Diagnosis and management
Alpha-gal syndrome (AGS) is a red meat food allergy caused by tick bites that is new to the UK. It was first described in Australia and the US in 20091 and the UK in 2019,2 caused by foreign ticks in travellers returning to the UK. These Scottish case reports confirm that the UK tick, Ixodes ricinus, is causing AGS red meat allergy in UK residents.
AGS is an allergic process, in contrast to Lyme disease. The latter is a zoonotic borrelial bacterial infection, where ticks transfer a bacterium from wild animals to humans.
The patient history of tick exposure and several bites builds up an immune response to tick saliva. Patients present with urticaria 4–6 hours after eating red meat and the diagnosis is confirmed with specific immunoglobulin E (IgE) serology. Treatment is limited to antihistamines and EpiPens, and avoiding meat products. Several medicines can precipitate an acute anaphylaxis. Prevention includes prompt tick removal without squeezing the tick, which prevents the injection of tick saliva antigen into genetically susceptible individuals.
Disease process and immunology
Ticks need a blood meal in their life cycle and lock onto the human for 24 hours, injecting alpha-gal anticoagulant in their saliva, to withdraw the human blood. This is when the Borellia parasite transfers from the tick’s stomach to cause Lyme disease3 or when the sensitisation process begins for AGS. Lyme disease requires one infected tick bite, whereas AGS requires several uninfected tick bites.
All IgE-mediated allergic responses require prior priming of the Th2 arm of the adaptive immune response, resulting in immune memory and B cell activation to produce specific IgE to the priming allergen. The first tick bite leads to immune priming but will not result in an allergic response to alpha-gal glycoprotein contained in red meat (Figure 1). It is on second and subsequent exposure that the type 1 hypersensitivity (IgE-mediated) reaction to alpha-gal will occur in individuals with the genetic susceptibility to make specific IgE to the alpha-gal sugar.
Figure 1. How alpha-gal IgE is made. APC = antigen-presenting cell. BCR = B cell receptor. IgE = immunoglobulin E. IL-4 = interleukin-4.
The alpha-gal antigen structurally resembles the blood group B antigen. Blood groups B and AB may be less likely to develop AGS. It is the first known allergy where a carbohydrate is the sole cause of IgE-mediated reactions. The alpha-gal antibody in humans may function as a barrier to zoonotic infections by enveloped viruses.
Type 1 hypersensitivity reactions are immediate, occurring within 30 minutes of exposure to the allergen.4
However, patients with AGS report waking with urticarial hives in the middle of the night, 4–6 hours after a barbecue. This initial delay may make it difficult for the patient and doctor to link the hives with mammalian meat. As the patient becomes more sensitised, the triggers will progress beyond red meat to meat products and can become a more immediate response, and anaphylaxis has been reported.5,6
Digestion of meat is probably required before release of the alpha-gal sugar in the small bowel and the immune response triggered.7
Epidemiology
Many people who live or work in tick-infested areas are bitten by ticks on a regular basis, but initial information suggests that AGS is a rare outcome dependent on individual immunogenetic susceptibility. Many tick species worldwide have been linked to AGS but the prevalence is unknown.6 Case series from Sweden report AGS in middle-aged patients who had previously tolerated meat with urticaria (90%), gastrointestinal symptoms (74%), angioedema (60%), anaphylaxis (47%), and linkage to tick exposure.6 The incidence of AGS in Scotland (Table 1) mirrors the geographical patterns of Lyme disease across NHS board areas, with 37% of suspected cases returning a positive alpha-gal-specific IgE in NHS Highland.
Table 1. The prevalence of alpha-gal syndrome in Scotland (NHS Borders, NHS Fife, NHS Highland, and NHS Tayside) using their lab data and 1.2 million population base
NHS Highland has the highest prevalence of diagnosed cases in all the 3.5 years under consideration, with 1 in 3 (32%) of those tested being positive for alpha-gal. Seventy-six per cent of cases are male, the age range is 27–77 (mean 48.9) years, and the annual incidence is 0.38 per 100 000 population [authors’ own extrapolation]. AGS in England and Wales is likely to mirror Lyme disease in the New Forest, Exmoor, Dartmoor, Thetford, and Cumbria in forest and parkland areas that support tick ecosystems.8
Patient impacts
Patients describe a hierarchy of meat and meat products triggering a response from red meat down to pork and processed meat products including haggis. Gelatine and dairy products are described as hidden triggers.
Several medicines contain alpha-gal and reactions to them should trigger questions about tick bites from GPs. These include biologic therapy for bowel cancer (cetuximab), gelatine plasma expanders, porcine heart valves, heparin, pancreatic enzyme replacement, and gelatine-containing vaccines (Zostavax and measles, mumps, and rubella).
The patient impact from AGS can be profound (Figure 2). Non-steroidal anti-inflammatory drugs, exercise, and alcohol can act as co-factors in all IgE-mediated reactions, increasing the risk or severity of the specific reaction.
Figure 2. Risk of reactions in the alpha-gal syndrome. MMR = measles, mumps, and rubella. NSAIDs = non-steroidal anti-inflammatory drugs.
Avoiding red meat and tick bites are the central actions for patients. If tick bites are avoided, the alpha-gal reactivity can reduce, but an individual’s propensity to produce alpha-gal-specific IgE will remain and can recur with more tick bites.
Dietetic advice is required, and patient support groups share triggers and solutions.
Climate change and human behaviours
The British Ixodes ricinus tick is active at temperatures above 7°C, has a 2-year life cycle, and is widely prevalent in wooded areas. The warmer and wetter weather of climate change may increase tick populations, but there is no method of widely measuring tick density beyond occasional academic field studies. Tick ecology is complex, with a changing interaction between wild animals and humans in woodland and gardens.8
Human behaviours have changed with ‘wellbeing’ encouraging the use of green spaces for exercise, sport, and camping. However, prompt removal of ticks with plastic twister or card devices will reduce disease transmission in Lyme disease and sensitisation in AGS. On balance there is far more health to be gained in the countryside than the risks of tick-borne disease.
Awareness for GPs
The diagnosis of AGS is confirmed by a history of tick exposure, delayed allergic responses to red meat, and serology demonstrating the presence of alpha-gal-specific IgE.6
AGS is rare and predominates in tick-infested areas. However, food allergy and intolerance are core aspects of general practice. The diagnosis of urticaria/hives is also a core aspect of general practice. GPs and dietitians in rural areas need to be particularly aware of this new cause of urticaria and potential anaphylaxis.
Notes
Provenance
Freely submitted; externally peer reviewed.
Competing interests
The authors have declared no competing interests.
- © British Journal of General Practice 2025
