clinical expression variability in presentation complicates diagnosis and management.
Diagnosis
Recognizing alpha-gal syndromes is complicated by non-specific symptoms and delayed onset. A thorough clinical history and careful evaluation, supported by laboratory testing, are essential for establishing the diagnosis.
When taking a history, keep possible AGS in mind and include questions about outdoor activities in regions having tick populations. However, half of the patients do not recall a tick bite. 9 Presentations that are more subtle, when only gastrointestinal symptoms predominate, may lead to misdiagnosis. 2, 3
Laboratory assessment involves measuring serum alpha-gal – specific IgE( looking for levels ≥0.1 kU / L), along with at least two of these three: timing of symptom onset, history of tick exposure and / or dietary intake of mammalian meat. While this protocol yields high sensitivity( 100 %) and specificity( 92 %), approximately 2 % of patients with suspected AGS may remain undiagnosed. 9 Elevated serum IgE to beef or pork also supports the diagnosis. Skin prick testing with meat extracts is not helpful since it often indicates false-negative results. 9
Irrespective of serum alpha-gal IgE findings, confirmation includes an oral food challenge under established guidelines, because 15-20 % of patients may later develop severe reactions that require medical intervention. 9
Management
Treating patients with AGS involves non-pharmacologic and medicinal therapies. Non-pharmaceutical measures focus on dietary avoidance of alpha-gal-containing foods derived from mammals, even including gelatin, collagen and glycerin, for at least one month. 11 The artificial thickening agent, carrageenan in yogurt, also contain alpha-gal and is also a no-go. 9 Consult an allergist before initiating monoclonal antibody treatment such as with cetuximab, since it might cause dangerous reactions. Alcohol, non-steroidal anti-inflammatory drugs and exercise increase serum allergen levels and should be avoided. 12 About 81 % of the patients who adhered to an alpha-gal free diet experienced improvement over 14 months of follow-up. 13 For anyone remaining symptomatic, avoidance of dairy products may be beneficial. 14
Pharmacologic strategies depend upon symptom severity. Maintaining vital signs with normal saline and in severe cases with epinephrine and / or dexamethasone is crucial. Long-acting oral antihistamines, such as levocetirizine or fexofenadine, are recommended for continuously symptomatic patients. 15 For gastrointestinal symptoms, oral cromolyn sodium solutions such as Gastrocom may provide relief. 12 In refractory cases, anti-IgE monoclonal antibodies such as omalizumab are considered, usually as part of allergist consultation. 16
Comment
People in tick-endemic areas often preventively cover their legs and feet with clothing and wear shoes / boots, selectively treated with permethrin. 11, 17 A whole-body tick check is subsequently recommended. When a tick is found, remove it without crushing and apply antiseptic to the affected area. Everyone with AGS ought to avoid repeated tick
18, 19
bites, because another allergic reaction could be more dangerous. They are reminded also not to eat mammalian meat. An epinephrine auto-injector pen should always be immediately available in case of anaphylaxis.
