|Other names: Red meat allergy, tick bite meat allergy, mammalian meat allergy, galactose-α-1,3-galactose (α-Gal) syndrome|
|Reaction is triggered products that contain alpha-gel, such as roast beef|
|Symptoms||Hives, nausea, diarrhea, shortness of breath, lightheadedness, abdominal pain|
|Usual onset||2 to 6 hrs post exposure|
|Causes||Bites from certain types of ticks|
|Diagnostic method||Based on symptom and blood tests|
|Prevention||Avoiding tick bites|
|Treatment||Avoiding products containing alpha-gel (meat and possibly dairy from mammals)|
Alpha-gal allergy, also known as red meat allergy, is a type of allergic reaction that occurs after exposure to products containing alpha-gal, such as eating red meat. Symptoms can include hives, nausea, diarrhea, shortness of breath, lightheadedness, and abdominal pain. Often onset is two to six hours after exposure. Complications can include anaphylaxis.
The condition is believed to be triggered by certain tick bites; such as lone star ticks in the USA, and paralysis ticks in Australia. The underlying mechanism involves the body producing immunoglobulin E (IgE) antibodies that react to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal). Other factors that may worsen the reaction include alcohol, recent exercise, spices, and NSAIDs. Diagnosis is based on symptom and testing IgE to alpha-gal blood levels.
Management involves avoiding products that contain alpha-gel. Often this means avoiding meat and possibly dairy from mammals. In certain cases gelatin needs to also be avoided. Medications that contain alpha-gal may include heparin and cetuximab. In those who developed anaphylaxis epinephrine is used. Further tick bites should be avoided, as this may worsen the condition. Prevention is by avoiding tick bites, such as by treating clothing with permethrin and using DEET.
Alpha-gal allergy has been reported in 17 countries on six continents. In certain parts of Australia about 113 per 100,000 are affected, while about 13 per 100,000 have the condition in Virginia and 4 per 100,000 in certain parts of Germany. The condition was first described in 2006 and 2007 by Sheryl van Nunen.
Signs and symptoms
The allergic reaction to alpha-gal typically has a delayed onset, occurring 3–8 hours after eating mammalian meat products. This is in contrast to the typical rapid onset of most food allergies.
Symptoms may include severe whole-body itching, hives, angioedema, gastrointestinal upset, and anaphylaxis. In 70% of cases the reaction is accompanied by respiratory distress and is particularly harmful to those with asthma.
Alpha-gal allergies develop after a person has been bitten by the lone star tick in the United States, the European castor bean tick, the paralysis tick or Ixodes (Endopalpiger) australiensis in Australia,Haemaphysalis longicornis in Japan, or a currently unknown tick in South Africa, possibly Amblyomma hebraeum. Alpha-gal is not naturally present in apes, Old World monkeys, or humans, but is in all other mammals. If a tick feeds on another mammal, the alpha-gal remains in its alimentary tract. The tick then injects the alpha-gal into a person's skin, which causes the immune system to release a flood of IgE antibodies to fight the foreign carbohydrate. Researchers still do not know which specific component of tick saliva causes the reaction.
A 2012 preliminary study found unexpectedly high rates of alpha-gal allergy in the Western and North Central parts of the United States. This suggests that unknown tick species may spread the allergy. The study even found alpha-gal allergy cases in Hawaii, where no ticks identified with the allergies live. Human factors were suggested, but no specific examples were provided.
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.
Recent research has shown that saliva from the lone star tick contains alpha-gal, and that saliva is injected into the blood stream. The immune system then releases IgE antibodies to fight this foreign sugar. After this reaction, the future intake of mammal meat with the same alpha-gal causes an allergic reaction. Symptoms of the allergy reaction are caused by too many IgE antibodies attacking the allergen, in this case the alpha-gal.
A traditional skin-prick allergy test for allergy to meat may give a false-negative answer. Determination of specific IgE to alpha-gal testing is commercially available, as well as IgE testing to specific red meats. Skin and basophil activation tests with cetuximab are the most sensitive, but high costs limit their use.
Debate exists around the best method of tick removal although recent consensus is to freeze them with an ether-containing spray (available at pharmacies and used for warts).
Unlike most food allergies, in some people, the alpha-gal allergy may recede over time, as long as the person is not bitten by another tick. The recovery period can take 8 months to 5 years.
The allergy was first formally identified as originating from tick bites in the United States in 2002 by Thomas Platts-Mills, and independently by Sheryl van Nunen in Australia in 2007.
Platts-Mills and Scott Commins were attempting to discover why some people were reacting negatively to the carbohydrate in the cancer drug cetuximab. They had previously hypothesized that a fungal infection or parasite could lead to the allergy. When Platts-Mills was bitten by a tick and developed alpha-gal allergies, his team came to the conclusion that a link existed between tick bites and the allergy. They found that the IgE antibody response to the mammalian oligosaccharide epitope, alpha-gal, was associated with both the immediate-onset anaphylaxis during first exposure to intravenous cetuximab and the delayed-onset anaphylaxis 3 to 6 hours after ingestion of mammalian food products, such as beef or pork.
In 2021 University of Tennessee's Entomologist Becky Trout Fryxell reported that more cases of Alpha-Gal syndrome are occurring from those who encounter the Lonestar Tick: " "She likes to feed on dogs, deer and seems to always find people as well," said Fryxell "It has the ability to transmit a lot of pathogens too. And it's also associated with a tick meat allergy which unfortunately is becoming pretty common." "
Van Nunen, an immunologist specialising in allergies, had been practicing in a tick-prone area of Sydney, when 25 patients reported having allergic reactions to red meat after being bitten by ticks. She later concluded that the relatively sudden rise in cases was the result of a local fox baiting program which began in 2003. Foxes were introduced to Australia and had decimated the local indigenous bandicoot population, hence the fox baiting program. However an unforeseen effect of the subsequent rise in the bandicoot population was the rise in ticks, as bandicoots are a major host for ticks, and thus the number of humans suffering tick bites.
Alpha-gal allergies are similar to pork–cat syndrome, hence mis-identification can occur. Pork–cat syndrome usually elicits an immediate allergic response, while a true alpha-gal allergy typically features a delayed allergic reaction of 3 to 8 hours after ingestion of the allergen.
In 2020 the U.S. Food and Drug Administration approved genetic modification of pigs so they do not produce alpha-gal sugars. Pigs developed with the trademarked name GalSafe may be able to be eaten safely by people with alpha-gal allergy. They may also produce alpha-gal-safe drugs, and their organs can also be used for xenotransplantation.
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