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Background: Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. The objective of this trial was to evaluate the efficacy and safety of baricitinib in patients with active SLE in a 52-week phase 3 study. Methods: In a multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase 3 study, SLE-BRAVE-I, patients (aged ≥18 years) with active SLE receiving stable background therapy were randomly assigned 1:1:1 to baricitinib 4 mg, 2 mg, or placebo once daily for 52 weeks with standard of care. Glucocorticoid tapering was encouraged but not required per protocol. The primary endpoint was the proportion of patients reaching an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo. The primary endpoint was assessed by logistic regression analysis with baseline disease activity, baseline corticosteroid dose, region, and treatment group in the model. Efficacy analyses were done on a modified intention-to-treat population, comprising all participants who were randomly assigned and received at least one dose of investigational product. Safety analyses were done on all randomly assigned participants who received at least one dose of investigational product and who did not discontinue from the study for the reason of lost to follow-up at the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT03616912. Findings: 760 participants were randomly assigned and received at least one dose of baricitinib 4 mg (n=252), baricitinib 2 mg (n=255), or placebo (n=253). A significantly greater proportion of participants who received baricitinib 4 mg (142 [57%]; odds ratio 1·57 [95% CI 1·09 to 2·27]; difference with placebo 10·8 [2·0 to 19·6]; p=0·016), but not baricitinib 2 mg (126 [50%]; 1·14 [0·79 to 1·65]; 3·9 [-4·9 to 12·6]; p=0·47), reached SRI-4 response compared with placebo (116 [46%]). There were no significant differences between the proportions of participants in either baricitinib group reaching any of the major secondary endpoints compared with placebo, including glucocorticoid tapering and time to first severe flare. 26 (10%) participants receiving baricitinib 4 mg had serious adverse events, 24 (9%) participants receiving baricitinib 2 mg, and 18 (7%) participants receiving placebo. The safety profile of baricitinib in participants with SLE was consistent with the known baricitinib safety profile. Interpretation: The primary endpoint in this study was met for the 4 mg baricitinib group. However, key secondary endpoints were not. No new safety signals were observed. [ABSTRACT FROM AUTHOR]

The development of early-onset cow's milk protein allergy and atopic dermatitis during the first months of life is multifactorial, including both genetic and nutritional aspects. This study aims to assess the impact of different feeding patterns on the incidence of cow's milk protein allergy, atopic dermatitis, and growth among infants with a family history of allergy. A total of 551 high-risk infants were randomly recruited from 3 European countries in three feeding regimens: exclusive breastfeeding, partially hydrolyzed formula, or standard formula with intact protein either exclusively or supplementary to breastfeeding. During the first 6 months of intervention, amongst infants with a family history of atopic dermatitis, 6.5% of partially hydrolyzed formula-fed infants and 22.7% of exclusively breastfed infants (p = 0.007) presented with atopic dermatitis respectively. Growth as assessed by weight increase did not differ between the aforementioned groups. Although cow's milk protein allergy was not related to the different milk feeding regimens in the whole cohort, when adjusting for high breast milk intake, the respective incident was significantly lower in the infants consuming partially hydrolyzed formula (p < 0.001). This data indicates that a specific partially hydrolyzed formula could serve as a more appropriate complement to breast milk compared to a standard intact protein formula in high-risk infants, to reduce the incidence of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: For children aged 6-11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. Objectives: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). Methods: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight < 60 or ≥ 60 kg, respectively) for patients who did not achieve an Investigator's Global Assessment (IGA) score of 0/1 (clear/almost clear skin) at week 16, or prior to week 16 as rescue treatment. Additional patients were uptitrated to a weight-tiered q2w regimen following a protocol amendment. Patients who maintained an IGA score of 0/1 continuously for a 12-week period after week 40 discontinued dupilumab. They were monitored for relapse and were reinitiated on dupilumab if required. Results: Data for 321 patients (mean age 8.6 years) were analyzed, 254 (79%) of whom had completed the scheduled 52-week visit at the database lock. Most treatment-emergent adverse events were mild/moderate. By week 52, 41% of patients achieved an IGA score of 0/1, and 97%, 82%, and 50%, respectively, had at least a 50%, 75%, and 90% improvement from the parent study baseline in Eczema Area and Severity Index (EASI). By week 52, 29% of patients in the overall population had clear/almost clear skin sustained for 12 weeks and had stopped medication; of these, 40% relapsed and were subsequently reinitiated on treatment, with a mean time to reinitiation of 13.5 (standard deviation 5.2) weeks. Following reinitiation of dupilumab, 41% of the patients with evaluable data at the time of database lock had regained an IGA 0/1 clinical response. Conclusions: Consistent with results seen in adults and adolescents, long-term treatment with dupilumab in children aged 6-11 years with severe AD showed an acceptable safety profile and incremental clinical benefit. A substantial proportion of children who stopped dupilumab treatment after achieving clear/almost clear skin subsequently experienced disease recurrence, and required reinitiation of dupilumab, suggesting that continuous treatment may be necessary for maintenance of clinical benefit. Trial registration: ClinicalTrials.gov Identifier NCT02612454. [ABSTRACT FROM AUTHOR]

