Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus.

BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

Characterization of omalizumab updosing patterns and predictive factors in chronic spontaneous urticaria: A prospective multicentric observational study.

BACKGROUND: Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. METHODS: We conducted a prospective, multicentric, real-life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients' profile, and an assessment of OMA efficacy and safety. RESULTS: We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing. CONCLUSION: One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels.

Impact of Chronic Spontaneous or Inducible Urticaria on Occupational Activity.

The impact of chronic urticaria on work has been scarcely reported, whereas its peak incidence is between the ages of 20 and 40. The aim of this study was to assess the occupational impact of chronic urticaria and its treatment, by combining objective and patient-reported data. A monocentric observational study was performed using questionnaires over a 1-year period from 2021 to 2022 in chronic urticaria patients who were in a period of professional activity and agreed to participate. Of the 88 patients included, 55.7% assessed the occupational impact of their chronic urticaria as significant, and even more severe when chronic urticaria was poorly controlled. Some 86% of patients had symptoms at work, in a third of cases aggravated by work. However, occupational physical factors were not associated with an aggravation of inducible chronic urticaria. A total of 20% reported treatment-related adverse effects affecting their work. Despite low absenteeism, presenteeism and reduced productivity were important (> 20%). Six patients (6.8%) had difficulties keeping their work. For 72.7% of the patients, the occupational physician was not informed. The occupational impact of chronic urticaria should be discussed during consultations, particularly when it is insufficiently controlled. The occupational physician should be informed in order to support patients' professional project.

A quantitative assay for the assessment of cutaneous human papillomaviruses and polyomaviruses over time: A proof-of-concept in two patients with atopic dermatitis and psoriasis.

The human skin virome, unlike commensal bacteria, is an under investigated component of the human skin microbiome. We developed a sensitive, quantitative assay to detect cutaneous human resident papillomaviruses (HPV) and polyomaviruses (HPyV) and we first used it to describe these viral populations at the skin surface of two patients with atopic dermatitis (AD) and psoriasis (PSO). We performed skin swabs on lesional and non-lesional skin in one AD and one PSO patient at M0, M1 and M3. After extraction, DNA was amplified using an original multiplex PCR technique before high throughput sequencing (HTS) of the amplicons (named AmpliSeq-HTS). Quantitative results were ultimately compared with monoplex quantitative PCRs (qPCRs) for previously detected viruses and were significantly correlated (R2 = 0.95, ρ = 0.75). Fifteen and 13 HPV types (mainly gamma and beta-HPVs) or HPyV species (mainly Merkel Cell Polyomavirus (MCPyV)) were detected on the skin of the AD and PSO patients, respectively. In both patients, the composition of the viral flora was variable across body sites but remained stable over time in non-lesional skin samples, mostly colonized with gamma-papillomaviruses. In lesional skin samples, beta-papillomaviruses and MCPyV were the major components of a viral flora more prone to vary over time especially with treatment and subsequent clinical improvement. We believe this method might be further used in extensive studies to further enhance the concept of an individual cutaneous viral fingerprint and the putative role of its alterations through various skin diseases and their treatments.

Training Family Medicine Residents in Dermoscopy Using an e-Learning Course: Pilot Interventional Study.

