Intrinsic risk factors may trigger alpha-gal syndrome
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Key takeaways:
- Patients with alpha-gal syndrome reported a history of childhood allergies.
- Family history is a significant risk factor in alpha-gal syndrome development.
Intrinsic factors such as blood type, medical history, allergies and family history contribute to the risk for developing alpha-gal syndrome, according to a study published in Annals of Allergy, Asthma & Immunology.
“This study is a follow-up to a 2023 CDC publication on alpha-gal syndrome (AGS) that found patients who were diagnosed with AGS were more likely to recall finding a tick on themselves, live near a wooded forest, and spend more time outdoors compared to patients who visited nearby clinics and were not diagnosed with AGS,” Marissa Taylor, MPH, leading author and epidemiologist in the Rickettsial Zoonoses Branch with CDC’s Division of Vector-Borne Diseases, told Healio.
This newer study looked at additional risk factors that could make patients more likely to develop AGS in a patient group in North Carolina. It is the first analysis of risk factors using case-control data.
“The study showed that people with AGS were more likely to report large marks or welts and/or longer healing times for insect bites or stings and childhood allergies when compared to patients who were not diagnosed with AGS (control patients),” Taylor said. “Antibody testing found that patients with AGS had IgE antibodies to a broad array of allergens.”
The study also showed that family history was significant in the risk associated with AGS development.
“Though we cannot say definitively that these factors are directly contributing to AGS risk, we found that people diagnosed with AGS were more likely to have a family member (parents, siblings and children related by blood) who were also diagnosed with AGS, had another food allergy and/or had an allergy to stinging or biting insects,” Taylor said.
Study design
Participants aged at least 18 years were enrolled between 2019 and 2020. Case patients enrolled at a university clinic in North Carolina presented with AGS and were required to have clinical symptoms consistent with AGS. They were not required to have laboratory confirmed AGS. Control patients enrolled in two nearby internal medicine clinics were required to have no AGS diagnosis or symptoms.
Blood taken on the first day of enrollment was tested using ABO reverse grouping reference cells which included type and Rh factor. Allergy testing measured specific IgE antibodies to alpha-gal, cow’s milk, stinging insects (fire ant, honey bee, paper wasp, white-faced hornet, yellow jacket), mosquito, chicken, turkey, codfish and cat serum albumin.
Data including demographic information, medical history, reported history of tick or chigger bites, allergy history and AGS history were collected from questionnaire forms and entered into a REDCap database. Patients were also asked about dietary history and family history of allergies (including AGS). Case patients were also asked about exposure to alpha-gal containing products, AGS reactions, time from exposure to symptom onset, time of day symptoms occurred and factors contributing to severity.
Study findings
The 81 case patients were older (median age, 58.5 years vs. 54 years) and less racially diverse (88% vs. 79% white) than the 191 control patients. Case vs. control patients also had higher education and income backgrounds. While all control patients lived in North Carolina, only 70% of case patients lived there.
Only 4% of case patients had blood type B compared with 11% of controls. Further, case patients were less likely than controls to have a B-antigen blood type (10% vs. 22%; OR = 0.4; 95% CI, 0.18-0.88).
The researchers also found that white case patients were less likely than white control patients to have B-antigen blood types (OR = 0.39; 95% CI, 0.15-0.9), but there was no difference between Black case patients and control patients.
Case patients were less likely to report hypertension (OR = 0.51; 95% CI, 0.29-0.88), type 2 diabetes (OR = 0.43; 95% CI, 0.18-1.06), heart disease/attack (OR = 0.5; 95% CI, 0.16-1.33), and asthma (OR = 0.55; 95% CI, 0.22-1.37). Case patients also were more likely to report vitamin D deficiency (OR = 1.89; 95% CI, 1.02-3.51.)
Compared with control patients, case patients reported larger marks and welts and longer healing times when stung by an insect (OR = 3.14; 95% CI, 1.81-5.47).
Other risk factors included childhood allergies that have since gone away (OR = 1.99; 95% CI, 1.02-3.89), food allergies other than to red meat (OR = 1.88; 95% CI, 0.99-3.56), allergic reactions that required medical care (OR = 1.93; 95% CI, 0.97-3.82) and anaphylaxis (OR = 1.87; 95% CI, 0.96-3.64).
Almost all case patients (98%) and a third (33%) of the control patients had positive alpha-gal specific IgE results.
Also, there was a greater likelihood of a history of family food allergy (OR = 2.70; 95% CI, 1.47-4.98), allergy to stinging or biting insects (OR = 2.44; 95% CI, 1.35-4.42) and alpha-gal allergy to red meat (OR = 8.33; 95% CI, 2.99-27.38) among case vs. control patients.
Among case patients, the most common organ system reactions were gastrointestinal, including abdominal pain/cramping (74%), and mucocutaneous, including hives (72%). As far as specific foods, case patients most commonly reacted to beef (97%) and dairy (61%) after ingestion.
Discussion
Healio asked Taylor about how the findings of this study can help health care providers better screen patients for AGS.
“Health care providers should consider AGS in patients with other allergies, sensitivity to insect bites and/or a history of childhood allergies,” Taylor said.
“Family history also should be taken when evaluating for AGS,” she continued. “Our study affirmed findings from previous studies that people with A or O blood types may be at higher risk of developing AGS than those with AB or B blood types.”
Taylor also emphasized that the study can be used for AGS patients who are looking for more information on how different foods and medical products can be tolerated.