Unexplained allergic reactions?  It could be the AlphaGal!


One of the more frustrating problems in acute care medicine is when someone has a meaningful allergic reaction and we can’t determine the cause.  Sometimes it is an irritating but non-threatening hives type reaction; or whelps, as my grew up in the South patients say.  Other times, it can be a life threatening anaphylactic reaction, with a drop in blood pressure and constricted airways.   For a fortunate few, such an episode is an isolated event.  But if the reaction is due to a major food group, like peanuts or seafood, and the person continues to consume it, the IgE mediated immune reactions will tend to get more severe, even life threatening, as exposure accumulates over time.

One such potentially serious food allergy that is becoming more commonly recognized and diagnosed is related to a sugar molecule called galactose-alpha-1,3,-galactose, or ‘alpha gal’ for short.  Twice in the last year I’ve had patients with worsening and unexplained hives reactions that turned out to have this unusual allergic trigger.  I stumbled onto this term during a literature search, and remember being amused at the label, thinking that an ‘alpha gal’ would of course be the she-wolf leader, providing meat for her clan.  And as it turns out, this alpha gal is a meat related issue, in a strange way.  Both of my patients had experienced tick bites in the previous year, with no apparent problem at the time.  However, in both cases, that bite propagated an immune cross-reactivity from this sugar group, resulting in a red meat IgE food allergy.  Cross reacting red meats include the beef, pork, lamb and venison food groups. Theoretically, any meat from an animal that nurses its young with milk is potentially a source for alpha-gal.   Organ meats from mammals such as kidney or liver can sometimes provoke more severe reactions.  One of the patients I mentioned above, whom I admitted through the ER, had a near fatal bronchospasm reaction to alpha gal and required intubation before the diagnosis was confirmed.

Unlike other severe food allergies, alpha gal reactions usually manifest 3-6 hours after ingestion, versus the 5-30 minutes we think of with severe peanut or shellfish reactions.  This can cloud the issue for both the doctor and the patient and misdirect one away from making this unusual but crucial diagnostic connection. Common components of allergy to alpha-gal can include hives, swelling of the lips, eyes, tongue, throat, respiratory distress, vomiting, diarrhea, increased heart rate and low blood pressure.  A recent study on the search for causes in what we call idiopathic anaphylaxis (1), (translation: your well-intentioned health professional has no idea what nearly killed you) found that out of the 24 males in their study, 6 tested positive for alpha gal.  They also found that these 6 had both: 1) a history of lone star tick bites and 2) a total resolution of their severe reactions when they avoided the ‘red meat’ group described above.  This was also the case for both of my patients, who are reaction free so far while they scrupulously avoid the red meat family.  Complaints over this restriction have abounded, especially as their family and friends feast on barbeque, but one of them has lost 20 lbs in the process, and they both have avoided ER visits, steroid shots and time in the ICU, so there is some consolation there.

What can we learn from their story?

  1. If you live in a tick prone state, Lyme is not the only reason to avoid the little critters and their bites.
  2. If you, or someone you know has recurrent allergic reactions that are evading a specific diagnosis, consider getting the alpha gal testing, which is the serum IgE level for galactose-alpha-1,3-galactose, and may include those for beef, pork, lamb as well. Virtually every clinical lab service offers some version of this test. You should also strongly consider avoiding all red meat while pursuing this lab workup to avoid further provoking a cumulative severity to the reaction.
  3. Be aware that in rare cases, some animal derived proteins can cross react with alpha -gal.  Cosby Stone, MD, a fellow in the Vanderbilt Asthma, Sinus and Allergy Program clinic, said that recent patients have led researchers to take a deeper look into alpha-gal as not only as a food allergy, but a allergy.   “We at Vanderbilt are working with excellent collaborators to lead in these discoveries to figure out how to keep alpha-gal patients safe when taking their medications,” Stone said. “This list of medications that we are paying close attention to includes antibodies derived from animals, like rattlesnake anti-venom and certain cancer treatments like Cetuximab. It also included products that contain gelatin, like certain vaccines or gel-based products. Heart valves that are harvested from pigs and used to replace a failed valve have also been reported to cause reactions or a more rapid breakdown of the valve in alpha-gal allergic patients.” (2)

For better or worse, red meat avoidance may be a long-term requirement for many with the alpha gal sensitivity.  But as one of my carne-deprived patients reflected, ‘Whenever I miss a steak, I take a moment to remember just how much I really enjoy breathing without ventilator assistance!

1.  Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis.  Carter, M.C. et. al.  Allergy. 2017 Nov 21. doi: 10.1111/all.13366. [Epub ahead of print]


2. https://medicalxpress.com/news/2018-04-alpha-gal-medication-red-meat-allergy.html

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