Immediate reactions to proton pump inhibitors: Clinical findings and testing outcomes.

Data are limited about the value of skin tests in the diagnosis of proton pump inhibitor (PPI)-induced hypersensitivity reactions and the cross-reactivity between PPIs. We aimed to assess the role of skin testing in the diagnosis of PPI-related immediate hypersensitivity reactions and the cross-reactivity patterns among PPIs. The study was designed in a prospective, national, multicentre nature. Sixty-five patients with a suggestive history of a PPI-induced immediate hypersensitivity reaction and 30 control subjects were included. Standardized skin prick and intradermal tests were carried out with a panel of PPIs. Single-blind, placebo-controlled oral provocation tests (OPTs) with the PPIs other than the culprit PPI that displayed negative results in skin tests (n = 61) and diagnostic OPTs with the suspected PPI (n = 12) were performed. The suspected PPIs were lansoprazole (n = 52), esomeprazole (n = 11), pantoprazole (n = 9), rabeprazole (n = 2), and omeprazole (n = 1). The sensitivity, specificity, and negative and positive predictive values of the skin tests with PPIs were 58.8%, 100%, 70.8%, and 100%, respectively. Fifteen of the 31 patients with a hypersensitivity reaction to lansoprazole had a positive OPT or skin test result with at least one of the alternative PPIs (8/52 pantoprazole, 6/52 omeprazole, 5/52 esomeprazole, 3/52 rabeprazole). Considering the high specificity, skin testing seems to be a useful method for the diagnosis of immediate-type hypersensitivity reactions to PPIs and for the evaluation of cross-reactivity among PPIs. However, OPT should be performed in case of negativity on skin tests.

Hypersensitivity reactions with proton pump inhibitors: five years of clinical experience.

The Cardiovascular Risk of Proton Pump Inhibitors and the Dangers of Polypharmacy

Proton Pump Inhibitor Therapy in Atazanavir-Treated Patients

Benzocaine anaphylaxis

Persistent Reflux Symptoms in the Proton Pump Inhibitor Era: The Changing Face of Gastroesophageal Reflux Disease

E‐Poster Presentations – A2) Gastric and Duodenal

Objective. Up to one-third of patients with gastroesophageal reflux disease (GERD) in primary care have residual symptoms despite proton pump inhibitor (PPI) therapy. We aimed to characterize partial response to PPIs among adult patients in UK primary care. Material and methods. Newly diagnosed GERD patients aged 20–79 years who were prescribed PPI for treatment of GERD were identified in The Health Improvement Network. Those with a treatment change suggesting partial response to PPIs (new treatment added to PPI, increased PPI dose, or switching PPI) during the subsequent 6 months were identified as potential cases and confirmed after manual review of each patient's complete computer medical record including free-text comments. Patients without these treatment changes were study controls. A nested case–control analysis was conducted using logistic regression. Results. The proportion of newly diagnosed GERD patients with partial response to PPI therapy was 18.6% (1201/6453). Partial response was associated with female gender (odds ratio [OR]: 1.20; 95% confidence interval [CI]: 1.05–1.37), anxiety or depression (OR: 1.15; 95% CI: 1.00–1.31), and prescription of ≥6 drugs in the month before GERD diagnosis (OR: 1.42; 95% CI: 1.14–1.78). Among new PPI users (n = 2907), partial response was associated with esophageal ulcer or Barrett's esophagus at initial diagnosis (OR: 3.14; 95% CI: 1.60–6.17). Conclusions. Approximately one in five newly diagnosed patients with GERD appear to have a partial response to PPI therapy. Female gender, polymedication, and a severe initial diagnosis may be associated with partial response.

To compare the effectiveness of histamine-2 receptor antagonists (H2RAs) vs. proton pump inhibitors (PPIs) for stress ulcer prophylaxis on the occurrence of upper gastrointestinal bleeding (UGIB) and other clinical outcomes in hospitalized patients with septic shock. Retrospective, multicenter, propensity-weighted cohort study. Conducted across 220 geographically diverse community and teaching hospitals in the United States. Adult patients (age ≥ 18 yr) with septic shock who were initiated on either H2RAs or PPIs on the day of hospital admission. H2RAs (famotidine) or PPIs (pantoprazole, omeprazole, esomeprazole, or lansoprazole). The primary outcome was the occurrence of UGIB during hospitalization. Secondary outcomes included in-hospital mortality, ventilator-associated pneumonia, Clostridioides difficile infection, and hospital length of stay. Propensity scores with inverse probability of treatment weighting (IPTW) were used to control for confounding. Among 15,102 patients (5,492 H2RA, 9,610 PPI), the mean age was 65.8 ± 14.9 years, 47.8% were female, and 58.1% received invasive mechanical ventilation during hospitalization. After IPTW adjustment, PPI use was associated with a lower occurrence of UGIB compared with H2RA (odds ratio [OR], 0.78; 95% CI, 0.64-0.96; p = 0.016). A sensitivity analysis comparing famotidine to pantoprazole confirmed this finding (OR, 0.80; 95% CI, 0.65-0.97; p = 0.025). No significant differences were observed in in-hospital mortality (OR, 0.98; 95% CI, 0.91-1.06; p = 0.691), ventilator-associated pneumonia (OR, 0.93; 95% CI, 0.83-1.04; p = 0.188), C. difficile infection (OR, 1.32; 95% CI, 0.82-2.13; p = 0.246), or hospital length of stay (incidence rate ratio, 1.01; 95% CI, 0.98-1.05; p = 0.417). In this large, diverse cohort of U.S. hospitalized adults with septic shock, PPI use for stress ulcer prophylaxis was associated with a significantly lower occurrence of UGIB compared with H2RA, with no significant differences in mortality, ventilator-associated pneumonia, C. difficile infection, or hospital length of stay.

