Alpha-gal allergy

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Alpha-gal allergy
Other names: Red meat allergy, tick bite meat allergy, mammalian meat allergy, galactose-α-1,3-galactose (α-Gal) syndrome[1][2]
Reaction is triggered products that contain alpha-gel, such as roast beef
SpecialtyAllergist
SymptomsHives, nausea, diarrhea, shortness of breath, lightheadedness, abdominal pain[1]
Usual onset2 to 6 hrs post exposure[1]
CausesBites from certain types of ticks[1]
Diagnostic methodBased on symptom and blood tests[3]
PreventionAvoiding tick bites[1][4]
TreatmentAvoiding products containing alpha-gel (meat and possibly dairy from mammals)[3][1]
MedicationEpinephrine[5]
FrequencyUncommon[5]

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.[1] Symptoms can include hives, nausea, diarrhea, shortness of breath, lightheadedness, and abdominal pain.[1] Often onset is two to six hours after exposure.[1] Complications can include anaphylaxis.[1]

The condition is believed to be triggered by certain tick bites; such as lone star ticks in the USA, and paralysis ticks in Australia.[1][2] The underlying mechanism involves the body producing immunoglobulin E (IgE) antibodies that react to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal).[6] Other factors that may worsen the reaction include alcohol, recent exercise, spices, and NSAIDs.[2] Diagnosis is based on symptom and testing IgE to alpha-gal blood levels.[3]

Management involves avoiding products that contain alpha-gel.[1] Often this means avoiding meat and possibly dairy from mammals.[3] In certain cases gelatin needs to also be avoided.[3] Medications that contain alpha-gal may include heparin and cetuximab.[6][7] In those who developed anaphylaxis epinephrine is used.[5] Further tick bites should be avoided, as this may worsen the condition.[1] Prevention is by avoiding tick bites, such as by treating clothing with permethrin and using DEET.[1][4]

Alpha-gal allergy has been reported in 17 countries on six continents.[2] 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.[2] The condition was first described in 2006 and 2007 by Sheryl van Nunen.[6][2]

Signs and symptoms

Progression of hives during an alpha gal reaction.[8]

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.[9] In 70% of cases the reaction is accompanied by respiratory distress and is particularly harmful to those with asthma.[10]

Cause

A lone star tick, which can result in the allergy
The paralysis tick, the hard-bodied tick most likely to be responsible in Australia

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,[11][12][12]Haemaphysalis longicornis in Japan,[13] or a currently unknown tick in South Africa, possibly Amblyomma hebraeum.[14][15] 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.[16] 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.[16][11] Researchers still do not know which specific component of tick saliva causes the reaction.[17]

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.[18] The study even found alpha-gal allergy cases in Hawaii, where no ticks identified with the allergies live.[17] Human factors were suggested, but no specific examples were provided.[18]

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.[11]

At least one instance of a man with an alpha-gal allergy going into anaphylaxis after receiving a heart valve transplant has been reported.[11] Some researchers have suggested that the alpha-gal in pig's tissue that surgeons use for xenografts might contribute to organ rejection.[19]

Mechanism

Recent research has shown that saliva from the lone star tick contains alpha-gal,[20] 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.[11][21]

Diagnosis

A traditional skin-prick allergy test for allergy to meat may give a false-negative answer.[22][23] Determination of specific IgE to alpha-gal testing is commercially available, as well as IgE testing to specific red meats.[24][9] Skin and basophil activation tests with cetuximab are the most sensitive, but high costs limit their use.[24]

Prevention

Main article: Ixodes holocyclus § Tick removal

Tick bites can be prevented by treating clothing and gear with products containing 0.5% permethrin and by avoiding areas inhabited by ticks.[25]

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).[26]

Management

So far, only two successful desensitizations have been performed on people with an alpha-gal allergy.[27]

Prognosis

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.[11][17][28]

