Atopic dermatitis is a prevalent inflammatory skin condition characterized by itch and dry skin, which affects 15-20% of children and 3-5% of adults. This article reviews epidemiological, clinical ...and experimental data to provide an overview of the most important disease mechanisms in atopic dermatitis. Genetic predisposition, environmental insults, atopic triggers, complex host immune response and skin barrier changes, and altered skin microbiota are discussed. Whilst our understanding of atopic dermatitis has improved dramatically in recent years, many basic aspects are still not understood. Further research is needed to fully understand this complex skin disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The European Medicines Agency recently limited the use of oral Janus kinase inhibitors in certain patient populations, including those with atopic dermatitis. This cross-sectional study used the ...Danish national registers and Danish Skin Cohort to assess the prevalence of risk factors that potentially impact choice of treatment with oral Janus kinase inhibitors in adult patients with atopic dermatitis. From the Danish national registers and Danish Skin Cohort, 18,618 and 3,573 adults with atopic dermatitis, respectively, were identified. Half of the patients (49.5%) had, at some point, been registered to have at least 1 risk factor that could impact treatment with oral Janus kinase inhibitors. Non-modifiable risk factors recorded were cancer (5.6%), major adverse cardiovascular events (2.6%), venous thromboembolism (2.0%), smoking history (15.6%), and age ≥ 65 years (12.4%). Among patients ≥ 65 years of age, the mean (standard deviation) number of risk factors were 3 (1.4), and almost half of these patients had, at some point, been registered to have 1 or more non-modifiable risk factors in addition to their age. In conclusion, risk factors that may impact treatment with oral Janus kinase inhibitors were frequent in Danish adults with atopic dermatitis, especially among older individuals. Dermatologists need support and continuously updated long-term safety data when risk-evaluating patients with atopic dermatitis prior to initiation of advanced.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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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.
Summary
The history of chromium as an allergen goes back more than a century, and includes an interventional success with national legislation that led to significant changes in the epidemiology of ...chromium allergy in construction workers. The 2015 EU Leather Regulation once again put a focus on chromium allergy, emphasizing that the investigation of chromium allergy is still far from complete. Our review article on chromium focuses on the allergen's chemical properties, its potential exposure sources, and the allergen's interaction with the skin, and also provides an overview of the regulations, and analyses the epidemiological pattern between nations and across continents. We provide an update on the allergen from a dermatological point of view, and conclude that much still remains to be discovered about the allergen, and that continued surveillance of exposure sources and prevalence rates is necessary.
In psoriasis patients, incidence rates of Crohn disease (CD) and ulcerative colitis (UC) have been increased in epidemiological studies and certain clinical trials, yet the association remains poorly ...understood. We studied a 20-year nationwide cohort of 235,038 Danish adults with psoriasis and a 1:1 matched reference group. Less than 1% of psoriasis patients developed CD or UC during follow-up. Incidence rates of CD were highest for younger women with psoriasis and patients with concurrent psoriatic arthritis, whereas men with psoriasis had particularly high incidence rates of UC compared with their non-psoriasis peers. Adjusted hazard ratios of CD were 1.84 (95% confidence interval CI= 1.47–2.29) and 2.38 (95% CI = 1.62–3.49) among psoriasis patients treated with topical and systemic nonbiologic therapy, respectively. No definite CD cases occurred during biologic therapy. For UC, adjusted hazard ratios were 1.49 (95% CI = 1.29–1.72), 1.51 (95% CI = 1.14–2.01), and 1.23 (95% CI = 0.39–3.86, P = 0.7197) for psoriasis patients receiving topical, systemic nonbiologic, and biologic therapy, respectively. Time to CD (but not UC) diagnosis was significantly longer for psoriasis patients compared with the general population, and patients receiving systemic treatment had the longest time to CD and UC. Psoriasis was associated with increased risk of CD and UC. Particular risk factors included sex and psoriatic arthritis.
