Drug Rash with Eosinophilia and Systemic Symptoms Syndrome Caused by Itraconazole in a 17-Year-Old Girl.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced hypersensitivity reaction. We report a case of DRESS syndrome in a 17-year-old female caused by itraconazole, confirmed by patch testing, that required treatment with both corticotherapy and cyclosporine. Our case highlights the importance of clinical suspicion of this syndrome in pediatric age and the novelty of an antifungal drug being identified as the culprit.

Mastocytosis: the safety of different COVID-19 vaccines / Mastocitose: segurança de diferentes vacinas contra a COVID-19

The COVID-19 pandemic has forced the development of vaccines to fight SARS-CoV-2. After vaccination began, reports of adverse reactions, including anaphylaxis, emerged. This raised concerns about the safety of COVID-19 vaccines in patients diagnosed with mastocytosis. The authors share their experience in administering different COVID-19 vaccines to patients diagnosed with mastocytosis.

A pandemia por COVID-19 obrigou ao rápido desenvolvimento de vacinas para combate ao SARS-CoV-2. Após o início da vacinação começaram a surgir relatos de reações adversas às vacinas, incluindo reações anafiláticas, surgindo dúvidas sobre a segurança das vacinas em doentes com mastocitose. Os autores apresentam a sua experiência em relação à administração de diferentes vacinas contra a COVID-19 em doentes com diagnóstico de mastocitose.

Predictors of anaphylaxis to peanut and tree nuts in a Mediterranean population.

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.

Validity, reliability, and responsiveness of daily monitoring visual analog scales in MASK-air®.

BACKGROUND: MASK-air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs. METHODS: Daily monitoring VAS data were assessed in MASK-air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol-5 Dimensions (EQ-5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI-AS) Questionnaire (work and activity impairment scores). Intra-rater reliability was assessed in users providing multiple daily VASs within the same day. Test-retest reliability was tested in clinically stable users, as defined by the EQ-5D VAS, CARAT, or "VAS Work" (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ-5D-VAS or "VAS Work" indicating clinical change. RESULTS: A total of 17,780 MASK-air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate-high (Spearman correlation coefficient range: 0.437-0.716). Intra-rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test-retest reliability ICCs ranged between 0.604 and 0.878-"VAS Work" and "VAS asthma" presented the highest ICCs. Moderate/large responsiveness effect sizes were observed-the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness. CONCLUSION: In MASK-air®, daily monitoring VASs have high intra-rater reliability and moderate-high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.

Feasibility and Acceptability of an Asthma App to Monitor Medication Adherence: Mixed Methods Study.

BACKGROUND: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). METHODS: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. RESULTS: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). CONCLUSIONS: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

Monitoring Adherence to Asthma Inhalers Using the InspirerMundi App: Analysis of Real-World, Medium-Term Feasibility Studies.

Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support. Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use. Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app ≥30 days was used as the cut-off for higher app use. Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25-P75) 16-36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3-45] days, translated on a median use rate of 15 [3-38]%. Median inhaler adherence assessed through the app was 34 [4-73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6-83]% and 43 [3-73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen. Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.

[ARIA 2019: An Integrated Care Pathway for Allergic Rhinitis in Portugal]. / ARIA 2019: Um Percurso Assistencial Integrado para a Rinite Alérgica em Portugal.

The Allergic Rhinitis and Its Impact on Asthma (ARIA) initiative started more than 20 years ago and has developed and disseminated evidence-based guidelines and projects in the field of allergic rhinitis. This initiative is currently focused on providing patient-centred guidelines that contribute to an integrated care pathway between the various levels of care and take advantage of digital solutions, and the introduction of integrated care pathways in clinical practice has been recommended. In this article we describe the adaptation for Portugal of the ARIA Integrated Care Pathways document. After a brief review of the epidemiology and impact of allergic rhinitis in Portugal and the activities carried out in Portugal within the ARIA initiative, we describe the broad knowledge base used for the development of recommendations for the pharmacological treatment of allergic rhinitis, and these recommendations are based on the GRADE methodology, real world evidence acquired by mobile technology (mHealth) and resulting from allergenic exposure chamber studies. What follows is a summary of integrated care pathways for allergen immunotherapy produced in 2019. Allergen immunotherapy is considered an example of precision medicine where the use of mHealth technologies will improve stratification for patient selection and response monitoring. These recommendations were considered as best practices of integrated patient-centred care supported by digital systems from Directorate General for Health and Food Safety of the European Union (DG Santé) and represent the ARIA Phase 4 Change Management strategy.

