Efficacy and Safety of Donidalorsen for Hereditary Angioedema.

BACKGROUND: Hereditary angioedema is a rare disorder characterized by episodic, potentially life-threatening swelling caused by kallikrein-kinin dysregulation. Long-term prophylaxis can stabilize this system. Donidalorsen, an antisense oligonucleotide, specifically reduces prekallikrein expression. METHODS: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary angioedema to receive donidalorsen (80 mg subcutaneously) or placebo once every 4 or 8 weeks. The primary end point was the time-normalized number of investigator-confirmed hereditary angioedema attacks per 4 weeks (attack rate) from week 1 to week 25. RESULTS: A total of 90 patients received donidalorsen every 4 weeks (45 patients), donidalorsen every 8 weeks (23 patients), or placebo (22 patients). The least-squares mean time-normalized attack rate was 0.44 (95% CI, 0.27 to 0.73) in the 4-week group, 1.02 (95% CI, 0.65 to 1.59) in the 8-week group, and 2.26 (95% CI, 1.66 to 3.09) in the placebo group. The mean attack rate from week 1 to week 25 was 81% lower (95% CI, 65 to 89) in the 4-week group than in the placebo group (P<0.001) and 55% lower (95% CI, 22 to 74) in the 8-week group than in the placebo group (P = 0.004); the median reduction in the attack rate from baseline was 90% in the 4-week group, 83% in the 8-week group, and 16% in the placebo group. The mean attack rate during weeks 5 to 25 was 87% lower (95% CI, 72 to 94) in the 4-week group than in the placebo group (P<0.001) and 60% lower (95% CI, 25 to 79) in the 8-week group than in the placebo group. Donidalorsen administered every 4 weeks resulted in an improvement in the least-squares mean total score for the change at week 25 on the Angioedema Quality-of-Life Questionnaire (scores range from 0 to 100, with a score of 100 indicating the worst possible quality of life) that was 18.6 points (95% CI, 9.5 to 27.7) better than that with placebo (P<0.001). The most common adverse events were erythema at the injection site, headache, and nasopharyngitis; 98% of adverse events were mild or moderate in severity. CONCLUSIONS: Donidalorsen treatment reduced the hereditary angioedema attack rate, a finding that supports potential prophylactic use for hereditary angioedema. (Funded by Ionis Pharmaceuticals; OASIS-HAE ClinicalTrials.gov number, NCT05139810.).

Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus.

BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

Working with companies that manufacture breastmilk substitutes: An EAACI position paper.

Breastmilk is the optimal source of nutrition for infants and should ideally be provided exclusively for the first 6 months of life, and alongside complementary food until 2 years of life. However, there are circumstances where a breastmilk substitute (BMS) may be required. This includes maternal and/or child conditions or personal preference. Whilst these circumstances should never be used as an opportunity to promote BMS, healthcare professionals (HCPs) need to have the knowledge of suitable alternatives and should always be guided by scientific and health motives when recommending a BMS. The Task Force 'Milk Formula Industry Sponsorship' from the European Academy of Allergy and Clinical Immunology (EAACI), provides with this publication recommendations for EAACI interactions with the BMS manufacturers and how this will be supervised.

Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Comprehensive mastocytosis data analysis from a single center.

Mastocytosis is a very rare disorder and is divided into three prognostically distinct variants by World Health Organization: Cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma or localized mast cell (MC) tumors. The wide range of complaints may cause patients to consult various clinics, with resulting mis- or underdiagnosis. Therefore, cooperation between different subspecialties is of paramount importance. In this article, we have compiled 104 adult mastocytosis cases diagnosed and followed in our Hematology and other clinics. 86 (82.7%) of 104 patients had systemic mastocytosis. Osteoporosis, disease-related complications, and secondary malignancies are important topics in this group. We know that indolent form has great survival. But smoldering or aggressive mastocytosis has a poor prognosis. CM and indolent SM have a significantly better prognosis compared to aggressive SM (p < 0.001). We found that the presence of more than 25% of mast cells in the bone marrow, the presence of concomitant marrow dysplasia, and the presence of disease-related complications affect survival (p < 0.001). In addition to the WHO classification, the IPSM scoring system is indicative of the prognosis in this rare disease.

How Does Pregnancy and Type of Delivery Affect the Clinical Course of Hereditary Angioedema?

