Connect
MJA
MJA

Tick-induced allergies: mammalian meat allergy and tick anaphylaxis

Sheryl A van Nunen
Med J Aust 2018; 208 (7): . || doi: 10.5694/mja17.00591
Published online: 16 April 2018

Summary

 

  • Mammalian meat allergy after tick bites and tick anaphylaxis are the most serious tick-induced allergies. They are often severe, should be largely avoidable and offer fascinating insights into the development and prevention of allergies.
  • Australian clinicians reported the first cases of tick anaphylaxis and discovered the association between tick bites and the development of mammalian meat allergy. The subsequent finding of the allergen epitope within the meat responsible for the allergic reaction, α-gal (galactose-α-1,3-galactose), stimulated further interest in this emergent allergy.
  • Reports of mammalian meat allergy associated with bites from several tick species have now come from every continent where humans are bitten by ticks. The number of diagnosed patients has continued to rise.
  • Clinically, mammalian meat allergy and tick anaphylaxis present quite differently. The prominent role of cofactors in triggering episodes of mammalian meat allergy can make its diagnosis difficult.
  • Management of mammalian meat allergy is complicated by the manifold potential therapeutic implications due to the widespread distribution of the mammalian meat allergen, α-gal. Exposures to α-gal-containing medications have proved lethal in a minority of people, and fatal tick anaphylaxis has been reported in Australia. Prevention of tick bites is prudent and practicable; killing the tick in situ is crucial to both primary and secondary prevention of allergic reactions.
  • Mechanisms in the development of mammalian meat allergy constitute a paradigm for how allergies might arise.

 


  • 1 Royal North Shore Hospital, Sydney, NSW
  • 2 Tick-Induced Allergies Research and Awareness Centre, Sydney, NSW


Correspondence: vannunen@med.usyd.edu.au

Competing interests:

No relevant disclosures.

