Allergy Notes, Evidence-based Information by Board-certified Physicians

Beyond Weight Loss: Could Popular GLP-1 Drugs Like Ozempic Help Keep Asthma Attacks at Bay?

2026-03-25T12:08:00.015-04:00

Popular GLP-1 receptor agonists - medications best known for revolutionizing diabetes care and weight management (think Ozempic, Wegovy, Mounjaro) - may offer an unexpected bonus: helping control asthma in people who are overweight or obese but do not have diabetes.

New research unveiled at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting analyzed real-world data from hundreds of patients with asthma. The results were striking: initiating treatment with a GLP-1 agonist was tied to significantly fewer severe asthma episodes (exacerbations) over time.

Overweight patients saw about a 14.6% lower risk of asthma flares.

Obese patients had a 12.2% reduction.

Those with morbid obesity experienced a 13.3% drop.

While GLP-1 drugs are already blockbuster treatments for metabolic conditions, this study (one of the largest of its kind in non-diabetic asthmatics) hints at broader benefits - possibly through reduced airway inflammation or other mechanisms.

The findings are promising but preliminary. They don't mean everyone with asthma should start these drugs - consult your allergist or pulmonologist. Still, it's an intriguing glimpse into how medications designed for one purpose might help in surprising ways for chronic respiratory conditions.

References:

https://www.aaaai.org/about/news/news/2026/glp1

Dupilumab + OIT for Food Allergy Desensitization

2026-03-24T11:59:00.020-04:00

Food allergies remain a major challenge, especially for those allergic to multiple foods like peanut and others. Oral immunotherapy (OIT) helps build tolerance, but side effects - particularly gastrointestinal symptoms - often limit success.

The COMBINE trial, presented at AAAAI 2026, tested adding dupilumab (a biologic blocking IL-4/IL-13 pathways, already used for asthma/eczema) to omalizumab-assisted multi-allergen OIT in 108 patients.

The good news: Dupilumab dramatically boosted desensitization. At the 32-week mark, 92% of patients on the dupilumab combo tolerated a high 4,043 mg peanut allergen dose during challenges—compared to just 63% without it.

The caveat: It didn't significantly increase sustained unresponsiveness (long-term tolerance off therapy) - 55% vs. 39%, not statistically different.

This could help patients who struggle with GI reactions or miss doses, but real-world use faces hurdles like cost and access. Ongoing work aims to uncover biomarkers to predict responders and refine biologic strategies for food allergy.

References:

https://www.hcplive.com/view/dupilumab-improves-desensitization-outcomes-oit-sayantani-sindher-md

New Hope for Peanut Allergy: Oral Remibrutinib (Rhapsido) Shows Rapid Protection

2026-03-23T11:50:00.026-04:00

A promising new oral treatment could transform how we manage severe food allergies. At the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in Philadelphia, researchers presented phase II trial results for remibrutinib (Rhapsido), an oral Bruton's tyrosine kinase (BTK) inhibitor developed by Novartis.

In the study, adults (ages 18-55) with confirmed peanut allergy received different doses of remibrutinib twice daily for 4 weeks or placebo. The goal was to see if the drug could help them tolerate peanut protein without a reaction.

The results were striking and dose-dependent:

- 40% of those on the lowest dose (10 mg twice daily) tolerated at least 600 mg of peanut protein - roughly 2.5 peanuts.

- 50% succeeded on 25 mg twice daily.

- An impressive 87% on the highest dose (100 mg twice daily) reached this threshold.

The safety profile looked reassuring, with no major concerns around infections, blood counts, liver enzymes, or other worrisome side effects.

Experts were enthusiastic. Session co-moderator Yamini Virkud, MD (UNC Chapel Hill) called it a potential "game changer" - an easy-to-take pill (no injections), shelf-stable, and fast-acting (protection in as little as 1 week vs. months for injectable omalizumab). This could offer real-world benefits, like extra protection during travel, camps, or accidental exposures.

While the results compare favorably to omalizumab (which showed ~67% tolerance in a multi-food allergy trial in children), remibrutinib has the advantage of being oral and quick to work.

Food allergies affect millions, and accidental exposures remain a constant fear. An effective oral therapy like this could dramatically improve quality of life - and maybe one day reduce reliance on strict avoidance alone.

References:

https://www.medpagetoday.com/meetingcoverage/aaaai/120100

Under-the-Tongue Treatment for Food Allergy: New Peanut Allergy Tablet Proves Safe in Early Trial Results

2026-03-22T11:47:00.018-04:00

Peanut allergy affects millions of children worldwide, often persisting lifelong and carrying the risk of severe reactions. Current management relies heavily on strict avoidance, but immunotherapy options are evolving.

Exciting early data from the ALLIANCE trial suggest a once-daily peanut SLIT tablet is well-tolerated in children, adolescents, and adults. In the open-label phases, most participants handled dose increases with only mild, local side effects like mouth itching - far fewer systemic issues than seen in some other therapies, and no serious events requiring epinephrine or causing study halts.

