Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

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.

Field sting reactions in patients receiving Hymenoptera venom immunotherapy: real-life experience.

BACKGROUND: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT. OBJECTIVE: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk. METHODS: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings. RESULTS: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT. CONCLUSIONS: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Hypersensitivity reactions to biologicals: An EAACI position paper.

Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

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.

Effectiveness of Low-Dose Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Real-Life Experience.

INTRODUCTION: Data showing effectiveness of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis (EGPA) are limited. METHODS: This is a single-center retrospective chart review of patients with EGPA treated with mepolizumab. Clinical, laboratory, functional parameters and asthma, rhinitis control, and quality of life scores (Asthma Control Test [ACT], Asthma Quality of Life Questionnaire [AQLQ], Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ], and SinoNasal Outcome Test [SNOT]-22) were evaluated at the baseline, 6th month, and 12th month. Complete response was defined as the absence of asthma and/or ear, nasal symptoms and exacerbations with a prednisone of ≤7.5 mg/day, partial response if it was achieved with a prednisone of >7.5 mg/day. RESULTS: Overall, 25 patients (18 F/7 M) with a median age of 47 years (23-76) were enrolled. Mepolizumab 100 mg/month was administered (dose increased to 300 mg/month in 3 patients). Mepolizumab significantly decreased daily dose of oral corticosteroid (OCS) from 11.04 mg to 3.65 mg together with a significant improvement in ACT, AQLQ, RQLQ, and SNOT-22 scores and a significant reduction in asthma exacerbations and blood eosinophil count at the 6th and 12th month (all p values <0.05). The mean forced expiratory volume in 1 s increased (at baseline: 1.88 L to 2.46 L at the 12th month [p = 0.037]). Seventy-six percent of patients responded completely at the 6th month and 81.25% at the 12th month. The complete responders at the 6th and 12th month were older than partial responders and nonresponders (p = 0.030 and p = 0.057, respectively). Patients with complete response at the 6th month were on lower doses of OCS than partial responders and nonresponders (p = 0.029). CONCLUSIONS: Low-dose mepolizumab was effective in EGPA patients by improving sinonasal and asthma outcomes, while reducing the need for OCS.

Mepolizumab Is an Effective Option in Severe Eosinophilic Asthma Regardless of Baseline Features: Single-Center Real-Life Data.

BACKGROUND: Mepolizumab has been approved as a treatment option for severe eosinophilic asthma (SEA) patients in our country. We aimed to evaluate the clinical and functional efficacy of mepolizumab in this group of patients in real life as well as the response rates to mepolizumab and the possible factors affecting the response. METHODS: The study was a retrospective chart review of patients with SEA treated with mepolizumab. The data were collected at baseline, and at the 6th and 12th month. RESULTS: A total of 62 patients (41F/21M) with a mean age of 44.41 ± 13.24 years were included in the study. They had poor symptom control with a mean asthma control test (ACT) score of 16.61 ± 5.59, frequent exacerbations with a mean of 3.4 ± 3.7 in the previous 12 months, and 80.6% required daily oral corticosteroid (OCS) with a median dosage of 8 mg/day as methylprednisolone. The ACT score increased to 22.47 ± 3.18 and 22.03 ± 4.31, respectively, and blood eosinophil count decreased from 1,146/µL to 89/µL and 85/µL at the 6th and 12th month, respectively. The mean FEV1 at baseline was 2.102 L there was an increase of 0.373 L at 6th month and 0.596 L at 12th month. The percentage of regular users of OCS decreased to 66.0% at 6th month with a median dosage of 4 mg and 52.6% at 12th month with a median dosage of 2 mg. Mepolizumab reduced the rate of exacerbations compared with the previous year from a mean of 3.40 to 0.15 at 6th month and 0.36 at 12th month. There was a significant improvement in Asthma Quality of Life Questionnaire (AQLQ), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Sino-nasal Outcome Test (SNOT-22) scores at both of time points. The rate of responders and super-responders at 6th month was 60% and 28%, respectively, and consequently, the overall response rate was 88%. At the 12th month, the super-responder rate increased to 44.7% as well as the overall response to 89.4%. The only difference between the nonresponders, responders, and super-responders at the 6th and 12th month was whether regular daily OCS was used pre-mepolizumab. All nonresponders at both 6th and 12th month were using OCS regularly, whereas most of super-responder used the OCS only during exacerbations. CONCLUSION: Mepolizumab effectively reduced asthma exacerbations, steroid requirement, blood eosinophil counts and improved asthma control, pulmonary function, sinonasal symptoms and quality of life. Our data suggest that mepolizumab would be effective in selected patients in real-life settings.