  • 1. van Nunen S. Tick-induced allergies: mammalian meat allergy, tick anaphylaxis and their significance. Asia Pac Allergy 2015; 5: 3-16.
  • 2. van Nunen S. Galactose-alpha-1,3-galactose, mammalian meat and anaphylaxis: a world-wide phenomenon? Curr Treat Options Allergy 2014; 1: 262-277.
  • 3. Rappo TB, Cottee AM, Ratchford AM, Burns BJ. Tick bite anaphylaxis: incidence and management in an Australian emergency department. Emerg Med Australas 2013; 25: 297-301.
  • 4. van Nunen S, O’Connor KS, Fernando SL, et al. The association between Ixodes holocyclus tick bite reactions and red meat allergy. Intern Med J 2007; 39: A132.
  • 5. van Nunen SA, O’Connor KS, Clarke LR, et al. An association between tick bite reactions and red meat allergy in humans. Med J Aust 2009; 190: 510-511. <MJA full text>
  • 6. Commins SP, Satinover SM, Hosen J, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol 2009; 123: 426-433.
  • 7. Jacquenet S, Moneret-Vautrin DA, Bihain BE. Mammalian meat-induced anaphylaxis: clinical relevance of anti-galactose-alpha-1,3-galactose IgE confirmed by means of skin tests to cetuximab. J Allergy Clin Immunol 2009; 124: 603-605.
  • 8. Nuñez R, Carballada F, Gonzalez-Quintela A, et al. Delayed mammalian meat-induced anaphylaxis due to galactose-α-1,3-galactose in 5 European patients. J Allergy Clin Immunol 2011; 128: 1122-1124.e1.
  • 9. Jappe U. Update on meat allergy. α-gal: a new epitope, a new entity? Hautarzt 2012; 63: 299-306.
  • 10. Lee JH, Kim JH, Kim TH, Kim SC. Delayed mammalian meat-induced anaphylaxis confirmed by skin test to cetuximab. J Dermatol 2013; 40: 577-578.
  • 11. Sekiya K, Fukutomi Y, Nakazawa T, et al. Delayed anaphylactic reaction to mammalian meat. J Invest Allergol Clin Immunol 2012; 22: 446-447.
  • 12. Hamsten C, Tran TAT, Starkhammar M, et al. Red meat allergy in Sweden: association with tick sensitization and B-negative blood groups. J Allergy Clin Immunol 2013; 132: 1431-1434.
  • 13. Michel S, Scherer K, Heijnen IA, Bircher AJ. Skin prick test and basophil reactivity to cetuximab in patients with IgE to alpha-gal and allergy to red meat. Allergy 2014; 69: 403-405.
  • 14. Wickner PG, Commins S. The first central American cases of delayed meat allergy with galactose-alpha-1,3-galactose positivity clustered among field biologists in Panama. Abstract 736; American Academy of Allergy, Asthma and Immunology Annual Meeting; San Diego, CA (US); 28 Feb – 4 Mar 2014.
  • 15. Shepherd M. Anaphylaxis shock warning over Highland tick bites. Edinburgh: Royal Environmental Health Institute of Scotland; 2015. https://www.rehis.com/sites/default/files/rehis_september_2015_e-newsletter_120915_1.pdf (viewed Feb 2018).
  • 16. Calamari AM, Poppa M, Villalta D, Pravettoni V. Alpha-gal anaphylaxis: the first case report from Italy. Eur Ann Allergy Clin Immunol 2015; 47: 161-162.
  • 17. Gray CL, van Zyl A, Strauss L. “Midnight anaphylaxis” to red meat in patients with alpha-gal sensitisation: a recent discovery in the food allergy world and a case report from South Africa. Curr Allergy Clin Immunol 2016; 29: 102-104.
  • 18. Chinuki Y, Ishiwata K, Yamaji K, et al. Haemaphysalis longicornis tick bites are a possible cause of red meat allergy in Japan. Allergy 2016; 71: 421-425.
  • 19. Cocco RR, Ensina LF, Aranda CS, Solé D. Galactose-α-1,3-galactose (alpha gal) allergy without anaphylaxis: a case report in Brazil. Clin Transl Allergy 2017; 7: 7.
  • 20. Kaloga M, Kourouma S, Kouassi YI, et al. Allergy to red meat: a diagnosis made by the patient and confirmed by an assay for IgE antibodies specific for alpha-1,3-galactose. Case Rep Dermatol 2016; 8: 10-13.
  • 21. Lied GA. Red meat allergy induced by tick bite: a Norwegian case report. Eur Ann Allergy Clin Immunol 2017; 49: 186-188.
  • 22. McGain F, Welton R, Solley GO, Winkel KD. First fatalities in tick anaphylaxis. J Allergy Clin Immunol Pract 2016; 4: 769-770.
