with obtaining complete or almost complete clearance of psoriasis or AD.Methods: A cross-sectional study of 4016 and 3842 adults with psoriasis and AD.Results: Patients with AD reported significantly greater importance of almost complete or complete skin clearance compared with patients with psoriasis. For both patient groups, almost complete was more important that complete skin clearance. Increasing disease severity and itch and skin pain were significantly associated with perceived importance of skin clearance for patients with both diseases. AD and psoriasis located on the face or neck and psoriasis located on the palms, soles, or genitals were significantly associated with patient-perceived importance of almost complete skin clearance. Only 7% and 27% of patients with severe AD and psoriasis, respectively, were currently receiving a systemic therapy.Limitations: Specific reasons for infrequent use of systemic treatments was not examined.Conclusion: Patients with psoriasis or AD expressed a strong request for almost complete or complete skin clearance. Patient education and effective therapies should be used to reduce disease severity. [ABSTRACT FROM AUTHOR]

Background Previous studies found conflicting results about the commonality of different atopic dermatitis (AD) signs and symptoms. Objective To determine the prevalences of AD characteristics and differences by region and age. Methods A systematic review was performed of all published studies in MEDLINE, EMBASE, SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan Electronic Periodical Services, and CiNii that analyzed the proportion of AD characteristics. Two reviewers performed a review study titles and/or abstracts and data abstraction. Results In all, 101 studies reported proportion of AD features with sufficient data for meta-analysis. The most prevalent AD features were pruritus, lichenification, and xerosis. There were differences in AD characteristics by study region. Flexural involvement was less commonly reported in India, the Americas, and Iran. Studies from East Asian reported more erythroderma and truncal, extensor, scalp, and auricular involvement. Studies from Southeast Asia reported more exudative eczema, truncal involvement, lichenification, and prurigo nodularis. Studies from Iran reported more head, face, and neck involvement; pityriasis alba; and xerosis. Studies from Africa reported more papular lichenoid lesions, palmar hyperlinearity, ichthyosis, and orbital darkening. Limitations Heterogeneity between studies and limited reporting of certain AD clinical characteristics. Conclusions AD characteristics are heterogeneous and vary by region and age. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a prevalent disease worldwide and is associated with systemic comorbidities representing a significant burden on patients, their families, and society. Therapeutic options for AD remain limited, in part because of a lack of well-characterized animal models. There has been increasing interest in developing experimental approaches to study the pathogenesis of human AD in vivo , in vitro , and in silico to better define pathophysiologic mechanisms and identify novel therapeutic targets and biomarkers that predict therapeutic response. This review critically appraises a range of models, including genetic mutations relevant to AD, experimental challenge of human skin in vivo , tissue culture models, integration of "omics" data sets, and development of predictive computational models. Although no one individual model recapitulates the complex AD pathophysiology, our review highlights insights gained into key elements of cutaneous biology, molecular pathways, and therapeutic target identification through each approach. Recent developments in computational analysis, including application of machine learning and a systems approach to data integration and predictive modeling, highlight the applicability of these methods to AD subclassification (endotyping), therapy development, and precision medicine. Such predictive modeling will highlight knowledge gaps, further inform refinement of biological models, and support new experimental and systems approaches to AD. [ABSTRACT FROM AUTHOR]

Background: Adult atopic dermatitis (AD) has been associated with several comorbidities, but cause-specific mortality risk is unknown.Objective: To examine cause-specific death rates and risk in adults with AD.Methods: We performed cross-linkage of nationwide health care and cause of death registers. Adult patients with AD were matched with 10 controls per study subject. We calculated incidence rates per 1000 person-years and hazard ratios (HRs) of cause-specific death with 95% confidence intervals (95% CIs) using Cox proportional hazards models.Results: A total of 8686 patients and 86,860 matched controls were studied. The risk for death due to any cause was significantly increased in patients with AD (HR 1.27, 95%CI 1.11-1.45). Significant causes included cardiovascular (HR 1.45; 95% CI 1.07-1.96), infectious (HR 3.71; 95% CI 1.43-9.60), and urogenital diseases (HR 5.51; 95% CI 1.54-19.80). No increased risk for death due to cancer, endocrine, neurologic, psychiatric, respiratory, or gastroenterologic disease was observed.Limitations: The results might not be generalizable to patients seen exclusively by primary care physicians.Conclusion: Adults with atopic dermatitis had slightly increased risk for death during follow-up. While the risk for death from cardiovascular, urogenital, and infectious diseases was slightly elevated among patients with AD, the absolute risk was very low. [ABSTRACT FROM AUTHOR]