INTRODUCTION: Knowledge on the clinical course of hereditary angioedema (HAE) during pregnancy, delivery, and breastfeeding is very limited. In this study, we aimed to evaluate the course of HAE during these periods. METHODS: The HAE attacks C1-INH prophylaxis before and during pregnancy and during breastfeeding, and the delivery types were retrospectively determined. The severity of attacks was assessed by a 10-point Visual Analogue Scale (VAS). RESULTS: We evaluated 88 pregnancies in 48 HAE patients among whom 20 were primiparous. Among those who had a HAE diagnosis during pregnancy (n = 34), the median attack numbers before pregnancy, during pregnancy, breastfeeding, and after breastfeeding were 17, 39, 24, and 14 (before pregnancy vs. pregnancy, p < 0.001; during pregnancy vs. breastfeeding, p = 0.001). The mean VASs (SD) were 6.59 (1.82), 8.33 (1.58), 7.32 (1.66), and 6.95 (1.90) (before pregnancy vs. pregnancy, p < 0.001; during pregnancy vs. breastfeeding, p = 0.016), respectively. Among those who received a HAE diagnosis after pregnancy (n = 54), the number (59.3%) and the severity (60%) of HAE attacks were high in pregnancy. 47 of the deliveries were normal vaginal delivery (NVD). Regional anesthesia was applied in 8 NVDs. 20 of caesarean deliveries were performed under general anesthesia, and 21 were under spinal anesthesia. Lowest numbers of attacks were found in patients who did not receive anesthesia during NVD (p = 0.001). CONCLUSION: The course of HAE can be worse during pregnancy and breastfeeding. NVD is related to fewer HAE attacks and prophylaxis with C1-INH during NVD is not necessary to prevent a HAE attack.

Plasma levels of oxysterols 7-ketocholesterol and cholestane-3ß, 5α, 6ß-triol in patients with allergic asthma.

The prevalence of allergic asthma is increasing on a global scale, reflecting changes in air pollution, climatic changes, and other environmental stimulants. In allergic conditions, oxidative stress occurs as a result of immune system activation. Oxidation of cholesterol leads to the formation of oxysterols. The main purpose of the study was to compare plasma levels of two oxysterols, namely 7-ketocholesterol (7-KC) and cholestane-3ß, 5α, 6ß-triol (C-triol), and a lipid peroxidation product, malondialdehyde (MDA) in allergic asthma patients with those of healthy controls, in order to provide information about the involvement of lipid peroxidation in allergic asthma.Oxysterols were quantified by LC-MS/MS in plasma samples of 120 asthma patients (90 females + 30 males) and 120 healthy controls (matched by age and sex). Plasma MDA level was analyzed by a spectrophotometric method.Plasma 7-KC (39.45 ± 20.37 ng/mL) and C-triol (25.61 ± 10.13 ng/mL) levels in patients were significantly higher than in healthy subjects (17.84 ± 4.26 ng/mL and 10.00 ± 3.90 ng/mL, respectively) (P < 0.001). Plasma MDA levels were also higher in asthmatic patients (4.98 ± 1.77 nmol/mL) than in healthy controls (1.14 ± 0.31 nmol/mL) (P < 0.001). All data support that lipid peroxidation products are involved in allergic asthma.Oxysterols were quantified for the first time in allergic asthma. Since the high plasma 7-KC and C-triol levels of allergic asthma patients correlate with high IgE levels, detection of these oxysterols by LC-MS/MS may be helpful in the clinical monitoring of allergic asthma. Current data may also lead to new approaches for the prevention, diagnosis, and treatment of the disease.Supplemental data for this article is available online at at.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Treatment patterns and outcomes in patients with chronic urticaria during pregnancy: Results of PREG-CU, a UCARE study.

BACKGROUND: Although chronic urticaria (CU) is a common and primarily affects females, there is little data on how pregnancy interacts with the disease. OBJECTIVE: To analyse the treatment use by CU patients before, during and after pregnancy as well as outcomes of pregnancy. METHODS: PREG-CU is an international, multicentre study of the Urticaria Centers of Reference and Excellence network. Data were collected via a 47-item-questionnaire completed by CU patients who became pregnant during their disease course. RESULTS: Questionnaires from 288 CU patients from 13 countries were analysed. During pregnancy, most patients (60%) used urticaria medication including standard-dose second generation H1-antihistamines (35.1%), first generation H1-antihistamines (7.6%), high-dose second-generation H1-antihistamines (5.6%) and omalizumab (5.6%). The preterm birth rate was 10.2%; rates were similar between patients who did and did not receive treatment during pregnancy (11.6% vs. 8.7%, respectively). Emergency referrals for CU and twin birth were risk factors for preterm birth. The caesarean delivery rate was 51.3%. More than 90% of new-borns were healthy at birth. There was no link between any patient or disease characteristics or treatments and medical problems at birth. CONCLUSION: Most CU patients used treatment during pregnancy especially second-generation antihistamines which seem to be safe during pregnancy regardless of the trimester. The rates of preterm births and medical problems of new-borns in CU patients were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals for CU increased the risk of preterm birth and emphasize the importance of sufficient treatment to keep urticaria under control during pregnancy.