Eosinophilic granulomatosis with polyangitis: A new target for biologicals.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome) is a rare systemic necrotizing granulomatous vasculitis in the spectrum of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Nevertheless, EGPA has specific clinical, biological and histological properties different from other AAVs [microscopic polyangiitis (MPA) and granulomatous polyangiitis (GPA)]. Recently, thanks to the studies conducted to understand the pathophysiology of EGPA, unlike neutrophils in other AAVs, the main cells involved in EGPA have been observed to be eosinophils. The key role of eosinophils in EGPA and recent development of targeted agents to treat other eosinophil-related diseases have created new therapeutic opportunities for EGPA. Conventional treatment of EGPA relies mainly on agents that decrease inflammation. Cornerstone therapy is systemic glucocorticoids, used as monotherapy or in combination with immunosuppressive agents. However, new therapeutic approaches are needed especially for persistent asthma symptoms, refractory disease, relapses and problems associated with corticosteroid dependence. Recently, the first large-scale randomized controlled clinical trial on polyangiitis and eosinophilic granulomatosis has demonstrated the efficacy of eosinophil-targeted biotherapy anti-interleukin-5 (IL-5) mepolizumab, and is approved for the management of EGPA. This finding opens a new era for EGPA management. This review provides an overview of eosinophilic granulomatosis with polyangiitis in the light of new targeted biological therapies.

Incidence and clinical course of COVID-19 in patients using omalizumab for chronic spontaneous urticaria and/or severe allergic asthma and using mepolizumab for severe eosinophilic asthma: A single center real life experience.

Introduction: To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents. Materials and Methods: A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease. Result: Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%). Conclusions: The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity.

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Change in Allergy Practice during the COVID-19 Pandemic.

BACKGROUND: International guidelines in asthma and allergy has been updated for COVID-19 pandemic and pandemic has caused dramatic changes in allergy and immunology services. However, it is not known whether specialty-specific recommendations for COVID-19 are followed by allergists. OBJECTIVES: By conducting this study, we aimed to determine the attitudes and experiences of adult/pediatric allergists on allergy management during COVID-19. METHOD: We used a 20-question survey to elicit data from allergists (residents and pediatric and adult allergists registered to the Turkish National Society of Allergy and Clinical Immunology) across Turkey via e-mail. We analyzed the data statistically for frequency distributions and descriptive analysis. RESULTS: A total of 183 allergists participated in the survey. Telemedicine was used for management of asthma (73%), allergic rhinitis (53%), atopic dermatitis (51%), chronic urticaria/angioedema (59%), drug hypersensitivity (45%), food allergy (48%), venom allergy (30%), anaphylaxis (22%), and hereditary angioedema (28%). Thirty-one percent of the respondents discontinued subcutaneous immunotherapy (SCIT) during the COVID-19 pandemic. Thirty-four percent of the physicians reported interruption of systemic steroid use in asthma patients, and 25% of the respondents discontinued biological therapy. CONCLUSIONS: Allergists in Turkey have been using telemedicine at a high rate during the COVID-19 pandemic for asthma and rhinitis. The continuation rate of SCIT was low while the discontinuation rate of biologicals and systemic steroid use in asthma was high in Turkey.Our study results and learning from the experiences of other countries and specialties may help to optimize allergy practice and compatibility with international guidelines.

