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Atopic dermatitis (AD) is a chronic skin disease affecting 10% of children in Europe. The treatment of AD is well codified; however, a gap sometimes exists between recommendations and medical practice. The objective of this study was to assess the practice of French pediatricians regarding the management of AD. We conducted a national practice survey from September 2021 to October 2021, using an online questionnaire emailed to pediatric physicians. A total of 83 pediatricians from 33 different departments responded to the survey. The clinical features of AD were known by the majority of pediatricians, but 15 (18%) found the diagnosis difficult to establish. All pediatricians prescribed daily applications of emollients and 78 (94%) prescribed topical corticosteroids (TCS) during AD flares, but misuses remained: only 29 (35%) pediatricians prescribed TCS when eczema (even if minimal) appeared and 43 (52%) did so at the onset of pruritus, while 45 (54%) prescribed them for extensive or disabling eczema, and 53 (64%) when eczema persisted after an initial treatment with emollients. Regarding diet, 12 (14%) pediatricians recommended a diet low on or free of cow milk, 10 (12%) systematically referred children with AD to an allergist, and 20 (24%) delayed food diversification. Despite improvements in AD management by French pediatricians in the past 15 years, barriers to its appropriate management still persist, including the misuse of TCS and inappropriate diets. [ABSTRACT FROM AUTHOR]

We explored patient satisfaction with baricitinib, an oral Janus kinase inhibitor, in patients with atopic dermatitis (AD) treated in routine clinical practice. Adults with moderate-to-severe AD treated with baricitinib in clinical practice for ≥4 weeks in France, Germany, and the UK completed a one-time online survey under market research methodologies. Treatment satisfaction was assessed using a Likert scale and abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9). Patients reported demographic, disease, and treatment information. Data were analyzed descriptively. The survey was completed by 170 patients with a mean age of 39.3 years (SD = 13.5), 59% (n = 101) were female. At baricitinib initiation, 79% rated their AD as "Severe", yet 28% reported body surface area (BSA) involvement ≥10%. Most were "Satisfied" or "Very satisfied" (76%/18%) with baricitinib, with high rates reported for controlling itch (36%/56%). Itch improvements were noted by 97% of patients. Some tapered/stopped (50%/32%) topical corticosteroid use, aligned with reported improvements on the patient global assessment and BSA. Mean TSQM-9 convenience score was 78.0 (SD = 14.0). Satisfaction with itch control was particularly high, reflected in rates of improvement in itch since starting baricitinib. On the TSQM-9, the convenience score was the highest. Many patients tapered/stopped concomitant topicals, indicating baricitinib's effect in controlling AD symptoms. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is frequently misdiagnosed and undertreated, resulting in increased morbidity. In 2019, the Atopic Dermatitis Quality of Care Initiative was launched globally to investigate barriers to AD care and note good practice interventions to improve care. The initiative included a literature review to define the challenges in AD and a survey of 32 AD centers to define good practice interventions. One topic studied was best practices for clinical assessment and diagnosis. The literature review revealed the primary gaps included difficulty differentiating AD from other skin disorders, diagnosing atypical AD, staging AD severity in individual patients, and delays in assessment and treatment due to referral time lag. The best clinical practices used by leading AD centers included the use of validated diagnostic criteria, established AD scoring tools including patient‐reported outcome measures and electronic health records (EHR), the formation of multidisciplinary teams (MDTs), and improved communication between health care providers (HCPs) and patients. Most centers worked with patient advocacy groups and implemented educational programs for HCPs. AD centers are overcoming issues in AD care. Educating health care providers and the public, using screening surveys, using established guidelines, and communicating with MCTs and patients through EHRs are the most frequently used strategies. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by unrelenting pruritus and recurrent eczematous lesions. It affects up to 15% of children and adolescents and up to 5% of adults, and confers a high and multifactorial burden to patients, families and society. With increasing awareness of this substantial burden, AD has become a priority for healthcare systems. Aim: The Atopic Dermatitis Quality of Care (ADQoC) initiative set out to describe good practices for addressing the challenges that impede the management of AD. Methods: The initiative carried out a literature review and surveyed 32 expert care centres, catalogued findings, and analysed and elucidated global challenges to AD care along with good practice implementations that can address them. Results: The four challenges to quality care for AD are: (i) misconceptions about AD; (ii) delayed referral and access to AD specialists; (iii) poor patient access to AD treatments and poor adherence to medications; and (iv) managing the complexity of AD and its comorbidities. The initiative highlighted 5 of 10 good practice implementations as high priority for any AD care centre to focus on: (i) clinical assessment and diagnosis; (ii) a structured multidisciplinary care team; (iii) monitoring and evaluating care quality; (iv) patient education and communication; and (v) collaboration and exchange with patient groups. Conclusion: These implementations can provide benefits for patients, healthcare providers and the healthcare system. They directly contribute to the efficacy of treatment, improved healthcare provider efficiency, improved education for patients and healthcare providers, and improved costs to healthcare systems. The initiative was launched on https://atopicdermatitiscare.kpmg.co.uk/ to provide an easy‐to‐use educational platform. [ABSTRACT FROM AUTHOR]

Background: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. Methods: To characterize the molecular signatures of chemical‐induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. Results: A clear segregation was observed between allergen‐ and irritant‐induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T‐cell responses. Our results also confirmed that: (a) unique pathways characterize allergen‐ and irritant‐induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine‐learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. Conclusion: These results highlight the value of molecular profiling of chemical‐induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. Methods: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. Results: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). Conclusions: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] Clinical Trial Registration: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026). Plain Language Summary: Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Dex5AhfAxs29XQspjFnxYi Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB) [ABSTRACT FROM AUTHOR]

Atopic Dermatitis (AD) is a chronic, relapsing inflammatory skin disease that carries a significant burden of disease and patient quality-of-life impairment. Several disorders known or supposed to be associated with AD were collected: atopic manifestations, cardiometabolic diseases, neuropsychiatric disorders, auto-immune or inflammatory diseases, addictions, neoplasia and patient-reported past skin infections. [Extracted from the article]

The article presents a case study of a 54-year-old surgeon with a history of atopic dermatitis (AD) who was referred by his occupational physician because of painful, chronic hand eczema, despite systemic treatment with dupilumab. Topics discussed include the reliability of patch testing in patients receiving dupilumab treatment, allergic contact dermatitis caused by glove compounds confirmed by patch testing, and the use of dupilumab in patients with persistent facial eczema.

