This week in Allergy & Immunology

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Welcome to This Week in Allergy & Immunology. This week we're covering 10 notable papers spanning eosinophilic gastrointestinal disease, biologic therapy and steroid safety in the airways, and the practical realities of food allergy and immune deficiency diagnosis. Let's dive in.

Eosinophilic disease of the gut is getting sharper definitions, both from consensus and from the laboratory. In Allergy, Lucendo and colleagues present Part 1 of the updated European guidelines on eosinophilic esophagitis, covering diagnosis, epidemiology and natural history in children and adults [1]. The panel of 32 experts from EUREOS, EAACI, ESPGHAN and the European Society of Pathology used GRADE methodology and a Delphi process requiring at least 80 percent agreement. They describe eosinophilic esophagitis as a heterogeneous type 2 inflammatory disease that has become the leading cause of dysphagia and food impaction, with annual incidence now above 10 per 100,000 and pooled prevalence above 60 per 100,000, exceeding 160 per 100,000 in some regions. Diagnosis still rests on symptoms of esophageal dysfunction plus at least 15 eosinophils per high-power field after excluding other causes, and the guideline explicitly separates the disease from asymptomatic esophageal eosinophilia. Two recommendations stand out for daily practice: the panel recommends at least six biopsies from at least two esophageal levels, because endoscopic appearance alone is not sensitive enough, and gastric or duodenal biopsies are no longer considered mandatory unless symptoms or endoscopic findings point there. Further down the bowel, Taylor and colleagues in the Journal of Allergy and Clinical Immunology tackle a harder diagnostic problem: telling eosinophilic colitis apart from eosinophil-rich inflammatory bowel disease [2]. Using 88 colonic biopsies from a multicenter cohort enriched for children and young adults, they built a 96-gene panel with two scores. An eosinophilic score discriminated active eosinophilic colitis from controls well and tracked peak eosinophil counts, but on its own it could not separate eosinophilic colitis from inflammatory bowel disease. A second, 18-gene inflammatory bowel disease score resolved that overlap almost perfectly and correlated with endoscopic activity. This is a small derivation study with wide uncertainty around its accuracy estimates, so it points toward a molecular tool rather than delivering one ready for routine use.

The airway papers this week are mostly about what biologics achieve outside trials, and about the costs of the systemic steroids they aim to replace. In the Journal of Allergy and Clinical Immunology: In Practice, DeMartino and colleagues report the CROSSROADS-4 analysis of tezepelumab in 527 patients with severe asthma drawn from a United States claims database [3]. Comparing the year before and the year after starting treatment, annual exacerbation rates fell by a little over half, and exacerbation-related healthcare use in every setting dropped by a similar margin. The reduction was larger, around sixty percent, among patients who started after early 2023, and it held across eosinophil-high and eosinophil-low patients, high and low IgE, biologic-naive and biologic-experienced patients, and those with COPD or nasal polyps. The design is a self-controlled pre-post comparison, which cannot fully separate drug effect from regression to the mean in patients selected for recent exacerbations, but it adds real-world support to trial data for a broad phenotype. From Japan, in Allergology International, Nakashima and colleagues followed 104 patients with refractory eosinophilic chronic rhinosinusitis with nasal polyps who stayed on dupilumab for more than three years at a single center [4]. Polyp scores, CT scores and smell improved within three months and were sustained. Among patients with comorbid asthma, average inhaled steroid dose fell by more than half, to around 240 micrograms of budesonide equivalent a day, and a growing share of patients came off maintenance inhaled steroids altogether. About one in five patients had persistent smell loss, and older age and longer disease duration, with cut-offs near 47 years and 7 years respectively, identified a group with roughly six times the odds of that outcome. It is retrospective and limited to patients who stayed on treatment, so the authors' framing of remission off conventional therapy is a hypothesis worth testing prospectively. The counterweight comes from Jang and colleagues, also in the Journal of Allergy and Clinical Immunology: In Practice, who used Korean national claims data in a self-controlled case series of 5,060 children and adolescents with newly diagnosed asthma [5]. Tendon and muscle disorders were roughly two and a half times more frequent during systemic corticosteroid exposure than outside it, and the risk stayed modestly raised for up to two weeks after the course ended. Because each child serves as their own control, fixed confounders are handled well, though claims coding of musculoskeletal events is imprecise. The finding adds an underappreciated harm to the case for minimizing oral steroid bursts in children.

