Tick-Induced Cutaneous and Allergic Manifestations: Differential Diagnosis Between Lyme Borreliosis and Alpha-Gal Syndrome
DOI:
https://doi.org/10.12775/QS.2026.64.73696Keywords
Lyme borreliosis, Lyme disease, alpha-gal syndrome, AGS, red meat allergy, tick-mediated allergy disease, utricaria, alpha-gal, erythema migransAbstract
Background. Ticks serve as common vectors for both the infectious Lyme Borreliosis and the allergic Alpha-Gal Syndrome creating significant diagnostic challenges when patients present with non-specific skin reactions. Distinguishing between these entities is vital to prevent the misdiagnosis and to ensure correct treatment, ranging from antibiotics for LB to strict dietary avoidance for AGS.
Aim. The primary objective of this review is to provide a comprehensive comparative analysis of the cutaneous and allergic manifestations induced by tick bites, specifically focusing on the differentiation between Lyme Borreliosis and Alpha-Gal Syndrome.
Materials and methods. A comprehensive literature search was performed across multiple scientific databases, including PubMed, Web of Science, Scopus, and Google Scholar, for peer-reviewed articles and clinical studies. The search focused on publications in English and Polish to ensure a broad geographical and clinical perspective on tick-borne pathologies.
Results. Lyme Borreliosis primarily presents as erythema migrans, whereas Alpha-Gal Syndrome manifests as a unique, delayed allergic reaction (urticaria or anaphylaxis) occurring 3–6 hours after mammalian meat consumption. A key clinical differentiator is the quality of the tick bite.
Conclusions. Tick bites represent a common origin for both infectious Lyme Borreliosis and the unique, IgE-mediated Alpha-Gal Syndrome, necessitating a precise differential diagnosis. Distinguishing between these entities is vital, as the hallmark delayed urticaria of Alpha-Gal Syndrome is frequently misdiagnosed as chronic idiopathic urticaria or misunderstood as a primary symptom of a bacterial infection. Enhanced clinical awareness and the implementation of molecular component diagnostics are essential for ensuring the correct therapeutic path, ranging from targeted antibiotic therapy to strict dietary exclusion.
References
1. Steinke JW, Platts-Mills TA, Commins SP. The alpha-gal story: lessons learned from connecting the dots. The J Allergy Clin Immunol. 2015;135(3):589-596; quiz 597.
2. Molaei G, Little EAH, Williams SC, Stafford KC. Bracing for the worst – range expansion of the lone star tick in the northeastern United States. New Engl J Med. 2019;381(23):2189-2192.
3. G. Trevisan, P. Cattonar, C. Nobile, V. Perkan, G. Stinc.o Dermatological manifestations of lyme borreliosis. Acta dermatovenerologia A.P.A. Vol 5, 96, No 3-4, 101-107
4. Patel C, Iweala OI. ‘Doc, will I ever eat steak again?’: diagnosis and management of alpha-gal syndrome. Curr Opin Pediatr. 2020;32(6):816–824. doi:10.1097/MOP.0000000000000955
5. Román-CarrascoP,HemmerW,Cabezas-CruzA,etal.Theα-Galsyndromeandpotential mechanisms. Frontiers in Allergy. 2021;2:783279.
6. Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, Perzanowski MS, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2011 May;127(5):1286-93.
7. Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM. Diagnosis and management of patients with the α-Gal syndrome. J Allergy Clin Immunol Pract. 2020;8(1):15-23.e11.
8. Román-CarrascoP,HemmerW,Cabezas-CruzA,etal.Theα-Galsyndromeandpotential mechanisms. Frontiers in Allergy. 2021;2:783279.
9. Weala OI, Choudhary SK, Addison CT, Commins SP. T and B lymphocyte transcriptional states differentiate between sensitized and unsensitized individuals in alpha-gal syndrome. Int J Mol Sci. 2021;22(6):3185.
10. Fischer J, Hebsaker J, Caponetto P, Platts-Mills TA, Biedermann T. Galactose-alpha-1,3-galactose sensitization is a prerequisite for pork-kidney allergy and cofactor-related mammalian meat anaphylaxis. J Allergy Clin Immunol. 2014;134(3):755-9.
11. Tripathi A, Commins SP, Heymann PW, Platts-Mills TA. Delayed anaphylaxis to redmeat masquerading as idiopathic anaphylaxis. J Allergy Clin Immunol Pract. 2014May-Jun;2(3):259-65.
12. Berger BW. Dermatologic manifestations of Lyme disease. Rev Infect Dis 1989, 11 (Suppl 6): S1475-81.
13. Trevisan G, Cinco M. Lyme Borreliosis in Childhood. Eur J Pediat Dermatol 1992; 2: 81-112
14. Mary Michael, tamara Gmitter. A Case of Disseminated Lyme Disease Presenting as Chronic Urticaria. Cureus. 2019 Seo 9;11(9):e5600. doi: 10.7759/cureus.5600
15. Patel C, Iweala OI. ‘Doc, will I ever eat steak again?’: diagnosis and management of alpha-gal syndrome. Curr Opin Pediatr. 2020;32(6):816–824. doi:10.1097/MOP.0000000000000955
16. Mabelane T, Basera W, Botha M, Thomas HF, Ramjith J, Levin ME. Predictive values of alpha-gal IgE levels and alpha-gal IgE: total IgE ratio and oral food challenge-proven meat allergy in a population with a high prevalence of reported red meat allergy. Pediatr Allergy Immunol. 2018;29(8):841–849.
17. Berg EA, Platts-Mills TA, Commins SP. Drug allergens and food - the cetuximab and galactose-alpha-1,3-galactose story. Ann Allergy Asthma Immunol. 2014 Feb;112(2):97-101.
