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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.

Abstract Background Methyl‐aminolevulinate‐based photodynamic therapy (MAL‐PDT) has been successfully used in early‐stage mycosis fungoides (MF) lesions. However, the long‐term outcome of initially responding lesions has not been systematically investigated to date. To address this issue, we hereby report a large series of early‐stage MF lesions treated with MAL‐PDT and followed up for 1 year after initial treatment. Objectives The objective of this study was to retrospectively evaluate short‐ and middle‐term clinical results of MAL‐PDT on early‐stage MF lesions (patches and plaques) and to identify characteristics possibly predictive of effectiveness. Methods Data from all early‐stage MF lesions (plaques and patches) treated with MAL‐PDT between 2010 and 2017 in a tertiary referral centre were retrospectively collected. Primary endpoints were initial clinical response rated as complete response (CR) or partial response (PR), and the rate of relapse of initially responding lesions was further evaluated 1 year after the last PDT session. Secondary endpoints addressed tolerance and the relevancy of predefined parameters possibly predictive of CR achievement. Results A total of 62 lesions from 30 patients with early‐stage MF (21 Ia, nine Ib) were treated and analysed. At the 6‐week evaluation, the overall clinical response rate (RR) was 87.25% (55% CR and 32.25% PR) with a mean of 2.7 PDT sessions per lesion. Twenty‐five percent of initially responding lesions relapsed locally within 1 year. Transient, although significant, pain occurred at least once in 30% of patients. In univariate analysis, the location of lesions on sun‐protected areas was the only parameter statistically related to CR, a result confirmed in multivariate analysis. Conclusions Overall, these data confirm the interest in the use of MAL‐PDT in early‐stage MF even for deep (folliculotropic) lesions with a higher efficiency on sun‐protected areas. Furthermore, this study demonstrates for the first time that the response is often sustained over time. Accordingly, MAL‐PDT should be considered in the management of early‐stage MF, especially in oligolesional forms or in residual lesions refractory to systemic treatment.

BackgroundSkin 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. ObjectiveThis study aimed to evaluate the evolution of dermoscopy knowledge among family doctors immediately and 1 and 3 months after e-learning training. MethodsWe 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. ResultsIn 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

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.

Abstract Background Eosinophilia is common in patients with atopic dermatitis (AD). Abrocitinib, an oral Janus kinase‐1 inhibitor and dupilumab, an anti–interleukin‐4 receptor‐α antibody, are approved for moderate‐to‐severe AD. Dupilumab has been associated with transient eosinophilia. Objectives To assess the effect of abrocitinib and dupilumab on eosinophils in patients from the phase 3 JADE COMPARE (NCT03720470) and JADE EXTEND (NCT03422822) trials. Methods In JADE COMPARE, patients received once‐daily oral abrocitinib (200/100 mg), placebo or subcutaneous dupilumab (300 mg, biweekly) with background topical therapy. In the ongoing long‐term JADE EXTEND study (Data cutoff: April 22, 2020), dupilumab‐treated patients from JADE COMPARE received once‐daily abrocitinib (200/100 mg) with background topical therapy. The proportion of patients with eosinophilia and hypereosinophilia, and association of eosinophilia with clinical efficacy was assessed. Adverse events (AEs) were also assessed. Results Of the 837 patients in JADE COMPARE, 58 (25.7%), 47 (19.7%) and 51 (21.1%) had eosinophilia at baseline in the abrocitinib 200 mg, abrocitinib 100 mg and dupilumab groups, respectively. At Week 16, eosinophilia decreased with abrocitinib 200 mg (9.3%) and abrocitinib 100 mg (19.0%) but not dupilumab (21.5%); no cases of hypereosinophilia were observed with abrocitinib 200 mg compared with abrocitinib 100 mg (1.9%) and dupilumab (2.3%). Decreases in median eosinophil counts were greater with abrocitinib 200 mg (difference, −100/mm3) and abrocitinib 100 mg (−70/mm3) than dupilumab (+25/mm3) or placebo (+30/mm3) at Week 16. Similar trends were observed in patients with comorbid asthma and allergic rhinitis. Eosinophilia decreased from baseline to Week 12 in dupilumab‐treated patients who switched to abrocitinib in JADE EXTEND. Decreased eosinophil counts with abrocitinib correlated positively with improvements in AD severity, itch and sleep loss. No eosinophilia‐associated AEs occurred. Conclusions Abrocitinib decreased eosinophilia in patients with moderate‐to‐severe AD who had baseline eosinophilia. Resolution of eosinophilia was associated with abrocitinib clinical efficacy.

