Eosinophilia and Hypereosinophilia: A Practical Approach to Navigating a Broad Differential Diagnosis

S. Wigerinck and P. Vandenberghe, European Journal of Haematology (2026): 1–15, https://doi.org/10.1111/ejh.70299.

Abstract

Eosinophilia, defined as an absolute eosinophil count (AEC) of ≥ 0.5 × 109/L, is a frequently encountered finding with a vast spectrum of potential underlying etiologies. Hypereosinophilia (HE) is defined as AEC > 1.5 × 109/L and may become life-threatening when eosinophil-induced organ damage occurs, defining the hypereosinophilic syndrome (HES). Among the many causes of HE, rare hematological malignancies, in particular the “myeloid/lymphoid neoplasms (MLN) with eosinophilia and tyrosine kinase (TK) gene fusions,” represent phenotypically and prognostically heterogeneous and challenging entities.

For this reason, the evaluation of HE constitutes a diagnostic and therapeutic challenge. In this review, we provide a concise overview of eosinophil biology, highlight their physiological role as regulators of immunity, tissue homeostasis, and inflammation, their involvement in diseases affecting nearly all organ systems, and in hematological malignancies in particular. Furthermore, we present a practical, stepwise diagnostic approach to HE, emphasizing early recognition of eosinophil-mediated organ dysfunction to initiate timely treatment, as well as red flags that should raise further hematologic evaluation, including molecular and cytogenetic investigations to identify an underlying clonal disorder. Treatment strategies depend on the underlying etiology and range from supportive care, over corticosteroids to targeted biological therapies and tyrosine kinase inhibitors (TKIs).

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Efficacy of Biological and Steroid Therapies in Adolescent and Adult Patients With Eosinophilic Esophagitis: A Systematic Review and Network Meta-Analysis With Meta-Regression

Al Hayek M, Lucendo AJ, Savarino E et al. Clin Gastroenterol Hepatol. 2026 Sep;24(9):2374-2386. doi: 10.1016/j.cgh.2026.04.003.

Abstract

Background & Aims

The therapeutic hierarchy of current pharmacologic options for eosinophilic esophagitis (EoE) has not been established. We performed a network meta-analysis to evaluate the comparative efficacy of pharmacological therapies for EoE.

Methods

PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception to May 25, 2025, for randomized controlled trials (RCTs) ≥12 weeks in duration comparing corticosteroids, biologics, or proton pump inhibitors with placebo or active comparators in participants aged ≥12 years. Key outcomes included changes in dysphagia from baseline and histologic remission (≤6 eosinophils/high-power field) at 12, 24, and 48 weeks. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Results

Graphical Abstract

Thirteen RCTs were included. For dysphagia improvement compared with placebo and active comparators, dupilumab 300 mg and cendakimab 360 mg demonstrated moderate-to-high-certainty benefit at 12 and 24 weeks, whereas budesonide oral suspension (BOS) 2 mg demonstrated moderate-to-high-certainty benefit at 12 weeks; no 24-week data were available for BOS. At 48 weeks, budesonide orodispersible tablets (BOT) 0.5 and 1 mg demonstrated high certainty benefits for dysphagia improvement compared with placebo and active comparators.

Chronic Symptomatic Dermographism in a Young Atopic Adult With Fluctuating Serum IgE Levels and no Correlation to Disease Activity: A Case Report

A. A. Shaju, S. Sadaf, M. Hasanuzzaman, and N. Nawal.  Clinical Case Reports 14, no. 8 (2026): e73352, https://doi.org/10.1002/ccr3.73352.

ABSTRACT

Chronic symptomatic dermographism is a challenging dermatologic condition characterized by recurrent wheals triggered by nonspecific physical stimuli, and management typically begins with H1-antihistamines, escalating as needed, with anti-IgE therapy such as omalizumab reserved for refractory cases based on clinical response rather than serum IgE levels. We report a 20-year-old male with a long-standing history of symptomatic dermographism and childhood atopy, provoked by minimal mechanical stimuli such as friction from clothing or light stroking of the skin, which significantly impaired his daily activities and academic performance. 

Multiple erythematous, raised, and edematous wheals of varying
sizes involving the extensor aspect of the forearm, with
ill-defined borders and blanching on pressure.

Diagnosis was made clinically and by exclusion of systemic disease, with laboratory investigations revealing fluctuating serum IgE levels over multiple measurements, ranging from markedly elevated to near-normal, without correlation to disease severity, highlighting the limitations of using IgE to guide therapy. Standard management included up-dosed second-generation H1-antihistamines (up to fourfold the standard dose) and intermittent short courses of oral corticosteroids resulting in partial disease control.

Common Food Emulsifiers Impair Epithelial Barrier Integrity and Trigger Pro-Inflammatory Responses and IgE Production

Yazici D, Hayashi Y, Pat Y et al. Allergy. 2026 Aug 8. doi: 10.1111/all.70473. 