  • 23. Mullins RJ, Wainstein BK, Barnes EH, et al. Increases in anaphylaxis fatalities in Australia from 1997 to 2013. Clin Exp Allergy 2016; 46: 1099-1110.
  • 24. van Wye JE, Hsu YP, Lane RS, et al. IgE antibodies in tick bite-induced anaphylaxis. J Allergy Clin Immunol 1991; 88: 968-970.
  • 25. van Wye JE, Hsu YP, Terr AI, Moss RB. Anaphylaxis from a tick bite. N Engl J Med 1991; 324: 777-778.
  • 26. Moneret-Vautrin DA, Beaudouin E, Kanny G, et al. Anaphylactic shock caused by ticks (Ixodes ricinus). J Allergy Clin Immunol 1998; 101: 144-145.
  • 27. Fernández-Soto P, Dávila I, Laffond E, et al. Tick-bite-induced anaphylaxis in Spain. Ann Trop Med Parasitol 2001; 95: 97-103.
  • 28. Fischer J, Yazdi AS, Biedermann T. Clinical spectrum of α-gal syndrome: from immediate-type to delayed immediate-type to mammalian innards and meat. Allergo J Int 2016; 25: 55-62.
  • 29. Acero S, Blanco R, Bartolomé B. Anaphylaxis due to a tick bite. Allergy 2003; 58: 824-825.
  • 30. Valls A, Pineda F, Belver M, et al. Anaphylactic shock caused by tick (Rhipicephalus sanguineous). J Investig Allergol Clin Immunol 2007; 17: 279-280.
  • 31. Mateos-Hernández L, Villar M, Moral A, et al. Tick-host conflict: immunoglobulin E antibodies to tick proteins in patients with anaphylaxis to tick bite. Oncotarget 2017; 8: 20630-20644.
  • 32. Gauci M, Loh RKS, Stone BF, Thong YH. Allergic reactions to the Australian paralysis tick, Ixodes holocyclus: diagnostic evaluation by skin test and radioimmunoassay. Clin Exp Allergy 1989; 19: 279-283.
  • 33. Graft DF, Schuberth KC, Kagey-Sobotka A, et al. A prospective study of the natural history of large local reactions after Hymenoptera stings in children. J Pediatr 1984; 104; 664-668.
  • 34. Galili U, Clark MR, Shohet SB, et al. Evolutionary relationship between the natural anti-gal antibody and the gal-alpha-1,3-gal epitope in primates. Proc Natl Acad Sci U S A 1987; 84: 1369-1373.
  • 35. Galili U, Mandrell RE, Hamadeh RM, et al. Interaction between human natural anti-alpha-galactosyl immunoglobulin G and bacteria of the human flora. Infect Immun 1988; 56: 1730-1737.
  • 36. Galili U. Evolution and pathophysiology of the human natural anti-α-galactosyl IgG (anti-gal) antibody. Springer Semin Immunopathol 2004; 15: 155-171.
  • 37. Commins S, Lucas S, Hosen J, et al. Anaphylaxis and IgE antibodies to galactose-alpha-1,3-galactose (alphaGal): insight from the identification of novel IgE ab to carbohydrates on mammalian proteins. J Allergy Clin Immunol 2008; 121: S25.
  • 38. Gauci M, Stone BF, Thong YH. Detection in allergic individuals of IgE specific for the Australian paralysis tick, Ixodes holocyclus. Int Arch Appl Immunol 1988; 85: 190-193.
  • 39. Gauci M, Stone BF, Thong YH. Isolation and immunological characterisation of allergens from salivary glands of the Australian paralysis tick, Ixodes holocyclus. Int Arch Appl Allergy Immunol 1988; 87: 208-212.
  • 40. Broady KW. Presentation of findings: tick allergens; TiARA (Tick-induced Allergies Research and Awareness) Committee Meeting. Royal North Shore Hospital; Sydney (Australia), 20 Aug 2013.
  • 41. Dorey C. Allergens of the Australian paralysis tick, Ixodes holocyclus [dissertation]. Sydney: University of Technology Sydney, 1998.
  • 42. Padula MP. The development of proteomic techniques to study the Australian paralysis tick [dissertation]. Sydney: University of Technology Sydney, 2008.
  • 43. Cooper PJ. Interactions between helminth parasites and allergy. Curr Opin Allergy Clin Immunol 2009; 9: 29-37.
  • 44. Tyagi N, Farnell EJ, Fitzsimmons CM, et al. Comparisons of allergenic and metazoan parasite proteins: allergy the price of immunity. PLoS Comput Biol 2015; 11: e1004546.
  • 45. Commins SP, Platts-Mills TA. Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol 2013; 13: 354-359.