History

The allergy was first formally identified as originating from tick bites in the United States in 2002 by Thomas Platts-Mills,[29] and independently by Sheryl van Nunen in Australia in 2007.[30][31][32]

Platts-Mills and Scott Commins were attempting to discover why some people were reacting negatively to the carbohydrate in the cancer drug cetuximab.[11][33] They had previously hypothesized that a fungal infection or parasite could lead to the allergy.[11][28] 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.[28] 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.[34]

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." "[35]

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.[36][37] 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.[38]

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.[39]

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.[40] They may also produce alpha-gal-safe drugs,[41] and their organs can also be used for xenotransplantation.[42]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Alpha-gal syndrome | CDC". Centers for Disease Control and Prevention. 28 March 2022. Archived from the original on 3 April 2019. Retrieved 12 July 2022.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Nunen, Sheryl A (April 2018). "Tick‐induced allergies: mammalian meat allergy and tick anaphylaxis". Medical Journal of Australia. 208 (7): 316–321. doi:10.5694/mja17.00591.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Platts-Mills, TAE; Li, RC; Keshavarz, B; Smith, AR; Wilson, JM (January 2020). "Diagnosis and Management of Patients with the α-Gal Syndrome". The journal of allergy and clinical immunology. In practice. 8 (1): 15-23.e1. doi:10.1016/j.jaip.2019.09.017. PMID 31568928.
  4. ↑ 4.0 4.1 "Preventing tick bites on people | CDC". Centers for Disease Control and Prevention. 1 July 2020. Archived from the original on 29 July 2021. Retrieved 12 July 2022.
  5. ↑ 5.0 5.1 5.2 "Meat Allergy". ACAAI Public Website. Archived from the original on 10 June 2022. Retrieved 12 July 2022.
  6. ↑ 6.0 6.1 6.2 Commins SP, Platts-Mills TA (February 2013). "Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (alpha-gal)". Current Allergy and Asthma Reports. 13 (1): 72–7. doi:10.1007/s11882-012-0315-y. PMC 3545071. PMID 23054628.
  7. ↑ "Products that may contain alpha-gal | Ticks | CDC". www.cdc.gov. 19 October 2021. Archived from the original on 6 July 2022. Retrieved 12 July 2022.
  8. ↑ Mabelane, T.; Ogunbanjo, G. A. (2019). "Ingestion of mammalian meat and alpha-gal allergy: Clinical relevance in primary care". African Journal of Primary Health Care & Family Medicine. 11 (1): e1–e5. doi:10.4102/phcfm.v11i1.1901. PMC 6494999. PMID 31038347. Mammalian meat and milk (cow and goat) contain alpha-gal.
  9. ↑ 9.0 9.1 "Viracor-IBT Laboratories Launches the First Assay to Identify a New Type of Delayed, IgE-based Allergic Reaction to Certain Meats" (Press release). Viracor-IBT Laboratories. September 13, 2010. Archived from the original on June 16, 2016. Retrieved October 17, 2016.
  10. ↑ Wolver SE, Sun DR, Commins SP, Schwartz LB (February 2013). "A peculiar cause of anaphylaxis: no more steak? The journey to discovery of a newly recognized allergy to galactose-alpha-1,3-galactose found in mammalian meat". Journal of General Internal Medicine. 28 (2): 322–5. doi:10.1007/s11606-012-2144-z. PMC 3614139. PMID 22815061.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 Zaraska M (December 3, 2013). "Want hives with that burger?". The Washington Post. pp. HEALTH, E01. Archived from the original on September 13, 2020. Retrieved July 5, 2022.