[GINA 2019 - step 1 and 2 treatment in asthma: Updates with reasons behind]. / GINA 2019 - astimda basamak 1 ve 2 tedavisi: Degisiklikler ve nedenleri.

Asthma is a heterogeneous lung disease characterized by chronic airway inflammation. It was suggested that patients with mild asthma symptoms could be managed with as-needed short-acting ß2-agonists (SABA) in previous years. In 2019, GINA made a radical change and recommended that SABA should not be used as monotherapy in patients with mild asthma, but instead as-needed low-dose inhaled corticosteroid (ICS)-formoterol or "additional low-dose ICS taken whenever SABA is taken" treatments should be commenced to relieve and control symptoms. The approach emerged in the light of the studies that indicate the increased risk of severe exacerbation and asthma-related death due to overuse of SABA. The present article aimed to enlighten the updates in GINA 2019 step 1 and 2 treatment, the grounds for these updates with the supportive studies.

[The role of fixed dose combinations of inhaled cortikosteroids, long acting beta-2 agonists, and long acting muscarinic antagonists (ICS/LABA/LAMA) in the treatment of asthma]. / Sabit doz inhale kortikosteroid, uzun etkili beta-2 agonist ve uzun etkili muskarinik reseptör antagonisti (IKS/LABA/LAMA) kombinasyonunun astim tedavisindeki yer.

The effective treatment of asthma is important in terms of improving the quality of life and decreasing the number of hospital admissions due to acute exacerbations. Parasymphatic activity is increased in patients with asthma. This is one of most important part of airway obstruction which has a great potential for reversibility. The evidence about the synergic interaction between inhaled corticosteroids (ICS), long acting beta-2 agonists (LABA), and long acting muscarinic antagonists (LAMA) encourages the use of LAMA in asthma. Tiotropium treatment was found to be successful in patients with recurrent exacerbations in whom asthma was uncontrolled despite treatment with other add on treatments that were recommended at GINA step 4. These findings triggered several clinical studies on fixed dose ICS/LABA/LAMA for asthma treatment. Three studies that have been published recently showed that fixed dose ICS/LABA/LAMA improved the lung functions and decreased the exacerbation rate without increasing the dose of ICS or LABA in asthma. In this review, the mechanisms of action of LAMA in asthma were summarized and possible role of fixed dose ICS/LABA/ LAMA in asthma treatment was discussed under the light of current literature.

[Biological Treatments in patients with ABPA]. / ABPA'li hastalarda biyolojik tedaviler.

Allergic Bronchopulmonary Aspergillosis (ABPA) is a pulmonary disease characterized by recurrent pulmonary opacities and bronchiectasis caused by Type 1 hypersensitivity to A. fumigatus. Asthma is an important part of the disease and is generally in severe form. It is thought that immunoglobulins against A. fumigatus, Th2-derived cytokines such as IL-4, IL-5 and IL-13 and eosinophilic inflammation play a role in the pathogenesis of the disease. Monoclonal antibody treatments targeting IL-4, IL-5, IL-13 and IgE, which are involved in pathogenesis, have been used in asthmatic patients before. The main treatment of ABPA for exacerbations and remissions is oral corticosteroids (OCS). However, in cases where the corticosteroid dose cannot be reduced or side effects develop, monoclonal agents may be added to the treatment. Monoclonal agents such as omalizumab, mepolizumab, benralizumab and dupilumab targeting cytokines involved to the patogenesis have been used in patients with ABPA. Omalizumab has shown a reduction in exacerbations and OCS requirements, improvement in asthma symptoms and improvement in pulmonary function parameters. With mepolizumab, a decrease in OCS dose, decrease in blood eosinophil count, clinical improvement and radiological improvement were observed. Benralizumab reduced, the number of eosinophil or even almost nullified as well as clinical recovery alongside with radiological improvement. With dupilumab, improvement in symptoms, discontinuation of OCS, but increase in eosinophil count at the beginning of treatment was reported. As a result, monoclonal antibodies were generally found to be successful and safe in patients with ABPA.