  • 46. James HR, Commins SP, Kelly LA, et al. Further evidence for tick bites as a cause of the IgE responses to alpha-gal that underlie a major increase in delayed anaphylaxis to meat. J Allergy Clin Immunol 2011; 127: AB243.
  • 47. Kennedy JL, Stallings AP, Platts-Mills TA, et al. Galactose-α-1,3-galactose and delayed anaphylaxis, angioedema and urticaria in children. Pediatrics 2013; 131: e1545-e1552.
  • 48. Mullins RJ, James H, Platts-Mills TA, Commins S. Relationship between red meat allergy and sensitization to gelatin and galactose-α-1,3-galactose. J Allergy Clin Immunol 2012; 129: 1334-1342.e1.
  • 49. Renaudin J, Jacquenet S, Metz-Favre C, et al. Interest of specific IgE measurement for galactose-alpha-1,3-galactose in unexplained urticaria and angioedema, predominantly nocturnal: about 6 cases. J Allergy Clin Immunol 2012; 129: AB177.
  • 50. Morisset M, Richard C, Astier C, et al. Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose. Allergy 2012; 67: 699-704.
  • 51. Morisset M, Richard C, Zanna H, et al. Allergy to cow’s milk related to IgE antibodies specific for galactose-alpha-1,3-galactose. Abstract 1617. European Academy of Allergology and Clinical Immunology Congress and World Allergy Organization; Milan (Italy); 22-26 June 2013.
  • 52. Caponetto P, Fischer J, Biedermann T. Gelatin-containing sweets can elicit anaphylaxis in a patient with sensitization to galactose-α-1,3-galactose. J Allergy Clin Immunol Pract 2013; 1: 302-303.
  • 53. Hamsten C, Starkhammar M, Tran TA, et al. Identification of galactose-α-1,3-galactose in the gastrointestinal tract of the tick Ixodes ricinus; possible relationship with red meat allergy. Allergy 2013; 68: 549-552.
  • 54. Jappe U, Platts-Mills T, Przybilla B, et al. IgE-reactivity to galactose-[alpha]-1,3-galactose: a prospective multicentre study on meat allergy, urticaria and anaphylaxis [abstract #202]. Proceedings for the Thirty-first European Academy of Allergy and Clinical Immunology Congress; Geneva, Switzerland; 2012 June 16–20.
  • 55. Baumgart KW, Mok A, Sivertsen T, et al. Allergen-specific IgE after anaphylaxis to tick or mammalian/marsupial meat in Australia. European Academy of Allergy and Clinical Immunology Congress; Copenhagen (Denmark); 7–11 June 2014. Allergy 2014; 69: 1-646.
  • 56. Platts-Mills TA, Commins SP. Emerging antigens involved in allergic responses. Curr Opin Immunol 2013; 25: 769-774.
  • 57. Fischer J, Yazdi A, Biedermann T. Mammalian meat allergy: a diagnostic challenge. Allergo J Int 2015; 24: 81-83.
  • 58. van Nunen SA, Said MG, Batty G. Use of expanded search criteria in diagnosing mammalian meat allergy provoked by previous tick bites in individuals who do not live where ticks are endemic. Abstract 2602. European Academy of Allergy and Clinical Immunology Congress and World Allergy Organization; Milan (Italy); 22-26 June 2013.
  • 59. Wölbing F, Fischer J, Köberle M, et al. About the role and underlying mechanisms of cofactors in anaphylaxis. Allergy 2013; 68: 1085-1092.
  • 60. Versluis A, van Os-Medendorp H, Kruizinga A, et al. Cofactors in allergic reactions to food: physical exercise and alcohol are the most important. Immun Inflamm Dis 2016; 4: 392-400.
  • 61. Commins SP, James HR, Stevens W, et al. Delayed clinical and ex vivo response to mammalian meat in patients with IgE to galactose-alpha-1,3-galactose. J Allergy Clin Immunol 2014; 134: 108-115.
  • 62. Gonzalez-Quintela A, Dam Laursen AS, Vidal C, et al. IgE antibodies to alpha-gal in the general population: relationship to tick bites, atopy, and cat ownership. Clin Exp Allergy 2014; 44: 1061-1068.
  • 63. Olafson PU. Ticks and the mammalian meat allergy. Beef Research 2014; 4: 1-3.
  • 64. Fischer J, Lupberger E, Hebsaker J, et al. Prevalence of type I sensitization to alpha-gal in forest service employees and hunters. Allergy 2017; 72: 1540-1547.
