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.

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.

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.

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.

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.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study.

BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. METHODS: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. RESULTS: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

The Allergic Rhinitis and its Impact on Asthma (ARIA) score of allergic rhinitis using mobile technology correlates with quality of life: The MASK study.

Mobile technology has been used to appraise allergic rhinitis control, but more data are needed. To better assess the importance of mobile technologies in rhinitis control, the ARIA (Allergic Rhinitis and its Impact on Asthma) score ranging from 0 to 4 of the Allergy Diary was compared with EQ-5D (EuroQuol) and WPAI-AS (Work Productivity and Activity Impairment in allergy) in 1288 users in 18 countries. This study showed that quality-of-life data (EQ-5D visual analogue scale and WPA-IS Question 9) are similar in users without rhinitis and in those with mild rhinitis (scores 0-2). Users with a score of 3 or 4 had a significant impairment in quality-of-life questionnaires.

Anaphylaxis in a food allergy outpatient department: one-year review.

Summary: Background. Anaphylaxis is an acute, potentially fatal, multi-organ allergic reac-tion. Our aim was to characterize the population with food induced anaphylaxis followed over a one-year period. Methods. Retrospective analysis of clinical files of patients with food anaphylaxis observed in our food allergy consultation during 2016. Results. Sixty-two patients were included. In the pediatric group, the implicated allergens were cow's milk, egg and fish and in the adults' group, the commonest allergens were nuts and wheat. Allergy to shrimp affected equally children and adults. The most frequent symptoms were urticaria (85.5%), angioedema (64.5%) and dyspnea (62.9%). Cofactors were present in 32.6% of patients, mainly exercise. Asthma and/or rhinitis were the most frequent comorbidities. Conclusion. In accordance to other studies, milk and egg were the most implicated allergens in children. Anaphylaxis in adults reflects the Mediterranean sensitization pattern. Exercise was the most relevant cofactor.

Pilot study of mobile phone technology in allergic rhinitis in European countries: the MASK-rhinitis study.

BACKGROUND: The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) assesses allergic rhinitis symptoms, disease control and impact on patients' lives. It is freely available in 20 countries (iOS and Android platforms). AIMS: To assess in a pilot study whether (i) Allergy Diary users were able to properly provide baseline characteristics (ii) simple phenotypic characteristics based upon data captured by the Allergy Diary could be identified and (iii) information gathered by this study could suggest novel research questions. METHODS: The Allergy Diary users were classified into six groups according to the baseline data that they entered into the App: (i) asymptomatic; (ii) nasal symptoms excluding rhinorrhea; (iii) rhinorrhea; (iv) rhinorrhea plus 1-2 nasal/ocular symptoms; (v) rhinorrhea plus ≥3 nasal/ocular symptoms; and (vi) rhinorrhea plus all nasal/ocular symptoms. RESULTS: By 1 June 2016, 3260 users had registered with the Allergy Diary and 2710 had completed the baseline questionnaire. Troublesome symptoms were found mainly in the users with the most symptoms. Around 50% of users with troublesome rhinitis and/or ocular symptoms suffered work impairment. Sleep was impaired by troublesome symptoms and nasal obstruction. CONCLUSIONS: This is the first App (iOS and Android) to have tested for allergic rhinitis and conjunctivitis. A simple questionnaire administered by cell phones enables the identification of phenotypic differences between a priori defined rhinitis groups. The results suggest novel concepts and research questions in allergic rhinitis that may not be identified using classical methods.

Urinary metabolomic profiling of asthmatics can be related to clinical characteristics.

Metabolomics has been increasingly explored to achieve an improved understanding of asthma. In the current observational and exploratory study, the first to have examined the relationship between oxidative stress extension, eosinophilic inflammation, and disease severity in asthmatic patients, metabolomics (using target aliphatic aldehydes and alkanes) was carried out using solid-phase microextraction (SPME) followed by a comprehensive two-dimensional gas chromatography coupled to mass spectrometry with a high-resolution time-of-flight analyzer (GC×GC-ToFMS). We were able to demonstrate that metabolomics can give valuable insights into asthma mechanisms once lipidic peroxidation assessed by urinary metabolomics is related to the clinical characteristics of nonobese asthmatics, such as disease severity, lung function, and eosinophilic inflammation. Nevertheless, considering our sample size, the obtained results require further validation using a much larger sample cohort.

Respiratory hypersensitivity reactions to NSAIDs in Europe: the global allergy and asthma network (GA2 LEN) survey.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAID-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders. METHODS: The GA2 LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo), a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status, and history of NSAID-induced hypersensitivity reactions were sent to participants by mail. Totally, 62 737 participants completed the questionnaires. RESULTS: The mean prevalence of NSAID-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%), and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%), and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis. CONCLUSION: Our study documented significant variation between European countries in the prevalence of NSAID-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.