This study highlights a potentially easier, home-based approach compared to oral immunotherapy.

References:

https://www.pharmacytimes.com/view/alliance-trial-peanut-sublingual-immunotherapy-is-well-tolerated-in-children-with-peanut-allergy

A Game-Changer for Multi-Food Allergies? Omalizumab Matches Oral Immunotherapy's Long-Term Success - With Far Less Hassle

2026-03-21T11:47:00.000-04:00

For patients and families dealing with multiple food allergies, new follow-up data from the landmark OUtMATCH trial bring encouraging news: the biologic medication omalizumab (Xolair) performs just as well as multi-food oral immunotherapy (mOIT).

In this analysis of 80–81 participants who completed initial treatment for 1–3 food allergies, both groups transitioned to real-world dietary consumption plans. Success meant regularly tolerating at least 300 mg per day of each allergen - roughly a meaningful, protective amount in accidental exposures or intentional inclusion.

Daily diary tracking at 3 and 6 months showed nearly identical outcomes: mOIT hit about 77% success at 3 months and 65% at 6 months, while omalizumab reached 66% and 63% (differences not statistically significant). Clinician reviews through a full 12 months confirmed the same pattern across foods, including peanut - no meaningful gaps between the approaches.

Safety remained comparable, with very few serious reactions (rare anaphylaxis) and only one new EoE case after omalizumab.

These Stage 3 results build on earlier OUtMATCH findings, where omalizumab proved superior to mOIT during active treatment due to fewer side effects and dropouts. Now, even after treatment stops, the benefits hold up similarly - suggesting omalizumab could be a game-changing, lower-burden option for multi-food desensitization.

Food allergy management is evolving fast - and for those with multiple triggers, this could open doors to more freedom and peace of mind. Always discuss with your allergist, as individual responses vary.

References:

https://opmed.doximity.com/articles/aaaai-omalizumab-as-effective-as-multi-food-oral-immunotherapy-for-multiple-food-allergies

Biologics vs. JAK Inhibitors for Atopic Dermatitis: Which One Wins for Your Patient? A 2026 Practical Guide

2026-03-08T12:31:00.045-04:00

Atopic Dermatitis (AD) remains a burdensome chronic inflammatory skin condition affecting quality of life, often accompanied by comorbidities such as asthma, allergic rhinitis, or food allergies. While most patients respond to topicals, 10 -30% require systemic therapy. The review article in JACI goes over targeted options beyond older immunosuppressants (e.g., cyclosporine, methotrexate), focusing on:

Biologics (monoclonal antibodies targeting type 2 inflammation):

- Dupilumab (blocks IL-4/IL-13) - widely used, approved from 6 months of age, strong for comorbid asthma or other type 2 diseases, but can cause conjunctivitis.

- Tralokinumab and lebrikizumab (IL-13 specific) - similar efficacy, potentially better ocular tolerability.

- Nemolizumab (targets IL-31) - stands out for rapid itch (pruritus) relief.

The biologics requires subcutaneous injections, have slower onset (4–8 weeks), but also require minimal lab monitoring, and have a generally favorable safety in patients with cardiovascular risks, infections, or malignancy history.

Janus Kinase (JAK) Inhibitors (oral, daily dosing):

- Abrocitinib, upadacitinib (primarily JAK1 selective), baricitinib (JAK1/2).

JAK inhibitors have faster onset and often superior short-term efficacy (especially high doses) in reducing eczema severity (EASI), itch (PP-NRS), and quality-of-life scores (DLQI/POEM), per network meta-analysis rankings.

However, they carry boxed warnings and require regular monitoring (CBC, lipids, liver function, infection screening) due to risks like venous thromboembolism (VTE), serious infections, herpes zoster, acne, nausea, and potential long-term concerns (malignancy). An elevated malignancy risk has been reported, although for abrocitinib, baricitinib, and upadacitinib the overall incidence remains low. They are contraindicated in pregnancy/breastfeeding.

The authors provide a stepped-care algorithm (starting with adherence, trigger avoidance, and phototherapy if possible), an "option grid" comparing factors side-by-side, and guidance on response evaluation (aim for clear improvement by 3 months, optimal by 6 months), tapering (possible with good control, especially biologics via extended intervals), and switching therapies.

Treatment choice is highly individualized:

Prefer biologics for patients with significant comorbidities, younger children, or when minimizing monitoring/risk is key.

Consider JAK inhibitors for rapid control of severe flares or when oral convenience and higher peak efficacy matter most.

Shared decision-making, considering patient preferences, age, comorbidities, and practical factors (injection vs. pill, monitoring burden), is essential.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01121-3/fulltext

2025: A Breakthrough Year for Chronic Urticaria - New FDA Approvals Reshaped Treatment

2026-03-07T12:18:00.030-05:00

Chronic urticaria, encompassing chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), affects a substantial portion of the population worldwide and imposes a heavy burden due to persistent symptoms like hives, itching, and angioedema, often inadequately controlled by standard treatments.

Current first-line therapy relies on nonsedating H1-antihistamines, with omalizumab (an anti-IgE biologic) as the mainstay for refractory cases.