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.

Background: Bradykinin angioedemas are a potentially serious side effect of angiotensin-converting enzyme inhibitors (ACEI) and more controversially of angiotensin II receptor blockers (ARB). Their challenging diagnosis is based on the absence of any recurrence after more than 6 months of drug discontinuation; otherwise mast-cell driven angioedemas as a differential diagnosis must be considered. Objective: The aim of this study was to determine the prevalence of recurrent angioedema in patients referred for ACEI/ARB-induced bradykinin angioedema, after more than 6 months of drug discontinuation. Methods: We included ACEI/ARB-treated patients referred for angioedema(s) without hives and unresponsive to antihistamines, after they discontinued ACEI/ARB for at least 6 months. Any C1-inhibitor deficiency was excluded. The primary endpoint was the prevalence of patients with recurrent angioedema after more than 6 months of drug discontinuation and/or developing hives during follow-up. The secondary endpoint was the identification of epidemiological factors associated with any final diagnosis. Results: Thirty-eight of 93 patients (41%) with a suspicion of ACEI/ARB-induced bradykinin angioedema still had recurrent angioedema (n = 27) or developed hives (n = 2) or both (n = 9) after 6 months of drug discontinuation. Good response to icatibant and facial but not oral localization were predictive for the final diagnosis of ACEI/ARB-induced bradykinin angioedema and mast-cell driven angioedema, respectively. Conclusion: In patients referred for acquired angioedema without wheals occurring during ACEI/ARB therapy, 59% finally had a diagnosis of ACEI/ARB-induced bradykinin angioedema whereas 41% were rather diagnosed with mast-cell driven angioedema. The overdiagnosis of ACEI/ARB-induced bradykinin angioedema may deteriorate the management of severe cardiovascular conditions.

Abstract Background Hereditary angioedema (HAE) is associated with a heavy burden of illness. Objective To evaluate use of lanadelumab in a French Authorization for Temporary Use (ATU) program. Methods ATU requests were made between October 12, 2018, and March 13, 2019; patients were followed through September 23, 2019. At entry, patients received lanadelumab 300 mg every 2 weeks. HAE attack characteristics were evaluated at day (D) 0 and months (M) 3 and 6. Patients completed the Angioedema Quality of Life (AE-QoL) questionnaire at initiation and monthly and the Angioedema Activity Score questionnaire daily in 28 day cycles (AAS28). Results In total, 77 patients received ≥ 1 lanadelumab dose; 69 had ≥ 1 quarterly follow-up visit (analyzed population). Mean (standard deviation [SD]) lanadelumab exposure was 240.4 (53.7) days. Lanadelumab dose was modified in 12 patients (mostly to every 4 weeks). For the analyzed population, compared with attacks/month (mean [SD]) within 6 months before ATU (2.68 [2.54]), fewer attacks occurred between initiation and first visit (0.16 [0.42]; P

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. [ABSTRACT FROM AUTHOR]

Acquired cold contact urticaria (ACU) is a putatively serious condition, because of the risk of anaphylactic shock whenever patients are massively exposed to cold atmosphere/water, raising the question of the prescription of an “emergency kit” with oral antihistamines and epinephrine auto-injector. We performed an online survey to evaluate how French-speaking urticaria experts manage ACU. According to the 2016 consensus recommendations on chronic inducible urticarias, all the participants perform at least 1 of the available provocation tests and 84.2%, 77.8%, and 88.9% prescribe on-label use of second generation anti-H1 antihistamines (2GAH1) as a first line treatment, updosed 2GAH1 as a second line treatment, and omalizumab as a third line treatment, respectively. Interestingly, 44.4% of the practitioners always prescribe a continuous background treatment, versus 11.1% prescribing only on-demand therapy. Also, 11.7% of participants always prescribe an epinephrine auto-injector, 70.6% sometimes do, and 17.6% never do. Finally, 89.5% authorize swimming under strict conditions but 36.8% and 68.4% contra-indicate other water sports and occupational cold exposure, respectively.