The article presents a case study of a 39-year-old woman with a known history of atopic dermatitis (AD) and referred to the dermato-allergology department due to persistent, painful, hyperkeratotic palmoplantar eczema despite the use of betamethasone dipropionate ointment and emollients. The patient was treated with intramuscular injections of methotrexate (MTX) and folic acid. The treatment of MTX was stopped after one year due to the improvement in AD lesions.

Foxp3-expressing regulatory T cells (Tregs) reside in tissues where they control inflammation and mediate tissue-specific functions. The skin of mice and humans contain a large number of Tregs; however, the mechanisms of how these cells function in skin remain largely unknown. In this article, we show that Tregs facilitate cutaneous wound healing. Highly activated Tregs accumulated in skin early after wounding, and specific ablation of these cells resulted in delayed wound re-epithelialization and kinetics of wound closure. Tregs in wounded skin attenuated IFN-γ production and proinflammatory macrophage accumulation. Upon wounding, Tregs induce expression of the epidermal growth factor receptor (EGFR). Lineage-specific deletion of EGFR in Tregs resulted in reduced Treg accumulation and activation in wounded skin, delayed wound closure, and increased proinflammatory macrophage accumulation. Taken together, our results reveal a novel role for Tregs in facilitating skin wound repair and suggest that they use the EGFR pathway to mediate these effects. [ABSTRACT FROM AUTHOR]

Introduction The purpose of this study was to estimate the prevalence of monoclonal immunoglobulin (MIg) among patients with systemic sclerosis (SSc) according to the capillary electrophoresis or immunofixation method of detection and to search for any related clinical correlations. Patients and methods Retrospective multicenter comparison of capillary electrophoresis and immunofixation results in SSc patients and of the characteristics of patients with and without MIg. Results The study included 244 SSc patients (216 women and 28 men, mean age: 55 ± 14 years). Median time since SSc diagnosis was 51 months [0–320]; disease was diffuse in 48% of cases. Ten percent of patients had cancer, including Waldenström macroglobulinemia (n = 1) and multiple myeloma (n = 3). Capillary electrophoresis showed a γ-globulin anomaly in 41% of cases, and immunofixation in 18%: MIg (13.5%) and restriction of heterogeneity (4.5%). Capillary electrophoresis failed to detect 60% of the 33 MIg patients. Measurable MIg concentrations were obtained from 7 patients. MIg patients were significantly older at SSc diagnosis than those without MIg (p = 0.002), had a lower diffusing capacity (p = 0.002), a higher prevalence of pulmonary hypertension and cancer (p = 0.002) and were more frequently positive for anti-mitochondrial and anti-beta2-glycoprotein-I antibodies (p = 0.03 and p = 0.02, respectively). Multivariate analyses showed that only age at test [hazard ratio 1.03 (95% CI, 1.00–1.07, p = 0.04)] and presence of cancer [hazard ratio 4.46 (95% CI, 1.6–12.4, p = 0.004)] were associated with MIg. Conclusion Immunofixation detected a high prevalence of MIg among SSc patients especially in patients aged 50-years or older. MIg was not detected by the standard capillary electrophoresis in 60% of cases and was significantly associated with cancer. [ABSTRACT FROM AUTHOR]

Résumé: Le consensus actuel indique que la vaccination rougeole-oreillons-rubéole (ROR) ne nécessite aucun bilan allergologique à visée prédictive et est parfaitement tolérée chez les allergiques aux protéines de l’œuf. Toutefois, les injections de ce vaccin, élaboré à partir de cellules embryonnaires de poulet, sont souvent écartées par la crainte d’un accident anaphylactique, alors même que la vaccination ROR est recommandée par les autorités de santé, spécialement en période de recrudescence de rougeole. L’intradermoréaction au ROR, effectuée dans un but prédictif avant un rappel de vaccination, avait été positive en lecture immédiate chez un enfant de 12ans souffrant d’une allergie grave à l’œuf. Le bilan allergologique avait mis en évidence une sensibilisation à la gélatine mais l’enfant avait parfaitement toléré l’injection de rappel du ROR effectuée selon un protocole d’induction de tolérance. La gélatine, un stabilisant présent dans de nombreux vaccins, est parfois responsable de réactions d’hypersensibilité allergique immédiates. Devant une réaction à l’injection du vaccin ROR, il faut donc penser également à cette molécule. La vaccination ROR est possible et bien tolérée en cas d’hypersensibilité immédiate allergique aux protéines de l’œuf, y compris lorsque cette allergie est associée à une sensibilisation contre la gélatine. [ABSTRACT FROM AUTHOR]

Abstract: Angiotensin-converting enzyme (ACE) inhibitor-related angioedema (AE) may be fatal in the absence of specific treatment. No consensus for this side effect currently exists. Also, the French national reference centre for angioedema (CREAK) decided to establish recommendations, developed by an expert group and proposed at a national meeting. A scientific committee conducted a comprehensive literature review and worked out with proposals. These proposals were submitted to a vote to the expert panel of CREAK at a national meeting. Proposals that had received the majority were retained. Diagnosis of ACE inhibitor-related AE is based on clinical events. Regarding the severity of the disease, this diagnosis has to be put forward in any patient currently treated with or who has been treated with ACE inhibitors in the previous 6 months. The diagnosis is important because AE does not respond to usual treatment of histamine-induced AE (antihistamines, corticosteroids, and epinephrine), but only to specific treatment of bradykinin-induced AE, as antagonists of bradykinin or concentrates of C1 inhibitor. The subsequent use of ACE is strictly contra-indicated. A report to pharmacovigilance centres of every case is essential. These recommendations should improve the standardization of the management of ACE inhibitor-related AE. [Copyright &y& Elsevier]

The article presents a case study of a 59-year-old woman who was diagnosed with hydroxyzine-induced hypersensitivity reaction. She has suffered from psoriasis and psoriatic arthritis during her childhood and has been treated with psoralen + ultraviolet A, retinoids, and methotrexate. It states the positive impact of ustekinumab treatment on the patient. Moreover, it notes the failure of the treatment process to prevent the development of her allergic dermatitis caused by hydroxyzine.