However, omalizumab achieves complete resolution in only about 45% of patients and rarely induces lasting remission after discontinuation.

Excitingly, the therapeutic landscape for refractory CSU has expanded dramatically in recent years, with several new approvals and promising agents targeting both IgE-dependent and non-IgE pathways.

Dupilumab (Dupixent), an IL-4/IL-13 inhibitor, gained FDA approval in April 2025 for H1-antihistamine-refractory CSU in adults and adolescents ≥12 years, validating the role of type 2 inflammation in CSU pathogenesis.

Remibrutinib (Rhapsido), the first oral Bruton's tyrosine kinase inhibitor (BTKi), received FDA approval in September 2025 for adults with symptomatic CSU despite antihistamines. Phase 3 trials (REMIX-1 and REMIX-2) showed rapid, significant reductions in Urticaria Activity Score (UAS7), itch, and hives, with about one-third of patients achieving complete symptom resolution by week 12.

Omalizumab biosimilars, such as Omlyclo are offering more accessible IgE-targeted options.

Emerging c-Kit inhibitors like barzolvolimab have demonstrated efficacy in CSU and CIndU, with effects persisting post-treatment in trials, highlighting mast cell targeting potential.

Other mechanisms in development include additional BTKis, JAK inhibitors, TYK2/JAK inhibitors, MRGPRX2 antagonists, and more.

While some candidates (e.g., fenebrutinib, THB001, EP262) were discontinued due to safety issues, and others (e.g., tezepelumab, mepolizumab, benralizumab, lirentelimab, AK006) due to insufficient efficacy, these outcomes have refined our understanding of CSU pathways.

Overall, 2025 marked a transformative year for CSU management, shifting toward more targeted, effective systemic therapies - both injectable biologics and convenient oral options - that promise better symptom control and quality of life for patients with refractory disease. The pipeline remains active, with phase 3 programs underway to further broaden choices.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01144-4/fulltext

Revolutionizing Respiratory Care: How Type 2 Biologics Are Changing the Game for Severe Asthma and Beyond

2026-03-06T11:59:00.017-05:00

In the rapidly evolving field of allergy and respiratory medicine, few advances have been as game-changing as the arrival of biologics that precisely target type 2 inflammation - the underlying driver in many cases of severe asthma, nasal polyps, and related conditions.

A new review in The Journal of Allergy and Clinical Immunology: In Practice offers a timely overview of the major players:

- omalizumab (anti-IgE)
- mepolizumab and reslizumab (anti-IL-5)
- benralizumab (anti-IL-5 receptor)
- dupilumab (anti-IL-4/IL-13)
- tezepelumab (anti-TSLP)

These monoclonal antibodies have dramatically reduced exacerbations, improved lung function, and cut reliance on oral corticosteroids for many patients.

The authors highlight how the introduction and broad use of these therapies mark an "unprecedented" shift in treatment paradigms, moving from broad immunosuppression to targeted pathway inhibition.

As real-world evidence grows, these biologics are increasingly considered earlier in the disease course for type 2–high patients - and their benefits may extend to other respiratory and allergic diseases sharing similar inflammatory pathways.

For allergists, pulmonologists, and patients struggling with uncontrolled symptoms, this class of drugs represents hope for better control and quality of life. The era of personalized, biology-driven respiratory care is here - and it's only expanding.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01181-X/fulltext

New Targeted Systemic Therapies Are Revolutionizing Allergy Care

2026-03-05T11:53:00.038-05:00

For decades, allergists and immunologists have prioritized topical treatments - like inhaled or nasal steroids, intranasal antihistamines, and topical steroids and calcineurin inhibitors - to minimize the risks associated with systemic steroids such as prednisone.

These localized approaches work well for many patients but fall short in severe or complex conditions like severe asthma, nasal polyps, extensive atopic dermatitis, hereditary angioedema (HAE), chronic spontaneous urticaria (CSU), or cases with multiple comorbid allergic diseases that demand broader, systemic impact.

Advances in molecular understanding of allergic and immunologic disorders have paved the way for a new era: highly targeted systemic therapies, including biologics and small-molecule inhibitors. These precision medicines attack specific pathways with impressive efficacy and far better safety profiles than traditional systemic options.

There are emerging systemic options for asthma and allergies, including repurposed drugs, novel targets (e.g., TSLP receptor, IL-33 axis, OX40 ligand), and even unconventional approaches like GLP-1 agonists or medium-chain triglycerides.

HAE management is shifting from outdated therapies to modern prophylactic and on-demand options - now including oral plasma kallikrein inhibitors, novel monoclonal antibodies, and hepatocyte-targeted antisense oligonucleotides.

Kinase inhibitors (e.g., JAK, BTK, KIT) selectively block key signaling in mast cells, type 2 cytokines, and more, marking a new frontier for urticaria and atopic dermatitis.

CSU treatments are advancing from anti-IgE (omalizumab) to kinase inhibitors and emerging targets like MRGPRX2 and Siglec.

