Consensus on the Clinical Approach to Moderate-to-Severe Atopic Dermatitis in Spain: A Delphi Survey

Background. The purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice. Methods. A cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of >= 80% of participants coincided in the categories of a 5-point Likert scale for that item. Results. A total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients. Conclusion. This study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain

Efficacy of Dupilumab in Atopic Dermatitis : The Patient's Perspective

Atopic dermatitis (AD), a predominantly type 2 inflammatory skin disease, affects approximately 2-5% of adults, with a high burden of disease. In moderate-to-severe AD, lesions can be extensive and pruritus intense with patients experiencing skin pain, sleep and mental health disturbances, and diminished quality of life (QoL). The objective of this study was to evaluate the efficacy of dupilumab for the treatment of AD from the patients' perspective using patient-reported outcome data from four clinical trials (CHRONOS, SOLO 1&2, and CAFÉ) in patients (N = 1553) receiving either the approved 300 mg q2w dupilumab with/without topical corticosteroids (TCS) dose or control (placebo or placebo + TCS). Patient Global Assessment of Disease Status (PGADS) was used to measure patients' well-being and Patient Global Assessment of Treatment Effect (PGATE) was used to measure treatment efficacy. Patients were asked "Considering all the ways in which your eczema affects you, indicate how well you are doing" to assess their perception of well-being and "How would you rate the way your eczema responded to the study medication?" to assess their perception of treatment effect. Possible responses for both metrics included poor, fair, good, very good, and excellent. In all four studies, a significantly higher proportion of dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" disease status from week 2 through study end versus control (CHRONOS, 52 weeks: 69.8% vs. 25.1%; SOLO 1&2, 16 weeks: 59.5% vs. 24.6%; CAFÉ, 16 weeks: 84.1% vs. 45.4%; all P < 0.0001), and significantly more dupilumab-treated patients reported "Good"/"Very Good"/"Excellent" treatment efficacy versus control (CHRONOS: 72.6% vs. 24.8%; SOLO 1&2: 65.0% vs. 21.1%; CAFÉ, 16 weeks: 85.0% vs. 36.1%; all P < 0.0001). Adult patients with AD perceived that dupilumab with/without concomitant TCS was highly efficacious and improved overall disease status and well-being as early as week 2 and throughout treatment periods up to 1 year. The online version of this article (10.1007/s13555-021-00621-w) contains supplementary material, which is available to authorized users

SEB-induced IL-13 production in CLA+ memory T cells defines Th2 high and Th2 low responders in atopic dermatitis

Staphylococcus aureus, memory skin-homing cutaneous lymphocyte-associated antigen (CLA)+ T cells and IL-13 constitute relevant players in atopic dermatitis (AD) pathogenesis.1 Since circulating CLA+ T cells reflect cutaneous abnormalities present in human inflammatory skin diseases,2 an ex vivo coculture model made of purified circulating CLA+/− effector and central memory T cells and autologous lesional epidermal cells was established. We show a CLA-dependent production of IL-13 upon activation with staphylococcal enterotoxin B (SEB) that allows the differentiation of the Th2 high and Th2 low groups, with distinct clinical correlations between both groups, within a clinically homogeneous population of adult non-treated moderate-to-severe AD patients

Sensitization to isothiazolinones in the Spanish Contact Dermatitis Registry (REIDAC): 2019–2021 epidemiological situation

Background: Current frequency and risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in Spain are not well known. Objectives: To study the frequency of sensitization, risk factors and simultaneous sensitization between the four isothiazolinones. Materials and Methods: We analysed all 2019-2021 consecutive patients patch-tested with MI (0.2% aq.), MCI/MI (0.02% aq.), BIT (0.1% pet.) and OIT (0.1% pet) within the Spanish Contact Dermatitis Registry (REIDAC). Results: A total of 2511 patients were analysed. Frequencies of sensitization were: any isothiazolinone 15.7%, MI 6.8%, MCI/MI 4.8%, BIT 3.5% and OIT 0.5%. MI and MCI/MI sensitization was associated with being occupationally active, hand dermatitis, detergents and age over 40. BIT sensitization was associated with leg dermatitis and age over 40. About one in nine MI-positive patients were positive to BIT, whereas one in five BIT-positive patients were positive to MI. Conclusions: Sensitization to MI, MCI/MI and BIT is still common in Spain, while sensitization to OIT is rare. Currently, sensitization to MI and MCI/MI seems to be occupationally related. Although its origin is unknown, sensitization to BIT is more frequent in patients aged over 40 years. Simultaneous sensitization between MI and BIT is uncommon.The Spanish Registry of Contact Dermatitis (REIDAC) is promoted by the Fundación Piel Sana (Academia Española de Dermatología y Venereología), which has received financial support from the Spanish Medicines and Health Products Agency (Agencia Española de Medicamentos y Productos Sanitarios. https://www.boe.es/boe/dias/2022/04/11/pdfs/BOE-A-2022-5975.pdf) and Sanofi. The funders were not involved in the design and conduct of the study, collection, management, analysis and interpretation of data, preparation, review, approval of the manuscript, or decision to submit the manuscript for publication

Pathogenic mechanisms underlying itch in atopic dermatitis: the emerging role of neuroimmune interactions

