A 51-year-old man presents to his primary care provider complaining of recent, recurrent episodes of angioedema. The patient previously had gone to the emergency department (ED) because of facial swelling. The ED physician diagnosed the swelling as angioedema related to stress and eating spicy foods. However, the patient has continued to experience episodes of angioedema since his ED visit, despite eliminating spicy foods and other triggers.

The patient states that he has had 4 episodes of severe angioedema over an 8-month period. He reports that with each episode, he experiences irritation of the left eye, sinus pressure, numbness and tingling in the mouth, and swelling of the lips, throat, and tongue. The symptoms usually begin 3 to 4 hours after he eats a large meal, with the most severe reactions occurring after “meat-heavy” meals including steak and barbecued pork.

The patient expresses concern that his symptoms will progress to anaphylaxis but notes that he has not needed the epinephrine auto-injector prescribed after his recent ED visit.  To treat symptoms, the patient takes 50 mg of diphenhydramine, which reduces the severity of symptoms, but facial edema continues for approximately 6 to 12 hours.  He does not take any other medications.

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The patient’s medical history is negative for rashes, changes in skin color, sores or new lesions, and headaches. He complains that he has a constricted airway during his reactions but denies shortness of breath, coughing, and wheezing. He has a history of persistent mild childhood asthma and intermittent adult asthma. He tested positive for seasonal allergies (grasses, trees, and cat dander) but has no history of food or drug allergies. He reports occasional alcohol use and cigar smoking and is up to date on all immunizations.

The patient lives in the Southeast and when questioned about tick exposure, he confirms having removed a tick about a year previously, after a long day spent outdoors.

Physical examination is unremarkable. However, photos of the patient taken during his recent ED visit show bilateral swelling in the lips, cheeks, and soft tissue under the jaw. The left side of his face appears more severely swollen than the right. The swelling is so severe that the patient appears to have difficulty closing his mouth. There is very mild periorbital swelling, and the sclera of both eyes are mildly pink and watery. No chemosis is present, and there is no noticeable skin change, redness, or urticaria on the face, trunk, or limbs.

Assessment and Plan

An immunoglobulin E (IgE) skin prick test (SPT) is ordered to rule out new allergies to protein in his diet. SPT is performed for commercial extracts of beef, pork, lamb, chicken, turkey, and milk, as well as cat and dog dander. The patient tests positive for hypersensitivity reaction to cat dander, revealing a 3- to 5-mm wheal with flare. All other SPT results are negative.

Considering the patient’s positive history of tick bite, blood samples are collected for an immunoassay to detect IgE to galactose-α-1,3-galactose (α-gal). The patient tests positive for IgE antibodies to α-gal with the serum assay. These results, along with the patient’s history of tick bite and angioedema after high-protein meals, confirm a diagnosis of red meat allergy, or α-gal syndrome.


Alpha-gal syndrome describes a spectrum of symptoms resulting from an IgE-mediated allergy to the disaccharide α-gal.1 The specific IgE immunoassay that confirms a diagnosis was first introduced in 2012.1 Thus, alpha-gal syndrome is a relatively new disease and researchers are investigating its exact mechanism of development.

Alpha-gal disaccharide is a blood group substance of non-primate mammals found on glycolipids and glycoproteins in the meat of beef, pork, and lamb, as well as goat, rabbit, squirrel, and horse.2 A patient with IgE-mediated α-gal allergy will develop an allergic response after eating meat from these animals (red meat).

There is a globally reported association between tick bites and IgE antibodies to α-gal.3 In the United States, Amblyomma americanum is identified as the culpable tick species. The range of A americanum, also known as the Lone Star tick, spans the Southeastern region of the United States, the same area from which most cases of allergic reactions to red meat are reported.2

IgE-mediated α-gal allergic reactions can range from urticaria to anaphylaxis,3 but they differ from typical allergic reactions to food. With typical food allergies, hypersensitivity reactions start immediately, within minutes to 2 hours of consumption or exposure.2 With an IgE-mediated response to α-gal, the reaction occurs at least 3 to 6 hours after consumption of red meat.1,4

Alpha-gal testing should be considered if a patient presents with symptoms that develop 3 to 6 hours after eating red meat or if the symptoms consistently occur at night without a clear association with mammalian meat.4 SPT should include commercial extracts of beef, pork, lamb, chicken, turkey, milk, and cat and dog dander. If the results are negative, immunoassays should be ordered to detect IgE antibodies to α-gal.1,4 Positive immunoassay results confirm a diagnosis of α-gal syndrome.

Current management consists of education to avoid mammalian meat products and prescription of injectable epinephrine for emergency situations. There is no intervention designed to control sensitization or reactions to α-gal.2

Although not clear at first, this case fits that of a patient with α-gal syndrome: his hypersensitivity reactions were preceded by a history of tick bite, a key element to α-gal syndrome pathophysiology. Thus, health care providers should strongly consider α-gal syndrome when a patient presents with idiopathic anaphylactic episodes and a history of a tick bite.

To prevent α-gal syndrome, health care providers should educate their patients to avoid areas where ticks are endemic, especially during hotter months, and to conduct a thorough tick check after outdoor activities.

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Hannah Feltner, MPAS, PA-C, is a physician assistant at the Wellin Head & Neck Tumor Center at the Medical University of South Carolina, in Charleston, South Carolina. Alicia Elam, PharmD, is an associate professor in the Physician Assistant Department of Augusta University, in Augusta, Georgia.


1. Fischer J, Yazdi AS, Biedermann T. Clinical spectrum of α-Gal syndrome: from immediate-type to delayed immediate-type reactions to mammalian innards and meat. Allergo J Int. 2016;25:55-62.
2. Tripathi A, Commins SP, Heymann PW, Platts-Mills TA. Delayed anaphylaxis to red meat masquerading as idiopathic anaphylaxis. J Allergy Clin Immunol Pract. 2014;2(3):259-265. 
3. Commins SP, Platts-Mills TA. Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol. 2013;13(4):354-359.
4. Steinke JW, Platts-Mills TA, Commins SP. The alpha-gal story: lessons learned from connecting the dots. J Allergy Clin Immunol. 2015;135(3):589-596.