18. Steinke JW, Platts-Mills TA, Commins SP. The alpha-gal story: lessons learned from connecting the dots. The J Allergy Clin Immunol. 2015;135(3):589-596; quiz 597.
19. Platts-Mills TAE, Li RC, Keshavarz B, et al. Diagnosis and management of patients with the α-Gal syndrome. Journal of Allergy and Clinical Immunology in Practice. 2020;8(1):15-23.
20. Richards NE, Richards RD Jr. Alpha-gal allergy as a cause of intestinal symptoms in a gastroenterology community practice. South Med J. 2021;114(3):169–173.
21. Pattanaik D, Lieberman P, Lieberman J, Pongdee T, Keene AT. The changing face of anaphylaxis in adults and adolescents. Ann Allergy Asthma Immunol. 2018;121(5):594-597.
22. 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(5):699–704.
23. Fischer J, Hebsaker J, Caponetto P, Platts-Mills TA, Biedermann T. Galactose-alpha-1,3-galactose sensitization is a prerequisite for pork-kidney allergy and cofactor-related mammalian meat anaphylaxis. J Allergy Clin Immunol. 2014;134(3):755–759
24. Fischer J, Hebsaker J, Caponetto P, Platts-Mills TA, Biedermann T. Galactose-alpha-1, 3-galactose sensitization is a prerequisite for pork-kidney allergy and cofactor-related mammalian meat anaphylaxis. J Allergy Clin Immunol. 2014;134(3):755-9.
25. Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM. Diagnosis and management of patients with the α-Gal syndrome. J Allergy Clin Immunol Pract. 2020;8(1):15-23.e11.
26. Wilson JM, Nguyen AT, Schuyler AJ, et al. IgE to the mammalian oligosaccharide galactose-alpha-1,3-galactose is associated with increased atheroma volume and plaques with unstable characteristics-brief report. Arterioscler Thromb Vasc Biol. 2018;38(7):1665–1669.
27. Kuravi KV, Sorrells LT, Nellis JR, et al. Allergic response to medical products in patients with alpha-gal syndrome. J Thorac Cardiovasc Surg. 2021. doi:10.1016/j.jtcvs.2021.03.100
28. KeshavarzB,SmithAR,WilsonJM,Platts-MillsTAE.Α-Galsyndromeunmaskedinchronic spontaneous urticaria cohorts. Annals of Allergy, Asthma & Immunology. 2019;123(5):454-461.
29. Iweala OI, Burks AW. Food allergy: our evolving understanding of its pathogenesis, prevention, and treatment. Curr Allergy Asthma Rep. 2016;16(5):37
30. Brestoff JR, Tesfazghi MT, Zaydman MA, et al. The B antigen protects against the development of red meat allergy. J Allergy Clin Immunol Pract. 2018;6(5):1790–1791.
31. Bircher AJ, Hofmeier KS, Link S, Heijnen I. Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review. Eur J Dermatol. 2017;27(1):3–9
32. Commins SP, James HR, Stevens W, Pochan SL, Land MH, King C, 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 Jul;134(1):108-15.
33. Steinke JW, Platts-Mills TA, Commins SP. The alpha-gal story: lessons learned from connecting the dots. The J Allergy Clin Immunol. 2015;135(3):589-596; quiz 597.
34. Carson AS, Gardner A, Iweala OI. Where’s the beef? Understanding allergic responses to red meat in alpha-gal syndrome. J Immunol. 2022;208 (2):267–277.
35. Commins SP, James HR, Stevens W, Pochan SL, Land MH, King C, 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 Jul;134(1):108-15.
36. Park Y, Kim D, Boorgula GD, et al. Alpha-gal and cross-reactive carbohydrate determinants in the N-glycans of salivary glands in the lone star tick, Amblyomma americanum. Vaccines. 2020;8(1):18.
37. im DW, Lee JS, Park KH, et al. Accurate assessment of alpha-gal syndrome using cetuximab and bovine thyroglobulin-specific IgE. Mol NutrFood Res. 2017;61(10):1601046.
38. Li J, Fulton RB, O’Connell R, Jang HS, Fernando SL. Specific-IgE to galactose-alpha-1,3-galactose (alpha-gal) has limited utility in diagnosing meat allergy in a tick-endemic population. Ann Allergy Asthma Immunol. 2018;121(4):509–511.
39. Commins SP, Platts-Mills TAE. Specific IgE to α-Gal-containing proteins: Diagnostic considerations. Journal of Allergy and Clinical Immunology. 2018;142(4):1189-1195
40. Iweala OI, Choudhary SK, Addison CT, et al. Glycolipid-mediated basophil activation in alpha-gal allergy. J Allergy Clin Immunol. 2020;146 (2):450–452.
41. Kollmann D, Nagl B, Ebner C, et al. The quantity and quality of alpha-gal-specific antibodies differ in individuals with and without delayed red meat allergy. Allergy. 2017;72(2):266–273.
42. Tripathi A, Commins SP, Heymann PW, Platts-Mills TA. Delayed anaphylaxis to red meat masquerading as idiopathic anaphylaxis. J Allergy Clin Immunol Pract. 2014 May-Jun;2(3):259-65.
43. Platts-Mills TAE, Li RC, Keshavarz B, Smith AR, Wilson JM. Diagnosis and management of patients with the α-Gal syndrome. J Allergy Clin Immunol Pract. 2020;8(1):15-23.e11.
44. Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, Perzanowski MS, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2011 May;127(5):1286-93.
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Copyright (c) 2026 Emilia Fitz, Mikołaj Brzeźniak , Justyna Daniek, Filip Kręcina, Weronika Kaczmarek, Kacper Gil, Krzysztof Drelich, Aleksander Karbowniczek, Julia Maria Mokracka, Alicja Grabarczyk
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