Scott P. Commins, MD, PhD, from UNC Health, specializes in food allergies, particularly alpha-gal allergy to red meat.

Scott Commins, MD, PhD

 has been part of the allergy literature for nearly 2 decades, yet it continues to be missed in clinical practice with striking regularity. As tick populations expand and case counts climb, the gap between what clinicians know about this condition and what they need to know is widening in ways that cost patients years of undiagnosed suffering.

Why Alpha-Gal Syndrome Is Frequently Missed

Most food allergies follow a predictable pattern: a person eats a trigger food and reacts within minutes to a couple of hours. AGS breaks that timeline entirely.

After a tick bite introduces the carbohydrate galactose-alpha-1,3-galactose (alpha-gal) into the body, a subset of individuals develop an IgE-mediated immune response that unfolds over 1 to 3 months. By the time symptoms first appear, the inciting bite may be long forgotten. When reactions do occur, they arrive 3 to 6 hours after eating mammalian meat or other alpha-gal-containing products, sometimes longer, a pattern early researchers nicknamed "midnight anaphylaxis."

Without a high index of suspicion, neither the patient nor the clinician connects the reaction to the meal. For many patients with AGS, the time from first reaction to correct diagnosis has historically stretched toward 7 years, a delay driven almost entirely by this atypical presentation and, until recently, a general lack of awareness of the condition among both affected individuals and clinicians.

Geography compounds the problem. AGS was long considered a southeastern US condition tied primarily to the lone star tick (

). However, the tick’s geographic range has expanded into increasingly diverse areas of the United States, bringing AGS risk beyond historically endemic regions. Confirmed cases have now emerged farther north, including in Maine following bites from Ixodes scapularis and in Washington State following exposure to Ixodes pacificus.

These reports raise the possibility that AGS transmission may not be limited to the lone star tick, although the role of 

 species in transmission remains an emerging area of investigation. Hotspots have also appeared on Long Island, Martha’s Vineyard, and in northern Minnesota. As white-tailed deer expand into peri-urban environments and carry tick populations with them, clinicians across the country should keep AGS in their differential.

Reactions hit 3 to 6 hours after eating mammalian meat

Caused mainly by Lone Star tick bites, now spreading north

~ 450,000 Americans affected, likely an undercount

Alpha-gal-specific IgE testing confirms diagnosis

Omalizumab (2024) shows early benefit in AGS

Blood testing for alpha-gal-specific IgE is the diagnostic standard, typically paired with testing for beef, pork, lamb, and sometimes milk, alongside total IgE. Providers may also assess baseline tryptase in patients with severe reactions and suspected alpha-gal allergy, though this isn't routine and is generally left to individual provider judgment.

A positive result alone does not confirm clinical allergy. In tick-endemic regions, 20% to 30% of tick-bitten individuals who eat red meat without symptoms can still test positive, a phenomenon known as irrelevant sensitization. When ordered for the right patient, one with a history of delayed symptoms after mammalian meat consumption, specific IgE testing is a highly effective confirmatory tool.

Clinical suspicion should drive the decision to test, and when it does, the results are meaningful. A study of U.S. military recruits found alpha-gal IgE sensitization rates of 39% in Arkansas, 35% in Oklahoma, and 29% in Missouri against a cohort-wide rate of just 6%, reinforcing how much geography and clinical context should inform the decision to test.

AGS Clinical Presentations and Symptom Variability

AGS does not present uniformly. The classic picture involves urticaria, angioedema, or anaphylaxis presenting hours after a mammalian meat meal. A meaningful subset of patients, however, presents with isolated gastrointestinal symptoms, abdominal pain, nausea, vomiting, and diarrhea with no skin or respiratory findings, and is routinely misdiagnosed with irritable bowel syndrome or food poisoning for years.

The American Gastroenterological Association has issued clinical practice guidance directing gastroenterologists to maintain a high index of suspicion for this presentation.

 Early signs can also include redness and itching of the palms and soles before systemic symptoms emerge.

Cofactors matter significantly. A patient may tolerate a steak one evening and react sharply the next when the same meal is accompanied by alcohol or preceded by exercise. These cofactor-dependent patterns mean patients will genuinely deny a consistent association between meat and symptoms because the reaction truly is not consistent. Alcohol and vigorous exercise are the 2 most commonly reported amplifiers and should be explored explicitly in the history.

Alpha-gal also hides in medications and vaccines, including heparin, certain antivenoms, gelatin-containing vaccines, and monoclonal antibodies produced in mammalian cell lines. Bioprosthetic heart valves raise theoretical long-term concerns as well. Each situation requires individualized risk-benefit discussion.

