Acid-suppressive medication and incidence of chronic childhood immune-mediated diseases: A scoping review.

BACKGROUND: Use of acid-suppressive medications (ASMs), for example, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), has been rising along with the incidence of pediatric immune-mediated diseases (IMDs). We conducted a scoping review to characterize the literature about prenatal or pediatric exposure to ASMs in relation to incident pediatric IMDs. METHODS: Electronic searches were conducted to identify studies from 2001 to 2023 on (a) prenatal or pediatric exposure to PPIs and/or H2RAs and (b) the risk of developing chronic IMDs during childhood. Eligible studies after title/abstract and full-text screening underwent data abstraction. RESULTS: Of 26 eligible studies, 11 focused on prenatal ASM exposure and 16 on pediatric exposure. Asthma was the most commonly investigated outcome (16 studies), followed by other allergic diseases (8), eosinophilic esophagitis (3), inflammatory bowel disease (2), and other autoimmune diseases (2). Positive associations between ASM exposure and pediatric IMD outcomes emerged in all but two recent studies, which reported null or negative associations with allergic diseases. The strength of associations was similar across exposure times (prenatal/pediatric), medications (PPIs/H2RAs), and outcomes. Dose-response relationships were often present (7/11 studies). Reported effects by trimester and age of exposure varied. Commonly reported limitations were residual confounding, exposure misclassification, and outcome misclassification. CONCLUSION: In summary, prenatal or pediatric exposure to PPIs and/or H2RAs has frequently, but not exclusively, been associated with the development of asthma, other allergic diseases, and chronic gastrointestinal IMDs. However, concerns remain about confounding and other sources of bias. Prescribers and families should be aware of these possible risks of ASMs.

Successful use of mepolizumab for severe hypereosinophilic vasculitis with c-ANCA positivity in a previously healthy 7-year-old boy.

An unusual case of a pediatric patient with severe eosinophilic vasculitis causing digital ischemia is reported. The patient responded well to the anti-IL-5 agent mepolizumab, lending support for use of mepolizumab in pediatric patients with hypereosinophilic syndromes.

Allergic Rhinitis.

Allergic rhinitis (AR) affects more than 400 million people worldwide, making it 1 of the most prevalent chronic diseases. Childhood AR is increasing, and almost half of patients with AR develop symptoms before age 6 years. Although a diagnosis of AR is associated with higher socioeconomic status, underserved and urban populations have more indoor aeroallergen sensitizations and are likely underdiagnosed with AR, further exacerbating health-care disparities. AR negatively impacts quality of life, school performance, and overall health outcomes. Untreated AR in children increases the risk for poor asthma control, increased asthma severity, and exacerbations. Many patients believe that they have seasonal allergies only but in reality have both perennial and seasonal AR, which may change the approach to allergen avoidance measures and treatment recommendations. Pharmacotherapy of AR has expanded, with many intranasal corticosteroids, intranasal antihistamines, and second-generation oral antihistamines approved for pediatric use. Allergen immunotherapy, including both subcutaneous and sublingual forms, are approved for children and are disease modifying, potentially reducing further allergen sensitization and progression to asthma. Many of the currently available biological therapies indicated for pediatric asthma and/or atopic diseases reduce AR symptoms as well. Children with moderate to severe or refractory AR or those with comorbidities should be referred to allergists for diagnostic testing and expanded management options, including immunotherapy and potential biological treatment.

Skin Testing Is Useful in Assessing Aeroallergen Sensitization in IgE Deficient Patients with Environmental Allergy-Like Symptoms.

BACKGROUND: The value of aeroallergen skin testing is not known in IgE deficient individuals (IgE<2.5 kU/L). OBJECTIVE: To investigate the utility of skin prick (SPT), intradermal skin testing (IDST) and measuring serum specific IgE (ssIgE) in IgE deficient patients presenting with environmental allergy-like symptoms. METHODS: Individuals with IgE deficiency who had both SPT and IDST performed between 2010 to 2020 were matched (age and gender) to three different groups of non-IgE deficient patients with IgE≥2.5 kU/L (normal IgE [2.5 ≤ IgE<100], high IgE [100≤IgE<1000] and very high IgE levels [≥1000 kU/L]) who also had skin testing performed for evaluation of environmental allergy-like symptoms. RESULTS: Among 34 IgE deficient patients who completed SPT and IDST, 52.9% (18/34) had at least one positive skin test (4 ± 3 positive tests/patient), compared with 91.2% in those with normal, 94.1% with high or 97.1% with very high IgE levels (p < 0.01). In contrast, only one of the IgE deficient patients had detectable ssIgE, while ssIgE levels were significantly higher in all other IgE subgroups. Allergic immunotherapy was prescribed for 22.2% of the IgE-deficient patients with positive skin tests, similar to those with normal (2/31, 6.5%, p = 0.21), high IgE (9/32, 28.1%, p = 0.25) and very high IgE levels (8/33, 23.5%, p = 0.07), with similar efficacy in their symptoms control. CONCLUSION: Individuals with IgE deficiency may present with environmental allergy-like symptoms. A combination of SPT and IDST is useful for diagnosing aeroallergen sensitizations in these patients, indicating the presence of skin mast cell-bound IgE in some of these individuals, despite very low serum IgE levels. Further studies are needed to assess the exact significance of positive skin tests and the benefits of immunotherapy in this group.