It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk. This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life. This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD. The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P =.0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P =.0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P =.001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection. This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether patients with atopic dermatitis (AD) have an altered prevalence or risk for contact sensitization. Increased exposure to chemicals in topical products together with impaired skin barrier function suggest a higher risk, whereas the immune profile suggests a lower risk.Objective: To perform a systematic review and meta-analysis of the association between AD and contact sensitization.Methods: The PubMed/Medline, Embase, and Cochrane databases were searched for articles that reported on contact sensitization in individuals with and without AD.Results: The literature search yielded 10,083 citations; 417 were selected based on title and abstract screening and 74 met inclusion criteria. In a pooled analysis, no significant difference in contact sensitization between AD and controls was evident (random effects model odds ratio [OR] = 0.891; 95% confidence interval [CI] = 0.771-1.03). There was a positive correlation in studies that compared AD patients with individuals from the general population (OR 1.50, 95% CI 1.23-1.93) but an inverse association when comparing with referred populations (OR 0.753, 95% CI 0.63-0.90).Limitations: Included studies used different tools to diagnose AD and did not always provide information on current or past disease. Patch test allergens varied between studies.Conclusion: No overall relationship between AD and contact sensitization was found. We recommend that clinicians consider patch testing AD patients when allergic contact dermatitis is suspected. [ABSTRACT FROM AUTHOR]

Background: Rosacea features increased neurovascular reactivity; migraine is a complex neurologic disorder characterized by recurrent episodes of headache associated with nausea and increased sensitivity to light and sound.Objective: We evaluated the prevalence and risk of new-onset migraine in patients with rosacea.Methods: All Danish individuals 18 years of age or older were linked in nationwide registers. Adjusted hazard ratios (HRs) were estimated by Cox regression.Results: In the total cohort (n = 4,361,688), there were 49,475 patients with rosacea. Baseline prevalence of migraine was 7.3% and 12.1% in the reference population and in patients with rosacea, respectively. The fully adjusted HR of migraine was 1.31 (95% confidence interval 1.23-1.39) for patients with rosacea. Patients with phymatous rosacea (n = 594) had no increased risk of migraine (adjusted HR 0.45; 95% confidence interval 0.11-1.80), whereas patients with ocular rosacea (n = 6977) had a 69% increased risk (adjusted HR 1.69; 95% confidence interval 1.43-1.99). Notably, the risk was higher among patients age 50 years or older than in younger individuals, and the risk was only significant among women.Limitations: We were unable to distinguish between migraine subtypes.Conclusion: We found a significantly higher prevalence and risk of incident migraine especially in female patients with rosacea. These data add to the accumulating evidence for a link between rosacea and the central nervous system. [ABSTRACT FROM AUTHOR]

