Molecular profiling in bee venom allergy: clinical and therapeutic characterization in a Portuguese cohort.

Summary: Background. Bee venom allergy (BVA) can trigger local and systemic allergic reactions, including anaphylaxis. Recently, the molecular sensitization profile has gained importance in the reaction's stratification and venom immunotherapy (VIT). Methods. Retrospective analysis of patients with hypersensitivity to BVA, confirmed by specific sIgE to Apis mellifera ≥0.35 kU/L and/or positive skin tests to bee venom commercial extract, evaluated in specialized consultation. Demographic, clinical, and laboratory data (including molecular Api m 1, 4, and 10) were analyzed, looking for risk factors associated with the severity of the index reaction and reactions during VIT. Results. 93 patients were included (55.9% male; median age of 46 years), 57.3% with atopic comorbidities, and 23.4% with cardiovascular comorbidities. The median specific IgE to Apis mellifera was 6.7 kU/L (IQR 1.0-20.3) kU/L. Regarding the molecular profile, the median IgE to Api m 1 was 0.5 kU/L (57.5% positive out of all measurements); Api m 4 - 0.01 kU/L (11.9% positive), and Api m 10 - 0.3 kU/L (50.0% positive). No patient was monosensitized to Api m 4. The median age of the most severe sting reaction was 36 (IQR 26-48) years, with a median severity (Müeller scale) of 3 (IQR 2-3). Forty-seven patients (50.5%) underwent VIT, with 35.6% of reactions recorded. Allergic reactions during VIT were recorded in 35.6% of cases. The severity of the index reaction correlated positively with older ages (p=0.040; r=0.249), in contrast to monosensitization to Api m 1, which was an independent predictor of milder reactions (p=0.015). Sensitization to Api m 10 was associated with a higher likelihood of reactions during VIT (p=0.038) but potentially less systemic reactions at re-stings (p=0.097). Conclusions. Molecular sensitization profile appears to be relevant not only to the severity of index reactions but also during VIT. Studies of a large cohort of patients with molecular profiles are essential to validate these results and improve the clinical and therapeutic approach to BVA.

Expression of IL-17RA in Innate Cells of Patients with Common Variable Immunodeficiency (CVID) and its Clinical Implications.

Summary: Background. Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by B-cell dysfunction and immunoglobulin production deficiency. Dysregulation of interleukin-17 (IL-17) and its receptor IL-17RA have been reported in various immune disorders. This study aimed to investigate the expression of IL-17RA in innate immune cells of CVID patients and its correlation with clinical manifestations. Methods. A cross-sectional study included 22 CVID patients and 14 age- and sex-matched healthy controls. IL-17RA expression was assessed in various immune cell subsets using flow cytometry. Demographic and clinical data were collected, and statistical analysis was performed. Results. CVID patients had elevated IL-17RA expression in neutrophils, non-classical monocytes, and dendritic cells compared to healthy controls. Patients with a history of intestinal microbial colonization, particularly with Campylobacter jejuni and Giardia intestinalis, showed significantly higher IL-17RA expression in innate cells. Elevated IL-17RA expression in monocytes and dendritic cells also correlated with higher fecal calprotectin levels in CVID patients, regardless of microbial colonization. Conclusions. The study suggests that despite previous reports of reduced circulating Th17 cells and IL-17 levels in CVID patients, IL-17RA expression in innate cells may be elevated, potentially indicating altered IL-17 signaling. This heightened IL-17RA expression could contribute to a persistent pro-inflammatory state, possibly due to microbial translocation or other inflammatory factors. The association of IL-17RA expression with gastrointestinal microbial colonization and its correlation with fecal calprotectin underscores the complexity of IL-17RA's role in CVID pathophysiology. Further research in larger cohorts could elucidate the implications of IL-17RA expression in both infectious and non-infectious inflammatory aspects of CVID.

COVID-19 infection and vaccination in patients with hereditary angioedema: a multicentric study.

Summary: Background. Due to similarities between the pathophysiological mechanisms of hereditary angioedema (HAE) and COVID-19, it has been hypothesized that SARS-CoV-2 infection may trigger HAE attacks or, alternatively, that HAE patients may experience different of COVID-19 disease severity. Furthermore, the potential for COVID-19 vaccination to trigger angioedema attacks in patients with HAE is still not completely defined. The objective is to characterize the exacerbations and clinical manifestations associated with COVID-19 infection and describe the adverse effects of COVID-19 vaccination in patients with HAE.Methods. Retrospective observational, descriptive, non-interventional, multicenter study conducted in four Allergy Units and Departments in Central Portugal between March 2020 and July 2022. HAE patient data were obtained from electronic medical records. Results. The study included 34 patients (67.6% female): 26 with HAE type 1, 5 with HAE type 2, and 3 with HAE with normal C1 inhibitor. Most patients with HAE type 1 and 2 were receiving long-term prophylaxis. Among the 32 patients who received COVID-19 vaccination, 86 doses, were administered with one angioedema attack (1.2%) associated with vaccination. A small increase in the average number of attacks was observed in the year following COVID vaccination (7.1 versus 6.2 in the previous year, p = 0.029), however, this difference is unlikely to be clinically significant, as the context of the COVID-19 pandemic likely introduced numerous confounders. During the study period, 16 HAE patients had COVID-19, all presenting with mild disease. Four out of 16 patients (25%) reported angioedema attacks during COVID-19, and 43.8% during the convalescence period (3 months after infection). Conclusions. Patients with HAE can safely receive COVID-19 vaccination. The severity of COVID-19 infection does not appear to be increased in HAE patients.