Evidence-based algorithm for atopic dermatitis in children and adults includes biologics (IL-4/IL-13/IL-31 pathways) and JAK inhibitors.

These targeted systemic therapies represent a game-changer, enabling precise, multi-organ treatment for chronic, debilitating conditions with reduced side effects. As the field evolves, further research into disease heterogeneity and biomarkers will refine their use even more.

Clinicians now have powerful, accessible resources in this issue to transform patient care - moving from symptom management to true disease modification. The future of allergy and immunology is here, and it's more targeted than ever.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01185-7/fulltext

Tezepelumab in Real-World Danish Severe Asthma Study: Benefits Even After Biologic Switches

2026-03-04T11:50:00.023-05:00

Tezepelumab, the "upstream" biologic that blocks TSLP to interrupt allergic and inflammatory pathways early, is gaining traction for severe asthma.

Researchers analyzed data from the Danish Severe Asthma Register on 270 patients started on tezepelumab. Notably, nearly two-thirds (63%) were switching from other biologics - suggesting clinicians turned to tezepelumab when previous options fall short.

After 12 months, the results were impressive across both groups:

- Exacerbations dropped by 69%.

- Maintenance oral corticosteroid use decreased significantly.

- Asthma symptoms improved

The majority achieved a clinical response - rates on par with other biologics in Denmark.

Even more encouraging: biologic-naïve patients were more than twice as likely to reach full clinical remission (35% vs. 15% in switchers).

These real-world findings reinforce tezepelumab's potential as a versatile option in severe asthma, effective in complex cases with mixed or low type 2 inflammation and a good choice for patients needing to switch therapies.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)00849-9/fulltext

Tezepelumab vs. Dupilumab in Severe Asthma: Head-to-Head Real-World Data Shows No Clear Winner

2026-03-03T11:41:00.027-05:00

In the evolving landscape of biologic therapies for severe asthma, two heavy hitters stand out: dupilumab (targeting IL-4/IL-13 downstream in the type 2 inflammatory pathway) and tezepelumab (blocking TSLP upstream, with potential broader effects across T2-high and T2-low phenotypes). While both are FDA-approved for severe asthma, direct comparative real-world evidence has been scarce -until now.

The study authors conclude that, in this real-world cohort, dupilumab and tezepelumab appear comparably effective at preventing exacerbations and reducing steroid reliance - no evidence that tezepelumab's upstream mechanism translated to superior outcomes overall.

For clinicians managing severe asthma, this suggests that - pending more data - either biologic is a reasonable option, guided by patient-specific factors like T2 biomarker profile, comorbidities, insurance/cost, administration preferences, and side-effect considerations rather than expecting a dramatic efficacy edge from one over the other.

As biologic options expand, studies like this help ground decisions in real-world practice rather than trial extrapolations alone.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01129-8/fulltext

Omalizumab Helps High-Risk Patients Tolerate Honeybee Venom Allergy Shots

2026-03-02T11:37:00.025-05:00

Venom immunotherapy (VIT) is the gold-standard, potentially life-saving treatment for honeybee venom allergy, but for some patients, the buildup phase triggers severe allergic reactions (SARs), making it tough or impossible to continue.

A new retrospective study from Fiona Stanley Hospital in Perth, Western Australia, reviewed 350 adults on honeybee VIT between 2015 and 2024. About 16% experienced SARs during standard therapy, and 10% ultimately received the anti-IgE monoclonal antibody omalizumab as an add-on to improve tolerance.

Key predictors for needing omalizumab included:

- history of severe sting-induced anaphylaxis
- co-existing asthma
- elevated baseline tryptase levels (a marker often linked to mast cell issues)

Among the 35 patients who used omalizumab during the VIT dose escalation (uptitration), 63% successfully reached maintenance dose without ongoing omalizumab support. Another 20% stopped due to persistent SARs, and 14% continued on omalizumab.

The most effective and well-tolerated approach was a semi-rush protocol: omalizumab 300 mg loading dose 2 weeks before starting a 12-week VIT buildup to 100 μg, followed by 150 mg every two weeks until maintenance was achieved.

For patients with recurrent severe reactions during standard honeybee VIT, adjuvant omalizumab offers a valuable option to enable safe desensitization. This larger real-world dataset strengthens the case for considering it earlier in high-risk cases, potentially transforming outcomes for those at greatest risk from bee stings. Always discuss with an allergist, as protocols should be individualized.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)00935-3/fulltext

Dupilumab-Induced Eosinophilia (DIBE) in CRSwNP Affected 48% of Patients

2026-03-01T11:31:00.026-05:00

A new real-world study from the Italian DUPIREAL network sheds light on how dupilumab, a biologic treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), affects blood eosinophil levels.

Researchers analyzed data from 564 patients with CRSwNP treated with dupilumab across 14 Italian centers. They defined dupilumab-induced blood eosinophilia (DIBE) as an absolute eosinophil count (AEC) increase of at least 50% from baseline (and >500 cells/mm³) or an AEC exceeding 1500 cells/mm³.

