A 5 y.o. girl presents to the adult ED by mistake. Her complaint is severe abdominal pain
Her mother gives the history and says for four months she co pain after eating and wakes up at night screaming with abdominal pain. Currently she has no pain. She has had three negative CTs at outside hospitals. She is given a screening evaluation and sent to Children’s where she got another CT.
The CT was normal. What could be wrong?
Our patient was positive for alpha-gal antibodies. She had a mammalian meat allergy which can cause IgE mediated allergic reactions after eating meat. The presentation can include rashes, wheezing or in many cases, just abdominal pain.
This allergic reaction is to a carbohydrate called galactose-alpha-1,3 galactose. It is found in most mammals but not in humans who have lost the GGTA1 gene and develop an immune response when exposed to alpha -gal. It is caused by exposure to to tick bites,, When the tick bites, it transfers alpha-gal to the bloodstream in its saliva. . It presents a different sort of IgE mediated allergic reaction and often is not immediate. It can be delayed up to 8 hours making it difficult to diagnose. The lone star tick is pictured below.
Interestingly, the association between the allergy and red meat was discovered by oncologists using cetuximab to treat metastatic colon cancer. They found severe anaphylactic reactions in some individuals exposed to cetuximab for the first time. This was only reported in southern states and was found to correlate with the distribution of the lone star tick. It was found that cetuximab contains alpha-gal and patients who had previously been exposed to tick saliva developed severe allergic reactions. The distribution of alpha-gal syndrome is shown below.
FUN FACT:
The structure of antigen B (B blood type) is very similar to alpha-gal and individuals with B blood type have a reduced immune response to alpha-gal probably because of constant exposure. Unfortunately this means when exposed to Infectious diseases with alpha-gal epitopes, those with B blood type do not mount a significant antibody response. Diseases with alpha-gal on the surface include malaria and tuberculosis. It has been postulated that individuals with B blood type would be more susceptible to these diseases because they do not mount a strong immune response.
Our patient underwent endoscopy in addition to her normal CT. This was normal and she was given an enema and discharged. Following discharge her alpha-gal IgE titers returned at 10.10.
She was advised to avoid beef, pork, lamb and dairy. Alpha-gal anaphylaxis has been reported with vaccines and other products which contain gelatin. This includes antivenoms, and multiple vaccines(MMR, yellow fever, rabies and shingles ) There are reports of bovine and porcine valves causing allergic reactions as well.
FUTURE RESEARCH
The first recommendation for treatment of alpha-gal syndrome is dietary restriction. Omalizumab has been studies as a way to reduce food allergy symptoms. In one study 12 of 14 patients were able to eat dairy without symptoms.
The diagnosis remains mostly clinical. It is difficult to tell if someone who has been sensitized(; as evidenced by IgE levels to alpha-gal in the blood) will actually be symptomatic. The IgE antibodies to alpha-gal can rise in response to bee stings or parasites. Other tests are being developed including basophil cell activation, mast cell activation and histamine release.
Commins S. Omalizumab reduces food allergy symptoms in patients with alpha-gal syndrome. The Journal of Allergy and clinical Immunology 2020 Vol 145(2) 468.
Vaz-rodrigues R, Mazuecos L, de la Fuente J. current and future strategies for the diagnosis and treatment of the alpha-gal syndrome (AGS). J Asthma Allergy 2022;15:957-970.
Cabezas-Cruz A, Mateos-Hernandez L, Alberdi P, et al. Effect of blood type on anti-alpha-gal immunity and the incidence of infectious diseases. Exp Mol Med 2017 Mar;49(3):e301.
Macdougall J, Thomas K, Iweala O. The meat of the matter: understnading and managing alpha=gal syndrome. Immunotargets Ther 2022;11:37-54.
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