What lab tests are used to diagnose an alpha-gal (alpha-galactose) allergy?

Laboratory Testing for Alpha-Gal Syndrome

Order a serum test for alpha-gal-specific IgE antibodies as the primary diagnostic laboratory test for alpha-gal syndrome. 1, 2

When to Order Testing

Consider ordering alpha-gal IgE testing in patients presenting with:

• Unexplained gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting) who live in or have visited alpha-gal prevalent regions (Southeast, mid-Atlantic, Midwest, and East Central United States) 1, 2
• History of tick bites, particularly from the Lone Star tick (Amblyomma americanum) 1, 2
• Delayed reactions occurring 3-5 hours after consuming mammalian meat (beef, pork, venison) 2, 3
• Night-time awakening with GI distress, which is particularly suggestive given the typical delay from evening meals 1, 2
• Urticaria, angioedema, or anaphylaxis with delayed onset after meat consumption 1

Do NOT test patients with red flag symptoms such as anemia, GI bleeding, or weight loss, as alpha-gal syndrome does not cause these symptoms 1

The Diagnostic Test

Serum alpha-gal-specific IgE antibody measurement is the laboratory test of choice 1, 2:

• Use fluorescence-labeled antibody assays (the term "RAST" is outdated and should be abandoned) 1
• Important caveat: Results from different laboratory systems (Phadia ImmunoCAP, Agilent Turbo-MP, Siemens Immulite 2000) are NOT comparable, and predictive values established for one system cannot be applied to others 1
• In populations with high prevalence of alpha-gal allergy, an IgE level >5.5 kU/L provides a 95% probability of clinically significant meat allergy 4
• An alpha-gal IgE to total IgE ratio >2.12% also provides 95% probability of meat allergy 4

Critical Interpretation Points

A positive alpha-gal IgE test alone does NOT establish the diagnosis 1, 2:

• Many sensitized individuals (up to 31% in some screening populations) remain completely asymptomatic to meat ingestion 1
• The diagnosis requires BOTH elevated alpha-gal IgE titers AND clinical symptoms that improve with an alpha-gal avoidance diet 1, 2
• Undetectable IgE levels can occasionally occur in patients with true IgE-mediated food allergy, so if clinical suspicion is high, further evaluation is necessary 1

Additional Testing Considerations

Do NOT routinely order:

• Total serum IgE (insufficient sensitivity and specificity for diagnosis) 1
• Standard commercial meat skin prick test extracts (not reliable for alpha-gal syndrome) 5
• Intradermal testing with standard extracts 1

Specialized tests (available only in select centers):

• Basophil activation testing can differentiate between symptomatic alpha-gal syndrome and asymptomatic sensitization, with the %CD63+/anti-FcεRI ratio and area under dose-response curves showing the best discrimination 6
• Prick-prick skin testing to fresh cooked meat may be considered in specialized settings 5

Diagnostic Algorithm After Testing

If alpha-gal IgE is elevated:

1. Direct the patient to adopt a strict alpha-gal avoidance diet eliminating all mammalian meat (beef, pork, venison) and related products (lard, dairy, ice cream) for at least one month 1, 2
2. Re-evaluate after the trial period to determine if symptoms improved 1
3. If symptoms resolve or significantly improve, the diagnosis is confirmed 1, 2
4. If no improvement occurs, pursue other causes for the symptoms 1

Refer to allergy/immunology if the patient has systemic symptoms including rash, hypotension, respiratory difficulty, or anaphylaxis 1, 2

Follow-Up Testing

• Consider rechecking alpha-gal IgE levels in 6-12 months, especially if tick bites are avoided 1, 2
• Decreasing IgE levels may indicate potential tolerance development and can guide reintroduction of dairy first, then potentially small amounts of mammalian meat 2, 5

Important Caveats

Reactions are inconsistent in alpha-gal syndrome—a patient who tolerates mammalian meat once may still have the allergy 2. Co-factors such as NSAIDs, physical activity, and alcohol can increase both risk and severity of reactions 2. Traditional oral food challenge testing is impractical due to the hours-long delay and inconsistent reactions 2.