48% of patients developed dupilumab-induced blood eosinophilia (DIBE).

17% of patients experienced DIBE >1500.

On average, blood AEC peaked around 3 months into treatment and declined by 12 months.

DIBE was significantly more common in patients with comorbid asthma.

This large real-life cohort confirms that DIBE is a common but mostly transient phenomenon during dupilumab therapy for CRSwNP. It tends to occur early, resolve over time, and is more frequent in patients with type 2 inflammatory comorbidities like asthma or recent steroid exposure.

Although dupilumab-induced blood eosinophilia (DIBE) is predominantly transient, some exceptions have been identified.

If you're on dupilumab or considering it for CRSwNP, regular blood monitoring can help track these changes.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01019-0/fulltext

Why Some Chronic Hives Patients May Not Respond Well to Omalizumab: New Biopredictors Identified

2026-02-28T13:15:00.022-05:00

Omalizumab (Xolair) is a biologic treatment for chronic spontaneous urticaria (CSU) when antihistamines fail. However, up to 40% may not respond optimally. A new retrospective analysis of phase III trials offers clues to identify those at higher risk of poorer response early on.

Researchers examined data from nearly 400 antihistamine-refractory CSU patients treated with omalizumab 300 mg every 4 weeks for 3 months. They focused on 3 proposed negative biopredictors at baseline:

- Low total IgE (≤40 IU/mL)

- Positive CU Index (CUI) test (indicating functional autoantibodies)

- Basopenia, measured by low blood histamine content (BHC ≤8 ng/mL)

Positive CUI emerged as a strong independent predictor (odds ratio 2.54, P=0.0002). For BHC, a cutoff of 6.4 ng/mL best distinguished responders from non-responders via ROC analysis.

In summary, patients with positive CUI, low BHC, or the combination of low IgE + low BHC face a higher likelihood of suboptimal response to omalizumab by week 12.

These biopredictors - available through routine or specialized lab tests - could help clinicians set realistic expectations, consider earlier escalation to alternative therapies, or personalize CSU management. While omalizumab remains highly effective overall, identifying potential slower or poorer responders upfront may improve care efficiency.

This reinforces growing evidence that autoimmune/inflammatory CSU subtypes (often linked to basopenia, autoantibodies, and low IgE) behave differently with anti-IgE therapy. More prospective validation is needed, but these findings add practical tools for everyday allergy and dermatology practice.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01134-1/fulltext

Chronic Urticaria: Making Breakthroughs if Managing a Challenging Disease

2026-02-27T13:21:00.030-05:00

The field of chronic spontaneous urticaria (CSU, also known as chronic hives) treatment has long progressed slowly.

For years, options for antihistamine-resistant cases were limited - mainly omalizumab (approved in 2014), corticosteroids, cyclosporine, or other alternatives - while other allergic conditions like asthma and atopic dermatitis saw rapid advances with new biologics and small molecules.

Recent breakthroughs are finally accelerating change. In the past year, the FDA approved dupilumab (Dupixent) in April 2025 and remibrutinib (Rhapsido, the first oral BTK inhibitor for CSU) later in 2025 for antihistamine-refractory CSU. These expand targeted options beyond omalizumab, with more agents (such as c-KIT and MRGPRX2 antagonists) on the horizon.

A key challenge has been understanding CSU's heterogeneity.

Some patients have an autoimmune endotype (e.g., type IIb with low IgE and IgG autoantibodies to FcεRI), while others show different patterns.

Omalizumab works well for many, especially those with higher baseline total serum IgE, but less reliably in low-IgE subgroups, where responses may be delayed or absent.

Negative prognostic factors like high C-reactive protein, eosinopenia, and basopenia link to greater severity and longer disease duration.

Predictive biomarkers are emerging: higher IgE predicts better/faster omalizumab response, while very low IgE, basopenia, or certain indices signal poorer control after 12 weeks.

A recent retrospective analysis (Le et al.) highlights that patients with low IgE (≤40 IU/mL), basopenia, or positive chronic urticaria index were more likely to have poorly controlled symptoms on omalizumab.

Encouragingly, newer therapies like dupilumab and remibrutinib show benefit across high- and low-IgE patients, potentially replacing older agents like cyclosporine for omalizumab non-responders.

The path ahead emphasizes:

- identifying endotypes
- validating point-of-care biomarkers (positive and negative)
- refining trials to guide personalized treatment.

With these recent approvals and ongoing research, the long, winding road to better CSU management is finally gaining momentum - offering real hope for patients with refractory disease.

References:

https://www.jaci-inpractice.org/article/S2213-2198(26)00001-2/fulltext

Hope for Some Alpha-Gal Patients: In-home Graded Protocol

2026-02-26T13:14:00.020-05:00

Alpha-gal syndrome (AGS), the unusual tick-borne allergy to red meat triggered by the lone star tick, forces many to give up beef, pork, lamb, and other mammalian products. Reactions often hit 3–6 hours after eating, making diagnosis tricky and traditional in-office food challenges impractical. While avoidance remains the standard advice, new evidence shows that for some patients, the allergy can fade over time.

