Alpha-Gal Syndrome

Alpha gal syndrome is an IgE-mediated allergy to galactose-alpha-1,3-galactose, a carbohydrate on mammalian meat and some products. It follows tick bites and typically causes reactions 2 to 6 hours after eating.

Pathophysiology. Bites from ticks (for example Amblyomma americanum in the United States, Ixodes ricinus in Europe, Ixodes holocyclus in Australia) introduce alpha gal and cause IgE sensitisation. Reactions follow exposure to alpha gal in mammalian meat, organ meat, some dairy, gelatin and other products.

The delay occurs because alpha gal is carried on glycolipids that are absorbed slowly in chylomicrons. Cofactors such as exercise, alcohol and aspirin lower the threshold.

Antibodies may fade after tick avoidance over 1 to 2 years, and bites reinforce them.

• Urticaria, itching and angio oedema 2 to 6 hours after eating beef, pork, lamb or venison
• Abdominal pain, vomiting and diarrhoea, sometimes without skin signs
• Anaphylaxis, often at night after an evening meal
• Reactions to gelatin, dairy, heparin of porcine origin, cetuximab (immediate), some medicines and bioprosthetic heart valves
• Unexplained recurrent anaphylaxis
• Itchy tick bite lesions that persist in sensitised patients

• Specific IgE to alpha gal: over 0.1 kUA/L supports sensitisation in a patient with a typical history, and higher values are more likely to be clinical.
• Total IgE and tryptase (during a reaction).
• Skin prick test with mammalian meat extracts or gelatin, or intradermal testing, may support the diagnosis.
• Basophil activation test where available.
• Oral food challenge is rarely needed, and carries a risk of severe delayed reaction.
• History of tick bites, residence or travel to endemic regions.

Differential diagnosis.

• Idiopathic anaphylaxis
• Food allergy to meat proteins (pork cat syndrome)
• Mast cell disorders (mastocytosis, mast cell activation syndrome)
• Irritable bowel syndrome and gallbladder disease
• Chronic spontaneous urticaria
• Delayed drug reactions

• Avoid mammalian meat (beef, pork, lamb, goat, venison) and organ meat. Chicken, turkey and fish are safe.
• Dairy and gelatin: many patients tolerate milk, cheese and butter. Patients with persistent reactions avoid dairy and gelatin in medicines and vaccines.
• Tick avoidance: protective clothing, repellents containing DEET, and tick checks, since new bites keep antibody levels high.
• Adrenaline auto injector: 150 microgram for 7.5 to 25 kg, 300 microgram for 25 to 50 kg, 500 microgram for over 50 kg, with a written action plan and training.
• Anaphylaxis: adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) into the anterolateral thigh, repeated after 5 minutes if no improvement, plus oxygen and intravenous fluids. Observe for at least 6 hours, and longer if the reaction is delayed.
• Mild reactions: cetirizine 10 mg orally once daily in adults (children 1 to 5 years 2.5 mg twice daily; 6 to 11 years 5 mg twice daily).
• Medicines and procedures: avoid cetuximab, and use non-mammalian-derived alternatives where possible (heparin, gelatin containing capsules or vaccines, bioprosthetic valves). Give pre-operative warning.
• Remission: if no tick bites occur for 1 to 2 years, specific IgE often falls, and a supervised challenge may allow meat to be reintroduced.

Special groups.

• People at risk of tick bites (outdoor workers, hunters): repeated bites may prevent remission.
• Patients needing a bioprosthetic heart valve: discuss mechanical or non-mammalian alternatives with the cardiac team.

Monitoring. Specific IgE to alpha gal every 6 to 12 months to judge remission. Review of diet and tick exposure at each visit. Check auto injector dose and expiry.

Referral and escalation. Refer to allergy for unexplained delayed anaphylaxis, recurrent urticaria after meals, or when a heart valve, heparin or cetuximab is planned. Emergency for anaphylaxis.