How important is patch testing with dental materials in real-life clinical practice?

Background: Allergy to dental materials in prostheses and implants that leads to dental device dysfunction is a challenging problem. Objective: In this prospective study, we aimed to investigate the diagnostic role and impact of dental patch test (DPT) results on the outcome of proceeding dental procedures with the collaboration of our allergy clinic and dental clinics. Methods: A total of 382 adult patients with oral or systemic signs or symptoms due to the applied dental materials were included. A DPT with 31 items was administered. The clinical findings after dental restoration according to the test results were assessed in the patients. Results: The most common positivity detected in the DPT was due to metals, among which nickel (29.1%) was the leading cause. The frequency of self-reported allergic diseases and metal allergy was significantly higher in patients with at least one positive result in the DPT (p = 0.004 and p < 0.001, respectively). Clinical improvement after the removal of dental restoration was seen in 82% of the patients who had a positive DPT result, whereas this rate was 54% among paatients with negative DPT results (p < 0.001). The only factor that predicted improvement after restoration was the positivity in the DPT result (odds ratio 3.96 [95% confidence interval, 0.21-7.09]; p < 0.001). Conclusion: Our study showed that a self-reported metal allergy was an important finding to predict allergic reactions to dental devices. Therefore, patients should be questioned for the presence of metal allergy-related signs and symptoms before exposure to the dental materials to prevent possible allergic reactions. Furthermore, DPT results are valuable to guide dental procedures in real life.

Comparison of 300 mg versus 600 mg daily maintenance doses of aspirin treatment after desensitization in N-ERD: A three-year multicentre experience.

Background: Aspirin treatment after desensitization (ATAD) is effective in preventing nasal polyps recurrence as well as respiratory symptoms in patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory diseases (N-ERD). However, there is no consensus on effective daily maintenance doses in ATAD. Therefore, we aimed to compare the effects of two different maintenance doses of aspirin on clinical outcomes for 1-3 years of ATAD. Methods: This was a retrospective, multicenter study that involved four tertiary centers. The maintenance doses of daily aspirin were 300 mg in one center and 600 mg in the remaining three. The data of patients who were on ATAD for 1-3 years were included. Study outcomes (nasal surgeries, sinusitis, asthma attacks, hospitalization, oral corticosteroid use, and medication uses) were assessed in a standardized way and recorded from case files. Results: The study initially included 125 subjects, 38 and 87 were receiving 300 and 600 mg daily aspirin for ATAD, respectively. Number of nasal polyp surgeries decreased after 1 -3 years compared with before ATAD in both groups (group 1, baseline: 0.44 ± 0.07 versus first year: 0.08 ± 0.05; p < 0.001 and baseline: 0.44 ± 0.07 versus 3rd year: 0.01 ± 0.01; p < 0.001; and group 2, baseline 0.42 ± 0.03 versus first year: 0.02 ± 0.02; p < 0.001 and baseline: 0.42 ± 0.03 versus 3rd year: 0.07 ± 0.03; p < 0.001). Conclusion: Given the comparable effects of 300 mg and 600 mg aspirin daily as maintenance treatment of ATAD on both asthma and sinonasal outcomes in N-ERD, our results suggest using 300 mg of aspirin daily in ATAD owing to its better safety profile.

Common but neglected problem in chronic spontaneous urticaria: Sleep disturbance.

Background: Association of chronic spontaneous urticaria (CSU) with sleep disturbance has not been evaluated in studies that involve a large number of patients. Objective: In this study, we aimed to evaluate the sleep attitude and circadian rhythm in patients with CSU. Methods: As the patient group, recently diagnosed 100 patients with CSU, 100 patients with allergic rhinitis (AR) as the patient control group, and 100 healthy controls (HCs) were included. The Pittsburgh Sleep Quality Index (PSQI) questionnaire, sleep hygiene index (SHI), Epworth Sleepiness Scale (ESS) questionnaire, and the morningness-eveningness questionnaire (MEQ) were filled to assess sleep quality and circadian rhythm. CSU disease activity was evaluated by urticaria activity score-7 (UAS-7). Patients with concomitant diseases, e.g., psychiatric illnesses, that possibly affect sleep status or those who use related medications and at moderate or high risk of obstructive sleep apnea according to the STOP-Bang questionnaire were excluded from the study. Results: PSQI, SHI, and ESS scores were higher, and the MEQ score was lower in patients with CSU and patients with AR than those in the HCs (p < 0.001, for each score). However, the scores were not different among the patients with CSU and the patients with AR. UAS-7 was only correlated with PSQI scores (r = 0.402, p < 0.001). In addition, blood eosinophil counts and the serum C Reactive Protein (CRP) level were correlated with sleep quality (p = 0.02). Conclusion: The poor sleep quality, impaired sleep hygiene, increased daytime sleepiness, and intermediate type of circadian rhythm were observed in the patients with CSU and the patients with AR. Physicians should be aware of sleep problems in patients with CSU that might affect their quality of life and the success of their treatment.

Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification.

BACKGROUND: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. METHODS: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. RESULTS: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. CONCLUSIONS: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic.

BACKGROUND: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID-19 pandemic and demonstrate clinical consequences of treatment disruptions in real life. METHODS: Visual analogue scale for quality of life (VAS-QoL), VAS for symptom scores (VAS-symptom), medication scores (MSs), and total symptom scores (TSS-6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT, and these scores were compared with the pre-pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2-month intervals (Group 3). RESULTS: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS-symptom, and TSS-6 scores of Group 3 patients during the pandemic were higher than the pre-pandemic scores (p = 0.005, p < 0.001, p < 0.001, respectively), whereas median VAS-QoL scores of Group 3 during the pandemic were lower than the pre-pandemic scores (p < 0.001). Median TSS-6 and VAS-symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison). Median VAS-QoL scores were the lowest in Group 3 compared with Group 1 and Group 2 (p < 0.001, p = 0.043, respectively). CONCLUSION: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms.

Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper.

BACKGROUND: Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized. METHOD: Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. RESULTS: No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. CONCLUSIONS: These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study.

BACKGROUND: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. METHODS: An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. RESULTS: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. CONCLUSION: ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Relationship between Blastocystis spp. with Accompanying Food Hypersensitivity and Chronic Spontaneous Urticaria.

INTRODUCTION: The relationship between Blastocystis spp. and chronic spontaneous urticaria (CSU) is unclear. The aim of this study was to evaluate the role of this parasitic infection on CSU and to search for risky groups in CSU patients with this parasite. METHODS: Seventy adult CSU patients with Blastocystis spp. in their stool samples forming Group A and 70 CSU patients without any parasite as Group B were prospectively compared regarding urticaria activity score-7 (UAS7), medication scores (MS), and laboratory parameters. All patients received CSU treatment, and additionally, those in group A received an antiparasitic antibiotic. Eight months later, the same parameters were compared between the ones in remission (group A1) and those still having CSU symptoms (group A2) in group A. RESULTS: UAS7 and MS were lower in group A than in group B (p: 0.007, p < 0.001) 8 months later, while the initial scores were similar. The presence of food hypersensitivity reactions (FHRs) was higher in group A than in group B (p < 0.001) and was detected as a significant risk factor in the presence of Blastocystis spp. infection (p: 0.002, OR [CI] = 0.151 [0.045-0.502]). In group A, UAS7, MS, serum total IgE levels, and blood eosinophil counts decreased 8 months later (p < 0.001, p < 0.001, p: 0.003, p: 0.004, respectively). Additionally, total IgE levels and eosinophil counts decreased in group A1 (p: 0.033, p: 0.002) while they did not change in group A2. DISCUSSION/CONCLUSION: The eradication of Blastocystis spp. can improve the disease activity in CSU and the presence of FHRs seems to be risky in CSU patients with Blastocystis spp.

Evaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control.

OBJECTIVE: There is evidence that reactive oxygen species, especially free radicals, produced during the immune and inflammatory response may play important roles in the development of asthma.We aimed to evaluate the levels of certain oxidative stress biomarkers and antioxidant capacity in asthma patients with different asthma control levels in comparison to healthy subjects. METHODS: A total of 120 adult allergic asthma patients and 120 healthy individuals were included in this study. Using spectrophotometric methods, we analyzed two oxidative stress markers, levels of malondialdehyde (MDA) and protein carbonyls (PC), as well as reduced glutathione (GSH), total antioxidant capacity (FRAP) and catalase activity as critical antioxidant defense parameters in the blood samples of allergic asthma patients and healthy controls. The patients were divided into 3 subgroups according to asthma control test (ACT) results: totally controlled (TCG), partially controlled (PCG) and uncontrolled (UCG) subgroups. All biomarkers were compared between the three patient subgroups, as well as between total asthma patients and control subjects. RESULTS: There were remarkable differences between the control group and the combined patient group for all parameters. A significant increase in MDA and PC, especially in the UCG (p < 0.01 and p < 0.05, respectively) was detected in comparison to other subgroups. Additionally, increased MDA and PC levels, as well as decreased GSH levels were observed in all subgroups individually in comparison to the control (p < 0.001). CONCLUSIONS: This research demonstrates the presence of severe oxidative stress, considering the increase in lipid peroxidation and protein oxidation, in patients with allergic asthma, even under controlled conditions.