Proton pump inhibitors (PPIs) are drugs capable of blocking the gastric pump H,K-ATPase in order to inhibit gastric acid secretion. Omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole belong to PPIs category. Although PPIs have a good safety profile, allergic reactions to these molecules can occur. The real rate of hypersensitive reactions to PPIs is unknown. The aim of this retrospective study is to evaluate the rate of hypersensitive reactions to PPIs in patients admitted to our Unit between 2008 and 2013 with a history of drug hypersensitivity. From a database of 1229 patients (921 women, 308 men) with adverse drug reaction we extrapolated the data about PPI reactions. Twelve patients (10 female, 2 men) had a positive history for hypersensitive reaction to PPI. Pantoprazole was the most frequently PPI involved. Based on patient personal history in some cases we performed an oral challenge test for an alternative anti-acid drug and none of them had adverse reactions. According to our experience and according to the literature and pharmacovigilance reports, ADR caused by PPIs are ever increasing. Adverse reactions to these drugs are still under-reported; however, considering the frequency of their prescription worldwide, the risk of severe allergic events is low. Further studies are needed to provide clearer data on the real incidence and prevalence about this matter. This should be useful to help physician in choosing the molecule to prescribe and, in case of hypersensitivity, the alternative molecule to test, also considering the possible cross-reactivity.

To update rapidly evolving concepts regarding the controversial entity of 'proton pump inhibitor (PPI)-responsive esophageal eosinophilia,' referring to patients with clinical, endoscopic and histologic features of eosinophilic esophagitis (EoE) who achieve remission on PPI therapy. Up to half of pediatric and adult patients with typical EoE symptoms and histology achieve clinico-pathologic remission on PPI therapy, irrespective of whether esophageal pH monitoring demonstrates abnormal acid reflux. In patients with clinical and histologic features of EoE, genotypic and phenotypic features of PPI responders and nonresponders are virtually indistinguishable, and different from those of patients with gastroesophageal reflux disease. In PPI responders, PPIs effects on esophageal Th2 inflammation and gene expression are similar to those of topical steroids in PPI nonresponders. These therapies, along with diets, recently have been shown to be potentially interchangeable in two small series. Proton pump inhibitor-responsive esophageal eosinophilia is an inappropriate disease descriptor, arbitrarily based on a response to a single drug, and should be abandoned. Patients who have esophageal eosinophilia and esophageal symptoms that resolve with PPI therapy have phenotypic, molecular, mechanistic, and therapeutic features indistinguishable from similar patients who do not respond to PPIs. These patients with PPI responsiveness should be considered within the spectrum of EoE.

Evidence for Cross-Reactivity Among Proton Pump Inhibitors (PPIs): A Case Report of Hypersensitivity to Three PPIs

¿Existe reactividad cruzada entre inhibidores de la bomba de protones?

Nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin are among the most frequently prescribed and used medications.1 With the development of video capsule endoscopy, the frequency and severity of NSAID enteropathy has become more evident.2 NSAID-induced enteropathy has a different pathological mechanism from gastroduodenal mucosal injury, so different treatments and preventative strategies are needed. NSAID-induced enteropathy is common. Approximately 70% of regular NSAID users develop injury in the small intestine, which is more common than gastroduodenal mucosal injuries.2 Endo et al.3 reported small-bowel mucosal breaks in 57.6% of patients receiving NSAIDs. There is a poor correlation between NSAID-induced damage and symptoms in the small intestine. NSAID-induced enteropathy is usually asymptomatic or has nonspecific symptoms, such as iron-deficiency anemia, occult blood, diarrhea, hypoalbuminemia, and malabsorption of vitamin B12. Endo et al.4 studied patients on low-dose aspirin with obscure gastrointestinal (GI) bleeding with capsule endoscopy and found that more than 95% of the patients had some mucosal injury in the small bowel. The enteropathy was characterized by multiple petechiae and loss of villi. It revealed that even low doses of NSAIDs could lead to the generation of erosions and ulcerations in the small intestine.5 Maiden et al.6 reported mucosal injury in the small bowel in 68% to 75% of volunteers after 2 weeks of therapy with 75 mg slow-release diclofenac taken twice daily. Recent studies have reported unwanted and more dangerous adverse effects in the small intestine if proton pump inhibitors (PPIs) are combined with NSAIDs.7 PPIs, by suppressing gastric acid secretion, are very effective for reducing NSAID-induced damage in the stomach but are without proven benefit in preventing NSAID-related damage in the rest of the GI tract.7 Moreover, PPIs alter the microbiome in the small intestine.8 Capsule endoscopy studies have revealed that adding PPIs to NSAIDs results in a higher frequency of mucosal lesions in the small intestine than the frequency observed in patients taking NSAIDs alone.9,10 Some investigators have reported that all patients taking both NSAIDs and PPIs have ulcerations in the small intestine.9 Most patients (80% to 100%) taking low-dose NSAIDs and PPI therapy have active mucosal lesions in the small bowel after 2 weeks of therapy.10 A recent prospective capsule endoscopy study found that enteric-coated aspirin and PPI were the two most important risk factors for the development of mucosal breaks in the small intestine.3 However, it should be considered that it was an observational cross-sectional study, and PPI use is a well-known marker of comorbidity that might not have been properly controlled for in the analysis.11 No human clinical trial has shown that the combination of a PPI and aspirin is associated with an increased risk of lower GI bleeding. Strategies to prevent aspirin- or NSAID-induced enteropathy include the identification and modification of associated risk factors and co-prescription of a protective agent.12 Shim et al.13 showed outcomes and long-term follow-up data in a nationwide multicenter study in Korea and reported that recurrence of NSAID-induced small bowel injury was not frequent (4.6%). Conservative management was also sufficient in most recurrent cases. The risk factors for recurrence were old age and hypertension. However, that study did not present accurate information of coadministered drugs after the initial episode of bleeding because of its retrospective design. However, after or during the first episode of small bowel bleeding, 64% of patients received PPIs. These patients might have added or continued to take PPIs for treatment of enteropathy alone as well as to lower the risk of upper GI bleeding. Six patients showed recurrence. There were no comparative data on PPI use between the recurrent and nonrecurrent cases. If it is supposed that all recurred cases were taking PPIs, the maximum possible recurrence rate for NSAID-PPI coadministration would be 6 of 61 (10%). The study did not analyze which type of aspirin the patients had used. However, in Korea, most of the aspirin prescribed for cardiovascular prevention is the enteric coated form. In the initial episode of bleeding, the most prominent capsule endoscopic findings were multiple ulcerations (59%) and erosions or aphthae (23%). However, the diagnosis of recurrence depended on clinical findings without a repeated capsule endoscopy. Lesions in the small intestine might tend to persist whether NSAID therapy is continued or not. NSAID- or low-dose aspirin-induced enteropathy is common but can be asymptomatic.11 Moreover, because of the difficulty in diagnosing it, as well as the lack of any proven-effective treatment for NSAID-induced enteropathy, the clinical relevance may be underestimated. Shim et al.13 showed a clinically benign course of enteropathy in long-term follow-up data. Further studies of drug interactions and risk factor analyses are required to determine an effective preventive strategy.

BackgroundManagement of Helicobacter pylori (H. pylori) infection requires co‐treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication.AimTo evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the ‘European Registry on Helicobacter pylori management’ (Hp‐EuReg).MethodsHp‐EuReg is a multicentre, prospective, non‐interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022.ResultsOverall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first‐line‐modified intention‐to‐treat effectiveness was achieved with the following treatments: (1) 14‐day therapies with clarithromycin‐amoxicillin‐bismuth and metronidazole‐tetracycline‐bismuth, both independently of the PPI dose prescribed; (2) All 10‐day (except 10‐day standard triple therapy) and 14‐day therapies with high‐dose PPIs; and (3) 10‐day quadruple therapies with clarithromycin‐amoxicillin‐bismuth, metronidazole‐tetracycline‐bismuth, and clarithromycin‐amoxicillin‐metronidazole (sequential), all with standard‐dose PPIs. In first‐line treatment, optimal effectiveness was obtained with high‐dose PPIs in all 14‐day treatments, in 10‐ and 14‐day bismuth quadruple therapies and in 10‐day sequential with standard‐dose PPIs. Optimal second‐line effectiveness was achieved with (1) metronidazole‐tetracycline‐bismuth quadruple therapy for 14‐ and 10 days with standard and high‐dose PPIs, respectively; and (2) levofloxacin‐amoxicillin triple therapy for 14 days with high‐dose PPIs. None of the 7‐day therapies in both treatment lines achieved optimal effectiveness.ConclusionsWe recommend, in first‐line treatment, the use of high‐dose PPIs in 14‐day triple therapy and in 10‐or 14‐day quadruple concomitant therapy in first‐line treatment, while standard‐dose PPIs would be sufficient in 10‐day bismuth quadruple therapies. On the other hand, in second‐line treatment, high‐dose PPIs would be more beneficial in 14‐day triple therapy with levofloxacin and amoxicillin or in 10‐day bismuth quadruple therapy either as a three‐in‐one single capsule or in the traditional scheme.