Diagnosis and Testing

A Guide to the Diagnosis of Alpha-gal Syndrome

Update

When this website was created, there wasn’t an up-to-date, comprehensive guide to the diagnosis and management of alpha-gal syndrome. Now two have been published, both written by leading experts. If you are a healthcare provider, or even a patient with a more than casual interest in alpha-gal syndrome, you will want to read these papers. Although this page draws heavily from both publications, it is not a substitute for them.

  1. Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients. Expert Review of Clinical Immunology. 2020 Jul 9:1-1.
  2. Platts-Mills TA, Li RC, Keshavarz B, Smith AR, Wilson JM. Diagnosis and management of patients with the α-Gal syndrome. The Journal of Allergy and Clinical Immunology: In Practice. 2020 Jan 1;8(1):15-23.

Allergies to Red Meat

There is more than one red meat allergy. The dominant forms that we know of are:

  • Alpha-gal syndrome: an allergy to the sugar galactose-alpha-1,3-galactose (alpha-gal) in red meat and other parts of mammals. AGS is the most common red meat allergy.
  • Primary meat allergy: an allergy to proteins in red meat
  • Pork-cat syndrome:  an allergy to pork caused by exposure to cats.

How is Alpha-gal Syndrome Diagnosed?

Leading expert, Scott Commins MD, PhD, writes:

In >90% of cases, the diagnosis of AGS can be made based on a history of delayed allergic reactions after eating non-primate mammalian meat (e.g. ‘red meat’ such as beef, pork, or lamb) and a positive blood test (>0.1 IU/mL) for IgE to alpha-galThe combination of both an appropriate clinical history and supporting blood test is necessary to establish an accurate AGS diagnosis (2).

If you experience symptoms after eating mammalian meat, your primary care physician or allergist should be able to determine whether you have alpha-gal syndrome; pork-cat syndrome; an allergy to protein in meat, like a primary beef allergy or a different health issue.

Doctors diagnose alpha-gal syndrome through a combination of clinical history and blood tests, including:

  • History of allergic reactions to mammalian meat, including symptoms, timing of symptoms, and age of onset
  • History of exposure to ticks, including the presence or absence of localized reactions to tick bites
  • A blood test for Galactose-alpha-1,3-galactose sIgE, often as part of a panel of tests, called an Alpha-gal Panel
  • Responsiveness to dietary changes

Prick test with extracts of beef or pork are unreliable and not recommended. (1,2)

Prick-prick skin testing used cooked meats are also used in some cases (2). Please see Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients for more information about this method.

Intradermal (ID) testing with meat extracts or gelatin are sometimes used in the diagnostic process, especially when blood tests are negative but there is a history of delayed reactions after ingestion of mammalian meat (1)(2). However, few clinics perform these tests (2).

Commins describes a multi-step protocol used by a referral center for diagnosing the 2% of patients with a history of reactions to mammalian products who test negative for alpha-gal IgE (2). This is detailed in Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients and can include:

  • The assessment of surrogate markers (beef, pork, lamb) by skin and serum IgE testing
  • Testing for cat serum albumin (Fel d2) to identify patients with pork-cat syndrome
  • Testing for IgE to both porcine and bovine gelatin
  • Skin testing using alpha-gal-containing biologics such as cetuximab
  • Basophil activation testing

This approach has led to diagnostic clarification in 78% of patients with seronegative testing who report compelling symptoms (2).

 

Occasionally, food challenges are used in diagnosis of AGS. Food challenges need to be conducted with the utmost care, because of the delayed and unpredictiable nature and severity of allergic reactions to alpha-gal. Commins reports that 15-20% of food challenge reactions in patients with AGS require one or more doses of epinephrine and/or emergency medical transport (2). In Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients Commins describes the limited set of circumstances in which alpha-gal food challenges are clinically appropriate (2).

What Blood Tests Do Doctors Use to Help Them Diagnose Alpha-gal Syndrome?

The Alpha-gal Panel

The set of blood tests that doctors usually use to help them diagnose alpha-gal syndrome is called an Alpha-gal Panel. It includes tests for beef, pork, lamb, and alpha-gal IgE.

  • In the U.S., Viracor Eurofins Clinical Diagnostics is the main lab that performs these test:
    • Alpha-Gal Panel
      Test Code: 403196P
      Tests in this Panel:
      *Galactose-alpha-1,3 galactose (Alpha-Gal) IgE
      *Beef (Bos spp) IgE
      *Pork (Sus spp) IgE
      *Lamb / Mutton (Ovis spp) IgE
  • Both Quest and Labcorp can send your blood samples to Viracor, if your doctor gives them the right codes. Double-check these codes using the links, in case they change:
  • Doctors also often order a test for total IgE  as well, as in some cases the ratio of alpha-gal IgE to total IgE is clinically significant (1), especially when total IgE is low.
  • Sometimes tests for milk and gelatin allergy are also included.

