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

•

CD4 CTLs expand around age 100 without signs of exhaustion

•

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

•

Large private CD4 CTL clones suggest repeated antigen exposure

•

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.

ARIA-EAACI 2025: Person-Centred, Digitally Enabled and Artificial Intelligence-Assisted Change Management in Airway Diseases

J. Bousquet, B. Sousa-Pinto, M. H. Shamji, et al. Clinical and Translational Allergy (2026): e70192, https://doi.org/10.1002/clt2.70192.

ABSTRACT

Person-centred, digitally enabled, AI-assisted care
pathways based on ARIA-EAACI guidelines
using MASK-air as a common tool:
 OECD Best Practice. AI, artificial intelligence;
AIT, allergen immunotherapy;
IPCRG, International Primary Care Respiratory Group;
IPF, International Pharmacist Federation;
OTC, over-the-counter.

Allergic Rhinitis and its Impact on Asthma (ARIA) was, up until 2017, a guideline using the best evidence (Grading of Recommendations, Assessment, Development and Evaluation, GRADE) and developed as a change management strategy. A second change management strategy—in collaboration with the European Academy of Allergy and Clinical Immunology (ARIA-EAACI)—was developed as a person-centred, digitally enabled, artificial intelligence-assisted care (person-centred care) with strong political involvement. The digital tools of ARIA are mainly based on MASK-air, an Organisation for Economic Co-operation and Development (OECD) Best Practice for integrated care for chronic diseases.

Maternal influences on infant gut microbiome and health

Sinha, T., Brushett, S., Fernández-Pato, A. et al.  Nature (2026). https://doi.org/10.1038/s41586-026-10922-9

Abstract

Mother-to-infant gut microbial transmission.

The establishment of the infant gut microbiome is critical for later health, yet how it is shaped by maternal and early-life factors remains unclear. Here we metagenomically sequenced 4,526 longitudinal faecal samples from 714 mother–infant pairs in the Dutch birth cohort Lifelines NEXT, spanning 12 weeks of pregnancy to 1 year postpartum. We integrated these data with 474 clinical and exposure variables, and with ultra-deep sequencing of breast milk and vaginal microbiomes. We observe that the maternal gut microbiome undergoes only subtle changes during pregnancy and postpartum, influenced by diet, infections and pre-pregnancy smoking.

Early and longitudinal response to sublingual immunotherapy across pediatric allergic multimorbidity patterns: A 3-year real-world cohort study

Gonzalez-Uribe V, Prieto-Gomez J, Moreno-Castro S et al.  Pediatr Allergy Immunol. 2026 Aug;37(8):e70462. doi: 10.1111/pai.70462. 

Abstract

Background

The timing of clinically meaningful benefit after pediatric sublingual immunotherapy (SLIT) across allergic multimorbidity patterns remains uncertain. We evaluated early and longitudinal response to SLIT in routine care.

Methods

This retrospective longitudinal cohort included patients aged 3–17 years who received individualized liquid‐drop SLIT and met prespecified adherence and treatment‐persistence criteria. Assessments were performed at baseline and months 6, 12, 18, 24, and 36. The primary outcome was achievement of the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) minimal clinically important difference (MCID; increase ≥0.5 points) at month 6.

Results

Among 1208 patients, 1095 had asthma and 954 allergic rhinitis. Overall, 666/1095 (60.8%) achieved month‐6 PAQLQ MCID: 515/671 (76.8%) with asthma plus allergic rhinitis (Asthma+AR), 103/254 (40.6%) with allergic asthma without AR, and 48/170 (28.2%) with asthma, AR, and atopic dermatitis (Asthma+AR + AD).

Efficacy and safety of oral treatments for allergic rhinitis in children: A network meta-analysis

Thomander T, Gil-Mata S, Riera-Serra P  et al. Pediatr Allergy Immunol. 2026 Aug;37(8):e70431. doi: 10.1111/pai.70431. 

Abstract

Background

Allergic rhinitis is the most common chronic disease in children. Information on efficacy and safety of oral allergic rhinitis treatments in children is scarce. We aimed to comprehensively evaluate the efficacy and safety of oral medications for allergic rhinitis in children.

Methods

We performed a systematic review, searching three bibliographic databases and clinicaltrials.gov for randomized controlled trials assessing the use of oral antihistamines (OAH) or leukotriene receptor antagonists (LTRA) in children (<12 years old) with seasonal or perennial allergic rhinitis. Evaluated outcomes included the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS), the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ), development of adverse or serious adverse events, and withdrawals due to adverse events. We performed network meta-analysis at both class and individual treatment levels. Certainty in the body of evidence was assessed using the GRADE approach for network meta-analysis.

Results

We included eight primary studies with 906 participants. Overall, OAH were more effective against placebo in improving the TNSS (mean difference (MD) = −1.60; 95%CI = −2.25 to −0.95).

Criteria for Control and Remission of Respiratory Allergic Disease With Allergen Immunotherapy: A Delphi Consensus

E. González-Mancebo, J. M. Beitia Mazuecos, A. I. Tabar Purroy, et al. Clinical and Translational Allergy
(2026): e70191, https://doi.org/10.1002/clt2.70191.

