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.

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.

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.

Management of Hypersensitivity Reactions to Proton Pump Inhibitors: A Retrospective Experience.

BACKGROUND: We previously reported perfect specificity and low sensitivity of skin tests in proton pump inhibitor (PPI)-induced immediate hypersensitivity reactions in a prospective multicenter study. Here, in a retrospective study, we aimed to further evaluate the diagnostic workup procedures and characteristics of the patients with suspected PPI hypersensitivity. METHODS: This national multicenter study was conducted as a retrospective chart review of patients with a history of PPI-induced immediate hypersensitivity reaction. A total of 60 patients were included. Results of diagnostic workup procedures (standardized skin-prick, intradermal, and oral-provocation tests with PPIs) and the characteristics of the patients were analyzed. RESULTS: Lansoprazole was the most commonly suspected drug with 41 patients (68.3%), followed by pantoprazole in 12 patients (20.0%), esomeprazole in 6 (10.0%), rabeprazole in 4 (6.7%), and omeprazole in 1 (1.7%). Anaphylaxis (40 patients, 66.7%) was the most common clinical presentation followed by urticaria (17 patients, 28.3%). Diagnostic skin tests with the culprit PPI were positive in 13/26 patients (50.0%). Diagnostic oral-provocation tests were negative in 6/8 patients; 5 of these 6 patients had skin test results with the culprit PPI, and all were negative. Ten patients had at least 1 cross-reactivity. Extensive cross-reactivity (between >2 PPIs) was detected in 4 patients. CONCLUSIONS: Lansoprazole was the most frequently implicated drug and anaphylaxis was the most frequent manifestation of PPI-induced hypersensitivity reactions. Physicians should be aware of the possible cross-reactivity among PPIs; however, a safe, alternative PPI can usually be detected by a thorough drug allergy workup.

Turkish version of the Drug Hypersensitivity Quality of Life Questionnaire: assessment of reliability and validity.

PURPOSE: The first disease-specific quality-of-life questionnaire in patients with drug hypersensitivity, Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q), was developed and validated recently. The aim of this study was to assess validity, reliability and responsiveness to interventions of the Turkish version of the DrHy-Q. METHODS: The Turkish version of the DrHy-Q was administered to prospectively enrolled 736 patients with drug hypersensitivity from ten allergy units. To assess validity, all patients completed the validated Turkish version of Psychological General Well-Being Index (PGWBI). For test-retest reliability, 182 patients completed the DrHy-Q 1 week after the first questionnaire administration without any intervention. Responsiveness was assessed on 97 patients who had a DrHy-Q recorded at a follow-up visit after the intervention. RESULTS: The internal consistency and test-retest reliability of the scale were adequate (Cronbach's alpha = 0.934, intra-class correlation coefficient = 0.783). The DrHy-Q scores showed weak negative correlations with the PGWBI total and domain scores (r = - 0.378 to -0.254, p < 0.001). DrHy-Q was able to discriminate the patients with one drug hypersensitivity reaction from the patients with two and above two reactions (p = 0.012 and p < 0.001, respectively), and the patients who experienced a respiratory reaction from the patients who did not (p = 0.018). However, it did not discriminate the patients with comorbid disease including psychiatric comorbidity (p > 0.05). The baseline DrHy-Q scores were significantly higher than the post-intervention scores (p = 0.008). CONCLUSION: The Turkish version of DrHy-Q is reliable and valid for evaluating quality of life in patients with drug hypersensitivity, and it appeared responsive to interventions.

Short-term preseasonal immunotherapy: is early clinical efficacy related to the basophil response?

BACKGROUND: An aluminum hydroxide-adsorbed depot allergoid preparation of six-grass pollen allergens has been developed for short-term preseasonal immunotherapy in pollinosis. However, only limited knowledge exists about its immunological and clinical effects. The aim of this study was to evaluate the basophil response, which can explain early clinical findings of short-term preseasonal allergoid immunotherapy in allergic rhinitis. METHODS: In a double-blind, placebo-controlled study, 31 patients allergic to grass pollens received one course of short-term preseasonal allergoid immunotherapy or placebo. Immunogenicity was assessed by the levels of specific IgG4, IgE antibodies and an allergen-induced CD203c basophil activation test. The primary clinical end point was the combined symptom and medication score/average combined score (ACS). RESULTS: There was a 52.9% difference in ACS between the treatment and placebo groups in favor of immunotherapy (p = 0.01). Active treatment induced Phleum pratense-specific IgG4 and IgE antibodies (p < 0.05). A decrease in allergen-induced basophil activation at submaximal allergen concentrations was demonstrated at the end of immunotherapy and at the peak of the grass pollen season after immunotherapy. CONCLUSIONS: This study shows that grass pollen-allergic patients treated with one course of short-term preseasonal allergoid immunotherapy exhibit a decrease in allergen-induced basophil activation, an increase in allergen-specific IgG4 antibodies and early clinical improvement.

[Biologics for the treatment of severe asthma: Current status report 2023]. / Agir astim tedavisinde biyolojikler: Güncel durum raporu 2023.