Alpha-gal IgE Only

Sometimes doctors order the test for alpha-gal IgE alone instead of the full Alpha-gal Panel. When they do this, they usually order additional tests, such as beef and pork, separately. Double-check these codes using the links, in case they change:

 The WRONG Test!

  • Unfortunately, very often the wrong blood test is performed. The test below is NOT the right test for diagnosing alpha-gal syndrome. It’s for diagnosing another condition, Fabry disease.
    • α-Galactosidase A Deficiency  This is the wrong test!
  • The main reasons why this test is sometimes mistakenly ordered are:
    • Even though a-galactosidase has nothing to do with alpha-gal syndrome, the names sound similar
    • Doctors and laboratory staff have trouble finding the correct test codes
  • You can help prevent this problem by bringing a copy of the correct test codes to both your doctor’s appointment and to the lab where you have your blood drawn. These are provided in the PDF below, which you can download and print.
  • Ask your doctor for a copy of your lab report, both for your records and so you can make sure the right test was ordered.

Europe

In Europe, blood testing for alpha-gal IgE is available via Phadia Thermofisher. 

The carbohydrate moiety alpha-gal is found in mammalian milk, as evidenced by the positive immunoassay results to cow’s milk. Consistent with prior studies, 11 of 12 subjects had negative immunoassay results to the casein component of cow’s milk, suggesting that this milk protein antigen is not a significant site of alpha-gal–based glycosylation (3).

Commins, et al

My allergist ordered the right test for the allergy to Alpha-gal, but the lab tech in the hospital couldn’t find a code for it, so when the test came back positive, the lab tech coded me positive for Fabry disease.

Bethany Welch

Talking to Your Doctor about Alpha-gal Syndrome

Since alpha-gal syndrome was only recently discovered, and knowledge about it is evolving rapidly, your doctor might not have heard of AGS or might have misconceptions about it.  It may help your doctor if you bring the following to your appointment:

Ask your doctor if they have access to Up-to-Date. If they do, recommend that they read the article on meat allergies, which is written by Scott P. Commins, MD, PhD, a leading expert on AGS.

It took 2 weeks to get diagnosed. My doctor told me there was no way I had alpha-gal syndrome, and said he was only running the test to prove me wrong.

Amber Roberts

What Do My Test Results Mean?

Your lab report may include some or all of the following test results

    Galactose-alpha-1,3-galactose IgE

    • This is a measure of your galactose-alpha-1,3-galactose (or alpha-gal for short) specific IgE antibodies.

    Pork IgE and Beef IgE

    • These are measures of your IgE antibodies to the proteins in beef and pork.
    • The samples used to perform these tests may contain both proteins and alpha-gal.

    Total IgE

    • This is a measure of all your IgE antibodies to all allergens, not just to one specific allergen.

      What the test results mean

      You need to ask your doctor what the numbers in your lab report mean. We are not qualified to interpret them for you. However, the following guide may help you talk to your doctor about your results.

      Galactose-alpha-1,3-galactose IgE and Total IgE

      • At the time this is being written, antibody levels > 0.10 kU/L are typically considered a positive test result (1).
      • Antibody levels >2 IU/ml or >2% of total IgE make the diagnosis of alpha-gal syndrome very likely (2).
      • Physicians at UVA recently saw a case with a convincing history whose total serum IgE was 6.0 IU/ml and alpha-gal IgE was 0.8 IU/ml. Thus, although the sIgE was < 1.0 IU/mL it was nonetheless > 10% of the total IgE. (2)
      • As with any allergy, false positives, and possibly subclinical positives, occur. This means that some people who test positive for alpha-gal IgE do not seem to exhibit symptoms after eating red meat. As reactivity to alpha-gal appears to occur on a spectrum, a portion of these people may react to some medications or medical products containing alpha-gal (3) and/or experience symptoms after eating mammalian organs, which contain more alpha-gal than mammalian muscle. (4)
      • False positives are more common with people whose alpha-gal IgE levels are <2 IU/ml and <2% of total IgE
      • As with any allergy, false negatives also occur, although they are less common. Anecdotal reports from people with AGS seem to suggest that a not insignificant number of people who are initially seropositive for alpha-gal IgE eventually revert to seronegative but continue to experience reactions. 

      Pork IgE and Beef Ig

      If you test positive for pork and/or beef IgE it may mean:

      • You are allergic to proteins in pork and/or beef. This is called “primary meat allergy.” It’s a different allergy than alpha-gal syndrome, but both make you allergic to red meat.

      OR

      • You are not allergic to proteins in pork or beef. You have alpha-gal syndrome. You tested positive because the test samples contain alpha-gal in addition to proteins. This is very common, especially with the beef test. 

