Galactose-Alpha-1,3-Galactose, Mammalian Meat and Anaphylaxis: A World-Wide Phenomenon?

Abstract

Opinion StatementMammalian meat allergy following tick bites is known to occur in Australia, North America, Europe, Asia, Africa and Central America. Over the last decade, the condition has become increasingly prevalent in tick-endemic areas of Australia and the USA. In mammalian meat-allergic individuals, gelatine allergy and/or cow's milk allergy may co-exist. Awareness of tick-induced allergies in health professionals and the general community is key to both a timely diagnosis and the prevention of mammalian meat allergy. Treatment of mammalian meat allergy is limited currently to avoidance of all mammalian meat, whilst gelatine allergy similarly mandates avoidance of mammalian-derived gelatine, especially intravenously administered gelatine-containing solutions. Adults with anaphylaxis to mammalian meat should have a convalescent tryptase estimation and investigations for mastocytosis should then be undertaken if the tryptase is significantly elevated. Before initiating treatment with certain therapeutic agents (e.g. cetuximab, gelatine-containing substances, bovine artificial blood), a careful assessment of the risk of anaphylaxis, including serological analysis for galactose-alpha-1,3-galactose-specific immunoglobulin E, should be undertaken in any individual who works, lives, volunteers or participates in leisure activities in a tick-endemic area, particularly where a history is obtained of a tick bite prior, or of mammalian meat or gelatine allergy. Strategies aimed at the prevention of tick bites are paramount for primary prevention and amelioration of mammalian meat allergy. Key points 1. Mammalian meat allergies are characterised by delayed anaphylaxis, urticaria and angioedema, occurring 2-10 h after the ingestion of mammalian meat and are commonly preceded by a tick bite. 2. Mammalian meat allergy may be confirmed by galactose-alpha-1,3-galactose and mammalian meat-specific immunoglobulin E estimations, cetuximab skin testing or skin prick testing with fresh, raw, organic meat extracts. 3. Confirmation of gelatine allergy requires intradermal testing if skin prick testing is negative and gelatine-specific immunoglobulin E is not detected. 4. Dietary exclusion of mammalian meat, mammalian gelatine and cow's milk products, as indicated by the individual clinical sensitivity profile, is the mainstay of treatment in allergy to galactose-alpha-1,3-galactose. 5. Mammalian meat-allergic patients should be aware of the risk of allergic reaction to cetuximab, gelatine and mammalian meat-containing therapeutic agents and health supplements and to check the ingredients carefully. 6. Search for co-existing mastocytosis when tryptase levels are elevated in convalescence. 7. Prevention of tick bites appears to limit the duration of the condition in some individuals and is essential to the primary prevention of mammalian meat allergy.

Tick‐induced allergies: mammalian meat allergy and tick anaphylaxis

“…Tick‐induced allergies comprise large local reactions to tick bites, mammalian meat allergy after tick bites, and tick anaphylaxis 1 , 2 . Ixodes holocyclus (the Australian paralysis tick) (Box 1) is responsible for the majority of bites in humans in Australia and is therefore the tick that causes most tick‐induced allergies 3 .…”

“…Large local allergic reactions to tick bites, while incapacitating at the time, are the least severe form of tick‐induced allergies. The commonest presentation of a serious tick‐induced allergy is mammalian meat allergy after a tick bite, which may manifest as anaphylaxis, recurrent angioedema or gut symptoms after ingestion of mammalian meat — all typically delayed by 3–6 hours 1 , 2 , 4 . ‐ 6 Mammalian meat allergy is an emergent allergy that has become increasingly prevalent in tick‐endemic areas of Australia and the United States, and has been reported worldwide where Ixodes spp, Amblyomma spp and Haemaphysalis longicornis are endemic and known to bite humans (Box 2).…”

ASCIA guidelines for prevention of anaphylaxis in schools, pre‐schools and childcare: 2015 update

“…A recent Australian study demonstrated confirmed FA incidence at age 12 months to be 10% with lower estimates for older children of 3–5% and 1–3% in adults in other studies . Anaphylaxis to stinging insects may occur (bees, wasps, Jack Jumper ants) and in some regions, from tick bites as well . Allergy to medications or latex are less common in childhood.…”

“…4 Anaphylaxis to stinging insects may occur (bees, wasps, Jack Jumper ants) and in some regions, from tick bites as well. 5 Allergy to medications or latex are less common in childhood.…”

Guillain-Barré and Alpha-gal Syndromes: Saccharides-induced Immune Responses

“…16,17 AGS is characterized by delayed anaphylaxis to red meat consumption and certain drugs, such as cetuximab, and immediate anaphylaxis to tick bites, and is becoming a global problem with increasing prevalence in all continents and with the involvement of several tick species. [16][17][18][19][20] Humans do not produce the carbohydrate α-Gal (Gal α 1-3Gal β 1-(3)4GlcNAc-R), 21 and the not yet fully understood immune response induced by tick bites that includes anti-α-Gal IgE antibodies break the oral tolerance to food allergens, resulting in a gut-related but not lung-related allergy. 16,20 The GGTA1 gene encoding for the α1,3-galactosyltransferase enzyme that synthetizes α-Gal in mammals was inactivated in humans, apes and Old World monkeys approximately 28 million years ago.…”