Severe asthma is associated with increased use of healthcare services, significant deterioration in the quality of life, and high disease and economic burden on patients and societies. Additional treatments are required for severe forms of asthma. Biological agents are recommended for the treatment of severe asthma. In this current status report, we aimed to evaluate the efficacy, effectiveness, and safety data of approved biologics; omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, in the treatment of severe asthma and appropriate patient profiles for these biologics. Pubmed and Cochrane databases based on randomized controlled trials, posthoc analyses, meta-analyses, and real-life studies examining the efficacy and effectiveness of biologics in severe asthma were searched, and the results of these studies on important asthma outcomes were reviewed. Existing studies have shown that all the approved biologic agents targeting cells, receptors, and mediators involved in type 2 inflammation in the bronchial wall in severe asthma significantly reduce asthma exacerbations, reduce the need for oral corticosteroids, and improve asthma control, quality of life, and pulmonary functions. Characterizing the asthma endotype and phenotype in patients with severe asthma and determining which treatment would be more appropriate for a particular patient is an essential step in personalized treatment.

Stepwise Approach in Asthma Revisited 2023: Expert Panel Opinion of Turkish Guideline of Asthma Diagnosis and Management Group.

Introduction of inhaled corticosteroids (ICS) has been the cornerstone of the long-term management of asthma. ICSs either alone or in combination with long-acting beta-2 agonists have been shown to be associated with favorable asthma outcomes. However, asthma control is still reported to be below expectations all around the world. Research in the last decades focusing on the use of ICS/formoterol both as maintenance and as needed (maintenance and reliever therapy approach) showed improved asthma outcomes. As a result of recent developments, Turkish Asthma Guidelines group aimed to revise asthma treatment recommendations. In general, we recommend physicians to consider the risk factors for poor asthma outcomes, patients' compliance and expectations and then to determine "a personalized treatment plan." Importantly, the use of short-acting beta-2 agonists alone as a symptom reliever in asthma patients not using regular ICS is no longer recommended. In stepwise treatment approach, we primarily recommend to use ICS-based controllers and initiate ICS as soon as possible. We define 2 different treatment tracks in stepwise approaches as maintenance and reliever therapy or fixed-dose therapy and equally recommend each track depending on the patient's risks as well as decision of physicians in a personalized manner. For both tracks, a strong recommendation was made in favor of using add-on treatments before initiating phenotype-specific treatment in step 5. A strong recommendation was also made in favor of using biologic agents and/or aspirin treatment after desensitization in severe asthma when indicated.

[Therapy with omalizumab in patients with severe persistent allergic asthma: a real life data in Turkey]. / Agir allerjik astimli hastalarda anti-IgE (omalizumab) tedavisi: Gerçek yasam verileri.

Omalizumab is a biologic agent, which has been shown to be effective in clinical trials in allergic, severe asthmatics. The aim of this study was to evaluate the clinical, functional effectiveness, and side effects of omalizumab in real-life conditions respectively. A total of 18 patients (female/male: 11/7) were included to the study. The mean ± SD age, total IgE, disease duration were 41.8 ± 11.2 years, 255.1 ± 197.3 kU/L, 12.8 ± 9.4 years, respectively. Eight patients had isolated mite, seven patients had mite + other inhalant allergen, three patients had only other allergen sensitivity. Mean duration of omalizumab treatment (months ± SD) was 15.1 ± 8.6 (min-max 1-29) months. Omalizumab dose was 150 mg/month in five patients, 300 mg/month in five, 300 mg/15 days in three, 375 mg/15 days in four, 225 mg/15 days in one patient. Data at the date of last visit were compared with one year prior to omalizumab treatment. Mean systemic steroid dose reduced by 83% (14.7 ± 14.6 vs. 3.2 ± 8 mg), number of other asthma medications reduced by 28% (3.6 ± 1.3 vs. 2.5 ± 1.3) (p< 0.05). FEV1% values (53.5 ± 21.2 vs. 64.5 ± 23.5) did not significantly change. Mean numbers of exacerbations (20 ± 57.6 vs. 0.4 ± 0.7), emergency visits (16.5 ± 46.1 vs. 0.4 ± 1.2), hospitalizations (2.1 ± 2.6 vs. 0.1 ± 0.3) decreased by 93%, 95%, 86%, respectively (p< 0.05). ACT scores increased by 94% (10.4 ± 3.4 vs. 20.4 ± 5.7) (p< 0.05). Fifteen patients (88%) were stated as responsive to treatment with omalizumab. Eleven patients (64.8%) stated that their expectations are met, three patients (17.6%) stated that their expectations are close to being met, three patients (17.6%) stated that their expectations are not met. A local side effect was seen in one patient. In conclusion, our data has shown that omalizumab is effective, and safe in severe allergic asthmatics under real-life conditions.

Prospects for new and emerging therapeutics in severe asthma: the role of biologics.

INTRODUCTION: Asthma is a common and heterogeneous disease. While current conventional therapies are effective in the majority of the patients, a significant subgroup remain uncontrolled despite these treatments. Different biological agents are currently approved or undergoing development for treatment of asthma, including anti-IgE, anti-interleukin (IL)-5, anti-IL-13, anti-IL-4 and anti-thymic stromal lymphopoietin agents. This review will focus on the currently available evidence regarding the new and emerging biological agents in severe asthma. Areas covered: A non-systematic review of the available English-language literature regarding severe asthma and biological agents was performed. We summarized and discussed the current evidence about the use of new and emerging biological agents in severe asthma. Expert commentary: Because of the heterogeneity of response to therapy in refractory asthma it is of utmost importance to correctly estimate patient outcomes before starting biological therapy to make patient selection more effective. Currently, the decision of which biologic to initiate in patients with uncontrolled severe asthma should be made based on the atopic status, blood eosinophil and total IgE levels, exacerbation history, safety profile, cost, frequency and route of administration.