In a recent retrospective study from an Allergy and Immunology clinic, researchers reviewed 263 AGS patients, 19 chose to try reintroducing red meat using a careful in-home graded protocol developed by the team.

The 9-day protocol starts small: patients begin with tiny portions of very lean mammalian meat in the morning (to allow time for delayed symptoms), gradually increasing to semi-fatty and then fattier cuts over the days.

They keep an epinephrine autoinjector on hand, stop immediately at any sign of reaction (like early GI upset or itching), and contact the clinic if needed.

The results? All 19 patients successfully completed the protocol and fully liberalized their diet - no restrictions on mammalian meat. One had mild itching (later blamed on anxiety) but restarted and finished successfully after a short break. No serious reactions or known relapses have been reported so far.

Compared to the full AGS group, those who cleared the allergy tended to have lower initial IgE levels, were more likely female, and less often had gastrointestinal symptoms (which may signal a tougher, more persistent form of the condition).

Tick avoidance appears key to letting IgE levels decline naturally - often halving each year without new bites.

This small but encouraging study suggests that for carefully selected patients with declining IgE and no recent reactions, a supervised home-based reintroduction can safely lift lifelong dietary limits. Larger studies are needed to refine the approach, but it offers real hope to those tired of avoiding steak forever.

Always consult an allergist before attempting any reintroduction - AGS remains serious, and this isn't one-size-fits-all advice.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)01132-8/fulltext

Are These New Biologics Game-Changers or Just More of the Same?

2026-02-25T13:06:00.029-05:00

Asthma and allergic diseases aren't one-size-fits-all. They're driven by intricate immune pathways, with type 2 (T2) inflammation playing a starring role - but far from the only one. Recent advances in immunology have opened the door to exciting new systemic treatments that go beyond traditional options, offering novel targets, longer dosing intervals, and even combination approaches.

A recent JACI clinical commentary breaks these emerging therapies into 4 key categories:

T2 cytokine inhibitors - Building on established biologics, newer agents refine targeting of key players like IL-4, IL-5, and IL-13 for better control in T2-high patients.

Alarmin blockers - These upstream therapies (e.g., targeting TSLP or IL-33) aim to shut down inflammation earlier, potentially benefiting a wider range of patients, including some with mixed or non-T2 profiles.

Effector cell modulators - Focusing on cells like eosinophils and mast cells to disrupt the downstream effects of inflammation.

Unconventional, broad immune, and non-T2 pathways - These tackle harder-to-treat cases where T2 mechanisms aren't dominant, addressing a critical unmet need.

While many of these therapies show strong promise - especially for severe, T2-driven asthma - challenges persist.

Identifying reliable predictive biomarkers, ensuring long-term safety, and effectively treating non-T2 inflammation remain hurdles.

References:

https://www.jaci-inpractice.org/article/S2213-2198(25)00823-2/fulltext

The Esophagus: Not Just a Tube, But a Smart Immune Organ

2026-02-24T13:02:00.010-05:00

Once seen as a simple food passageway, the esophagus is now recognized as a dynamic immune organ.

Its stratified squamous epithelium forms a tough barrier, reinforced by mucins and unique processes like citrullination.

A distinct early-life microbiome shapes epithelial development and immune responses. Key players include pattern recognition receptors, IL-1 family cytokines (IL-33, TSLP), a carefully balanced protease–antiprotease system, and neuroimmune circuits that link sensation, immunity, and barrier control.

Genetic variants (e.g., in TSLP, CAPN14, FLG, SPINK5) increase vulnerability to environmental triggers, driving diseases like eosinophilic esophagitis (EoE) and GERD through barrier breakdown and chronic inflammation.

This new understanding is fueling targeted therapies - immune modulation, barrier repair, and cytokine blockers- while opening research avenues in microbiome-immune crosstalk, single-cell profiling, and precision medicine for allergic, inflammatory, and neoplastic esophageal conditions.

In short: the esophagus actively senses the environment and maintains mucosal peace through sophisticated immune networks. Unlocking these mechanisms promises better treatments for challenging esophageal diseases.

References:

https://www.jacionline.org/article/S0091-6749(25)01184-4/fulltext

Artificial intelligence in Allergy and Immunology - JACI review

2026-02-23T12:56:00.034-05:00

Artificial intelligence (AI) is rapidly transforming medicine, and a recent review in The Journal of Allergy and Clinical Immunology (February 2026) explores it.

Recent AI Breakthroughs and Their Relevance

Advances in large language models (LLMs) (e.g., ChatGPT-like systems), multimodal AI (handling text, images, and other data), and AI agents (autonomous systems for decision-making and task execution) are driving progress.

These tools excel at processing unstructured data like clinical notes, predicting disease progression, matching patients to trials, and even analyzing genetic or proteomic "text."