Contact dermatitis from black henna tattoo in child due to paraphenylenediamine

Temporary henna tattoos have become increasingly popular, particularly among children and teenagers. The word “henna” is of Persian origin, and it is prepared from the plant Lawsonia inermis belonging to the family Lythraceae. Concerning allergic reactions, natural henna paste is rarely responsible for contact dermatitis, which is more frequent if paraphenylenediamine (PPD) is added to the paste. The authors present a case of female child with erythematous exanthems that appeared after the application of black henna tattoo. A diagnosis of contact dermatitis to black henna tattoo was hypothesised. Epicutaneous tests were performed at the Immunoalergology Department of the Coimbra University Hospital using standard European battery and natural henna paste. The tests revealed positive reaction to PPD (AU)

Sensitization to genuine markers of timothy grass pollen (Phleum pratense) in the North-Central region of Portugal.

Summary: Pollens are the main cause of respiratory allergies which prevalence is increasing. The most important cause of pollinosis in Europe and especially in the Mediterranean countries as Portugal is Poaceae family pollen. Timothy grass (Phleum pratense) is one of the most common pollen sources, and one of the best characterized allergenic grasses. The major allergens Phl p1 and Phl p5 are considered markers of genuine grass pollen sensitization. A characterization of Phl p1 and Phl p5 sensitization in the North-Central region of Portugal was made in children and adults. Phl p1 sensitization was the most frequent.

Key elements in hypersensitivity reactions to chemotherapy: experience with rapid drug desensitization in gynaecological cancer in a Tertiary Hospital.

Summary: Rapid drug desensitization (RDD) is a procedure performed when no alternative drug is considered equally effective. The aim of our study is to describe the experience with RDD to cytostatics in patients being treated for gynaecological cancer in a tertiary hospital, over a period of 5 years. In this paper, we review 22 cases and 107 episodes of RDD; 86.3% of patients had advanced disease and the mortality rate at the time of data collection was 50.0%. RDD was performed on 81.8% patients for platinum, 13.6% for taxanes, and 4.5% for anthracyclines. The reintroduction of antineoplastic drugs in all patients with a previous history of immediate hypersensitivity reaction demonstrated the safety and efficacy of this procedure. There was serious complication (anaphylaxis) in only one case.

Treatment of allergic rhinitis during and outside the pollen season using mobile technology. A MASK study.

BACKGROUND: The analysis of mobile health (mHealth) data has generated innovative insights into improving allergic rhinitis control, but additive information is needed. A cross-sectional real-world observational study was undertaken in 17 European countries during and outside the estimated pollen season. The aim was to collect novel information including the phenotypic characteristics of the users. METHODS: The Allergy Diary-MASK-air-mobile phone app, freely available via Google Play and App, was used to collect the data of daily visual analogue scales (VASs) for overall allergic symptoms and medication use. Fluticasone Furoate (FF), Mometasone Furoate (MF), Azelastine Fluticasone Proprionate combination (MPAzeFlu) and eight oral H1-antihistamines were studied. Phenotypic characteristics were recorded at entry. The ARIA severity score was derived from entry data. This was an a priori planned analysis. RESULTS: 9037 users filled in 70,286 days of VAS in 2016, 2017 and 2018. The ARIA severity score was lower outside than during the pollen season. Severity was similar for all treatment groups during the pollen season, and lower in the MPAzeFlu group outside the pollen season. Days with MPAzeFlu had lower VAS levels and a higher frequency of monotherapy than the other treatments during the season. Outside the season, days with MPAzeFlu also had a higher frequency of monotherapy. The number of reported days was significantly higher with MPAzeFlu during and outside the season than with MF, FF or oral H1-antihistamines. CONCLUSIONS: This study shows that the overall efficacy of treatments is similar during and outside the pollen season and indicates that medications are similarly effective during the year.

Anaphylaxis in an emergency department: a retrospective 10-year study in a tertiary hospital.