Country-based report: the safety of omalizumab treatment in pregnant patients with asthma

Background/aim: We aimed to report outcomes of pregnant patients with asthma under omalizumab treatment and their infants in our country. Materials and methods: Patients with asthma who received omalizumab for at least 6 months and at least one dose during their pregnancy were retrospectively evaluated using a questionnaire regarding their disease and therapy and the health of their infants. Results: Twenty pregnant patients and their 23 infant's data were analyzed. The mean delivery age was 31.8 ± 7.4 years. They received omalizumab for 28.9 ± 21.8 months. Eight (36.4%) patients showed exacerbation of the disease during pregnancy. Forced expiratory volume in 1 s (FEV1) and asthma control test (ACT) scores at the starting time of omalizumab administration, first month of the pregnancy, and after delivery were 71 ± 18%, 83.4 ± 10.5%, and 80.5 ± 13% (FEV1), and 11.9 ± 4.9, 20.2 ± 2.6, and 20.4 ± 2.2 (ACT), respectively. One patient gave birth to twin infants, two patients to two infants each in different years, and 17 to one infant each. Three (13%) infants had low birth weight and five (21.7%) were born prematurely. No congenital anomalies were detected. Seven (30.4%) infants presented atopic diseases during their life. Conclusion: Omalizumab treatment during pregnancy seems to be safe for both patients and their infants.

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement.

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.

Hypersensitivity reactions to proton-pump inhibitors: Clinical presentation, diagnosis, and management.

Background: Proton-pump inhibitors (PPI) are one of the most commonly prescribed drugs, and they are generally well tolerated. However, several immediate and delayed hypersensitivity reactions due to PPIs have been reported. Objective: To review the clinical characteristics and management of immune-mediated immediate and delayed hypersensitivity reactions to PPIs. Methods: We performed a search of a medical literature data base from January 1980 to October 2019 by using keywords that included "proton-pump inhibitors" and "hypersensitivity." Results: Anaphylaxis is the most-common clinical presentation in patients with immediate hypersensitivity reactions to PPIs, followed by urticaria and/or angioedema. Occupational contact dermatitis, maculopapular eruption, fixed drug eruption, symmetrical drug-related intertriginous and flexural exanthema, and severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis have also been reported with PPIs. Conclusion: The current knowledge and severity of the reported reactions indicated the importance of consideration of a causal relationship between hypersensitivity reactions and PPIs, and awareness of the existence of cross-reactivity among PPIs.

[Anti-IL-5 treatments in severe eosinophilic asthma: real life datas]. / Agir eozinofilik astimda anti-IL-5 tedaviler: gerçek yasam verileri.

Randomized controlled studies have shown that anti-IL-5 treatments reduce the need for oral corticosteroids, annual asthma exacerbation and hospitalization rates, blood eosinophil count and increase FEV1 values, asthma control, and quality of life in patients with eosinophilic severe asthma. Although the number of real-life studies with anti-IL-5 is limited, there are 10 real life studies with mepolizumab, one real life study with benralizumab and one real life study with reslizumab in the current literature. Similar to randomized controlled trials, real-life studies reported that a reduction in the need for oral corticosteroids, annual asthma exacerbation and hospitalization rates, and blood eosinophil counts and increase FEV1 values, asthma control test and quality of life scores, Response criteria were defined in some of the real-life studies and although different response rates were given according to these criteria, most of the patients with severe eosinophilic asthma showed high response rates to anti-IL-5 treatments. In real-life studies evaluating the safety of anti-IL-5 treatments, the most common adverse effect is mild local injection site reaction that does not require treatment, in conclusion, real-life studies suggest that all three anti-IL-5 treatments in clinical practice are effective and well tolerated.