      OR

      • Some people who test negative for alpha-gal and beef IgE, but positive for pork IgE, may have pork-cat syndrome. (5)

      Example:

      See below two sets of test results. These are from a real patient.

      Clinical History

      The patient has a clinical history of:

      1. Multiple tick bites
      2. Delayed allergic reactions to beef, pork, dairy, gelatin, dairy, mammalian byproducts in both food and medications, and carrageenan.
      3. These reactions began a few weeks after the tick bites
      4. Symptoms include hives, angioedema, anaphylaxis, and abdominal pain occurring 1-10 hours after ingestion of meat and other foods with ingredients derived from mammals

      How these results were interpreted:

      1. The elevated galactose-α-1,3-galactose (alpha-gal) IgE levels and the ratio of galactose-α-1,3-galactose (alpha-gal) IgE to total IgE in conjunction with the patient’s clinical history suggest that the patient has alpha-gal syndrome.
      2. The elevated pork and beef IgE do not mean that the patient is allergic to beef and pork proteins. Most likely, alpha-gal in the beef and pork samples used for the test produced the positive results. This is common. Since the patient tests positive for alpha-gal IgE and has delayed reactions after ingesting mammalian meat, these test results don’t have much meaning. Regardless of whether they tested positive or negative for beef and pork protein IgE, they are allergic to alpha-gal in beef and pork.
      3. The negative result for porcine gelatin means that the patient is not allergic to the protein in porcine gelatin. However, since the patient tests positive for alpha-gal, which is also in gelatin, they may also react to gelatin. Studies show that patients who are allergic to alpha-gal may have anaphylactic reactions to both ingested and parenterally administered gelatin.

      What is this patient allergic to?

      1. This patient is not allergic to proteins in porcine gelatin and likely is also not allergic to any proteins in meat.
      2. This patient is allergic to galactose-α-1,3-galactose (alpha-gal) which is found in all mammalian cells, tissues, and fluids including all mammalian meats, dairy, and gelatin.
      3. Despite testing negative for IgE to gelatin, this patient reacts to even small amounts of gelatin in foods and medications.

      Does my galactose-alpha-1,3-galactose (alpha-gal) IgE level tell me how reactive I will be to alpha-gal?

      No. This number does not tell you how reactive you will be to foods, drugs, or other products with alpha-gal in them. It is only useful for predicting whether you will react to them at all.

      • Some people with high levels of alpha-gal IgE are not very reactive to it.
      • Some people with low levels of alpha-gal IgE are very reactive to it.
      • Researchers are studying whether the ratio of alpha-gal IgE/total IgE is correlated with how reactive to alpha-gal people are, but the results of this research have not yet been published.

      “I don’t know if I would call it a true false positive or a subclinical positive (6).”

      Dr. Erin McGintee

      More Information

      For more information about the symptoms of alpha-gal syndrome click here.

      For tips about what to do once you have a diagnosis click here

      References–in development

      1. Platts-Mills TA, Li RC, Keshavarz B, Smith AR, Wilson JM. Diagnosis and management of patients with the α-Gal syndrome. The Journal of Allergy and Clinical Immunology: In Practice. 2020 Jan 1;8(1):15-23.

      2. Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients. Expert Review of Clinical Immunology. 2020 Jul 9:1-1.

      3. Commins SP, James HR, Stevens W, Pochan SL, Land MH, King C, Mozzicato S, Platts-Mills TA. Delayed clinical and ex vivo response to mammalian meat in patients with IgE to galactose-alpha-1, 3-galactose. Journal of allergy and clinical immunology. 2014 Jul 1;134(1):108-15.

      Additional References for What Do My Test Results Mean?

      1. Viracor

      2. Platts-Mills, T. A., et al. (2019). “Diagnosis and management of patients with the alpha-Gal syndrome.” J Allergy Clin Immunol Pract.

      3. Chung, C. H., et al. (2008). Cetuximab-Induced Anaphylaxis and IgE Specific for Galactose-α-1,3-Galactose. N Engl J Med 2008; 358:1109-1117

      4. Fischer, J. and T. Biedermann (2016). “Delayed immediate-type hypersensitivity to red meat and innards: current insights into a novel disease entity.” Journal Der Deutschen Dermatologischen Gesellschaft 14(1): 38-43.

      5. Posthumus, J. et al. (2013). “Initial Description of Pork-Cat Syndrome in the United States ” The Journal of allergy and clinical immunology vol. 131,3 : 923-5. 

      6. McGintee, E. (2015). “Meat Allergy Triggered by a Tick Bite with Erin McGintee, MD.” Video-taped lecture. Retrieved from https://youtu.be/hj96Vvr1WhQ.

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