ABSTRACT

Background

Allergic rhinitis, conjunctivitis and asthma are prevalent IgE-mediated respiratory diseases that frequently coexist and impair quality of life. Allergen immunotherapy (AIT) has clinical benefits and potential disease-modifying effects. Until recently, standardised definitions of disease control and remission were lacking in routine clinical practice, particularly for allergic rhinitis and conjunctivitis. This study aimed to propose preliminary definitions of control and remission in patients receiving AIT and to assess expert consensus using the Delphi methodology.

Methods

A scientific committee developed a survey based on a literature review and expert input, addressing symptoms, medication use, quality of life, exacerbations and tools for objective and subjective assessment. Forty allergists participated in a two-round Delphi study. Consensus was predefined as ≥ 70% agreement on a 9-point Likert scale.

Results

Criteria for allergic conjunctivitis control and remission achieved with AIT.

Consensus was achieved for all items after two rounds.

Guideline-recommended inflammatory testing in symptomatic dermographism: a real-world study

Bizjak-Suran M and Stojanovič L (2026) Front. Immunol. 17:1901562. doi: 10.3389/fimmu.2026.1901562

Abstract

Introduction: Symptomatic dermographism (SD) is the most common form of chronic inducible urticaria and is increasingly recognized as a burdensome disease. The 2026 international urticaria guideline recommends eliciting dermographism and threshold testing for diagnosis and includes differential blood count and erythrocyte sedimentation rate or C-reactive protein (CRP) as an extended diagnostic work-up in patients with SD. However, the clinical usefulness of these inflammatory tests in SD remains incompletely characterized.

Methods: In this retrospective real-world cohort study, we examined whether routine inflammatory markers provide interpretable signals in SD, using chronic spontaneous urticaria (CSU) as a reference comparator and serum protein electrophoresis-derived markers, including the inflammatory protein ratio (IPR) ([alpha-1 + alpha-2]/albumin × 100), as exploratory measures of inflammation.

Processionary Moth Exposure in Europe: Toxic-Irritant and Immunoglobulin E-Mediated Endotypes, Diagnosis and Management

Dasari P, Haas J, Rohe W et al. Clin Exp Allergy. 2026 Aug 5. doi: 10.1111/cea.70415.

ABSTRACT

Graphical Abstract

Processionary moths (Thaumetopoea spp.), particularly the oak processionary moth (Thaumetopoea processionea), are an increasingly relevant cause of allergic and toxic disease in Europe, occurring in the context of reported range expansion, changing environmental conditions and persistent contamination with airborne urticating hairs (setae). Clinical manifestations range from toxic–irritant dermatitis and ocular injury to respiratory symptoms, while a subset of exposed individuals develops genuine IgE-mediated disease, including rhinoconjunctivitis, asthma, and rare cases of anaphylaxis.

Antihistamines for atopic dermatitis (eczema): systematic review and network meta-analysis of randomised trials

Chu A W L, Wen A, Guyatt G H et al. BMJ 2026; 394 :e100163 doi:10.1136/bmj-2026-100163

Abstract

Objective To systematically synthesise the benefits and harms of add-on oral antihistamines for managing atopic dermatitis (eczema).

Design Systematic review and network meta-analysis of randomised trials.

Data sources Medline, Embase, CENTRAL, the United States Food and Drug Administration, and the European Medicines Agency databases from database inception to 5 May 2025.

Study selection Randomised trials assessing add-on oral H1 antihistamines, H2 blockers, mast cell stabilisers (nedocromil sodium and sodium cromoglycate), or their combinations. Paired reviewers independently screened records, extracted data, and assessed risk of bias using a modified Cochrane Risk of Bias tool version 2.

Methods Random effects bayesian meta-analyses synthesised atopic dermatitis severity (oSCORAD—objective scoring atopic dermatitis, 0-83; minimal important difference 8.2; lower better), itch severity (numerical rating scale, 0-10; minimal important difference 3; lower better), sleep disturbance, atopic dermatitis related quality of life, and harms. The network meta-analysis GRADE (Grading of Recommendations Assessment, Development and Evaluation) and Core GRADE approaches informed certainty of evidence ratings.

Network plot of randomised trials examining effects of add-on
antihistamines and mast cell stabilisers on clinician reported
atopic dermatitis severity organised by treatment class
and individual treatments. 

Results 47 trials enrolled 6230 children and adults with primarily moderate to severe atopic dermatitis. With moderate certainty, compared with placebo, adding a first generation or second generation H1 antihistamine likely resulted in a small reduction in atopic dermatitis severity (mean difference -1.87, 95% credible interval -3.47 to -0.27) and itch severity (-0.89, -1.41 to -0.37). Although statistically detectable, these effects are well below established minimal important differences (smallest change in an outcome that a patient would identify as important).