  12. ↑ 12.0 12.1 Kwak M, Somerville C, van Nunen S (July 2018). "A novel Australian tick Ixodes (Endopalpiger) australiensis inducing mammalian meat allergy after tick bite". Asia Pacific Allergy. 8 (3): e31. doi:10.5415/apallergy.2018.8.e31. PMC 6073180. PMID 30079309.
  13. ↑ Cabezas-Cruz, Alejandro; Hodžić, Adnan; Román-Carrasco, Patricia; Mateos-Hernández, Lourdes; Duscher, Georg Gerhard; Sinha, Deepak Kumar; Hemmer, Wolfgang; Swoboda, Ines; Estrada-Peña, Agustín; de la Fuente, José (2019-05-31). "Environmental and Molecular Drivers of the α-Gal Syndrome". Frontiers in Immunology. 10: 1210. doi:10.3389/fimmu.2019.01210. PMC 6554561. PMID 31214181.
  14. ↑ Facey-Thomas H (2018-01-08). "Alpha-Gal". Allergy Foundation South Africa. Archived from the original on 2020-01-17. Retrieved 2022-07-05.
  15. ↑ Mabelane (2018). "Predictive values of alpha-gal IgE levels and alpha-gal IgE:total IgE ratio and oral food challenge proven meat allergy in a population with a high prevalence of reported red meat allergy". Pediatric Allergy and Immunology. 29 (8): 841–849. doi:10.1111/pai.12969. PMID 30144162. S2CID 52082108.
  16. ↑ 16.0 16.1 Williams L (December 27, 2013). "Just one bite". Sydney Morning Herald. Australia. p. 20. Archived from the original on March 1, 2014. Retrieved July 5, 2022.
  17. ↑ 17.0 17.1 17.2 Kroen GC (November 16, 2012), Ticked Off About a Growing Allergy to Meat, ScienceNOW, archived from the original on November 1, 2021, retrieved March 24, 2014
  18. ↑ 18.0 18.1 Chan AL (November 9, 2012). "Where Meat Allergy From Ticks Is Most Common". Healthy Living.
  19. ↑ Travis J (November 1995). "The xeno-solution: perils and promise of transplanting animal organs into people". Science News. 148 (19): 298–301. doi:10.2307/4018063. JSTOR 4018063. PMID 11653203.
  20. ↑ Crispell, Gary; Commins, Scott P.; Archer-Hartman, Stephanie A.; Choudhary, Shailesh; Dharmarajan, Guha; Azadi, Parastoo; Karim, Shahid (17 May 2019). "Discovery of Alpha-Gal-Containing Antigens in North American Tick Species Believed to Induce Red Meat Allergy". Frontiers in Immunology. 10: 1056. doi:10.3389/fimmu.2019.01056. PMC 6533943. PMID 31156631. Archived from the original on 22 January 2020. Retrieved 5 July 2022.
  21. ↑ "Hundreds on East End get meat allergy from Lone Star tick's bite". Newsday. Jul 30, 2017. Archived from the original on 2017-07-31. Retrieved 2017-08-01.
  22. ↑ "'Alpha-Gal' Syndrome". Cornell Cooperative Extension in Suffolk County. Cornell University. Archived from the original on 2022-04-19. Retrieved 2022-07-05.
  23. ↑ Krishna N, Krishna S, Krishna R (November 2017). "P112 Correlation between clinical findings and laboratory tests for alpha gal sensitivity". Annals of Allergy, Asthma & Immunology. 119 (5): S37. doi:10.1016/j.anai.2017.08.136.
  24. ↑ 24.0 24.1 Bircher AJ, Hofmeier KS, Link S, Heijnen I (February 2017). "Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review". European Journal of Dermatology. 27 (1): 3–9. doi:10.1684/ejd.2016.2908. PMID 27873733. S2CID 2400078.
  25. ↑ CDC (2020-07-01). "Preventing tick bites on people | CDC". Centers for Disease Control and Prevention. Archived from the original on 2021-07-29. Retrieved 2021-07-22.
  26. ↑ "TIARA - Tick Induced Allergies Research and Awareness". TIARA - Tick Induced Allergies Research and Awareness. Archived from the original on 2021-06-08. Retrieved 2021-07-21.