A iniciativa Allergic Rhinitis and Its Impact on Asthma (ARIA) teve início há mais de 20 anos e tem elaborado e disseminado orientações baseadas em evidência, e desenvolvido projetos na área da rinite alérgica. Esta iniciativa está atualmente focada em proporcionar orientações centradas no doente que contribuam para um percurso integrado entre os vários níveis de cuidados e que tirem partido de soluções digitais, tendo sido recomendada a introdução na prática clínica de percursos assistenciais integrados. Neste artigo descrevemos a adaptação para Portugal do documento ARIA Integrated Care Pathways. Após breve revisão sobre a epidemiologia e o impacto da rinite alérgica em Portugal e das atividades realizadas em Portugal no âmbito da iniciativa ARIA, é descrito o conjunto alargado de conhecimento utilizado para o desenvolvimento das recomendações para o tratamento farmacológico da rinite alérgica, recomendações essas baseadas na metodologia GRADE, evidência do mundo real adquirida por tecnologia móvel (mHealth) e resultante de estudos de câmara de exposição alergénica. Em seguida, são resumidos os percursos assistenciais integrados para imunoterapia com alergénios produzidas em 2019. Considera-se a imunoterapia com alergénios um exemplo de medicina de precisão e em que a utilização de tecnologias mHealth permitirá melhorar a estratificação para seleção dos doentes e monitorização da resposta. Estas recomendações foram consideradas como 'boas práticas' dos cuidados integrados centrados no doente apoiados por sistemas digitais da DG Santé (Direção Geral de Saúde e de Segurança Alimentar da União Europeia) e representam a estratégia de gestão da mudança da fase 4 do ARIA.

Refractory chronic urticaria in adults: clinical characterization and predictors of severity.

BACKGROUND: Chronic urticaria (CU) is defined as recurrent urticaria lasting for more than 6 weeks. OBJECTIVES: We aimed to characterize the phenotypes of patients with CU refractory to standard dose anti-H1 antihistamine treatment and search for clinical predictors of poor disease control. METHODS: Retrospective collection of data regarding clinical characteristics, comorbidities, treatment, and disease control of all adult refractory CU patients presenting to the Allergy and Immunology Department during 1 year. RESULTS: Sixty-one adult patients were included, 74% females, average age 44.5 years (18 to 84 years old). Most patients (78.7%) had initiated CU less than 1 year before enrolment. Chronic spontaneous urticaria (CSU) accounted for 55.7% of the patients, CSU associated with chronic inducible urticaria (CIndU) as a comorbidity for 44.3%, and angioedema was present in 55.7%. Medically-confirmed psychiatric disorders were present in 78.7%. Complementary diagnostic tests were performed in cases with more severe presentation (UAS7 ≥ 28 and/or UCT < 12) or with longer evolution (> 1 year), corresponding to 42 tested patient. Evidence for autoimmunity (positive anti-thyroid peroxidase antibodies, anti-nuclear antibodies or autologous serum test) was found in 45.2% (n = 19/42), and high C-reactive protein was present in 14.3% (n = 6/42), half of these also had positive antinuclear antibodies. Forty-six patients (75.4%) had at least one significant exacerbation, requiring medical appointment, emergency room, hospitalization or job absenteeism. The number of exacerbations correlated with the presence of angioedema (p = 0.022), with a recent diagnosis (< 1 year), and with higher UAS7 severity (p = 0.006). Although ClndU was associated with poor symptom control (p = 0.022), it was also associated with less exacerbations requiring medical observation or hospitalization (p = 0.015). All patients were using antihistamines and 21.3% (n = 13) of them were also under treatment with omalizumab, ciclosporine or montelukast for disease control. CONCLUSIONS: Autoimmunity can affect about half of the patients with severe or long-term CU. UAS7 and angioedema are associated with disease exacerbations. UAS7 and UCT presented unequal accuracy, with UAS7 better associating with the occurrence of exacerbations and treatment doses. Patients with refractory CU frequently present psychiatric disorders. Accurate diagnostic tests, namely autoimmune parameters and inflammatory markers, should be recommended in some individual cases.

Asthma management with breath-triggered inhalers: innovation through design.

BACKGROUND: Asthma affects the lives of hundred million people around the World. Despite notable progresses in disease management, asthma control remains largely insufficient worldwide, influencing patients' wellbeing and quality of life. Poor patient handling of inhaling devices has been identified as a major persistent problem that significantly reduces inhaled drugs' efficacy and is associated with poor adherence to treatment, impairing clinical results such as asthma control and increasing disease-related costs. We herein review key research and development (R&D) innovation in inhaler devices, highlighting major real-world critical errors in the handling and inhalation technique with current devices and considering potential solutions. Furthermore, we discuss current evidence regarding breath-triggered inhalers (BTI). MAIN BODY: The two most common significant problems with inhalers are coordinating actuation and inhalation with pressurized metered-dose inhalers (pMDIs), and the need to inhale forcibly with a dry powder inhaler. BTI R&D plans were designed to overcome these problems. Its newest device k-haler® has several other important features, generating a less forceful aerosol plume than previous pMDIs, with efficient drug delivery and lung deposition, even in patients with low inspiratory flow. The local and systemic bioavailability of fluticasone propionate and formoterol (FP/FORM) administered via k-haler® has been shown to be therapeutically equivalent when administered via the previous FP/FORM pMDI. This device requires very few steps and has been considered easy to use (even at first attempt) and preferred by the patients in a randomized crossover study. In our country, FP/FORM k-haler is available without additional costs compared to FP/FORM pMDI. All devices continue to require education and regular checking of the correct inhalation technique. CONCLUSION: BTI R&D can bring advantage over current available inhalers, avoiding the two most common identified critical errors in inhalation technique. K-haler® BTI is currently available, without an increased cost, and approved for adolescents and adults with asthma in whom treatment with inhaled combined therapy with long-acting beta2-agonists and corticosteroids is indicated. Its attractive and practical design to facilitate its use has been awarded. K-haler® represents added value through innovation to fulfill actual asthma patient needs, thus with potential relevant impact in asthma management and effective control.