In allergy/immunology, early applications include:

- Predicting asthma from electronic health records
- Diagnosing allergies via epigenetic patterns
- Detecting eczema or atopic dermatitis from skin images
- Interpreting skin prick tests, conjunctival provocation photos, or airway CT scans with high accuracy
- Monitoring airborne allergens (e.g., pollen) using low-cost sensors
- Enhancing patient education, health literacy (e.g., explaining asthma info), and administrative tasks like digital scribing

Despite over 1,000 FDA-approved AI medical devices by mid-2024, none specifically target allergy and immunology.

Key Challenges to Implementation

Data issues: Privacy risks, bias, incomplete records, and lack of standardized/large datasets.

Technical limits: Hallucinations (confident but wrong outputs), domain-specific knowledge gaps, and performance drift over time.

Practical barriers: Workflow integration, clinician trust/training needs, regulatory evolution (e.g., EU AI Act), liability concerns, and unclear reimbursement.

The "AI chasm": Most work stays in research/proof-of-concept; few randomized trials demonstrate real clinical value.

AI holds potential to improve diagnosis, personalize treatment, reduce administrative burden, enhance prevention (e.g., pollen forecasting), and accelerate research in allergy and immunology.

The full open-access review is available in JACI (DOI: 10.1016/j.jaci.2025.08.022).

https://www.jacionline.org/article/S0091-6749(25)00939-X/fulltext

Staph Aureus on the Skin Associated With Severe Food Allergic Reactions Via a Cascade: IL-33, IL-3, IL-4

2026-02-22T12:51:00.023-05:00

People with atopic dermatitis (eczema) often have Staphylococcus aureus (Staph) colonizing their skin, and this has been linked to food allergies. But until recently, the exact way this connection works has been unclear.

A new study published in Immunity (Das et al., 2025) uncovers a surprising chain of events that explains how skin Staph can drive oral anaphylaxis - severe allergic reactions after eating foods.

Researchers observed higher levels of IL-4 (a key allergy-promoting molecule) in the blood of patients with both atopic dermatitis and food allergies. Using mouse models, they showed that when a food protein (like ovalbumin) is applied to the skin together with Staph or its toxin Staphylococcal enterotoxin B (SEB), it sets off a cascade:

Skin cells (keratinocytes) release IL-33.

This prompts T cells to release IL-3.

IL-3 draws basophils (a type of immune cell) into the lymph nodes that drain the skin.

Basophils then produce IL-4, which supercharges dendritic cells to strongly promote Th2 responses (the allergy-driving arm of the immune system).

This leads to elevated systemic IL-4.

High IL-4 weakens the intestinal barrier, making the gut more permeable.

More food antigens leak through, triggering mast cells in the gut and causing exaggerated allergic reactions - including anaphylaxis - to foods the person was sensitized to through the skin.

In short, Staph on inflamed skin doesn't just stay local - it amplifies a Th2 response that "primes" the gut for dangerous overreactions to ingested allergens.

This breakthrough highlights a novel pathway linking skin bacteria to food anaphylaxis and could open new avenues for treating or preventing severe food allergies in people with eczema - perhaps through targeting Staph, IL-4, or basophils.

For the full study: https://doi.org/10.1016/j.immuni.2025.09.001

Predicting Outcomes in Common Variable Immunodeficiency (CVID)

2026-02-21T12:47:00.026-05:00

Common variable immunodeficiency (CVID) is a diverse group of primary immune disorders characterized primarily by low antibody levels, leading to frequent infections as well as serious non-infectious complications like organ damage, autoimmunity, and even cancer.

These issues can significantly shorten life expectancy, but until recently, clinicians lacked reliable ways to predict which patients were at highest risk.

A large multicenter study of 209 CVID patients (compared against healthy controls) has identified key biomarkers that strongly correlate with disease course and survival. Researchers focused on serum immunoglobulins, T-cell subsets (especially naive CD4+ T cells), B-cell/plasma cell defects, and natural killer (NK) cells.

Infectious complications, particularly recurrent respiratory infections, were closely tied to low serum immunoglobulins — especially IgA.

Non-infectious complications (such as splenomegaly, lymphadenopathy, interstitial lung disease, cytopenias, enteropathy, liver disease, and lymphoma) were more strongly linked to specific immune cell defects:

Late-onset combined immunodeficiency (LOCID) — marked by severe reduction in naive CD4+ T cells — emerged as a major risk factor for many of these complications.

A pronounced defect in classical CD27+ memory B cells (27MBC−), often accompanied by lower NK cells and IgM, was associated with higher risks of enteropathy and (together with LOCID and low IgA) liver disease.

Most importantly for patient prognosis:

Lower serum IgG, presence of LOCID, and especially the absence of CD27+ memory B cells were the strongest predictors of shorter survival and earlier death.

Genetic risk alleles associated with CVID did not independently predict outcomes in this cohort.

These biomarker profiles offer clinicians a practical toolset to stratify risk, guide closer monitoring, and tailor management for CVID patients. By identifying those at greatest risk of severe complications early, this approach could help improve long-term outcomes and quality of life in this challenging condition.