Summary: Background. Anaphylaxis is a potentially fatal medical emergency. The frequency of hospital admissions for anaphylaxis seems to be increasing in the recent decades. Objective. Characterize the patients admitted for anaphylaxis to the adult emergency department (ED) of a tertiary care hospital over a 10-year period, discriminating aetiologies, clinical features and therapy administered. Methods. Retrospective, descriptive and inferential study, evaluating age, sex, Manchester triage system, suspected allergen, site of allergen exposure, comorbidities, cofactors, clinical findings and symptoms, treatment and management. Patients admitted between January 2007 and December 2016 were included. Results. Forty-three patients were enrolled: 23 males, mean age 54.3 ± 16.2 years, n = 22 had history of allergic disease. Two patients were triaged as non-urgent. The most frequently suspected causes of anaphylaxis were: drugs (33%, n = 14), Hymenoptera venoms (23%, n = 10), foods (21%, n = 9) and iodinated contrast products (12%, n = 5). Adrenaline was used in 88% of the episodes (n = 38), 55% of which (n = 21) intramuscularly. Mortality was registered in one case. At discharge, adrenaline auto-injector was prescribed in 7% (n = 3) of the patients, and Allergy and Clinical Immunology consultation (ACIC) was requested in 65% of the episodes (n = 28). Statistically significant associations (p minor 0.05) were established: a, anaphylaxis to drugs associated with a low intramuscular adrenaline use and with frequent oxygen therapy; b, anaphylaxis to food associated with intramuscular adrenaline administration; c, anaphylaxis to Hymenoptera venom associated with male sex; and d, anaphylaxis to iodinated contrasts associated with referral to ACIC and with shock. All obese patients developed shock. Conclusions. Anaphylaxis is a life-threatening condition that requires early recognition. Although most patients received adrenaline, administration was not always performed by the recommended route and only a few patients were prescribed adrenaline auto-injector.

The Portuguese version of Rhinitis and Asthma Patient's Perspective (RAPP): Validation and assessment.

BACKGROUND: Allergic rhinitis (AR) and asthma are two common chronic diseases that often coexist. There is a need for a validated tool to evaluate HRQoL of Portuguese speakers with asthma and/or rhinitis patients in clinical practice. OBJECTIVES: To adapt and validate RhinAsthma Patient Perspective (RAPP) in Portuguese. METHODS: The RAPP questionnaire was translated into Portuguese. Asthmatics with comorbidities and rhinitis attending the allergy department of Coimbra University Hospital were asked to complete the Portuguese translation of RAPP, in addition to the SF-12, ACT, and a Symptomatologic VAS twice, with a 4-week interval between visits. During Visit 2, a Global Rating Scale (GRS) was completed to assess any change in health status. Scale dimensions, internal consistency and convergent validity, reliability, discriminant ability and responsiveness to change, as well as Minimal Clinical Difference were assessed. RESULTS: Factor and confirmatory analysis confirm the unidimensional structure of the questionnaire. Internal consistency has been shown to be satisfactory (0.82 visit 1 and 0.86 at visit 2). The tool is able to discriminate between patients on the basis of asthma severity, asthma control level, and rhinitis severity; convergent validity showed a significant correlation with SF-2 Physical component (r=-0.46 and 0.42, p at Visits 1 and 2). An ICC of 0.97 and a CCC=0.94 indicate that the tool is highly reliable. Responsiveness was shown in detecting a significant association with GRS changes (r=0.41, p<0.01) and ACT (r=-0.47, p<0.01) but not with VAS. (r=.14, n.s.). MID value was 2 points. CONCLUSIONS: The Portuguese version of RAPP has been demonstrated to have good measurement properties and sensitivity to health changes, which will provide a valid, reliable and standardized HRQoL measurement in patients with asthma and comorbid allergic rhinitis in clinical practice.

Pru p 3 sublingual immunotherapy ultra-rush protocol is safe and clinically effective.

Summary: Introduction. Sublingual immunotherapy (SLIT) with Pru p 3 can prevent severe allergic reactions to LTP-containing foods, but the standard initiation protocol is time-consuming. Objectives. Establish the safety of a novel ultra-rush initiation protocol for SLIT with Pru p 3. Methods. Prospective study comparing the side effects of the standard vs novel ultra-rush initiation protocols of SLIT with Pru p 3 in patients with anaphylaxis to LTP. Results. Fifteen patients were included (standard initiation, 5; ultra-rush initiation, 10), 80% females. All patients had oropharyngeal pruritus during initiation, 80% with spontaneous recovery, but no other gastro-intestinal, respiratory, cutaneous or systemic side effects occurred in any patient of both groups. Conclusion. The novel ultra-rush protocol halved the build-up time without increasing side effects.

Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma.

AIMS: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. METHODS: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. STAKEHOLDERS: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. RESULTS: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU GRANTS 2018: MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). LESSONS LEARNT: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.