References
1
Lesmana E, Rao S, Keehn A, et al.: Clinical presentation and outcomes of Alpha-gal syndrome. Clin Gastroenterol Hepatol 2025; 23( 1): 69 – 78. doi: 10.1016 / j. cgh. 2024.06.044
2
Commins SP, Platts-Mills TA: Delayed anaphylaxis to red meat in patients with IgE specific for galactosealpha-1,3-galactose( alpha-gal). Curr Allergy Asthma Rep. 2013, 13:72-77. 10.1007 / s11882- 012-0315-y
3
Steinke JW, Platts-Mills TA, Commins SP: The alpha-gal story: lessons learned from connecting the dots. J Allergy Clin Immunol. 2015, 135:589-596; quiz 597. 10.1016 / j. jaci. 2014.12.1947
4
Chung CH, Mirakhur B, Chan E, et al.: Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008, 358:1109-1117. 10.1056 / NEJMoa074943
5
Thompson JM, Carpenter A, Kersh GJ, et al.: Geographic distribution of suspected Alpha-gal syndrome cases— United States, January 2017 – December 2022. MMWR Morb Mortal Wkly Rep 2023; 72( 30): 815 – 820. doi: 10.15585 / mmwr. mm7230a2
6
Carpenter A, Drexler NA, McCormick DW, et al. Health care provider knowledge regarding Alpha-gal syndrome— United States, March – May 2022. MMWR Morb Mortal Wkly Rep 2023; 72( 30): 809 – 814. doi: 10.15585 / mmwr. mm7230a1
7
Commins SP, Platts-Mills TA: Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol. 2013,13:354-359. 10.1097 / ACI. 0b013e3283624560
8
Román-Carrasco P, Lieder B, Somoza V, et al. Only α-gal bound tolipids, but not to proteins, is transported across enterocytes as an IgE-reactive molecule that can induce effector cell activation. Allergy 2019; 74( 10): 1956 – 1968. doi: 10.1111 / all. 13873
9
Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients. Expert Rev Clin Immunol 2020; 16( 7): 667 – 677. doi: 10.1080 / 1744666X. 2020.1782745
10
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( 2): 426 – 433. doi: 10.1016 / j. jaci. 2008.10.052
11
McGill SK, Hashash JG, Platts-Mills TA. AGA clinical practice update on Alpha-gal syndrome for the GI clinician: commentary. Clin Gastroenterol Hepatol 2023; 21( 4): 891 – 896. doi: 10.1016 / j. cgh. 2022.12.035
12
Platts-Mills TAE, Commins SP, Biedermann T, et al. On the cause and consequences of IgE to galactose-a-1,3-galactose: a report from the National Institute of Allergy and Infectious Diseases work shop on understanding IgE mediated mammalian meat allergy. J Allergy Clin Immunol 2020; 145( 4): 1061 – 1071. doi: 10.1016 / j. jaci. 2020.01.047
13
Croglio MP, Commins SP, McGill SK. Isolated gastrointestinal alpha-gal meat allergy is a cause for gastrointestinal distress without anaphylaxis. Gastroenterology 2021; 160( 6): 2178 – 2180. e1. doi: 10.1053 / j. gastro. 2021.01.218
14
Commins SP. Invited commentary: alpha-gal allergy: tip of the iceberg to a pivotal immune response. Curr Allergy Asthma Rep 2016; 16( 9): 61. doi: 10.1007 / s11882-016-0641-6
15
Horak F, Zieglmayer PU, Zieglmayer R, et al.: Levocetirizine has a longer duration of action on improving total nasal symptoms score than fexofenadine after single administration. Br J Clin Pharmacol 2005; 60( 1): 24 – 31. doi: 10.1111 / j. 1365-2125. 2005.02377. x
16
Commins S. Omalizumab reduces food allergy symptoms in patients with Alpha-gal syndrome( abstract AB145). J Allergy Clin Immunol2020; 145( 2 suppl): AB145.
17
Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice guidelines by the Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology: 2020 guidelines for the prevention, diagnosis, and treatment of Lyme disease [ published correction appears in Neurology 2021; 96( 6): 296 ]. Neurology 2021; 96( 6): 262-273. doi: 10.1212 / WNL. 0000000000011151
18
Commins SP, James HR, Kelly LA, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharidegalactose-a-1,3-galactose. J Allergy Clin Immunol 2011; 127( 5): 1286 1293e6. doi: 10.1016 / j. jaci. 2011.02.019
19
Crispell G, Commins SP, Archer-Hartman SA, et al. Discovery of alpha-gal-containing antigens in North American tick species believed to induce red meat allergy. Front Immunol 2019; 10:1056. doi: 10.3389 / fi mmu. 2019.01056
Dr. Saleem is working as a general practitioner at a community hospital in Pakistan and will be applying for the Internal Medicine Residency Match 2027.( non-member)
Dr. Lippman is an emeritus professor of psychiatry at UofL and currently practices primary care medicine at Louisville’ s Family Community Clinic.
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