Food allergy this week spans how we confirm the diagnosis, how we recognize milder phenotypes, and how school policy shapes children's lives. Kuwabara and colleagues, in Allergology International, systematically reviewed studies in which both open oral food challenges and double-blind placebo-controlled challenges were performed [6]. Only eight studies qualified, and risk of bias was high. Sensitivity of open challenges was around ninety percent and negative predictive value roughly ninety percent or higher, while positive predictive value ranged enormously, from zero to close to ninety percent. The authors conclude that a negative open challenge appears reliable, but a positive open challenge cannot yet be treated as equivalent to a blinded one, and the evidence base is too thin to replace the reference standard. In the Journal of Allergy and Clinical Immunology: In Practice, Cosper and colleagues describe a United States pediatric cohort of food protein-induced enterocolitis syndrome that compared children who fully met the 2017 consensus criteria for acute FPIES with those who only partially met them [7]. The available abstract is brief, but the authors frame their findings as reinforcing the existence of milder FPIES phenotypes that strict criteria may miss, which matters for how the diagnosis is applied in clinic. Finally, in the Journal of Allergy and Clinical Immunology, Gray and colleagues surveyed 652 child-parent pairs to ask whether peanut and tree nut restrictive policies in schools and daycares cause harm [8]. They found no association between such policies and bullying, child or parent anxiety, or parental quality of life. In younger children, from daycare through elementary school, restrictive policies were associated with better food allergy-related quality of life, and parents across all grades reported more comfort when a policy was in place. The cross-sectional survey design and a recruitment base of mostly mothers from one center and social media limit causal claims, but the data counter a common worry that these policies stigmatize children.

Two papers address the immunologist's role in diagnosing immune deficiency, whether acquired or inborn. Chong and colleagues at Mayo Clinic, in the Journal of Allergy and Clinical Immunology: In Practice, reviewed 1,184 patients receiving their first rituximab infusion [9]. IgG had been checked within the prior year in just over half of patients, up sharply from historical rates below fifteen percent, but testing ranged from about one in seven dermatology patients to roughly four in five neurology patients. Among patients tested within 60 days, more than a quarter already had hypogammaglobulinemia, including four in five patients with nephrotic syndrome, yet only about one in ten of those with low IgG received immunoglobulin before treatment. The authors note that optimal management of baseline hypogammaglobulinemia remains undefined, but the data make a case for standardizing pre-treatment assessment. Rounding out the week, a review in Current Allergy and Asthma Reports offers a mechanism-informed, stepwise framework for genetic testing in suspected inborn errors of immunity, using disorders such as RAG deficiency, AIRE, FOXP3, IL2 receptor defects, FAS and CARD11 gain of function as worked examples [10]. Its emphasis is on matching test choice to the clinical and immune phenotype and recognizing where current testing falls short, rather than new data.

If you only have time for one paper this week, make it the European eosinophilic esophagitis guideline from Lucendo and colleagues in Allergy [1]. It resets the diagnostic standard across children and adults, settling questions on biopsy number and on whether gastric and duodenal biopsies are routinely needed.

Here is what this week's evidence adds up to in Allergy & Immunology. First, eosinophilic esophagitis diagnosis now has updated European consensus favoring at least six biopsies from two levels without routine gastric or duodenal sampling, while a molecular panel for colonic eosinophilia is promising but still at an early, small-sample stage. Second, real-world data for tezepelumab in asthma and dupilumab in nasal polyps are consistent with trial benefits, including inhaled steroid de-escalation, though both studies are retrospective and uncontrolled. Third, systemic steroid bursts in children carry a measurable short-term risk of tendon and muscle problems, adding to the observational case for limiting them. Fourth, a negative open food challenge appears dependable, school nut restriction policies show no sign of psychosocial harm, and milder FPIES phenotypes are gaining recognition, though each rests on limited or cross-sectional evidence. Finally, low IgG is common before rituximab, testing remains inconsistent, and how best to manage it is unsettled.

That's your roundup for This Week in Allergy & Immunology. The full transcript and references are available on the episode page. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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