  27. ↑ Unal D, Coskun R, Demir S, Gelincik A, Colakoglu B, Buyukozturk S (2017). "Successful beef desensitization in 2 adult patients with a delayed-type reaction to red meat". The Journal of Allergy and Clinical Immunology. In Practice. 5 (2): 502–503. doi:10.1016/j.jaip.2016.12.008. PMID 28132797.
  28. ↑ 28.0 28.1 28.2 Goetz G (June 26, 2012). "Red Meat Allergy Likely Cause by Tick Bites". Food Safety News. Archived from the original on August 2, 2021. Retrieved July 5, 2022.
  29. ↑ "NIAID Scientists Link Cases of Unexplained Anaphylaxis to Red Meat Allergy". National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. U.S. Department of Health and Human Services. 28 November 2017. Archived from the original on 22 June 2022. Retrieved 5 July 2022.
  30. ↑ Velasquez-Manoff, Moises (2018-07-24). "What the Mystery of the Tick-Borne Meat Allergy Could Reveal". The New York Times. Archived from the original on 2019-03-27. Retrieved 2019-03-08.
  31. ↑ McKenna, Maryn (2018-12-11). "What is behind the spread of a mysterious allergy to meat?". The Guardian. Archived from the original on 2019-04-25. Retrieved 2019-03-08.
  32. ↑ "Mammalian meat allergy: People on the northern beaches becoming allergic to red meat after tick bites". www.news.com.au. 2016-06-13. Archived from the original on 2019-12-21. Retrieved 2019-03-08.
  33. ↑ Commins SP, Platts-Mills TA (October 2009). "Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant". The Journal of Allergy and Clinical Immunology. 124 (4): 652–7. doi:10.1016/j.jaci.2009.08.026. PMC 2774206. PMID 19815111.
  34. ↑ Berg EA, Platts-Mills TA, Commins SP (February 2014). "Drug allergens and food--the cetuximab and galactose-α-1,3-galactose story". Annals of Allergy, Asthma & Immunology. 112 (2): 97–101. doi:10.1016/j.anai.2013.11.014. PMC 3964477. PMID 24468247.
  35. ↑ Lunsford, Erica (July 12, 2021). "Entomologist warns about tickborne meat allergy". WVLT TV News, Knoxville TN. Archived from the original on 2021-07-21. Retrieved 2021-07-21.
  36. ↑ McMahon, Alle (2019-01-18). "How tick bites can make some people allergic to meat and milk". ABC News. Archived from the original on 2019-03-07. Retrieved 2019-03-08.
  37. ↑ "Mammalian meat allergy: a tick-ing time bomb?". Australian Veterinary Association. Archived from the original on 2019-03-27. Retrieved 2019-03-08.
  38. ↑ "Tick-induced allergies, with Associate Professor Sheryl van Nunen". MJA Podcasts. Medical Journal of Australia. 2018. Episode 27. Archived from the original on 2019-03-27. Retrieved 2019-03-08.
  39. ↑ Zaraska M (December 3, 2013). "Cat owners can also develop meat allergy". The Washington Post. pp. HEALTH, E05. Archived from the original on June 25, 2018.
  40. ↑ Dolgin, Elie (2021-04-01). "First GM pigs for allergies. Could xenotransplants be next?". Nature Biotechnology. 39 (4): 397–400. doi:10.1038/s41587-021-00885-9. ISSN 1546-1696. Archived from the original on 2022-06-17. Retrieved 2022-07-05.
  41. ↑ Commissioner, Office of the (2020-12-14). "FDA Approves First-of-its-Kind Intentional Genomic Alteration in Line of Domestic Pigs for Both Human Food, Potential Therapeutic Uses". FDA. Archived from the original on 2021-10-30. Retrieved 2021-10-30.
  42. ↑ "Progress in Xenotransplantation Opens Door to New Supply of Critically Needed Organs". NYU Langone News. Archived from the original on 2021-10-30. Retrieved 2021-10-30.

Further reading

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