Itch is a frequent dermatological sensation that can occur in a variety of skin conditions, including atopic dermatitis, inflammatory disorders characterised by eczematous lesions and chronic itch. The pathogenic mechanisms that lead to itch in atopic dermatitis are not fully understood. The current knowledge of its aetiology highlights the complex interplay among multiple pathogenic factors such as epidermal barrier dysfunction, immune dysregulation, and its interaction with the nervous system. Furthermore, a relationship between itch intensity and certain factors such as stress, sleep disturbance, and pollutant exposure has often been shown in patients with itch. This article reviews the current advances in the processes behind itch signalling from the skin to the nervous system, focusing on atopic dermatitis pathophysiology. Studies investigating the underlying pathogenic mechanisms of atopic dermatitis have shown that itch management at the nervous system level may be sufficient to reduce itch sensation and improve skin lesions.The study was funded through LaCaixa Banking Foundation Junior Leader Programme (LCF/BQ/PI18/11630005) to AE.Peer reviewe

Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis

Abrocitinib is a JAK1 selective inhibitor recently approved for the treatment of moderate-to-severe atopic dermatitis in adults. It has demonstrated efficacy and safety in several clinical trials, both in children and adults, in monotherapy, and compared with dupilumab. The expected EASI-75 response rate estimates at week 12 are 62.9% (95% CrI 42.5–79.9%) for abrocitinib 200 mg and 43.0% (95% CrI 24.8–64.0%) for abrocitinib 100 mg. Abrocitinib has shown a faster effect than dupilumab as regards early alleviation of itch. Because of the incomplete target selectivity of JAK inhibitors, when abrocitinib treatment is considered, laboratory screening is necessary, latent tuberculosis must be screened for, active infections are a contraindication, and special caution must be exerted in treating elderly patients and those predisposed to thromboembolic events. Even though recent meta-analyses of clinical trials have not shown that atopic dermatitis, or its treatment with JAK inhibitors or dupilumab, modify the risk of deep venous thrombosis or pulmonary embolism, long-term follow-up studies will better define the safety profile of abrocitinib

Efficacy and Safety of JAK1 Inhibitor Abrocitinib in Atopic Dermatitis

Abrocitinib is a JAK1 selective inhibitor recently approved for the treatment of moderate-to-severe atopic dermatitis in adults. It has demonstrated efficacy and safety in several clinical trials, both in children and adults, in monotherapy, and compared with dupilumab. The expected EASI-75 response rate estimates at week 12 are 62.9% (95% CrI 42.5-79.9%) for abrocitinib 200 mg and 43.0% (95% CrI 24.8-64.0%) for abrocitinib 100 mg. Abrocitinib has shown a faster effect than dupilumab as regards early alleviation of itch. Because of the incomplete target selectivity of JAK inhibitors, when abrocitinib treatment is considered, laboratory screening is necessary, latent tuberculosis must be screened for, active infections are a contraindication, and special caution must be exerted in treating elderly patients and those predisposed to thromboembolic events. Even though recent meta-analyses of clinical trials have not shown that atopic dermatitis, or its treatment with JAK inhibitors or dupilumab, modify the risk of deep venous thrombosis or pulmonary embolism, long-term follow-up studies will better define the safety profile of abrocitinib

Documento de información y consenso para el manejo diagnóstico y terapéutico del prurito asociado a la enfermedad renal crónica en pacientes en hemodiálisis en España

Resumen: El prurito asociado a la enfermedad renal crónica (Pa-ERC) es una de las comorbilidades más comunes e incapacitantes en los pacientes con ERC avanzada. Además, está asociado a un mayor riesgo de mortalidad, peor calidad de vida, aparición de trastornos del sueño, alteraciones de la salud mental y mayor uso de recursos sanitarios. La presentación clínica del Pa-ERC es muy heterogénea, lo que dificulta su diagnóstico y su tratamiento. Actualmente, no existen guías a nivel nacional sobre el manejo del Pa-ERC.El objetivo de este documento es proporcionar unas recomendaciones de consenso a nivel nacional para el manejo diagnóstico y terapéutico del Pa-ERC.La elaboración del documento se realizó en tres fases: la realización de una propuesta de algoritmo de manejo diagnóstico y terapéutico por parte de un grupo reducido de especialistas en nefrología; la validación de la propuesta por un grupo más amplio de nefrólogos y, finalmente, una segunda validación por un grupo multidisciplinar en el que se incluyeron, además, especialistas en dermatología.El algoritmo de manejo diagnóstico y terapéutico trata de cubrir la actual necesidad por una falta de directrices específicas para el control adecuado del Pa-ERC en España. A la vez, introduce el uso de difelicefalina, el primer y único fármaco aprobado específicamente para el Pa-ERC de pacientes en hemodiálisis, con un buen perfil de seguridad y eficacia. Abstract: Chronic kidney disease-associated pruritus (CKD-aP) is one of the most common and disabling comorbidities in patients with advanced CKD. In addition, it is associated with an increased risk of mortality, poorer quality of life, sleep disorders, mental health disorders, and increased use of health care resources. The clinical presentation of CKD-aP is very heterogeneous, making it difficult to diagnose and treat. Currently, there are no national guidelines on the management of CKD-aP.The aim of this document is to provide national consensus recommendations for the diagnostic and therapeutic management of CKD-aP.The document was prepared in three phases: a diagnostic and therapeutic management algorithm was proposed by a small group of nephrology specialists; the proposal was validated by a larger group of nephrologists; and a second validation by a multidisciplinary group that also included dermatology specialists.The diagnostic and therapeutic management algorithm attempts to cover the current need of a lack of specific guidelines for the adequate management of CKD-aP. At the same time, it introduces the use of difelikefalin, the first and only drug specifically approved for CKD-aP, with a good safety and efficacy profile