  • 65. McKay WJS. Tick bite and allergy. Med J Aust 1940; 1: 458-459.
  • 66. Trinca JC. Insect allergy in Australia. Results of a five-year survey. Med J Aust 1964; 2: 659-663.
  • 67. Banfield JF. Tick bites in man. Med J Aust 1966; 2: 600-601.
  • 68. Kemp A. Tick bites. Med J Aust 1986; 144: 615.
  • 69. Brown AF, Hamilton DL. Tick bite anaphylaxis in Australia. J Accid Emerg Med 1998; 15: 111-113.
  • 70. Sánchez M, Venturini M, Blasco A, et al. Tick bite anaphylaxis in a patient allergic to bee venom. J Investig Allergol Clin Immunol 2014; 24: 284-285.
  • 71. van Nunen S, Basten A, Cowdery N, et al. Tick removal techniques practised by tick anaphylaxis sufferers. Intern Med J 2014; 44: 1-37.
  • 72. Gauci M, Stone BF, Thong YH. Detection in allergic individuals of IgE specific for the Australian paralysis tick, Ixodes holocyclus. Int Arch Allergy Appl Immunol 1988; 85: 190-193.
  • 73. Gauci M, Stone BF, Thong YH. Isolation and immunological characterisation of allergens from salivary glands of the Australian paralysis tick Ixodes holocyclus. Int Arch Allergy Appl Immunol 1988; 87: 208-212.
  • 74. Galili U. Anti-gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits. Immunology 2013; 140: 1-11.
  • 75. Pointreau Y, Commins SP, Calais G, et al. Fatal infusion reactions to cetuximab: role of immunoglobulin E-mediated anaphylaxis. J Clin Oncol 2012; 30: 334; author reply 335.
  • 76. Stone CA, Hemler JA, Commins SP, et al. Anaphylaxis after zoster vaccine: implicating alpha-gal allergy as a possible mechanism. J Allergy Clin Immunol 2017; 139: 1710-1713.e2
  • 77. Naso F, Gandaglia A, Bottio T, et al. First quantification of alpha-gal epitope in current glutaraldehyde-fixed heart valve bioprostheses. Xenotransplantation 2013; 20: 252-261.
  • 78. Fournier PE, Thuny F, Grisoli D, et al. A deadly aversion to pork. Lancet 2011; 377: 1542.
  • 79. Mozzicato SM, Tripathi A, Posthumus JB, et al. Porcine or bovine valve replacement in 3 patients with IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. J Allergy Clin Immunol Pract 2014; 2: 637-638.
  • 80. Fischer J, Eberlein B, Hilger C, et al. Alpha-gal is a possible target of IgE-mediated reactivity to antivenom. Allergy 2017; 72: 764-771.
  • 81. Commins SP, Jerath MR, Cox K, et al. Delayed anaphylaxis to alpha-gal, an oligosaccharide in mammalian meat. Allergol Int 2016; 65: 16-20.
  • 82. Australasian Society of Clinical Immunology and Allergy. Tick allergy [website]. Sydney: ASCIA; 2016. https://www.allergy.org.au/patients/insect-allergy-bites-and-stings/tick-allergy (viewed Nov 2017).
  • 83. Stone BF. Dealing with ticks affecting humans in Australia, especially the Australian paralysis tick Ixodes holocyclus. St Lucia (Australia); Department of Microbiology and Parasitology, School of Molecular and Microbial Sciences, University of Queensland; 2000.
  • 84. Due C, Fox W, Medlock JM, et al. Tick bite prevention and tick removal. BMJ 2013; 347: f7123.
  • 85. Ferreira BR, Silva JS. Successive tick infestations selectively promote a T-helper 2 cytokine profile in mice. Immunology 1999; 96: 434-439.
  • 86. Jyo T, Kuwabara M, Kodommari Y, et al. Cases of immediate-type allergy in oyster shuckers due to galacto-oligosaccharide. J Hiroshima Med Assoc 1993; 25: 19-26.
  • 87. Goh DL, Chua KY, Chew FT, et al. Immunochemical characterization of edible bird’s nest allergens. J Allergy Clin Immunol 2001; 107: 1082-1087.
  • 88. Araujo RN, Franco PF, Rodrigues H, et al. Amblyomma sculptum tick saliva: α-gal identification, antibody response and possible association with red meat allergy in Brazil. Int J Parasitol 2016; 46: 213-220.
  • 89. Commins SP, Karim S. Development of a novel murine model of alpha-gal meat allergy. J Allergy Clin Immunol 2017; 139: AB193.

Author

remove_circle_outline Delete Author
add_circle_outline Add Author

Comment
Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.