Red Meat Allergies After Lone Star Tick Bites

In This Article

Abstract and Introduction
Methods
Results
Discussion
Conclusions
References
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Abstract and Introduction

Abstract

Red meat allergies have followed tick bites on every continent except Antarctica. The sensitizing antigen is galactose-α-1,3-galactose (α-gal), an oligosaccharide constituent of nonprimate blood and meat, acquired by ticks during animal bloodfeeding. Because red meat allergy after tick bites is a worldwide phenomenon, the objectives of this review were to describe the global epidemiology of red meat allergy after tick bites and its immunological mechanisms; to identify the human risk factors for red meat allergy after tick bites; to identify the most common tick vectors of red meat allergy worldwide; to describe the clinical manifestations, diagnostic confirmation, and management of patients with red meat allergy after tick bites; and to recommend strategies for the prevention of tick bites. To meet these objectives, Internet search engines were queried with keywords to select scientific articles for review. The keywords included ticks, tick bites, allergy, anaphylaxis, and meat allergy. The study period was defined as 1980–2019. The major risk factors for red meat allergy after tick bites included male sex, non-B blood type, systemic mastocytosis, a bioprosthetic (bovine or porcine) heart valve, and preexisting allergies to gelatin or animal dander. Following confirmation by challenge testing, patients with red meat allergies should avoid red meats, foods containing gelatin, and intravenous immunotherapy with monoclonal antibodies such as cetuximab and infliximab produced in SP2/0 mouse cell lines. Red meat allergy after tick bites represents an emerging threat from tick bites in addition to infectious diseases.

Introduction

Immunoglobulin E (IgE)–mediated allergic reactions to tick bites were first described in Australia in the 1980s following paralysis tick (Ixodes holocyclus) bites.^[1] These reactions were characterized by urticaria, angioedema, and, in some cases, anaphylaxis.^[2] In 2007, 25 patients who lived in a paralysis tick-endemic region near Sydney, Australia, developed red meat allergies after paralysis tick bites.^[2] All of the cases presented as anaphylaxis or combinations of urticaria, angioedema, and anaphylaxis.^[2] An immunological cross-reaction between arthropod-injected and foodborne antigens was suspected.^[2]

The sensitizing antigen in these and later tick bite–linked red meat allergy cases worldwide was identified as galactose-α-1,3-galactose (α-gal).^[3–6] α-Gal, an oligosaccharide constituent of all nonprimate, mammalian red meats, structurally resembles human blood group antigen B.^[3–6] Ticks obtain α-gal sugars while feeding on host animals and inject small amounts of α-gal into the human circulation during bloodfeeding.^[4–6] The antigen injection sensitizes high-risk individuals to α-gal in red meats, including beef, pork, lamb, goat, rabbit, horse, kangaroo, and other wild game meats.^[3–6]

As a result of the increasing worldwide prevalence of reported cases of red meat allergy following tick bites, the objectives of this review are to describe the global epidemiology of red meat allergy after tick bites and its immunological mechanisms; to identify the human risk factors for developing red meat allergy after tick bites; to notify individuals of their regional risks of acquiring red meat allergy after local tick bites; to identify the most common tick vectors of red meat allergy worldwide; to describe the clinical manifestations, diagnostic confirmation, and management of patients with red meat allergy after tick bites; and to recommend strategies for the prevention of tick bites.

Table 1. Scientific articles reviewed, referenced, and stratified by types
	Review articles	Case reports and case series	Epidemiological investigations	Immunological investigations	Laboratory investigations
Articles reviewed^a (n = 51)	16	12	2	15	6
Articles referenced (n = 37)	10	10	2	10	5

^aArticles not reviewed: tickborne infectious disease and tick paralysis reviews, clinicopathological case conference reports, press releases, perspectives, and opinion-editorial articles.

Table 2. Selected global reports of red meat allergy after tick bites: 2007–2018 ^{2–4,11–19}
Year	Country	Implicated ticks/common names	No. patients	Significance of reports	Ref
2007	Australia	Ixodes holocyclus/paralysis tick	25	1st reports of delayed red meat allergy after tick bites; 1st confirmed galactose-α-1,3-galactose (α-gal) as the responsible epitope; positive skin prick tests with rawextracts of goat kangaroo, venison, and rabbit	2
2009	US	Amblyomma americanum/Lone Star tick	24	1st reports from US; confirmed fewer to no further episodes after all red meat avoidance	3
2009	Australia	Ixodes holocyclus/paralysis tick	25	Confirmed delayed-onset allergic reactions; described positive intradermal cetuximab skin tests^a	4
2011	Spain	Ixodes Ricinus/sheep tick	5	1st reports from Europe; described positive cetuximab skin prick tests	11
2012	Japan	Amblyomma testudinarium (suspected, induces α-gal IgE)	1	1st report from Asia; described delayed-onset anaphylaxis with oral pork ingestion test	12
2013	Germany	Ixodes Ricinus/sheep tick	21	Confirmed coexisting gelatin (animal collagen from rendered cattle hoofs/bones and pig skin) allergies as risk factors for anaphylaxis after tick bites	13, 14
2013	Sweden	Ixodes ricinus/sheep tick	5	1st reports from Scandinavia	15
2013	France	Ixodes ricinus/sheep tick	1	Described cow's milk product allergy (cheese and yogurt) following tick bite	16
2013	Sweden	Ixodes Ricinus/sheep tick	39	Described moose meat allergies after tick bites	15
2014	Panama	Amblyomma cajennense/cayenne tick	1	1st reports from Central America and 1st report of another species in the Americas capable of causing red meat allergies	17
2017	US	Amblyomma americanum/Lone Star tick	4	Described male sex and coexisting systemic mastocytosis as risk factors for red meat allergies after tick bites	18
2018	Australia	Ixodes (Endopalpiger) australiensis	6	1st report of the association of red meat allergy following a tick bite froma novel, second tick species in the same country; until then, all regional red meat allergies followed bites by a single tick species	19

IgE, immunoglobulin E.
^aCetuximab is a monoclonal antibody cancer chemotherapeutic drug produced in mouse cell lines that can cause anaphylaxis in patients sensitized to α-gal by milk or gelatin allergies or by tick bites.

Table 3. Foods documented by challenge to cause α-gal-related allergic reactions
Domestic red meat products	Wild animal red meat products	Other red meat-related products
Beef Pork Lamb Goat Horse	Deer Rabbit Kangaroo	Cow's milk Gelatin Yogurt

α-gal, galactose-α-1,3-galactose.

Table 4. Risk factors for red meat allergies in α-gal-sensitized patients
Food allergies	Animal allergies	Medications	Miscellaneous conditions	Regional tick bites (species)
Cheese Cow's milk Gelatin Yogurt	Cat dander Other furred animal dander	Medication capsules containing gelatin Gelatin-based plasma expanders Animal-based pancreatic enzymes Chimeric mouse (SP2/0 cell line)-human mAbs: cetuximab, infliximab Possible other SP2/0-derived mAbs: abciximab, basiliximab, canakinumab, golimumab, ustekinumab	Nongroup B blood type Systemic mastocytosis Bovine heart valve Porcine heart valve	US: Lone Star tick (Amblyomma americanum) Central America: Cayenne tick (Amblyomma cajennense) Europe: Sheep tick (Ixodes ricinus) Asia (Japan, South Korea): Amblyomma testudinarium Africa: Red meat allergy after tick bites reported in South Africa, but no tick species described to date. Australia: Paralysis tick (Ixodes holocyclus)