BACKGROUND: Skin cancers are the most common group of cancers diagnosed worldwide. Aging and sun exposure increase their risk. The decline in the number of dermatologists is pushing the issue of dermatological screening back onto family doctors. Dermoscopy is an easy-to-use tool that increases the sensitivity of melanoma diagnosis by 60% to 90%, but its use is limited due to lack of training. The characteristics of "ideal" dermoscopy training have yet to be established. We created a Moodle (Moodle HQ)-based e-learning course to train family medicine residents in dermoscopy. OBJECTIVE: This study aimed to evaluate the evolution of dermoscopy knowledge among family doctors immediately and 1 and 3 months after e-learning training. METHODS: We conducted a prospective interventional study between April and November 2020 to evaluate an educational program intended for family medicine residents at the University of Montpellier-Nîmes, France. They were asked to complete an e-learning course consisting of 2 modules, with an assessment quiz repeated at 1 (M1) and 3 months (M3). The course was based on a 2-step algorithm, a method of dermoscopic analysis of pigmented skin lesions that is internationally accepted. The objectives of modules 1 and 2 were to differentiate melanocytic lesions from nonmelanocytic lesions and to precisely identify skin lesions by looking for dermoscopic morphological criteria specific to each lesion. Each module consisted of 15 questions with immediate feedback after each question. RESULTS: In total, 134 residents were included, and 66.4% (n=89) and 47% (n=63) of trainees fully participated in the evaluation of module 1 and module 2, respectively. This study showed a significant score improvement 3 months after the training course in 92.1% (n=82) of participants for module 1 and 87.3% (n=55) of participants for module 2 (P<.001). The majority of the participants expressed satisfaction (n=48, 90.6%) with the training course, and 96.3% (n=51) planned to use a dermatoscope in their future practice. Regarding final scores, the only variable that was statistically significant was the resident's initial scores (P=.003) for module 1. No measured variable was found to be associated with retention (midtraining or final evaluation) for module 2. Residents who had completed at least 1 dermatology rotation during medical school had significantly higher initial scores in module 1 at M0 (P=.03). Residents who reported having completed at least 1 dermatology rotation during their family medicine training had a statistically significant higher score at M1 for module 1 and M3 for module 2 (P=.01 and P=.001). CONCLUSIONS: The integration of an e-learning training course in dermoscopy into the curriculum of FM residents results in a significant improvement in their diagnosis skills and meets their expectations. Developing a program combining an e-learning course and face-to-face training for residents is likely to result in more frequent and effective dermoscopy use by family doctors.

Efficiency and tolerance of second-line triple BRAF inhibitor/MEK inhibitor/anti-PD1 combined therapy in BRAF mutated melanoma patients with central nervous system metastases occurring during first-line combined targeted therapy: a real-life survey.

Although current systemic therapies significantly improved the outcome of advanced melanoma, the prognosis of patient with central nervous system (CNS) metastases remains poor especially when clinically symptomatic. We aimed to investigate the efficiency of CNS targets and tolerance of second-line combined anti-PD1/dual-targeted anti-BRAF/anti-MEK therapy implemented in patients with CNS progression after initially efficient first-line combined targeted therapy in patients with BRAF-mutated melanoma in a real-life setting. A monocentric retrospective analysis including all such patients treated from January 2017 to January 2022 was conducted in our tertiary referral center. The response of CNS lesions to second-line triple therapy was assessed through monthly clinical and at least quarterly morphological (according to RECIST criteria) evaluation. Tolerance data were also collected. Seventeen patients were included with a mean follow-up of 2.59 (±2.43) months. Only 1 patient displayed a significant clinical and morphological response. No statistically significant difference was observed between patients receiving or not additional local therapy (mainly radiotherapy) as to response achievement. Immunotherapy was permanently discontinued in 1 patient owing to grade 4 toxicity. Mean PFS and OS after CNS progression were 2.59 and 4.12 months, respectively. In this real-life survey, the subsequent addition of anti-PD1 to combined targeted therapy in melanoma patients with upfront CNS metastases did not result in significant response of CNS targets in most BRAF mutated melanoma patients with secondary CNS progression after initially successful first-line combined targeted therapy.

Real-life management of atopic dermatitis patients with an inadequate response to on-label use of dupilumab.

In patients with moderate to severe atopic dermatitis (AD) showing an inadequate response to dupilumab 300mg/2weeks, few real-life studies reported the response to alternative regimen maintaining dupilumab. To assess and analyze the response to an increased dose of dupilumab or its combination with cyclosporin A (CsA), methotrexate (MTX), or itraconazole (ITRA), all adult AD patients from 7 French University Hospitals were retrospectively included if they achieved an inadequate response to dupilumab 300mg/2weeks and were subsequently treated with an increased dose of dupilumab (300mg every 7 or 10 days), or a combination of dupilumab 300mg/2weeks with CsA, MTX or ITRA. The response after 3 months, along with epidemiological, clinical, and therapeutic baseline characteristics, were collected. Overall, 68.75% of the 48 included patients achieved an improved response, including 45.8% of complete response (CR). No strategy proved significantly better. Patients showing an initial no response never achieved a further CR versus 52.4% of patients with an initial partial response (p = 0.025). Digestive intolerance and tachycardia led to MTX and ITRA discontinuation in 3 patients. Increasing the dose of dupilumab or combining it with CsA, MTX, or ITRA could be alternative and safe options, to be evaluated in further medico-economic studies.

Non-Skin Related Symptoms Are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results From the Chronic Urticaria Registry.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection). OBJECTIVE: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. METHODS: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older. RESULTS: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001). CONCLUSIONS: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.