The article presents a case study of a 43-year-old woman who experienced dermatitis of the neck and scalp after hair colouring, which was done every six weeks. The woman underwent open skin tests, which reveal positive allergic contact dermatitis for the hair dye and negative for the colouring cream. The article discusses allergic contact dermatitis caused by hair dye, wherein the allergens are formed during the oxidation of precursor colorants.

Background: Quinolone hypersensitivity reactions are being more frequently reported. Skin tests in investigations of patients are known to not be fully reliable. The provocation test thus remains the gold standard in the definitive diagnosis of allergy, despite the risks involved. The aim of this study was to evaluate basophil activation tests (BATs) in the diagnosis of immediate-type reactions to quinolones. Methods: Thirty-four patients who presented an immediate-type hypersensivity reaction less than an hour after quinolone administration were studied. The allergologic workup of these patients consisted of a careful clinical history, a skin test and a BAT with the culprit quinolone. If not contraindicated, and in the case of high probability of a nonallergic reaction, provocation tests were performed to assess the nonimmunologic nature of the hypersensitivity. Results: Among the 34 patients studied, 17 (50%) presented a negative BAT to the suspected quinolone, while the other 17 (50%) patients presented a positive BAT for quinolone at the time of their reaction. Among the 17 patients with negative BATs, 15 (2 of whom had had positive skin tests) had quinolone successfully reintroduced. Conclusions: Our report suggests that the BAT, if negative for the culprit quinolone, is a valuable tool in the decision whether or not to perform provocation tests in patients with a history of immediate-type reaction to quinolones, in order to exclude an allergic reaction. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The diagnosis of drug allergy is based on clinical history and skin tests. Although medical literature reports a risk of allergic reactions during skin tests, our experience, based upon several thousands of patients since 1998, strongly suggests that skin tests with drugs are well tolerated. Patients and methods: In this prospective study, we analysed the adverse effects observed during skin testing of 183 patients explored for suspected drug-induced immediate hypersensitivity, such as urticaria, angioedema, bronchospasm, and anaphylactic shock, between November 2004 and March 2005. Patients were first tested with prick-tests, and with intradermal tests (IDT) at 1/1000 and 1/100 dilutions of the prick solution only when the prick-tests were negative. Results: One hundred and seventy-nine prick-tests and 169 IDT were realised with drugs diluted by the hospital''s chemist. Nine of the 183 patients (5.0%) were diagnosed as having drug-induced immediate-type hypersensitivity, based on a severe suggestive initial reaction and immediate responses in prick or IDT. No reaction was observed during prick testing. IDT induced a non-severe reaction, with less severe symptoms than the initial accident, in one patient only. Conclusion: Our results confirm the excellent tolerance of prick-tests. Also, they strongly suggest that it is important to investigate drug hypersensitivity with a well-defined protocol, in a hospital setting, starting with pricks and using low concentrations of drugs in IDT. [Copyright &y& Elsevier]

While the early introduction of food allergens in the infant diet has been shown to be effective at preventing the development of food allergy (FA), its implementation in real life has been associated with various challenges. Interventions aimed at correcting skin barrier dysfunction have been explored in recent decades as a distinct or complementary mean to prevent allergic sensitization through the skin and subsequent development of FA. Studies assessing the application of emollient from birth have yielded conflicting results, and meta‐analyses have demonstrated either no effect or only a slight positive effect on FA prevention. However, a careful review of the clinical trials reveals that different emollients were used, which may have explained some of the discrepancies between study results. Emollient application protocols also varied widely between studies. While firm conclusions cannot be drawn with regard to their overall efficacy at preventing FA, the available data provide valuable insight into the characteristics that could be associated with a more effective intervention. Namely, successful trials tended to use emollients with an acidic pH of 5.5, applied over the entire body, and combined with topical corticosteroids in affected areas. Consensus on the optimal strategy to restore skin barrier function could help improve the homogeneity and clinical relevance of future trials on this topic. In the meantime, clinicians should avoid products associated with worse outcomes. [ABSTRACT FROM AUTHOR]

Background: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. Objective: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. Methods: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. Results: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. Conclusion: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. Trial Registries: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822. [ABSTRACT FROM AUTHOR]

Background: Tissue‐resident memory T (TRM) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease. Methods: We assessed the impact of a standard topical corticosteroid (TCS) treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal TRM cells in a preclinical model of ACD to 2,4‐dinitrofluorobenzene. TA 0.01% was applied at different time points of ACD response and we monitored skin inflammation and tracked CD8+ CD69+ CD103+ TRM by flow cytometry and RNA sequencing. Results: The impact of TA on TRM formation depended on treatment regimen: (i) in a preventive mode, that is, in sensitized mice before challenge, TA transiently inhibited the infiltration of effector T cells and the accumulation of TRM upon hapten challenge. In contrast, (ii) in a curative mode, that is, at the peak of the ACD response, TA blocked skin inflammation but failed to prevent the formation of TRM. Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin TRM, but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific TRM progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, TRM re‐expansion correlated with the decreased clearance of hapten moieties from the skin induced by repeated TA applications. Conclusions: Our results demonstrate that TCS successfully treat ACD inflammation, but are mostly ineffective in impeding the formation and expansion of allergen‐specific TRM, which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Allergic contact dermatitis to gloves is mostly induced by rubber accelerators. The European baseline series (EBS) appears insufficient to detect glove allergy. Since 2017, it is recommended to use the European rubber series (ERS) and to test the patients' own gloves. Objectives: To investigate the clinical profile of glove‐wearing patients with hand eczema (HE) and to evaluate their sensitisation profile to glove allergens and the value of testing the patients' own gloves. Methods: We conducted a French multicentre study of patients evaluated for HE between 2018 and 2020 and tested with the EBS, the ERS and their own gloves in patch tests and semi‐open (SO) tests. Results: A total of 279 patients were included; 32.6% of patients had positive tests to their own gloves or to glove allergens. Almost 45% of the sensitisations to glove allergens were detected only by the ERS. Among the patients tested both in patch tests and SO tests with their own gloves with positive results, 28% had positive SO tests only. Polyvinylchloride (PVC) gloves were positive in four patients. Conclusion: Our series confirms the need to test the ERS. All the patients' gloves must also be tested including PVC gloves. SO tests with gloves are useful as a complement to patch tests. [ABSTRACT FROM AUTHOR]