IMPORTANCE: The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative ...disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss. OBJECTIVE: To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea. DESIGN, SETTING, AND PARTICIPANTS: A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015. MAIN OUTCOMES AND MEASURES: The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models. RESULTS: A total of 5 404 692 individuals were included in the reference population; of these, 22 387 individuals (9812 43.8% women; mean SD age at diagnosis, 75.9 10.2 years) received a diagnosis of Parkinson disease during the study period and 68 053 individuals (45 712 67.2% women; mean age, 42.2 16.5 years) were registered as having rosacea. The IRs of Parkinson disease per 10 000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2-fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 95% CI, 1.67-2.48), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 95% CI, 0.97-0.99). CONCLUSIONS AND RELEVANCE: Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared pathogenic mechanisms involving elevated matrix metalloproteinase activity. The clinical consequences of this association require further study.
Summary
Background
Chronic hand eczema (CHE) is a burdensome disease, and new well‐documented, safe and efficacious treatments are warranted. In a recent CHE phase IIa trial, the pan‐Janus kinase ...(JAK) inhibitor delgocitinib in an ointment formulation was found to be efficacious and well tolerated.
Objectives
This trial assessed the dose response, efficacy and safety of delgocitinib cream in CHE.
Methods
In this double‐blind, phase IIb dose‐ranging trial, adults with CHE and a recent history of inadequate response or contraindication to topical corticosteroids were randomized to delgocitinib cream 1, 3, 8, 20 mg g–1 or vehicle treatment twice daily for 16 weeks. The primary endpoint was the Investigator’s Global Assessment for CHE (IGA‐CHE) treatment success 0 (clear) or 1 (almost clear) with a ≥ two‐point improvement from baseline to week 16. Secondary endpoints were the time to IGA‐CHE treatment success and changes in Hand Eczema Severity Index (HECSI); other endpoints were itch and pain numerical rating scale (NRS) scores, and Patient’s Global Assessment (PaGA) at week 16.
Results
Patients (n = 258) were randomized 1 : 1 : 1 : 1 : 1 to delgocitinib cream 1, 3, 8, 20 mg g–1 or vehicle. A significant dose–response relationship was established for IGA‐CHE (P < 0.025). IGA‐CHE treatment success at week 16 was achieved in 21.2% (1 mg g–1), 7.8% (3 mg g–1), 36.5% (8 mg g–1), 37.7% (20 mg g–1) and 8.0% (vehicle) of patients. Delgocitinib 8 and 20 mg g–1 showed a treatment effect against vehicle (P < 0.001). Similarly, there were improvements in HECSI, itch and pain NRS scores, and PaGA. Delgocitinib cream was well tolerated with the majority of adverse events being mild or moderate and considered unrelated to treatment. The most frequently reported adverse events were nasopharyngitis (17.3–29.4% in delgocitinib groups vs. 40% in vehicle group), eczema (5.8–11.3% in delgocitinib groups vs. 16.0% in vehicle group) and headache (3.8–11.5% in delgocitinib groups vs. 4.0% in vehicle group).
Conclusions
In this trial, delgocitinib cream showed a dose–response relationship in terms of efficacy and was well tolerated.
This article reports the efficacy and safety results from the first chronic hand eczema trial with the topical pan‐JAK inhibitor delgocitinib in a cream formulation.
Linked Comment: M.L.A. Schuttelaar. Br J Dermatol 2022; 187:7–8.
Plain language summary available online
To the Editor: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a particularly high prevalence in countries with a Western lifestyle.1 AD can have a substantial negative effect on ...a patient's quality of life and is associated with a higher risk of depression, increased consumption of tobacco and alcohol, and a sedentary lifestyle.2,3 Recently, there has been a growing interest in the putative cardiovascular comorbidities of dermatologic diseases. In patients with psoriasis, an increased prevalence of cardiovascular risk factors but possibly also proinflammatory mediators appears to contribute to an increased cardiovascular risk.4 However, studies investigating links between cardiovascular disease and AD are few in number, although recent studies have found positive associations between AD and cardiovascular risk factors, ischemic stroke, and myocardial infarction (MI).3,5,6 Importantly, it remains unclear whether the inflammatory nature of AD or the increased burden of AD-associated cardiovascular risk factors are primary determinants of the apparent increased risk. ...this population-based study examined the effect of AD on the risk of adverse cardiovascular outcomes among Danish adults, taking selected lifestyle factors into account.
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