The Cooperative approach or Cooperative learning approach is defined as a model of group learning in which students are assigned to cooperate in teams for gaining a common purpose whereas they have to show their independence in completing sectional tasks. This learning style, to some extent, has been used in Reading classes at Thu Dau Mot University along with other methods for boosting students’ working motivation. From the mentioned premise, the paper investigated English-majored students’ favorable activities in Reading classrooms to clarify student’s learning motives as well as their willingness to work in group during the lessons. A survey questionnaire on selective activities was sent to the fourth–year English majors to measure the respondents’ attitudes. Accordingly, the paper focuses on the following aspects: (1) students’ attitudes towards reading skills, (2) their preferred classroom activities, and (3) their expected achievements from the course. Consequently, it is found out that there was a kind of intrinsic motivation among learners in the course, the students are interested in self-conducted activities, and that cooperative learning activities might foster students’ love for reading.

With the availability of English teaching and learning facilities in most schools as well as in English language centers in Vietnam nowadays, storytelling is believed to be one of the most suitable techniques to improve young learners’ communicative competences; therefore, it should be further investigated and promoted. With the aim of fully exploiting storytelling in Vietnamese English language teaching contexts, the research is designed to discuss and evaluate its effectiveness as a teaching technique to enhance young learners’ speaking and listening skills - a well-matched couple of oral competences. Conducted with mixed research methods through the use of questionnaires, interview and observation, the outcomes, conclusions, theories as well as evaluations and recommendations put forward in the study are of great validity and reliability. Based on the rationale of this teaching technique, some models and activities for teaching demonstration are designed and carried out in real language environments in order to evaluate its advantages as well as disadvantages. From what have been discovered, the study can serve as a reference for teachers who wish to enhance their students’ listening and speaking skills by means of storytelling.

Optimal doses of total skin electron beam therapy for mycosis fungoides remain to be established. Clinical efficiency and adverse effects of middle-dose (25 Gy) vs. low-dose (10–12 Gy) total skin electron beam therapy were retrospectively compared in a series of 14 and 12 mycosis fungoides, respectively. Overall skin response rate was 96.2% (92.9% middle-dose and 100% low-dose; not significant (NS)). Overall complete and partial skin response rates were 57.7% (42.9% middle-dose and 75% low-dose; NS) and 38.5% (50% middle-dose and 25% low-dose; NS), respectively. All responding patients relapsed after an overall median time of 5 months (7 months middle-dose vs. 4 months low-dose; p = 0.164, NS). Tolerance was equally fair in both groups, with only grade 1 and 2 adverse events observed in 100% vs. 66.7% of patients in middle-dose and low-dose groups (NS). Although no significant difference was observed, middle-dose protocol may be recommended owing to a longer relapse-free survival for a similar tolerance.

Low-dose methotrexate is widely used in mycosis fungoides and Sézary syndrome, but few studies have evaluated this treatment. The aim of this study was to evaluate the benefit/risk ratio of this regimen on skin lesions. A retrospective survey of a series of patients treated for mycosis fungoides or Sézary syndrome with low-dose methotrexate and followed for at least one year in a tertiary referral centre was performed. From a total of 48 patients, complete response and partial response were achieved in 10 (21%) and 25 (52%) patients, respectively, with no significant difference in response rates between mycosis fungoides and Sézary syndrome. Of the responders, 20 out of 35 (57%) relapsed after a median time of 11 months. Forty-four of the total of 48 patients discontinued methotrexate, mainly due to primary or secondary failure and/or limiting toxicity (9 patients). Overall, the benefit/risk ratio of low-dose methotrexate in mycosis fungoides and Sézary syndrome appears favorable and this treat­ment remains a valid option in mycosis fungoides/Sézary syndrome. However, its activity is limited in duration and significant toxicity may occur in some patients.

Few would deny that at the very first stage of learning, language learners have to spend most of their time on practising listening skills in communication inside and outside class. They have to listen to others speaking, listen to themselves while talking and even implicitly while reading and writing. Listening is an important way of acquiring the language as well as picking up the structures and vocabulary. With a careful observation of the current situation of Vietnamese learners’ listening competencies and a thorough review of reference materials in English language teaching and learning, it is hoped that the study will help heighten students’ awareness of the problematic sounds that they encounter when listening to colloquial, casual and connected speech.

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