Awareness Gaps and the Case for Earlier AGS Diagnosis

The 2023 CDC MMWR survey found that roughly 42% of healthcare providers had never heard of AGS and an additional 35% lacked confidence in their ability to diagnose or manage it.

Surveillance infrastructure is only now catching up. Arkansas mandated reporting in September 2023, and cases there climbed from just over 300 that year to nearly 3800 by 2025.

More than a dozen states now require reporting

, and Oklahoma recently added AGS to its reportable disease list.

 Without that infrastructure, the CDC's estimate of 450,000 affected Americans is almost certainly an undercount.

An earlier diagnosis also opens a window for resolution. Patients who avoid further tick bites and maintain dietary avoidance often see alpha-gal IgE levels decline over 3 to 5 years, with many eventually able to reintroduce mammalian products. That outcome depends entirely on timely recognition.

 as the first medication to reduce allergic reactions in IgE-mediated food allergy patients aged ≥ 1 years, and early data suggest benefit for patients with AGS who react to small accidental and cross-contamination exposures despite avoidance.

Clinicians should note that omalizumab is produced in Chinese hamster ovary cells that may variably express alpha-gal, creating a theoretical anaphylaxis risk that warrants appropriate precautions at initiation. Metformin has also produced early anecdotal signals as a potential treatment, with some patients resuming mammalian products after use, but no controlled trial data exists yet.

AGS is no longer a regional curiosity. It is a geographically expanding, clinically variable, and potentially fatal condition that primary care providers, allergists, gastroenterologists, and emergency clinicians all need to recognize. Raising that index of suspicion, systematically and across specialties, remains the most important step the clinical community can take for the hundreds of thousands of patients whose AGS remains undiagnosed.

Butler WK, Oltean HN, Dykstra EA, et al. Onset of Alpha-Gal Syndrome after Tick Bite, Washington, USA. 

Saunders EF, Sohail H, Myles DJ, et al. Alpha-Gal Syndrome after Ixodes scapularis Tick Bite and Statewide Surveillance, Maine, USA, 2014–2023. 

Ailsworth SM, Susi A, Workman LJ, et al. Alpha-Gal IgE Prevalence Patterns in the United States: An Investigation of 3,000 Military Recruits. 

McGill SK, Hashash JG, Platts-Mills TA. AGA Clinical Practice Update on Alpha-Gal Syndrome for the GI Clinician: Commentary. 

Carpenter A, Drexler NA, McCormick DW, et al. Health Care Provider Knowledge Regarding Alpha-gal Syndrome — United States, March–May 2022. MMWR Morb Mortal Wkly Rep 2023;72:809–814. DOI: 

Alpha-gal syndrome cases rising in Arkansas. KTLO. Published May 6, 2026. Accessed September 3, 2026. 

https://www.ktlo.com/2026/05/06/alpha-gal-syndrome-cases-rising-in-arkansas/

Dowdell R. Alpha-gal syndrome added to Oklahoma’s reportable disease list. Newson6. Published May 11, 2026. Accessed September 3, 2026. 

https://www.newson6.com/health/alpha-gal-syndrome-added-to-oklahomas-reportable-disease-list

Emerging Tick Bite-Associated Meat Allergy Potentially Affects Thousands. CDC. Published July 27, 2023. Accessed September 3, 2026. 

https://www.cdc.gov/media/releases/2023/p0727-emerging-tick-bites.html

Smith T. FDA Approves Omalizumab as First Treatment of 1 or More Food Allergies for Children, Adults. HCPLive. Published February 16, 2024. Accessed September 3, 2026.

https://www.hcplive.com/view/fda-approves-omalozumab-first-treatment-of-1-or-more-food-allergies-for-children-adults

Articles

Alpha-gal syndrome remains underrecognized because its IgE-mediated reactions occur 3–6 hours after mammalian product exposure, often months after the inciting tick bite, obscuring causal links and prolonging diagnosis. Geographic expansion beyond the lone star tick has broadened risk across the U.S., including possible Ixodes-associated cases. Diagnosis relies on alpha-gal–specific IgE interpreted in clinical context due to frequent irrelevant sensitization. Presentations range from anaphylaxis to isolated GI syndromes with cofactor dependence, making systematic vigilance essential.

Alpha-gal syndrome remains vastly underdiagnosed, with expanding tick geography and delayed reactions complicating recognition across specialties.

Alpha-Gal Syndrome: Closing an Underrecognized Allergy Diagnostic Gap 

How Climate Change is Making Your Patients' Allergies Worse

As climate change intensifies, it is not just the environment that suffers—seasonal

are getting worse, too. Global warming has led to increased droughts, wildfires, intense storms, heat waves, and rising sea levels, factors that can contribute to allergies and asthma.