Abrocitinib is an oral Janus kinase 1 inhibitor with demonstrated efficacy in moderate-to-severe atopic dermatitis (AD). To evaluate the long-term safety profile of abrocitinib and provide relevant information for practitioners. Data from patients who received ≥1 dose of abrocitinib 200 mg or 100 mg in the JADE clinical program were pooled in two cohorts. The consistent-dose (CD) cohort comprised patients who received the same abrocitinib dose during the entire exposure time in parent phase 3 studies and/or the long-term extension study JADE EXTEND (NCT03422822). Parent studies were: JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only) and JADE REGIMEN (NCT03627767); in JADE REGIMEN only patients from the open-label run-in phase (200 mg only) who did not subsequently enter the randomized phase were included. Patients from the phase 2b study (NCT02780167) were also included in the CD cohort. The variable-dose (VD) cohort comprised patients who received different doses of abrocitinib (200 and 100 mg) throughout exposure time in the parent study JADE REGIMEN and in JADE EXTEND, if enrolled. Patients included in the VD cohort completed the open-label period of JADE REGIMEN (abrocitinib 200 mg only) and entered the randomized phase (abrocitinib 200 mg, abrocitinib 100 mg or placebo); some patients subsequently entered the JADE REGIMEN rescue phase (abrocitinib 200 mg) and/or JADE EXTEND (abrocitinib 200 or 100 mg). The data cutoff was 16 April 2021. A Cox regression analysis evaluated risk factors for specific events of interest. Data from 3582 patients (4313.4 patient-years) were analysed: 2784 patients in the CD cohort (abrocitinib 200 mg, n=1761, abrocitinib 100 mg, n=1023) and 798 patients in the VD cohort. Duration of exposure was ≥48 weeks in 43.6%, 66.9% and 86.1% and ≥96 weeks in 18.0%, 23.2% and 45.4% of patients in the CD 200 mg, 100 mg and VD cohorts, respectively. In the CD and VD cohorts, the median age was 30.0 and 29.0 years; 490 (17.6%) and 145 patients (18.2%) were adolescents, and 143 (5.1%) and 30 patients (3.8%) were aged ≥65 years at screening, respectively. Incidence rates (IRs; unique patients with events per 100 patient-years) of serious adverse events (SAEs), deaths, and treatment-emergent adverse events of special interest are shown in Table 1. IRs for SAEs were consistent across abrocitinib doses but were higher in patients aged ≥65 years vs. younger patients. Serious infections were the most frequent SAEs; frequency was not dose related. Herpes zoster (HZ), herpes simplex and pneumonia were the most frequent serious infections. From a Cox regression analysis, potential risk factors for treatment-emergent HZ included abrocitinib dose, baseline age, medical history of HZ, absolute lymphocyte count <1000 mm−3 prior to infection and region. Most (95%) adjudicated opportunistic HZ infections were cutaneous; 2 (5%) were extracutaneous (one serious disseminated varicella-zoster virus infection, one serious HZ meningitis). IRs for nonmelanoma skin cancer, malignancy (excluding nonmelanoma skin cancer), thrombocytopenia and lymphopenia were higher in patients aged ≥65 years vs. younger patients but were not dose related. Abrocitinib has an acceptable long-term safety profile in this large analysis of patients with moderate-to-severe AD. Risk of SAEs, HZ infection, malignancies and hematologic abnormalities increased with older age; HZ risk was also related to dose and prior HZ infection. [ABSTRACT FROM AUTHOR]

Dear Editor, Therapeutic patient education (TPE) is an effective way to manage chronic skin diseases such as atopic dermatitis (AD). The main themes of these tools were AD knowledge ( I n i = 51, 50%), compliance ( I n i = 33, 33%) and monitoring of AD ( I n i = 17, 17%; Figure 1a). Our objective was to identify the most frequently used available TPE tools for caregivers of patients with AD. [Extracted from the article]

The article reports on 50-year-old woman presented in November 2007 with a localized eczematous condition on the upper right buttock.. It discusses that acrylates form a big group of chemical substances gained from acrylic acid. It infers that patch testing did not identify any other potential allergen found in the product.