Background: Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin disorders. Mortality is increased in psoriasis, yet no studies on mortality in AD are currently available.Objective: We investigated 10-year mortality after hospitalization for AD compared with psoriasis and the general population.Methods: Between 1996 and 2002 all Danes aged 18 years or older with a first-time hospitalization as a result of AD or psoriasis and AD-matched healthy control subjects were examined in nationwide registers. Multivariable (adjusted for age, sex, socioeconomic status, Charlson Comorbidity Index score, smoking, and medication) hazard ratios were estimated by Cox regression.Results: The study comprised 576 and 951 hospitalized patients with AD and psoriasis, respectively, with a maximum follow-up time of 10 years. During the study period, there were 65 and 286 deaths among patients with AD and psoriasis. Risk of death was decreased in patients with AD versus psoriasis (hazard ratio 0.75; 95% confidence interval 0.57-1.00), but higher than in general population control subjects (n = 5760) (hazard ratio 1.71; 95% confidence interval 1.20-2.44). Patients hospitalized with AD died on average 8.3 years younger than control subjects.Limitations: Lifestyle may have affected the risk.Conclusions: The 10-year mortality was significantly lower after hospitalization for AD compared with psoriasis, but increased when compared with the general population. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown a higher prevalence of cardiovascular (CV) risk factors in patients with rosacea. However, it remains unknown whether rosacea represents an independent CV risk factor.Objective: We evaluated the risk of myocardial infarction, stroke, CV death, major adverse CV events, and all-cause mortality, respectively.Methods: Between January 1, 1997, and December 31, 2012, a total of 4948 patients with rosacea were identified and matched with 23,823 control subjects. We used Poisson regression to calculate incidence rate ratios.Results: Adjusted incidence rate ratios were 0.75 (95% confidence intervals [CI] 0.57-1.00) for myocardial infarction, 1.08 (95% CI 0.86-1.35) for ischemic stroke, 1.01 (95% CI 0.61-1.67) for hemorrhagic stroke, 0.99 (95% CI 0.80-1.24) for CV death, 0.99 (95% CI 0.86-1.15) for major adverse CV events, and 0.95 (95% CI 0.85-1.06) for all-cause mortality.Limitations: We were unable to distinguish between the different subtypes and severities of rosacea.Conclusions: In this population-based study, rosacea was not associated with increased risk of adverse CV outcomes or death. [ABSTRACT FROM AUTHOR]

The basis for the sudden and dramatic increase in atopic dermatitis (AD) and related atopic diseases in the second half of the 20th century is unclear. The hygiene hypothesis proposes that the transition from rural to urban living leads to reduced childhood exposure to pathogenic microorganisms. Hence instead of having the normal T H 1 bias and immune tolerance because of repeated exposure to pathogens, urban dwellers have T H 2 cell immune activity and atopic disease in a more sterile environment. Various other environmental exposures have been implicated in the explosion of AD (and atopic disorders in general), including breast-feeding, tobacco smoking, alcohol consumption, and exposure to domesticated furry pets. Notably, the key role of a compromised barrier of neonatal skin as a predisposing factor in the development of childhood AD has recently been demonstrated. In this article we review the salubrious effects of suberythemogenic doses of UVB irradiation for the skin barrier. We then discuss how the lack of sufficient UVB exposure could have contributed to the rapid increase in the incidence of AD in developed countries. This hypothesis offers a separate but not competing partial explanation, which should be viewed as not discounting the role of the etiopathogenic factors that also could influence the prevalence of atopic disorders. [ABSTRACT FROM AUTHOR]

The epidermis protects human subjects from exogenous stressors and helps to maintain internal fluid and electrolyte homeostasis. Filaggrin is a crucial epidermal protein that is important for the formation of the corneocyte, as well as the generation of its intracellular metabolites, which contribute to stratum corneum hydration and pH. The levels of filaggrin and its degradation products are influenced not only by the filaggrin genotype but also by inflammation and exogenous stressors. Pertinently, filaggrin deficiency is observed in patients with atopic dermatitis regardless of filaggrin mutation status, suggesting that the absence of filaggrin is a key factor in the pathogenesis of this skin condition. In this article we review the various causes of low filaggrin levels, centralizing the functional and morphologic role of a deficiency in filaggrin, its metabolites, or both in the etiopathogenesis of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Abstract: Aseptic loosening and osteolysis are the most frequent late complications of total hip arthroplasty (THA) leading to revision of the prosthesis. This review aims to demonstrate how histopathological studies contribute to our understanding of the mechanisms of aseptic loosening/osteolysis development. Only studies analysing periprosthetic tissues retrieved from failed implants in humans were included. Data from 101 studies (5532 patients with failure of THA implants) published in English or German between 1974 and 2013 were included. “Control” samples were reported in 45 of the 101 studies. The most frequently examined tissues were the bone–implant interface membrane and pseudosynovial tissues. Histopathological studies contribute importantly to determination of key cell populations underlying the biological mechanisms of aseptic loosening and osteolysis. The studies demonstrated the key molecules of the host response at the protein level (chemokines, cytokines, nitric oxide metabolites, metalloproteinases). However, these studies also have important limitations. Tissues harvested at revision surgery reflect specifically end-stage failure and may not adequately reveal the evolution of pathophysiological events that lead to prosthetic loosening and osteolysis. One possible solution is to examine tissues harvested from stable total hip arthroplasties that have been revised at various time periods due to dislocation or periprosthetic fracture in multicenter studies. [Copyright &y& Elsevier]