According to the American Public Health Association, the 3 main causes of allergy include ambient air pollution, mold, and pollen.

 The organization also reported that 30% of adults and 40% of children experience nasal allergies.

Featuring Scott Commins, MD, PhD (top left), Sharmilee Nyenhuis, MD (bottom left), Mahboobeh Mahdavinia, MD, PhD (top right), and Kent Lam, MD (bottom right)

Credit: UNC School of Medicine, UChicago Medicine, McGovern Medical School, Macon & Joan Brock Virginia

2025 American Academy of Allergy, Asthma, & Immunology (AAAAI) 

spoke with several experts on climate change’s impact on allergies, exploring strategies clinicians can adopt to mitigate worsening allergic conditions.

, from the University of Texas Health Houston

 from Eastern Virginia Medical School at Old Dominion University

Extended Pollen Seasons and Increased Allergen Potency

Nyenhuis emphasized that pollen seasons are lengthening, especially in the western and southwestern United States, where freeze days have increased by nearly 20.

 This prolonged exposure intensifies symptoms and raises the risk of new allergies. She also noted that air pollution, particularly diesel particles, can amplify pollen’s allergenicity, worsening allergic reactions.

To help patients, Nyenhuis recommended indoor air filtration, wearing masks outdoors, and using hyper-local pollen data instead of historical weather app forecasts, which are becoming less reliable due to climate change.

Air Pollution’s Role in Allergy Development

Mahdavinia explained that air pollutants disrupt the respiratory tract’s epithelial barriers, leading to inflammation and microbiome imbalances in the nose and lungs.

 This can eliminate beneficial bacteria, allowing harmful microbes to thrive and increasing allergy risks. Mahdavinia called for expanded pollen monitoring and broader allergen testing as plant distributions shift.

Climate Change and Emerging Food Allergies

Commins discussed pollen food syndrome, in which pollen absorbed through the skin triggers food allergies.

 He also warned about the rising prevalence of alpha-gal syndrome, a meat allergy caused by tick bites. Warmer winters have expanded tick populations, increasing cases in the US, Europe, Australia, and Asia.

As climate change drives new allergy risks, clinicians must stay alert for evolving conditions such as pollen food syndrome and alpha-gal syndrome. Experts stress the importance of refining allergy diagnostics, improving access to immunotherapy, and implementing preventive strategies to protect patients in an increasingly allergenic environment.

Relevant disclosures include GlaxoSmithKline for Nyenhuis, GENZYME CORPORATION, Optinose US, Inc, and Blueprint Medicines Corporation for Mahdavinia, Regeneron Healthcare Solutions, Genetech USA, and AstraZeneca Pharmaceuticals for Commins, and Optinose US, AERIN MEDICAL, GENZYME CORPORATION, Medtronic, GlaxoSmithKline, Regeneron Pharmaceuticals, and AstraZeneca Pharmaceuticals for Lam.

. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.apha.org/-/media/files/pdf/topics/climate/asthma_allergies.pdf. Accessed March 20, 2025.

Derman, C. Adapting Allergy Care Due to Increased Pollen Seasons, with Sharmilee Nyenhuis, MD. HCPLive. March 1, 2025. 

https://www.hcplive.com/view/adapting-allergy-care-due-increased-pollen-seasons-sharmilee-nyenhuis-md

Derman, C. How Air Pollutants Contribute to Allergies, with Mahboobeh Mahdavinia, MD, PhD. HCPLive. March 1, 2025. 

https://www.hcplive.com/view/how-air-pollutants-contribute-to-allergies-with-mahboobeh-mahdavinia-md-phd

Derman, C. Climate Change’s Impact on Allergies, with Scott Commins, MD, PhD. HCPLive. March 2, 2025. 

https://www.hcplive.com/view/climate-change-s-impact-on-allergies-scott-commins-md-phd

Climate change exacerbates seasonal allergies through increased air pollution, prolonged pollen seasons, and rising allergen potency. Experts highlight the role of air pollutants in disrupting respiratory barriers, leading to inflammation and microbiome imbalances. Emerging conditions like pollen food syndrome and alpha-gal syndrome are becoming more prevalent due to environmental shifts. Clinicians are urged to refine diagnostics, expand allergen testing, and adopt preventive strategies. The importance of using hyper-local pollen data and indoor air filtration is emphasized to mitigate allergy risks in an increasingly allergenic environment.

Climate change worsens allergies by lengthening pollen seasons, increasing air pollution, and driving new food allergies. Experts offer strategies for clinicians.