Background: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. Objective: To examine the incidence, characteristics and risk factors of dupilumab‐induced ocular adverse events. Methods: A prospective, multicenter, and real‐life study in adult AD patients treated with dupilumab. Results: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab‐induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938–30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635–21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158–13.90]; p = 0.031) were independent factors associated with dupilumab‐induced blepharoconjunctivitis. Limitations: Our follow‐up period was 16 weeks and some late‐onset time effects may still occur. Conclusion: This study showed that most dupilumab‐induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study. [ABSTRACT FROM AUTHOR]

T cell-and non T cell-mediated delayed hypersensitivity to dupilumab We hypothesize that Patient 1 was sensitized to T-cell epitopes in the tralokinumab primary sequence with cross-reactivity with dupilumab[6]; (ii) an Arthus-like reaction, that is, an immune complex-mediated reaction produced under conditions of excess antigens, for the second patient. We report the cases of a 52-year-old (Patient 1) and a 56-year-old (Patient 2) female patients, followed for severe AD with multiple previous treatment failures. [Extracted from the article]

Baricitinib is an oral selective Janus kinase 1/2 inhibitor approved for moderate-to-severe atopic dermatitis (AD) in adults. To evaluate absolute Eczema Area and Severity Index (EASI) and SCORing of Atopic Dermatitis (SCORAD) outcomes over 16 weeks and to link disease severity categories to quality of life (QoL) improvements. This post-hoc analysis included patients enrolled in Phase3 monotherapy (BREEZE-AD1/AD2) and topical corticosteroid (TCS) combination therapy (BREEZE-AD7) trials and analyzed baricitinib 2 and 4 mg vs. placebo. Categorical outcomes were analyzed using Fisher's exact test. Significantly more baricitinib-treated patients reached EASI ≤ 7 and SCORAD < 25 as early as week 1 in monotherapy and week 2 in TCS combination therapy, compared to placebo. Significant response vs. placebo was sustained until week 16 for EASI ≤ 7 (AD1/2 [p-value vs. placebo]: 2 mg = 19.9%, 4 mg = 25.4% [p = 0.001] and AD7: 2 mg = 40.4% [p = 0.087], 4 mg = 48.6% [p = 0.003]) and SCORAD < 25 (AD1/2: 2 mg = 12.2%, 4 mg = 19.4% [p = 0.001] and AD7: 2 mg = 30.3% [p = 0.025], 4 mg = 34.2% [p = 0.004]) severity categories. These effects were accompanied by rapid improvements in QoL. Baricitinib-treated patients rapidly achieved recommended absolute EASI and SCORAD treatment outcomes which were sustained until week 16. Improvements in QoL were greater than EASI severity categories reflected, indicating that physician-assessed scores do not necessarily correlate with patients' impression of AD severity. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is the first biotherapy available for the treatment of moderate‐to‐severe childhood atopic dermatitis (AD). Objective: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice. Methods: Patients aged 6–11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial. Results: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial. Limitations: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information. Conclusion: These real‐life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group. [ABSTRACT FROM AUTHOR]

Background: Cancer patients are being exposed to antineoplastic drugs more frequently and for longer periods, resulting in a higher risk of hypersensitivity reactions. The aim of this study was to assess the pharmaceutical time and direct cost of drug allergy explorations following immediate hypersensitivity reactions to antineoplastic agents. Methods: A micro-costing method was used to collect data on consumption of human and material resources for allergy exploration preparations. The monetisation was carried out on the basis of prices and hourly wage costs applied in 2018. The number and type of allergy explorations prepared by the pharmacy as well as nature of antineoplastic drugs tested, and the number of culprit drugs reintroductions were collected. Results: Almost 1.5 h is required to realise allergy tests for one patient including pharmacist time for prescription analysis and pharmacy technician's time for tests preparation. The mean manufacturing cost of these tests is estimated at €62.87 (€57.82–65.49) per culprit drug for one patient. Programming patients according to culprit drugs tested allows rationalising healthcare provider time and increasing efficiency. From January 2010 to December 2018, 277 patients were tested and 490 allergy explorations were performed, corresponding to more than 5000 preparations. Mostly, the culprit drug could be reintroduced (n = 383, 78.2%) allowing patients to receive the best possible treatment. Conclusion: Management of hypersensitivity reactions is constantly progressing, as it contributes to improving patient care in oncology. This activity is time-consuming for the pharmacy team but allows patients with previous hypersensitivity reaction to continue effective treatment. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient’s quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD.Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression.Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 − 7.8 vs − 2.8; ADvocate2 − 7.3 vs − 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 − 7.43 vs − 1.51; ADvocate2 − 4.95 vs − 0.82) and PROMIS Depression (ADvocate1 − 7.42 vs − 2.46; ADvocate2 − 4.28 vs − 2.00).Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline.ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).Methods: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient’s quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD.Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression.Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 − 7.8 vs − 2.8; ADvocate2 − 7.3 vs − 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 − 7.43 vs − 1.51; ADvocate2 − 4.95 vs − 0.82) and PROMIS Depression (ADvocate1 − 7.42 vs − 2.46; ADvocate2 − 4.28 vs − 2.00).Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline.ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).Results: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient’s quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD.Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression.Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 − 7.8 vs − 2.8; ADvocate2 − 7.3 vs − 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 − 7.43 vs − 1.51; ADvocate2 − 4.95 vs − 0.82) and PROMIS Depression (ADvocate1 − 7.42 vs − 2.46; ADvocate2 − 4.28 vs − 2.00).Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline.ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).Conclusions: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient’s quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD.Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression.Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 − 7.8 vs − 2.8; ADvocate2 − 7.3 vs − 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 − 7.43 vs − 1.51; ADvocate2 − 4.95 vs − 0.82) and PROMIS Depression (ADvocate1 − 7.42 vs − 2.46; ADvocate2 − 4.28 vs − 2.00).Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline.ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).Trial Registration: Atopic dermatitis (AD) is a chronic inflammatory skin disease for which signs and symptoms have a negative impact on a patient’s quality of life (QoL) and mental health. Here, we assess the impact of lebrikizumab on QoL and mental health after 16 weeks of treatment in patients with moderate-to-severe AD.Data were analyzed over 16 weeks from two separate phase 3, randomized, placebo-controlled, monotherapy trials (ADvocate1 and ADvocate2). Patient-reported outcomes were assessed using the following measures: Dermatology Life Quality Index (DLQI), EQ-5D-5L visual analogue scale (VAS), EQ-5D-5L index scores (UK and US), Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, and PROMIS Depression.Treatment with lebrikizumab 250 mg every 2 weeks in two studies led to statistically significant improvements (based on nominal p values) versus placebo in DLQI since week 4 (the first timepoint assessed) for the following measures: change from baseline in DLQI total score (ADvocate1 − 7.8 vs − 2.8; ADvocate2 − 7.3 vs − 3.9), proportion of patients with DLQI ≥ 4-point improvement (ADvocate1 69.5% vs 36.2%; ADvocate2 60.5% vs 42.6%), DLQI total score ≤ 5 (ADvocate1 36.7% vs 8.8%; ADvocate2 29.6% vs 10.8%), and DLQI (0, 1) (ADvocate1 12.3% vs 1.7%; ADvocate2 9.2% vs 1.7%). Improvements in DLQI measures, EQ-5D-5L index scores (UK and US), and EQ-5D-5L VAS were sustained through week 16. Additionally, lebrikizumab improved PROMIS Anxiety and PROMIS Depression scores, and improvements were higher in patients with at least a mild score (≥ 55) versus placebo for PROMIS Anxiety (ADvocate1 − 7.43 vs − 1.51; ADvocate2 − 4.95 vs − 0.82) and PROMIS Depression (ADvocate1 − 7.42 vs − 2.46; ADvocate2 − 4.28 vs − 2.00).Treatment with monotherapy 250 mg lebrikizumab for 16 weeks provided clinically meaningful improvements in outcomes related to QoL and mental health for patients with moderate-to-severe AD. Lebrikizumab-treated patients reported improvements in DLQI as early as week 4, the first measure since baseline.ClinicalTrials.gov Registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2). [ABSTRACT FROM AUTHOR]