References:

https://www.jacionline.org/article/S0091-6749(25)01079-6/fulltext

New Risk Score Predicts Nasal Polyp Recurrence After Sinus Surgery for CRSwNP

2026-02-20T12:44:00.015-05:00

Nasal polyps often return after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). A new study validates a simple Risk Predictor Score (RPS) to identify who is most likely to experience early recurrence.

The RPS combines:

Tissue biomarkers: eosinophil cationic protein (ECP), IL-5, and anti-dsDNA IgG

Clinical factors: asthma status and pre-surgery modified Lund-Mackay radiographic score

In an independent validation group, the score predicted recurrence well (AUC = 0.76), close to the original training set (AUC = 0.89).

Patients were divided into three risk groups:

High risk → median recurrence at 38 months

Intermediate risk → median recurrence at 54 months

Low risk → median recurrence at 60 months

This validated RPS helps doctors identify high-risk patients early, potentially guiding closer follow-up, more aggressive medical therapy, or personalized treatment plans to delay or prevent polyp regrowth.

References:

https://www.jacionline.org/article/S0091-6749(25)01123-6/fulltext

Oral ITK Inhibitor Soquelitinib in Development for Atopic Dermatitis

2026-02-19T17:03:00.024-05:00

Corvus Pharmaceuticals released positive Cohort 4 data for soquelitinib, an oral ITK inhibitor, in moderate-to-severe atopic dermatitis.

In this 8-week, randomized, placebo-controlled extension:

Soquelitinib 200 mg BID reduced EASI score by 72% vs 40% on placebo.

75% reached EASI-75, 25% EASI-90, 33% IGA 0/1 (clear/almost clear).

The upstream T-cell approach reduced Th2/Th17 cytokines and boosted regulatory T cells, offering a novel immunotherapy angle distinct from current biologics.

Early data suggest soquelitinib could become a potent, convenient oral option for refractory AD.

There is ongoing anticipation for OX40/OX40L inhibitors (e.g., rocatinlimab, amlitelimab) as a new therapeutic class for AD.

There is a research shift toward upstream immune modulation (e.g., T-cell targeting via OX40L or ITK) for potentially more durable or convenient AD control, with several candidates advancing toward regulatory filings.

Atopic dermatitis maintenance (click to enlarge the image).

References:

https://corvuspharma.gcs-web.com/news-releases/news-release-details/corvus-pharmaceuticals-announces-positive-data-cohort-4

Monoclonal Antibody Targeting OX40L (Amlitelimab) In Development for Atopic Dermatitis

2026-02-18T16:55:00.030-05:00

Sanofi's amlitelimab, a fully human non-T cell-depleting monoclonal antibody targeting OX40L, delivered strong Phase 3 results in moderate-to-severe atopic dermatitis (AD) for patients 12+.

In the SHORE study (with topical therapies), it met all primary and key secondary endpoints at Week 24. Benefits emerged as early as Week 2, with efficacy increasing over time.

The COAST 2 study (monotherapy) supported efficacy but missed one co-primary endpoint tied to perceptible erythema.

Building on positive COAST 1 data, amlitelimab showed good tolerability (similar to placebo; common AEs: nasopharyngitis, upper respiratory infections) and offers flexible every-4-week or every-12-week dosing after loading - potentially easing the burden of current monthly biologics.

There is ongoing anticipation for OX40/OX40L inhibitors (e.g., rocatinlimab, amlitelimab) as a new therapeutic class for AD.

Atopic dermatitis maintenance (click to enlarge the image).

References:

https://www.sanofi.com/en/media-room/press-releases/2026/2026-01-23-06-00-00-3224400

EoE Pipeline Update: Dupilumab Leads, But Exciting Contenders Are Closing In

2026-02-17T16:50:00.000-05:00

The evolving therapeutic landscape for eosinophilic esophagitis (EoE) highlights dupilumab as the cornerstone biologic treatment, with a promising pipeline of emerging agents.

Dupilumab remains the only approved biologic for EoE (FDA approval in 2022, with expansions to younger patients), effectively targeting IL-4/IL-13 pathways to reduce inflammation, improve histology, and alleviate symptoms like dysphagia.

Ongoing developments include:

Cendakimab (an anti-IL-13 monoclonal antibody) has shown strong Phase 3 results, with significant and sustained improvements in symptoms, eosinophil counts, and endoscopic features through 48 weeks.

Tezepelumab (anti-TSLP) continues in its Phase 3 CROSSING trial (expected completion around 2027), building on earlier promising data.

Vonoprazan (a potassium-competitive acid blocker) is advancing into Phase 2 studies for EoE, offering potential as an enhanced acid suppression option beyond traditional PPIs.

Topical corticosteroids (e.g., budesonide formulations) and PPIs stay essential first-line therapies, while broader reviews emphasize precision approaches, comprehensive endpoints, and addressing symptom-histology discordance.

The field is progressing toward more targeted, disease-modifying options to prevent complications like fibrosis.

Eosinophilic Esophagitis: Management in 4 steps (click here to enlarge the image).

References:

https://pmc.ncbi.nlm.nih.gov/articles/PMC12735788/