Background: Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) in a range of data sources with mixed conclusions. Objectives: We compared the incidence of IBD – ulcerative colitis (UC) and Crohn disease (CD) – in patients with a CISD vs. similar persons without a CISD. Methods: In this cohort study using nationwide, longitudinal, commercial insurance claims data from the USA, we identified adults and children who were seen by a dermatologist between 2004 and 2020, and diagnosed with either psoriasis, atopic dermatitis, alopecia areata, vitiligo or hidradenitis suppurativa. Comparator patients were identified through risk-set sampling; they were eligible if they were seen by a dermatologist at least twice and not diagnosed with a CISD. Patient follow-up lasted until either IBD diagnosis, death, disenrolment or end of data stream, whichever came first. IBD events, UC or CD, were identified via validated algorithms: hospitalization or diagnosis with endoscopic confirmation. Incidence rates were computed before and after adjustment via propensity-score decile stratification to account for IBD risk factors. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated to compare the incidence of IBD in CISD vs. non-CISD. Results: We identified patients with atopic dermatitis (n = 123 614), psoriasis (n = 83 049), alopecia areata (n = 18 135), vitiligo (n = 9003) or hidradenitis suppurativa (n = 6806), and comparator patients without a CISD (n = 2 376 120). During a median follow-up time of 718 days, and after applying propensity-score adjustment for IBD risk factors, we observed increased risk of both UC (HRUC 2·30, 95% CI 1·61-3·28) and CD (HRCD 2·70, 1·69-4·32) in patients with hidradenitis suppurativa, an increased risk of CD (HRCD 1·23, 1·03-1·46) but not UC (HRUC 1·01, 0·89-1·14) in psoriasis, and no increased risk of IBD in atopic dermatitis (HRUC 1·02, 0·92-1·12; HRCD 1·08, 0·94-1·23), alopecia areata (HRUC 1·18, 0·89-1·56; HRCD 1·26, 0·86-1·86) or vitiligo (HRUC 1·14, 0·77-1·68; HRCD 1·45, 0·87-2·41). Conclusions: IBD was increased in patients with hidradenitis suppurativa. CD alone was increased in patients with psoriasis. Neither UC nor CD was increased in patients with atopic dermatitis, alopecia areata or vitiligo. What is already known about this topic? Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) utilizing a range of data sources, with mixed conclusions. What does this study add? This large-scale, claims-based cohort study expands current knowledge by providing background rates for IBD across multiple CISDs using consistent methods and within a single, nationally representative patient population. We observed a relative increased risk of IBD in patients with hidradenitis suppurativa, but the overall incidence rate difference of IBD was generally low. Crohn disease alone was significantly increased in patients with psoriasis, and neither ulcerative colitis nor Crohn disease was increased in patients with atopic dermatitis, vitiligo or alopecia areata. [ABSTRACT FROM AUTHOR]

In this clinical study we evaluated an especially designed bed equipment for in-patients with severe atopic dermatitis. Ten adult patients aged between 18 to 74 years have been investigated for 10 to 12 days. We assessed severity of atopic dermatitis, severity of pruritus, and disturbance of sleep quality during the night. The median Three- Item-Score for atopic dermatitis was 11.5 ± 1.6 before and improved to 3 ± 1.3. Using the 5D Itch Score, pruritus decreased from 7 ± 1 to 3 ± 1.1. According to the Modified Sleep-Habits Questionnaire the median value improved from 3.7 ± 2.7 to 1.5 ± 2 suggesting a pronounced improvement of sleep quality. Adverse events or intolerabilities have not been observed. Our data argue for a positive effect of an especially designed bed equipment on severity of atopic dermatitis and pruritus and beneficial effects on the quality of night sleep. This supports the healing process. [ABSTRACT FROM AUTHOR]