Background: Diagnosis of contact allergy (CA) to Amerchol L‐101 (AL‐101), a marker for lanolin allergy, is problematic. Positive patch test reactions are frequently doubtful or weakly positive and difficult to associate with clinical relevance. Objective: To gain further insight on the allergic or irritant nature of skin reactions induced by AL‐101 patch test. Methods: We re‐tested in a dose–response fashion, 10 subjects with AL‐101 CA and performed comprehensive transcriptomic analysis (gene arrays, quantitative real‐time polymerase chain reaction [qRT‐PCR]) of samples of their skin reactions. Results: Eight of the 10 CA subjects reacted positively upon re‐test, whereas two did not react. Most of AL‐101 positive patch tests expressed an allergy signature with strong activation of gene modules associated with adaptive immunity and downregulation of cornification pathway genes. In addition, the breadth of gene modulation correlated with the magnitude of patch test reactions and the concentration of AL‐101 applied. However, we observed that some of the positive patch test reactions to AL‐101 expressed no/few allergy biomarkers, suggesting the induction of an irritant skin inflammation in these samples. Conclusions: This study confirms that AL‐101 is an allergen that can cause both contact allergy and contact irritation. Our results also highlight that molecular profiling might help to strengthen clinical diagnosis. [ABSTRACT FROM AUTHOR]

A correction for the article "Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate‑to‑Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program" by October 13, 2021, which was published in the previous issue of the periodical.

Introduction: Atopic dermatitis (AD) is an inflammatory skin disease in which activation of specific T cells directed towards environmental allergens plays an important role. Environmental allergens' penetration through the skin is facilitated by the skin barrier impairment what causes xerosis and transepidermal water loss (TEWL) increase. As AD is a chronic disease, there are many factors responsible for exacerbations during the course of the disease, including environmental stress. Aim: Evaluation of the correlation between the level of psychological stress and epidermal barrier function in AD patients. Material and methods: Eight AD patients were included in the study during which two consultations were performed in one month's time. During each visit patients completed psychological questionnaires and had TEWL of uninvolved skin measured. The TEWL was also evaluated before and after the educational session which took place during the first visit. Results: The study did not show any statistically significant correlation between the level of psychological stress, epidermal barrier function (measured by TEWL) and AD severity both at the beginning of the study (before and after the educational session) and a month later (allp > 0.05). Conclusions: Negative observations could result from a small number of participants and a short follow-up period. However, consecutive studies excluding these limitations may play an important role in understanding the influence of stress on the skin barrier in atopic dermatitis and have reliable clinical implications. [ABSTRACT FROM AUTHOR]

Impact of an e-learning programme on pharmacists' management of atopic dermatitis Capitalizing on the possibilities presented by current digital tools, we report here the efficacy of a free e-learning programme that sustainably improved participants' level of knowledge regarding AD management. Thus, the e-learning programme significantly improved pharmacists' AD management knowledge, which was sustained over a 9-month period. [Extracted from the article]

The article presents a study on immunophenotyping on skin and blood to determine the severity of skin symptoms of toxic epidermal necrolysis (TEN), a cutaneous adverse drug reaction. It discusses the characterization of TEN, findings on the main leucocytes in TEN blisters at the acute phase based on mass cytometry, and the expansion of unique CDR3 clonotypes in blister cells.

Insights into the real-world treatment paradigm and long-term burden of atopic dermatitis (AD) are needed to inform clinical and health policy decisions. The prospective, observational EUROSTAD study enrolled adults with moderate-to-severe AD starting or switching systemic therapy (51 sites in 10 European countries). We report the baseline characteristics, treatment patterns, and outcomes of these patients using descriptive statistics. A 12-month enrollment period of EUROSTAD was completed and 308 patients were enrolled: average age 37 years, AD duration 25 years, 43% were female. Most patients reported use of systemic therapy (93%) and ≥1 atopic comorbidity (82%). Mean [standard deviation] disease severity/burden measures were high: Investigator's Global Assessment (3.1 [0.8]), Eczema Area and Severity Index (16.2 [10.9]), Peak Pruritus Numerical Rating Scale (5.5 [2.5]), sleep impairment Visual Analog Scale (49.8 [31.6]) scores, and time lost from work (4.1 [13.7] days/year) or usual activities (16.8 [38.7] days/year). Most patients showed borderline or clinical levels of anxiety (59%) and/or depression (63%) using the Hospital Anxiety and Depression Scale. Adults with moderate-to-severe AD starting/switching systemic treatment enrolled in EUROSTAD have a high burden of longstanding disease despite continuous use of topical drugs, emollients, and systemic therapies. [ABSTRACT FROM AUTHOR]

