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Case Reports
20 June 2023

α-Gal Syndrome: A Case Report of Diagnosis and Meat Reintroduction

Publication: Annals of Internal Medicine: Clinical Cases
Volume 2, Number 6


We report a patient case of a 52-year-old man, with known tick bites, presenting with multiple episodes of generalized urticaria and angioedema that woke him from sleep 8 hours after eating beef. This history, combined with positive galactose-α-1,3-galactose (α-gal serology), led to the diagnosis of α-gal syndrome. Over a 5-year period, he abstained from mammalian meat, avoided further tick bites, and α-gal levels decreased. He was successfully challenged in an allergist's office with meat with no adverse reactions. This case details the process by which our team reviewed available evidence to risk-stratify meat reintroduction in the absence of official guidelines.


Galactose-α-1,3-galactose (α-gal) syndrome is an immunoglobulin E (IgE)-mediated allergy to an oligosaccharide commonly expressed in nonprimate mammalian meat such as beef, pork, and lamb (1). This syndrome was first reported after a geographic correlation was observed between patients who experienced anaphylaxis to cetuximab (a chemotherapeutic monoclonal antibody) and patients who reported anaphylaxis to red meat (1, 2). Further investigation revealed a consistent history of tick bites among all patients (1, 2).


Increase awareness of α-gal syndrome among internists, review the process of diagnosis, and understand risk-stratification for meat reintroduction in the absence of official guidelines.

Case Report

A 52-year-old man from eastern Long Island was referred to our clinic for evaluation of a pruritic rash and angioedema. One week before presentation, the patient experienced generalized urticaria and angioedema that woke him from sleep within 8 hours of eating beef. The rash started on his extremities and later spread to become generalized pruritic hives. The patient took diphenhydramine and his symptoms resolved within 4 hours. He had been regularly eating mammalian meat without adverse reactions. He previously had 2 similar nocturnal episodes but could not recall a clear trigger for those events. Notably, he reported a history of multiple tick bites.
At initial presentation, a specific serum α-gal IgE (sIgE) was obtained and found to be elevated to 39.9 kU/L. A diagnosis of α-gal syndrome was made, and the patient was advised to abstain from mammalian meat. He reported no further episodes of hives and angioedema. He continued to consume dairy products including high-fat ice cream and cheese without adverse reactions. The patient was seen annually for follow-up over a 5-year period and his α-gal sIgE levels gradually declined from 39.9 kU/L to 1.77 kU/L (Figure 1). Notably, the patient was bitten by a lone star tick during this follow-up period and his α-gal sIgE doubled from 2.28 kU/L to 4.60 kU/L (Figure 1).
Figure 1. α-gal IgE levels over 5 years of foPlease delete the caption from the PDF/original of Figure 1.llow-up.
Figure 1. α-gal IgE levels over 5 years of follow-up.
As his α-gal sIgE levels gradually decreased, and the patient expressed the strong desire to reintroduce mammalian meat to his diet; the decision was made to perform an oral challenge. His α-gal sIgE level before the oral challenge was 1.77 kU/L. The patient had an oral challenge of 100 g of ground beef prepared as a well-done hamburger with cheese consumed. He was observed for 8 hours and remained asymptomatic during the entire observation. Since the patient's successful oral challenge, he has resumed consuming mammalian meat without any further reactions.


