What is Alpha-Gal Syndrome?

 

Alpha-gal syndrome is a recently identified type of food allergy to mammalian meat and by-products. In the United States, the condition most often begins when a Lone Star tick bite transmits a sugar molecule called alpha-gal into the body. In some people, this triggers an immune system reaction that later produces mild to severe allergic reactions when they eat or come in contact with any mammalian meat, milk and by-products.

The alpha-gal molecule is found in all mammals apart from humans, old world monkeys and apes. Anti-gal is a human natural antibody that interacts specifically with the mammalian carbohydrate structure gal alpha- 1-3Gal beta 1-4Glcnac-R, termed, the alpha-galactosyl epitope. Where alpha-gal is absent from humans, apes and old world monkeys, it is abundant in the New World monkeys, prosimians, and nonprimate mammals.

The Lone Star tick is found predominantly in the southeastern United States, and most cases of alpha-gal syndrome occur in this region. The condition appears to be spreading farther north and west, however, as deer carry the Lone Star tick to new parts of the United States. Alpha-gal syndrome also has been diagnosed in Europe, Australia, and Asia, where other types of ticks carry alpha-gal molecules.

Researchers now believe that some people who have frequent, unexplained anaphylactic reactions — and who test negative for other food allergies — may be affected by alpha-gal syndrome. There’s no treatment other than avoiding mammalian meat and by-products.

Avoiding tick bites is the key to prevention. Protect against tick bites by wearing long pants and long-sleeved shirts and using insect repellents when you’re in wooded, grassy areas. Do a thorough, full-body tick check after spending time outside.

Symptoms

Signs and symptoms of an alpha-gal allergic reaction are often delayed compared with other food allergies. Most reactions to common food allergens — peanuts or shellfish, for example — happen within minutes of exposure. In alpha-gal syndrome, signs and symptoms typically don’t appear for three to six hours after eating mammalian meat or by-products. Patients can experience allergic reactions to a variety of mammalian products: dairy products, gelatin, lanolin (which can be found in cosmetics and personal care products), magnesium stearate, and certain vaccines and medications can pose a serious problem.

Alpha-Gal Syndrome patients may also need to be careful with breathing in vapors or smoke from any mammalian meat or by-products as some patients will experience allergic reactions after inhaling the fumes. Patients with Alpha-Gal Syndrome may experience an allergic response to pet dander.

Signs and symptoms of alpha-gal syndrome may include:

  • Hives, itching, or itchy, scaly skin (eczema)
  • Swelling of the lips, face, tongue and throat, or other body parts
  • Wheezing or shortness of breath
  • A runny nose
  • Abdominal pain, diarrhea, nausea or vomiting
  • Sneezing
  • Headaches
  • Anaphylaxis, a severe, potentially deadly allergic reaction that restricts breathing

We have seen a rise in patient’s with Alpha-Gal Syndrome going onto devolop a condition call Mast Cell Activation Syndrome.

Causes

Most people who develop alpha-gal syndrome in the U.S. develop the condition when a Lone Star tick bites them. Bites from other types of ticks can lead to the condition in Europe, Australia and Asia.

Alpha-gal is present in the anticancer drug cetuximab, as well as the intravenous fluid replacements Gelofusine and Haemaccel. Blood thinners derived from porcine intestine and replacement heart valves derived from porcine tissue may also contain alpha-gal.[

At least one instance of a man with an alpha-gal allergy going into anaphylaxis after receiving a heart valve transplant has been reported.[ Some researchers have suggested that the alpha-gal in pig’s tissue that surgeons use for xenografts might contribute to organ rejection.

Tick bites

Ticks that cause alpha-gal syndrome (the Lone Star Tick
in the United States, the European castor bean tick, the paralysis tick in Australia and a currently unknown tick in South Africa) are believed to carry alpha-gal molecules from the blood of the animals they commonly bite, such as cows and sheep. When a carrier tick bites a human, the tick injects alpha-gal into the person’s body.

For unknown reasons, some people have such a strong immune response to these molecules that they can no longer eat red meat without a mild to severe allergic reaction. People who are exposed to many tick bites over time may develop more-severe symptoms.

Testing

Due to lack of knowledge, labs have been known to order the incorrect “Galatose” test resulting in a false negative readings for Alpha-Gal Syndrome. It is very important that your doctor orders the correct testing.

403196P – Alpha Gal Panel – Viracor… viracor-eurofins.com

LabCorp Alpha-Gal panel code is 807003

Quest Lab Alpha-Gal panel code is 95241

Pharmacist’s Role

 


To prevent anaphylaxis, affected patients should avoid any medication, supplements, foods, etc that may contain the alpha-gal epitope; this is their only treatment option. A comprehensive list of medications containing alpha-gal or animal by-products is unavailable at this time. Alpha-gal allergy testing is commercially available and requires a serum sample.