Among the six patients who stopped treatment owing to AD remission, the median duration of treatment was 57 weeks (IQR 44-25-65-25). From a total of 968 patients treated with dupilumab during the study period, 150 patients (15-5%) discontinued treatment after a median treatment duration of 5 months [interquartile range (IQR) 3-10]. Dear Editor, Dupilumab, an anti-interleukin-4 monoclonal antibody, has shown a positive benefit-risk ratio when treating moderate-to-severe atopic dermatitis (AD) in clinical studies.1 High persistence for patients on dupilumab has recently been reported in a clinical practice setting, with 77% of patients remaining in treatment for 12 months in a retrospective study that included 1963 patients with AD; however, reasons for discontinuation were not investigated.2 Investigating the reasons for treatment discontinuation in chronic diseases permits the assessment of both the safety and the effectiveness of a given treatment in a clinical practice setting. [Extracted from the article]

Linked article: This article is commented on by A. Wollenberg et al., pp. e155–e156 in this issue. To view this article visit https://doi.org/10.1111/jdv.15377. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a common inflammatory disease of the skin, which may have a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to quantify the economic burden (direct and indirect costs) of moderate-to-severe AD and evaluate the prevalence and impact of psychosocial comorbidities among patients in the European Union-5 (France, Germany, Italy, Spain, and the UK).Data were analyzed from the 2017 EU5 National Health and Wellness Survey. Respondents with a physician diagnosis of AD/eczema who were considered to have moderate-to-severe AD based on a Dermatology Life Quality Index (DLQI) score  ≥ 6 were included. Direct costs, indirect costs, and psychosocial comorbidities (sleep difficulties and anxiety based on self-report, depression based on the Patient Health Questionnaire-9) were reported descriptively. Generalized linear models were used to examine the relationship between psychosocial comorbidities and health outcomes (the Short Form-36 version 2 [SF-36v2], EuroQoL 5-dimension 5-level, Work Productivity and Activity Impairment questionnaire, and healthcare resource utilization).Overall, 1014 patients were included in the analysis. Total annual direct costs ranged from €2242 to €6924 and total annual indirect costs ranged from €7277 to €14,236, depending on the level of disease severity. Sleep difficulties, anxiety, and depression were reported by 61.6%, 52.7%, and 75.8% of patients, respectively. These comorbidities were significantly associated with reduced physical and mental component summary scores from SF-36v2 and increased overall work impairment (p < 0.05 for all).A significant economic burden was observed for patients with moderate-to-severe AD. Sleep difficulties, depression, and anxiety were observed in more than half of moderate-to-severe AD patients and were significantly associated with decrements in HRQoL and with work-related impairment. Reducing the burden of these psychosocial comorbidities in AD could have significant benefit to patients and society.Methods: Atopic dermatitis (AD) is a common inflammatory disease of the skin, which may have a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to quantify the economic burden (direct and indirect costs) of moderate-to-severe AD and evaluate the prevalence and impact of psychosocial comorbidities among patients in the European Union-5 (France, Germany, Italy, Spain, and the UK).Data were analyzed from the 2017 EU5 National Health and Wellness Survey. Respondents with a physician diagnosis of AD/eczema who were considered to have moderate-to-severe AD based on a Dermatology Life Quality Index (DLQI) score  ≥ 6 were included. Direct costs, indirect costs, and psychosocial comorbidities (sleep difficulties and anxiety based on self-report, depression based on the Patient Health Questionnaire-9) were reported descriptively. Generalized linear models were used to examine the relationship between psychosocial comorbidities and health outcomes (the Short Form-36 version 2 [SF-36v2], EuroQoL 5-dimension 5-level, Work Productivity and Activity Impairment questionnaire, and healthcare resource utilization).Overall, 1014 patients were included in the analysis. Total annual direct costs ranged from €2242 to €6924 and total annual indirect costs ranged from €7277 to €14,236, depending on the level of disease severity. Sleep difficulties, anxiety, and depression were reported by 61.6%, 52.7%, and 75.8% of patients, respectively. These comorbidities were significantly associated with reduced physical and mental component summary scores from SF-36v2 and increased overall work impairment (p < 0.05 for all).A significant economic burden was observed for patients with moderate-to-severe AD. Sleep difficulties, depression, and anxiety were observed in more than half of moderate-to-severe AD patients and were significantly associated with decrements in HRQoL and with work-related impairment. Reducing the burden of these psychosocial comorbidities in AD could have significant benefit to patients and society.Results: Atopic dermatitis (AD) is a common inflammatory disease of the skin, which may have a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to quantify the economic burden (direct and indirect costs) of moderate-to-severe AD and evaluate the prevalence and impact of psychosocial comorbidities among patients in the European Union-5 (France, Germany, Italy, Spain, and the UK).Data were analyzed from the 2017 EU5 National Health and Wellness Survey. Respondents with a physician diagnosis of AD/eczema who were considered to have moderate-to-severe AD based on a Dermatology Life Quality Index (DLQI) score  ≥ 6 were included. Direct costs, indirect costs, and psychosocial comorbidities (sleep difficulties and anxiety based on self-report, depression based on the Patient Health Questionnaire-9) were reported descriptively. Generalized linear models were used to examine the relationship between psychosocial comorbidities and health outcomes (the Short Form-36 version 2 [SF-36v2], EuroQoL 5-dimension 5-level, Work Productivity and Activity Impairment questionnaire, and healthcare resource utilization).Overall, 1014 patients were included in the analysis. Total annual direct costs ranged from €2242 to €6924 and total annual indirect costs ranged from €7277 to €14,236, depending on the level of disease severity. Sleep difficulties, anxiety, and depression were reported by 61.6%, 52.7%, and 75.8% of patients, respectively. These comorbidities were significantly associated with reduced physical and mental component summary scores from SF-36v2 and increased overall work impairment (p < 0.05 for all).A significant economic burden was observed for patients with moderate-to-severe AD. Sleep difficulties, depression, and anxiety were observed in more than half of moderate-to-severe AD patients and were significantly associated with decrements in HRQoL and with work-related impairment. Reducing the burden of these psychosocial comorbidities in AD could have significant benefit to patients and society.Conclusions: Atopic dermatitis (AD) is a common inflammatory disease of the skin, which may have a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to quantify the economic burden (direct and indirect costs) of moderate-to-severe AD and evaluate the prevalence and impact of psychosocial comorbidities among patients in the European Union-5 (France, Germany, Italy, Spain, and the UK).Data were analyzed from the 2017 EU5 National Health and Wellness Survey. Respondents with a physician diagnosis of AD/eczema who were considered to have moderate-to-severe AD based on a Dermatology Life Quality Index (DLQI) score  ≥ 6 were included. Direct costs, indirect costs, and psychosocial comorbidities (sleep difficulties and anxiety based on self-report, depression based on the Patient Health Questionnaire-9) were reported descriptively. Generalized linear models were used to examine the relationship between psychosocial comorbidities and health outcomes (the Short Form-36 version 2 [SF-36v2], EuroQoL 5-dimension 5-level, Work Productivity and Activity Impairment questionnaire, and healthcare resource utilization).Overall, 1014 patients were included in the analysis. Total annual direct costs ranged from €2242 to €6924 and total annual indirect costs ranged from €7277 to €14,236, depending on the level of disease severity. Sleep difficulties, anxiety, and depression were reported by 61.6%, 52.7%, and 75.8% of patients, respectively. These comorbidities were significantly associated with reduced physical and mental component summary scores from SF-36v2 and increased overall work impairment (p < 0.05 for all).A significant economic burden was observed for patients with moderate-to-severe AD. Sleep difficulties, depression, and anxiety were observed in more than half of moderate-to-severe AD patients and were significantly associated with decrements in HRQoL and with work-related impairment. Reducing the burden of these psychosocial comorbidities in AD could have significant benefit to patients and society. [ABSTRACT FROM AUTHOR]