Successful Drug Desensitization to Ustekinumab in a Patient with Crohn's Disease.

Ustekinumab is a monoclonal antibody used as treatment for various inflammatory conditions. We present a pediatric patient with Crohn's disease who did not tolerate infliximab and was then changed to ustekinumab. He developed anaphylaxis to the medication after the second dose. A drug desensitization protocol was created by the allergy team leading to successful administration of both intravenous and then subcutaneous ustekinumab. As monoclonal agents become mainstays of therapy for inflammatory conditions, there are increased reports of allergic reactions. Prior reports and protocols of ustekinumab desensitization have not been reported. This case report highlights successful desensitization to ustekinumab as well as the importance of a multidisciplinary approach to addressing treatment needs of patients who develop life-threatening reactions to such medications.

Successful Graded Dose Challenge to Iodixanol Radiocontrast Media in a Patient With Delayed Anaphylaxis to Iohexol.

We present a case of an 82-year-old male with known radiocontrast media (RCM) hypersensitivity who was admitted to our hospital with gangrene of his right toe. The plan for revascularization of his lower extremity required an angiogram. This presented a management challenge as the patient had experienced 2 episodes of delayed anaphylaxis to Omnipaque (iohexol) RCM, and based on a literature review, there was no known or established precedent on a safe procedure in these situations. The patient was premedicated and given a graded dose challenge of an alternative RCM (iodixanol) prior to the radiographic study. He was given 1% of the total expected dose 1 hour before to the procedure and an additional 10% for the 30 minutes prior. He was then given the final dose in the operating room. Following angiogram, the patient was monitored for 18 hours in the postanesthesia care unit, with no adverse reactions. He was placed on a prednisone taper for 1 week, with daily diphenhydramine. The patient remained asymptomatic throughout the hospital course. This novel approach to RCM hypersensitivity management lends itself to a hope that graded dose challenges may play a greater role in the management of these patients.

Pediatric Oncology Provider Views on Performing a Biopsy of Solid Tumors in Children with Relapsed or Refractory Disease for the Purpose of Genomic Profiling.

BACKGROUND: Patients with relapsed and refractory solid tumors have a poor prognosis. Recent advances in genomic technology have made it feasible to screen tumors for actionable mutations, with the anticipation that this may provide benefit to patients. METHODS: Pediatric oncologists were emailed an anonymous 34-question survey assessing their willingness to offer a rebiopsy to patients with relapsed disease for the purpose of tumor genomic profiling. They were presented with two scenarios evaluating morbidity and invasiveness of the procedures using the clinical examples of medulloblastoma and Ewing sarcoma. RESULTS: A total of 195 pediatric oncologists responded to the questionnaire. Morbidity and invasiveness of the procedure demonstrated significant differences in provider willingness to refer their patients for rebiopsy. The pretest probability was a major variable influencing provider willingness to offer a rebiopsy. Respondents were more likely to offer a rebiopsy if the likelihood was high that the results would have an impact on clinical management than if the biopsy was for histologic confirmation alone (mean 89 vs. 56 %; p = 0.017). Compared with the rate of a rebiopsy for histologic confirmation, significantly fewer providers were willing to offer a rebiopsy if they were led to believe the likelihood of finding an actionable mutation was low (mean 45 vs. 56 %; p = 0.021). CONCLUSION: The scenario showed that the pretest probability of finding an actionable mutation was influential in determining provider willingness to offer a rebiopsy for the purpose of tumor genomic profiling. Further research is warranted to evaluate the benefit of tumor genomic profiling in terms of patient outcomes.