Alpha-gal Syndrome (Red Meat Allergy)

Column Author and Editor: Chris Day, MD | Pediatric Infectious Diseases; Director, Transplant Infectious Disease Services; Medical Director, Travel Medicine; Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Assistant Professor of Pediatrics, University of Kansas School of Medicine

Alpha-gal syndrome (AGS), also known as red meat allergy, mammalian meat allergy or tick bite meat allergy, is an emerging condition characterized by allergic reactions to galactose-a-1,3-galactose. This oligosaccharide is predominately found in meat and other products derived from non-primate mammals. AGS is IgE mediated but, unlike most IgE-mediated reactions (which have an onset typically within an hour), has a delayed onset of two to six hours after consumption of alpha-gal-containing products. The presentation is variable with symptoms ranging from irritable bowel-like diarrhea and abdominal pain to nausea and vomiting, urticaria, angioedema, or anaphylaxis.¹ A diagnosis of AGS is made in the setting of a compatible syndrome with confirmation by immunoassays to detect IgE to alpha-gal and potentially by additional allergy testing if the immunoassay is negative.

The syndrome in the United States is typically related to bites of the lone star tick (Amblyomma americanum), which is found in a large region of the U.S. (Figure 1), including Missouri and eastern Kansas. Other tick species are associated with AGS on other continents; there may be tick species other than the lone star tick that are sometimes responsible in North America as well. The exact mechanism by which AGS occurs has not been fully delineated, but tick saliva is known to contain alpha-gal as well as a number of immunomodulatory components that may promote the maladaptive response of generating IgE to alpha-gal in humans.² Data on testing for alpha-gal (obtained from Eurofins Viracor, which provided almost all of the laboratory testing for the syndrome prior to 2022) analyzed by the Centers for Disease Control and Prevention (CDC) suggest that parts of Missouri and Kansas are among the regions in the United States with the highest incidence of AGS (Figure 2). Cases of AGS as counted by the number of positive assays appear to be increasing from 2017 to 2021 with 90,018 apparent cases over the period. While a majority of the cases were in adults, 2,478 of the positive assays were in children ages 0-9 years and 8,007 in individuals 10-19 years.³

Awareness of AGS among providers in primary care seems to be low. A recent survey found that 78% of providers (internists, family practitioners, physician assistants, nurse practitioners and pediatricians) had little to no knowledge of the syndrome. Pediatricians did have the most knowledge of these groups with 12.3% answering all three questions on the survey correctly. While a subset of patients receives a diagnosis promptly (within the first year), the remaining 79% of patients take an average of 7.1 years to be appropriately diagnosed. Patients with less access to care, including difficulty accessing allergists, will be disadvantaged in getting appropriately diagnosed and managed.⁴

Management of AGS involves avoidance of triggering foods, including beef, pork, lamb and rabbit. Some people may need to avoid dairy products and gelatin. Poultry and fish do not contain alpha-gal and can be eaten. Rarely, some people with severe AGS may need to avoid certain vaccines or medications that contain small amounts of alpha-gal.¹

Prevention of AGS means avoiding tick bites. Tick precautions include dressing appropriately for outdoor activities: For woods or high grass when ticks are active, appropriate dress ideally includes long pants tucked into socks and long-sleeved shirts with cuffs. All outer garments should be treated with permethrin. DEET on exposed skin is also an effective tick-repellant. Walking in the middle of trails to avoid the vegetation on which ticks are waiting can also be effective. Tick checks should be performed after outdoor activity, and ticks should be removed properly.⁵

References:

1. Alpha-gal syndrome. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD). CDC.gov. July 28, 2023. https://www.cdc.gov/ticks/alpha-gal/index.html
2. Román-Carrasco P, Hemmer W, Cabezas-Cruz A, Hodžić A, de la Fuente J, Swoboda I. The α-Gal syndrome and potential mechanisms. Front Allergy. 2021;2:783279. PMID: 35386980. PMCID: PMC8974695. doi:10.3389/falgy.2021.783279
3. Thompson JM, Carpenter A, Kersh GJ, Wachs T, Commins SP, Salzer JS. Geographic distribution of suspected alpha-gal syndrome cases — United States, January 2017–December 2022. MMWR Morb Mortal Wkly Rep. 2023;72:815-820. doi:15585/mmwr.mm7230a2
4. 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:15585/mmwr.mm7230a1
5. Preventing tick bites. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD). CDC.gov. July 1, 2020. https://www.cdc.gov/ticks/avoid/on_people.html

Figure 1. Lone Star Tick Distribution (Source: CDC.gov)