Cases of severe allergic reactions to red meat and dairy are climbing across the world. This has baffled physicians and researchers since the manifestations differ from other food-borne allergies, and the cases are often common in tick-endemic areas. The connection between ticks and allergy to red meat products was first established in 2008 after oncologists reported unexpected allergic reactions to the cancer drug cetuximab. This drug contains a sugar molecule called alpha-gal. Later studies revealed that the allergic reactions to red meat and dairy are a manifestation of alpha-gal allergy or alpha-gal syndrome. Further studies then linked the development of alpha-gal syndrome to tick bites.
Alpha-Gal Syndrome as a Tick-Borne Disease: How a Tick Bite Can Make People Allergic to Meat and Dairy Products
Background: Prevalence and Definition of Alpha-Gal Syndrome
Chinese medical researchers M. Zhan, J. Yin, T. Xu, and L. Wen described alpha-gal syndrome as an underrated serious disease in their 2024 review. This is due to both its increasing incidence across the world and the fact that its delayed manifestations include urticaria, anaphylaxis, or even death. The U.S. Centers for Disease Control and Prevention identified 110000 cases from 2010 to 2022 in the U.S., but estimated that as many as 450000 Americans were affected.
A submission-based study of nearly 295000 individuals in the U.S. tested between 2017 and 2022 found that 90018 or 30.5 percent had positive results. In Denmark, based on alpha-gal sensitization tests involving 11000 adults, sensitization increased from 1.3 percent in 1991 to 3.2 percent in 2017. Alpha-gal syndrome has been reported across North and South America, Europe, both in Southern and Western Africa, East and South Asia, Australia, and New Zealand.
Note that alpha-gal syndrome is an acquired allergy characterized by an allergic reaction to a sugar molecule called alpha-gal. This molecule is present in most mammals but absent in humans. It can be found in mammalian skeletal muscles, visceral organs, and smooth muscles. Individuals with alpha-gal syndrome can have severe allergic responses to consuming mammalian meat and other mammal-derived products like milk, milk derivatives, and gelatin or collagen.
Hypothetical Cause: Alpha-Gal Syndrome as a Tick-Borne Disease
There are different causes of mammalian meat allergy. Proteins in meat, like bovine serum albumin and porcine albumin, make affected people allergic to beef and pork meat. Some people also develop allergies to pork meat due to sensitization to cat serum albumin. These non-alpha-gal allergies produce immediate reactions. What makes alpha-gal syndrome different is that it is caused by an allergic reaction to a sugar molecule. Its onset is also not immediate.
Researchers have drawn the link between ticks and the development of alpha-gal syndrome. Data from the review of M. Zhan et al. indicate that alpha-gal sensitization is common in tick-endemic areas, like in certain regions in the Atlantic with high concentrations of lone-star ticks. These ticks affect a wide range of domesticated and wild animals like cattle, dogs, horses, deer, and squirrels. The black-legged tick species, which affects deer species, has also been implicated.
Tick bites cause alpha-gal syndrome. The entire process is unknown. The literature hypothesizes that ticks can harbor the sugar molecule in their saliva as they feed on mammals. Hence, when they bite humans, alpha-gal is then transmitted. The bite causes an immune reaction. This primes the immune system to respond strongly to foreign molecules like alpha-gal. The immune system sees it as a foreign sugar molecule and produces specific IgE antibodies against it.
Humans can tolerate small amounts of alpha-gal from the diet. However, due to the direct skin route and triggered immune response from the tick bite, the immune system considers it a harmful foreign substance. This process is called sensitization. Hence, when an individual sensitized to alpha-gal consumes mammalian meat or related food products, the molecules are absorbed into the bloodstream hours after eating. This causes the delayed allergic reaction.
Implications: Presentation and Burden of Alpha-Gal Syndrome
Allergic symptoms typically manifest 1 to 3 months after the initial tick bite and about 2 to 8 hours following consumption of mammalian meat. These reactions can include hives, swelling, severe abdominal pain, nausea, anaphylaxis, and other systemic effects. Exact diagnosis can be difficult since a large portion of healthcare providers are still unaware of the syndrome. This leaves people oblivious to their existing health burden and unprepared for allergic reactions.
Note that the delayed onset of symptoms also makes alpha-gal syndrome dangerous. Unsuspecting individuals might not have the medications like antihistamines and epinephrine pens for dealing with their allergic reactions. Incidents can occur in the middle of the night if an undiagnosed person consumed meat for dinner. This delay means an individual might be alone, asleep, and unaware when the allergic reaction starts, thus giving him or her less time to get help.
The syndrome may improve over time. Successful desensitization for alpha-gal syndrome has also been reported in multiple cases. The problem is that desensitization is not permanent. Another tick bite can result in recurrence. Tick populations are also booming. This is driven by factors such as rising deer numbers, human encroachment into tick habitats, and climate change. This expansion increases the risk of alpha-gal sensitization beyond previously known ranges.
FURTHER READINGS AND REFERENCES
- Centers for Disease Control and Prevention. 2023. “Emerging Tick Bite-Associated Meat Allergy Potentially Affects Thousands.” CDC Newsroom. Centers for Disease Control and Prevention. Available online
- Leth‐Møller, K. B., van Hage, M., Apostolovic, D., Sørensen, J. A., Vestergaard, C., Madsen, F., Kjær, L. J., Hansen, T., Jonsson, A., Thomsen, S. F., and Linneberg, A. 2024. “Increasing Prevalence of Galactose‐α‐1,3‐Galactose Sensitization in the Danish General Adult Population.” Allergy. 80(1): 297-308. DOI: 1111/all.16360
- Thompson, J. M., Carpenter, A., Kersh, G. J., Wachs, T., Commins, S. P., and Salzer, J. S. 2023. “Geographic Distribution of Suspected Alpha-gal Syndrome Cases — United States, January 2017–December 2022.” Morbidity and Mortality Weekly Report. 72(30): 815–820. DOI: 15585/mmwr.mm7230a2