Background: The therapeutic options in atopic dermatitis rely on consensus‐based guidelines, also established for psoriasis and chronic urticaria. However, the therapeutic approach in atopic dermatitis, especially in the moderate‐to‐severe forms of the disease, seems less aggressive than in psoriasis and in chronic urticaria with a less frequent use of systemic agents. Objectives: To compare in real‐life conditions the therapeutic management of adults with atopic dermatitis with those with psoriasis and chronic urticaria. Methods: A transversal analysis was performed in May 2017, using retrospective data from a monocentric database. Data on epidemiology, severity, therapeutic educational intervention and systemic treatments were analysed from 401 patients with atopic dermatitis, compared with data from 230 patients with chronic urticaria and 535 patients with psoriasis. Results: A high proportion (73%) of atopic dermatitis patients presented with a moderate‐to‐severe form of the disease compared to only 39% of chronic urticaria and 17% of psoriasis patients. Most of atopic dermatitis patients (78%) had completed a therapeutic educational programme, while the adherence was lower in chronic urticaria (35%) and in psoriasis (3%) patients. A systemic treatment, including biologicals, was recorded in 8% of atopic dermatitis patients, while it concerned 26% and 47% of chronic urticaria and psoriasis patients, respectively. Conclusions: We confirmed that atopic dermatitis treatment mostly relies on topical treatments. Only a minority of moderate‐to‐severe atopic dermatitis patients who are eligible for a systemic treatment receive such therapy. This may suggest promoting a more frequent use of systemic agents in moderate‐to‐severe atopic dermatitis. Linked Commentary: P. Gisondi et al. J Eur Acad Dermatol Venereol 2020; 34: 2168–2169. https://doi.org/10.1111/jdv.16876 [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) patients receive many antibiotic treatments for recurrent respiratory infections and frequently report antibiotic hypersensitivity reactions (HSRs). In this retrospective study, medical records of CF patients were reviewed to clarify the clinical features, the culprit antibiotics, and the prevalence of antibiotic HSRs in the CF population. From 601 CF patients, 95 suspected antibiotic HSRs occurred in 60 patients (prevalence of 10.0%). β‐Lactams were the most common inducers, but cotrimoxazole was also frequently involved. Seventy‐six of 95 suspected HSRs were assessed by allergy workup including skin tests (43/76 reactions) and/or drug reintroduction as a full course of the culprit antibiotic (73 of 76 reactions). From the 43 suspected HSRs that were skin‐tested, only three had positive skin tests and were not subjected to drug readministration. All the other 73 suspected HSRs received a full course of the culprit antibiotic: HSR symptoms recurred in 10 of 73 cases and therefore were considered as confirmed antibiotic HSRs; for the remaining 63 suspected HSRs that did not relapse after drug readministration, the diagnosis of antibiotic HSRs was excluded. In summary, 13 of 76 suspected HSRs were confirmed as antibiotic HSRs. The prevalence of suspected and confirmed antibiotic HSRs in CF patients appears similar to that reported in the general population. Of note, most of the antibiotic suspected HSRs are not confirmed after allergology workup. A complete allergy workup appears therefore crucial to make a correct diagnosis and to avoid unnecessary contraindication of major antibiotics. [ABSTRACT FROM AUTHOR]

Trials assessing dupilumab in atopic dermatitis (AD) showed transient eosinophilia in less than 2% of patients.1 The frequency of hypereosinophilia (HE), defined as eosinophil blood count (EBC) >=1500/mm SP 3 sp ,2 was higher (15.8%) in our previous real-life cohort of AD patients treated with dupilumab.3 Since symptomatic HE was reported in asthma trials, we aimed to assess the clinical impact of HE in AD patients receiving dupilumab. Dupilumab-associated hypereosinophilia in patients treated for moderate-to-severe atopic dermatitis Fifty-nine patients with HE were included among a total of 653 patients receiving dupilumab from 12 hospital centres (Table 1), allowing us to estimate a mean prevalence of HE under dupilumab of 9% {95% CI [7.0-11.6]}. [Extracted from the article]