ABSTRACT

Graphical Abstract

The global rise in allergic and autoimmune diseases since the 1960s has been associated with environmental disruptions of epithelial barriers, particularly in the gastrointestinal tract. Among the implicated factors are food emulsifiers, which have become increasingly prevalent in processed foods such as peanut butter. This study investigates the biological effects of two commonly used food emulsifiers in peanut butter, soy lecithin and diacetyl tartaric acid esters of mono- and diglycerides (DATEM), on gastrointestinal tissue responses and immune responses using advanced in vitro gut-on-a-chip models, human adult stem cell-derived colon organoids-on-a-chip, and murine models.

Microneedles for allergy skin testing: Comprehensive analysis of agreement, accuracy, and pain

Sirichuwong M, Kanchanapoomi K, Piboonpocanun S et al. J Allergy Clin Immunol Glob. 2026 Jul 23;5(5):100765. doi: 10.1016/j.jacig.2026.100765. 

Abstract

Background

The skin prick test (SPT) is a standard method for identifying allergic sensitization. However, pain and needle phobia often compromise pediatric compliance. Microneedle devices offer a minimally invasive alternative to conventional lancets.

Objective

We evaluated the agreement, diagnostic accuracy, and patient tolerability of a novel microneedle compared to a lancet for SPT.

Schematic illustration of novel microneedle device and SPT procedure.

Methods

Subjects with allergic rhinitis underwent SPT using both devices with Dermatophagoides pteronyssinus (Dp) extract, histamine, and saline controls. Net mean wheal diameters (MWD) were calculated by subtracting the saline MWD from the Dp and histamine MWDs. Agreement was assessed by Bland-Altman analysis and Cohen kappa (k), diagnostic performance by receiver operating characteristic analysis, and pain by a visual analog scale.

Results

Bland-Altman plots showing difference versus average
of MWDs between microneedle device and lancet. 

Of 150 subjects (aged 8-60 years), 53.3% were sensitized to Dp. Both devices produced significantly larger Dp and histamine MWDs than saline MWD (P < .001). Median [interquartile range] Dp MWD was smaller with microneedle (2 [0-8.13] mm) than lancet (4 [0-12.5 mm], P < .001).

EAACI Guidelines on Environmental Science for Allergy and Asthma—Evidence-Based Recommendations for Prevention and Public Health Action to Mitigate the Impact of Pollen Exposure on Respiratory Allergy

L. Cecchi, I. Annesi-Maesano, B. Biagioni, et al.  Allergy (2026): 1–25, https://doi.org/10.1111/all.70423.

ABSTRACT

Developed using the GRADE methodology, these EAACI guidelines provide evidence-based recommendations on the effectiveness of pollen reduction/avoidance strategies for allergic rhinitis (AR) and asthma, the utility of biomarkers for monitoring pollen-induced asthma and the efficiency of mitigation measures and of public health strategies. Systematic and narrative reviews and health economic analysis support the recommendations. According to GRADE, the certainty of evidence was moderate to very low, therefore conditional recommendations are provided to guide healthcare professionals, patients, and policymakers in developing personalized, preventive, and scalable interventions.

Optimising allergic rhinitis management in primary care using the respiratory allergy optimiser: results from the AERO study

van Geer-Postmus, I., Ryan, D., Arling, C. et al.  npj Prim. Care Respir. Med. (2026). https://doi.org/10.1038/s41533-026-00551-0

Abstract

Digital tools may support healthcare professionals in providing guideline-directed management for patients with allergic rhinitis (AR). This study aimed to develop and implement the Respiratory Allergy Optimiser, a digital decision-support tool aligned with AR guideline recommendations, and evaluate its effect on symptom severity in primary care. The AERO study was an interventional study conducted in 11 general practices in the Netherlands (August-November 2025). Adult patients with a diagnosis of AR and/or allergic conjunctivitis and/or prescribed AR medication (past three years) were eligible. The Respiratory Allergy Optimiser assessed symptom severity using a visual analogue scale (VAS, 0–100 mm) and collected information on patient and disease characteristics, symptoms, medication use, adherence, and nasal spray technique.

CD4 CTLs in supercentenarians: Signs of adaptive expansion in healthy aging

Hashimoto K, Kojima-Ishiyama M, Inokuchi H et al. Cell Reports, 2026; 0

Highlights

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CD4 CTLs expand around age 100 without signs of exhaustion

•

A CD27−CD28+ state marks the intermediate helper-to-killer transition

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Large private CD4 CTL clones suggest repeated antigen exposure

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Single clones diversify cytokine profiles after ex vivo stimulation

Summary

Graphical Abstract

Our previous study identified CD4 cytotoxic T lymphocytes (CD4 CTLs) as a hallmark of supercentenarians. CD4 CTLs have primarily been studied in disease contexts; however, their role in healthy aging remains unclear. Using single-cell immune profiling, we analyzed T cells from supercentenarians and found that CD4 CTLs begin to expand around the age of 100, characterized by sequential CD27/CD28 loss without exhaustion.