Editorial - Allergic Rhinitis and Its Impact on Asthma (ARIA) Guidelines: Moving Towards Living Guidelines With Regionally Tailored Recommendations

Sousa-Pinto B, Vieira RJ, Klimek L et al.  Allergy Asthma Immunol Res. 2026 Jul;18(4):467-469. doi: 10.4168/aair.2026.18.4.467. 

The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines had their first edition in 1999 (published in 2001),1 with subsequent revisions published in 2008,2 2010,3 2016,4 and 2020.5 Interestingly, ARIA 2016 was used as the case scenario on how to read a health Grading of Recommendations Assessment, Development and Evaluation (GRADE)-based guidelines. Motivated by novel advances in the field, a new revision of the ARIA guidelines focused on the treatment of allergic rhinitis (AR) is currently being developed. This revision is endorsed by the European Academy of Allergy and Clinical Immunology (ARIA-EAACI 2024–2025 guidelines) and follows the GRADE approach.6 The first 2 reports of the ARIA-EAACI 2024–2025 guidelines have been published,7, 8 with one focusing on intranasal treatments and the other on oral and ocular treatments for AR. A third report is being prepared, and it will focus on treatment strategies, such as use of co-medication and the use of rhinitis treatment on an as-needed basis...

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Distinction between allergic rhinitis alone and allergic rhinitis + asthma in MASK-air® real-world studies; a ARIA-WAO task force review

Bernardo Sousa-Pinto MD, PhD, Rafael José Vieira MD, PhD, Ana Margarida Pereira PhD et al. World Allergy Organization Journal Volume 19, Issue 8, August 2026, 101435

Abstract

The recent ARIA-MeDALL hypothesis proposed in 2023 that allergic rhinitis (AR) alone and allergic rhinitis and asthma (A) multimorbidity (AR + A) represent 2 distinct diseases. To improve the knowledge on this topic, we have gathered data from real-world studies using MASK-air®. According to our analyses: (i) An “extreme allergy phenotype” [A + AR + C, Conjunctivitis] was confirmed and found to be more severe (symptoms and work productivity) than single diseases alone. (ii) Patients with AR + A required more rhinitis medications, and had more severe VAS levels for nasal and ocular symptoms than those with AR alone in all countries tested. (iii) In clusters with poorly controlled AR, the frequency of co-medicating with more than 1 rhinitis drug was higher in AR + A than in AR alone. 

Impact on work and VAS global depending
on the RCA multimorbidity

(iv) In the CONSTANCES general population cohort, a co-medication pattern (intranasal corticosteroid and oral H1-antihistamines) was associated with the presence of AR + A (vs AR alone).

Treatment of Multifood Allergy With Omalizumab or Multiallergen Oral Immunotherapy: A Randomized Clinical Trial

Wood RA, Togias A, Burk CM, et al.  JAMA Pediatr. Published online July 27, 2026. doi:10.1001/jamapediatrics.2026.2910

Key Points

Question How do omalizumab and oral immunotherapy (OIT) compare in the treatment of patients with multifood allergy?

Findings In this randomized clinical trial comparing omalizumab with multiallergen OIT (MOIT) in 117 participants with multifood allergy, omalizumab was superior in terms of both efficacy and safety.

Meaning Although the intention-to-treat analysis found a higher rate of treatment success in those receiving omalizumab, there was no difference in efficacy after accounting for the high rate of study withdrawals in the group of participants treated with omalizumab-facilitated MOIT.

Abstract

Importance Food allergy is common, affecting up to 8% to 10% of children and adults. Treatment options include oral immunotherapy (OIT) and omalizumab, an anti–immunoglobulin E (IgE) monoclonal antibody.

Objective To compare omalizumab with OIT for the treatment of patients with multifood allergy.

Treatment of Multifood Allergy With Omalizumab 

or Multiallergen 

Oral Immunotherapy

Visual Abstract

Design, Setting, and Participants This was a double-blind, placebo-controlled, randomized clinical trial comparing omalizumab with omalizumab-facilitated multiallergen OIT (MOIT) in participants who completed stage 1 of the Omalizumab as Monotherapy and as Adjunct Therapy to Multiallergen OIT in Children and Adults With Food Allergy (OUTMATCH) trial, which led to the approval of omalizumab.

Respiratory mucosal vaccines for emerging viruses: promise and challenges

Beeton K, Case JB.  J Virol. 2026 Jul 23:e0174825. doi: 10.1128/jvi.01748-25.

ABSTRACT

Mediators of respiratory mucosal immunity. 

Systemically administered vaccines were instrumental in reducing severe disease, hospitalizations, and deaths during the SARS-CoV-2 pandemic. However, they often failed to consistently elicit robust immunity at mucosal sites. This minireview examines a central role for respiratory mucosal immunity in protection against emerging viral pathogens and highlights key takeaways from the SARS-CoV-2 pandemic. Evidence from SARS-CoV-2 and influenza studies demonstrates that mucosal vaccination uniquely induces secretory IgA, as well as resident memory B and T cells within the upper and lower airways, thereby promoting broader and more potent protection.