In the United States, sensitization to α-gal occurs after exposure to bites from the lone star tick (Amblyomma americanum) (1). Although this tick is seen with the greatest density in southern states (3), it is also known to be present on Long Island (3). The exact mechanism of this allergy is unknown; however, it is postulated that components of the tick saliva, glycosylated lipids and proteins or microorganisms, induce an IgE response (1, 4).
Patients typically develop this allergy in adulthood, after previously tolerating mammalian meat (2). Reactions range from mild pruritic hives to severe anaphylaxis requiring hospitalization. Typical IgE-mediated hypersensitivity reactions occur within minutes after exposure to an allergen. However, this syndrome is hallmarked by an unusually delayed reaction, usually 3 to 8 hours, following consumption of mammalian meat (5). This delayed symptom onset can pose a diagnostic conundrum because identification of a trigger is problematic. The diagnosis is made through careful history-taking, identification of tick exposure, and positive α-gal sIgE serology (2). Patients with α-gal sIgE of more than 2% of the total serum IgE is highly suggestive for diagnosis (2, 6); however, there is no definitive sIgE level that determines diagnosis. Interestingly, patients can have sensitization to α-gal without clinical reactivity, and only 1% to 8% of patients with α-gal sIgE experience symptoms with meat ingestion (7).
Current management of α-gal syndrome involves avoidance of mammalian meats and tick bites (2, 7), and referral to an allergist may be recommended. Additionally, as with all allergic reactions, patients may use an antihistamine for very mild symptoms; intramuscular epinephrine is the treatment of choice for anaphylaxis (5). This diagnosis can have a significant impact on patient lifestyle given mammalian meats are a staple in the Western diet, making meat reintroduction an important component of management. In settings of limited access to an allergist or unfamiliarity with this syndrome, meat reintroduction becomes challenging. There are currently no official guidelines outlining the exact process of meat reintroduction or a specified sIgE level at which it is safe to reintroduce meat. Use of a α-gal sIgE level less than 2.0 kU/L in patients tolerating high-fat ice cream before meat reintroduction has been suggested to be associated with lower likelihood of continued meat reactivity with reintroduction (7). Meat reintroduction is also suggested once α-gal sIgE level is less than 2% of total IgE (8).
An added difficulty regarding meat reintroduction is the unclear correlation between IgE levels and severity of reaction (6). Determining a volume of meat, type of meat, duration of observation, period without tick bite exposure, and appropriate α-gal level to perform the oral challenge are important factors when considering the format of the oral challenge for reliability of results and patient safety.
Evidence suggests that in an absence of tick bites, a patient's level of α-gal sIgE will gradually decrease (9), facilitating the reintroduction of foods containing α-gal. Interestingly, our patient's sIgE level decreased over time, but had a 2-fold increase (2.28 kU/L to 4.60 kU/L) after being bitten by a lone star tick, before declining again.
The most common meats documented to elicit allergic responses are beef, pork, venison, and lamb, with reactions usually occurring within 3 to 8 hours (5). Interestingly, fattier types of meat appear to elicit allergic reactions more consistently (6, 10), and tiers of foods associated with risk for reaction have been described because even meat by-products such as lard, gelatin, bovine supplements, and suet have elicited reactions in some patients (5, 6, 8). A large series reports on oral challenges with 140 g of pork sausage; however, false negatives may occur, and a larger volume may be necessary, particularly for patients weighing more than 70 kg (7). One report used a 24-step modified red meat desensitization protocol in a 10-year-old girl with a α-gal sIgE of 5.2 kU/L (11). Our patient weighed 82.6 kg with an α-gal sIgE of 1.77 kU/L at the time of the oral challenge, consumed 100 g of well-done ground beef, and was observed for 8 hours.
It is unclear if our patient would have reacted to a larger preparation. Ambiguity remains regarding optimal preparation in terms of fat content and volume for challenges. Additionally, patient education regarding potential decreased threshold for reactions associated with cofactors like alcohol, exercise, and nonsteroidal anti-inflammatory drugs (2, 7) are important aspects of patient education following diagnosis or during diet and lifestyle discussions in patients with α-gal syndrome (7).
α-gal syndrome must be part of the differential diagnosis for patients presenting with recurrent episodes of urticaria with an unclear proximity to an identifiable trigger. Assessment of tick exposure is crucial and referral to an allergist may be helpful when managing this syndrome. This patient case highlights the persistent challenges of diagnosing and managing this syndrome given the lack of official guidelines. The establishment of clear guidelines is needed to aid the practicing physician in risk-stratification of meat reintroduction for patients with α-gal, either in the office or in the home.

Supplemental Material

Author Disclosure Forms (PDF)


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Information & Authors


Published In

cover image Annals of Internal Medicine: Clinical Cases
Annals of Internal Medicine: Clinical Cases
Volume 2Number 6June 2023


Published in issue: June 2023
Published online: 20 June 2023




Ari Heffes-Doon, MD [email protected]
NYU Long Island School of Medicine, Mineola, New York
Erin Banta, MD [email protected]
NYU Long Island School of Medicine, Mineola, New York
NYU Grossman School of Medicine, New York, New York
Corresponding Author
Ari Heffes-Doon, MD; 259 1st Street, Mineola, NY 11501; e-mail, [email protected].

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Ari Heffes-Doon, Erin Banta, Nathanael Horne. α-Gal Syndrome: A Case Report of Diagnosis and Meat Reintroduction. AIM Clinical Cases.2023;2:e220836. [Epub 20 June 2023]. doi:10.7326/aimcc.2022.0836

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