Asthma, atopic dermatitis, and allergic rhinitis display a marked circadian variation with the maximum of disease activity during the night. Due to the consecutive disruption of sleep architecture, affected children often suffer from daytime sleepiness and have reduced quality of life. Currently there is a diagnostic gap in detecting nocturnal asthma and allergy symptoms, leading to a significant underestimation of the frequency. Caring for children with asthma, atopic dermatitis, and/or rhinitis should include standardized detection of nocturnal symptoms and a regular assessment of sleep quality and potential daytime sleepiness. Vice versa, in the differential diagnostic of a child with enhanced daytime sleepiness, the very frequent atopic diseases should be routinely considered. As asthma and obstructive sleep apnea syndrome often occur together, the presence of one of these two diseases should prompt the systematic search for the other one. [ABSTRACT FROM AUTHOR]

Difficulties: Evaluating patients with atopic dermatitis or atopic hand eczema is a unique challenge for the occupational dermatologist. It is not only necessary to distinguish atopic dermatitis or atopic hand eczema from other forms of eczema and arrive at a appropriate diagnosis but in many instances it is also difficult to determine causation because the role of exogenous as well as endogenous factors needs to be established by the expert. Only when this process is completed can a recommendation concerning the liability of the insurer be made. Assessment of disease continuing after termination of occupational exposure: It can be difficult to determine the causation if the eczema that was primarily caused by occupational exposure does not fade away after the activity responsible for the initial damage has been terminated. As there is no commonly accepted algorithm to decide if the skin lesion is still caused by the former contact to the responsible agents on the job or if endogenous factors are responsible for the skin disease after the occupational exposure has been terminated, every case must be meticulously judged by taking into consideration the conflicting individual factors. [ABSTRACT FROM AUTHOR]

Asthma and allergic rhinitis are chronic inflammatory airway diseases which often occur concomitantly. The objective of the LARA program was to identify the comorbidities and characteristics of asthma (A), intermittent or persistent rhinitis (IPR) and physician defined atopic dermatitis (AD) in 6- to 16-year old asthmatic Swiss children and adolescents. Overall, 126 general practitioners and paediatricians collected the data of 670 asthmatics. Approximately one third of the asthmatic children in Switzerland had well-controlled asthma. Almost two thirds of these asthmatics suffered from concomitant IPR. The latter presented with significantly less symptoms while the treatment rates with inhaled corticosteroids (approximately 90%) and leukotriene-receptorantagonists (approximately 50%) were comparable. However, there were almost twice as many passive smokers in the less well-controlled group. The prevalence of AD was similar in both groups. IPR and AD may play an important role as risk factors in the future development of asthma. [ABSTRACT FROM AUTHOR]

Atopic dermatitis as well as psoriasis are characterized as common, chronic, often long lasting disorders of the cutis. In case of (a) a refractory out-patient therapy, (b) an acute severe exacerbation of skin lesions, (c) functional impairment of hands and feet, (d) suberythroderma or erythroderma, (e) complex topical as well as systemic treatment modalities, (f) complicating somatic or psychological comorbidity, a referral to in-patient treatment at high altitude must be considered. The therapy at the Hoch-gebirgsklinik Davos (1'560 m above see level) is characterized by application of natural-borne UV radiation all year round, missing house dust mite allergen, massive reduction of pollens and mycotic spores, improvement of skin perfusion as well as a reduction in itching (as compared to low altitude regions). Last but not least, silence and distance from home and company may show benefits for psychological an cutaneous well-being the 24-hour daily presence of dermatology experts, a broad armamentarium of topical an systemic treatment modalities as well as wide range of up-to-date diagnostic and therapeutic tools have to be further mentioned. [ABSTRACT FROM AUTHOR]

Orointestinal mycoses are localized mainly in the oral cavity and in the oesphagus. Candida oesophagitis is not only found in AIDS-patients, also in patients of risk admitted to intensive care units. Upper intertinoscopies were made in 124 patients. Oesophageal candidosis was found in 6 patients, two of them had also Candida plaques in the stomach. The patients of the intensive care unit had an Apache-II-score of 26.7, those with Candida antibodies was observed with 59 of 124 patients (47.6%), including all patients with oesophageal candidosis. Obviously also Candida infections of other localizations must be suspected. There was a correlation between the severity of endoscopic aspects and the invasiveness observed microscopically. [ABSTRACT FROM AUTHOR]

Regarding Candida in dermatology, two pathogenetic pathways must be taken into account: 1. on infection of the skin 2. immunological reactions with skin alterations as a result of Candida infection or colonization in the mouth and/or intestine. Case reports describe typical situations of napkin dermatitis, intertriginous candidosis, the intrauterine Candida infection of the foetus, Candida granuloma, Candida folliculitis and Candida paronychia. In the second part results of investigations of patients suffering from psoriasis, atopic dermatitis and urticaria are presented. There were no differences in the colonization with Candida albicans and in the level of Candida antibody titres between patients and a healthy control group. [ABSTRACT FROM AUTHOR]