As previously mentioned, many animal by-products may contain the alpha-gal epitope. Gelatin, derived from beef, is one .9 Animal-derived magnesium stearate is another. Cetuximab, a chimeric mouse–human IgG1 monoclonal antibody against epidermal growth factor receptor, contains the alpha-gal epitope in its Fab arm portion and has been known to cause the alpha-gal allergy.11 Additional medications, inactive ingredients, and procedures are also known to contain or utilize the alpha-gal epitope such as:

  •  Creon 102
  • Protein powders with whey2
  • Xenograft surgery
    The issue with xenograft surgery has been resolved by using knock-out pigs lacking the alpha-gal epitope.4
     
    To obtain information on animal by-product content, health care providers must contact manufacturers. Manufacturers do not currently report alpha-gal content in their package inserts or test for alpha-gal content in products. Inactive ingredient information can change at any time, and the FDA does not require manufacturers to disseminate this information. To prevent unnecessary exposure to alpha-gal, pharmacists should ensure that alpha-gal allergic patients avoid meat-containing medications. To provide timely patient care, alpha-gal information needs to be readily available, which is an area in which pharmacists can make an impact.1
     
    Drug Information Service Contribution
    At an academic medical center, a patient with the alpha-gal allergy with allergic reactions to antihypertensive medications presented to an immunologist. The medications contained gelatin and magnesium stearate. The drug information service proceeded to create an alpha-gal content database to support the selection of an appropriate antihypertensive pharmacotherapy regimen for patients who have the alpha-gal allergy. Pharmacists contacted manufacturers with the broadest range of antihypertensive medications, and asked, “Do your products contain galactose-alpha-1,3-galactose, alpha-gal, mammalian meat, or any animal by-products?” No manufacturers tested for the presence of alpha-gal in their product, but animal by-product content was available. All manufacturers took more than 24 hours to respond, and some required 1 or more call-back attempts.
  • Based on correspondence with manufacturers, the Table lists medications that do not contain animal by-products, suggesting they are alpha-gal-free. The drug information service continues to review and add medications to its database. It has reviewed hyperlipidemia medications, narcotics, and dermatologic creams to date.Table: Medications that Do Not Contain Animal By-products (per the manufacturer)
Medication Manufacturer
Amlodipine Qualitest
Atenolol Mylan, Sandoz
Losartan potassium tablet, film coated Sandoz
Valsartan tablet Sandoz
Oxycodone liquid Lannett
Clotrimazole Natureplex

Although alpha-gal content cannot be completely ruled out, products without animal by-products theoretically may be used to safely treat patients with a documented alpha-gal allergy. One limitation of this database is that manufacturers do not routinely test for alpha-gal, so definitive conclusions cannot be drawn. However, the lack of information is intrinsic to the subject matter and not a database flaw.

The rising incidence and the serious nature of the alpha-gal allergy underscores the importance of properly managing patients. There is a need for more information on this topic. This database simplifies the task of verifying critical information and promotes timely decision making. The flexible design also allows for expansion to offer a complete reference. In the future, this database aims to compile all alpha-gal–related information into 1 central location for all medication classes.1

Conclusion
Pharmacists should be cognizant of patients presenting with anaphylaxis symptom, with a history of exposure to ticks and of consuming mammalian meats. The delay in symptom presentation may be attributed to the time required to digest meats. As pharmacists, knowing a patient’s full history will enhance recognition of the allergy.

Resources for pharmacists include the Alpha-Gal Allergy Awareness Web site (www.alpha-gal.org). The Robert Wood Johnson University Hospital drug information service database is available for use by pharmacists by calling 732-937-8842.

Additional research is required on the effect of alpha-gal in medications for patients with the alpha-gal allergy. Pharmacists, especially in the emergency department and ambulatory care settings who see patients with tick bites, should be aware of this allergy and medication’s potential to elicit symptoms.

Looking for an online support group?


Mast Cell &Tick-Borne Disease Awareness Group. https://www.facebook.com/groups/MastCellandTickBorneDiseaseAwarness

Alpha-Gal Support by following the link below. https://m.facebook.com/groups/148815612155459?refid=12&tn=H

REFERENCES

  1. Alpha-gal syndrome. Mayo Clinic website. https://www.mayoclinic.org/diseases-conditions/alpha-gal-syndrome/symptoms-causes/syc-20428608?fbclid=IwAR2XOuXrbynsDp18X-2CLcv01hIhCbZEMjmaZxzcF7_I5eLG3F57UOIPT2I
  2. Alpha-Gal and Red Meat Allergy. American Academy of Allergy, Asthma, & Immunology website. https://www.aaaai.org/conditions-and-treatments/library/allergy-library/alpha-gal
  3. Wilson JM, Schuyler AJ, Schroeder N, Platts-Mills TAE. Galactose-α-1,3-Galactose: Atypical Food Allergen or Model IgE Hypersensitivity? Current Allergy and Asthma Reports. 2017; 17(1): 8. doi: 10.1007/s11882-017-0672-7