Drug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis. The objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis. We performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy. The study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA, drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA, tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a somewhat higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis, drug survival was generally highest for guselkumab. Differing treatment responses to drugs with various modes of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history. None [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Nickel and cobalt allergy remain frequent in dermatitis patients. It is important to determine possible nickel and cobalt exposures at work as these may offer important information to regulators and physicians who perform patch testing. Clinical relevance of metal exposure is usually assessed by the treating physician via the medical history and by presentation of allergic contact dermatitis. Objectives: To screen unused non-powered hand-held work tools for nickel and cobalt release by using colorimetric spot tests. Materials & methods: A random selection of 200 non-powered hand-held work tools for sale in 2 retailers of home improvement and construction products were analyzed qualitatively for metal release using the colorimetric nickel and cobalt spot tests. Results: Nickel release was identified from 5% of 200 work tools using the dimethylglyoxime (DMG) test. In 8 of 10, positive results were located to the metal ring that acts like a cuff and is located at the end of the grip. The positive DMG test results were not related to specific categories of work tools. The cobalt spot test gave no positive test reactions. Conclusions: It appears that the proportion of work tools that release nickel, in amounts that may result in allergic nickel dermatitis, has decreased markedly, when results were compared with a Swedish study performed more than a decade ago. No cobalt release was detected but it should be underscored that hard-metal tools were not examined. Other sources of cobalt may explain the relatively high levels of cobalt allergy in dermatitis patients. [Copyright &y& Elsevier]

Background: An increased prevalence of nickel allergy prompted the Danish government to prohibit excessive nickel release (ie, >0.5 μg nickel/cm2/wk) from consumer products in 1990. Concomitant allergy to nickel and cobalt is often observed among patients with dermatitis, probably as a result of cosensitization. Objectives: The study investigated the development of nickel and cobalt allergy among Danish female patients with dermatitis tested between 1985 and 2007. This was done to examine whether Danish nickel regulation has reduced the prevalence of nickel allergy and to examine whether the prevalence of cobalt allergy has increased as a result of the nickel regulation. Methods: A retrospective analysis of all patch test data from our database was performed (n = 10,335). Comparisons were made using a chi-square test for trend. Logistic regression analyses were used to test for associations. Results: The prevalence of nickel allergy decreased significantly among those aged 5 to 30 years from 27.6% in 1985 to 16.8% in 2007 (P trend < .002) but increased among those aged 31 to 49 years from 21.3% to 33.8% in the same period (P trend < .001). The median age was significantly higher among patients with isolated cobalt allergy than among patients with nickel allergy (P < .001). Limitations: No information on causative exposures was available. Conclusions: Nickel allergy decreased among young female patients with dermatitis between 1985 and 2007 whereas it increased among older patients, probably as a result of a cohort effect. The prevalence of cobalt allergy remained relatively unchanged. [Copyright &y& Elsevier]

Background: Nickel sensitization is frequent among US patients with dermatitis and in the general population. In Europe, decreasing prevalences of nickel sensitization are observed as a result of the European Union Nickel Directive. However, no directive exists in the United States. Objectives: We sought to examine nickel release from inexpensive earrings and discuss possible methods of reducing nickel exposure among consumers. Methods: A total of 34 different stores and artists were visited. A total of 277 earrings were purchased and examined with the dimethylglyoxime (DMG) test. Results: DMG-positive earrings were identified from local artists (69%) and tourist stores (42.9%) but also chain stores targeting young (24.1%) and mature (1.7%) women. No correlation between price and outcome of DMG testing was identified. Limitations: Our study does not reflect buying trends in the United States. Pretreatment of earrings with artificial sweat was not performed and the DMG may lead to both false-positive and false–negative results. Conclusions: Nickel exposure from inexpensive earrings is frequent in the United States. A regulatory governmental intervention may be warranted. [Copyright &y& Elsevier]