Alpha-gal syndrome testing increases but positive test proportions remain stable
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Key takeaways:
- The number of sent tests in Nashville increased from eight in 2013 to 185 in 2021.
- 54% of cases were confirmed as alpha-gal syndrome.
- The mean annual proportion of confirmed cases was 0.59 cases per test sent.
The number of patients tested for alpha-gal syndrome increased across middle Tennessee from 2013 to 2022, but the proportion of confirmed cases remained stable, according to a letter published in Annals of Allergy, Asthma & Immunology.
These increases corresponded with increases in awareness of alpha-gal syndrome, Kevin Liu, MD, MPH, division of general internal medicine and public health, Vanderbilt University Medical Center, and colleagues wrote.
The study reviewed 757 patients evaluated for alpha-gal syndrome in a hospital system in Nashville, Tennessee, between 2013 and 2022, based on Council of State and Territorial Epidemiologists (CSTE) discussions to focus on high-pretest probability patients with suspected tick exposure.
These patients either had received an alpha-gal specific-IgE (sIgE) test or had ICD-10 diagnoses of an unspecified allergy; other food allergy; other galactose metabolism disorder; or a bite or sting by a nonvenomous insect or other nonvenomous arthropod.
Clinical criteria via the CSTE include the acute onset of one or more allergic and gastrointestinal symptoms within 2 to 10 hours of ingesting mammalian meat or mammalian-derived meat products or within 2 hours after receiving intramuscular, intravenous or subcutaneous vaccination or medication that includes alpha-gal, in addition to having no clear alternative diagnosis.
The cohort included 409 (54%) with confirmed alpha-gal syndrome, meeting both clinical and confirmatory laboratory testing; 343 (45.3%) who were classified as non-cases of alpha-gal syndrome; one case classified as probable alpha-gal syndrome, since it met clinical criteria and presumptive laboratory evidence; and four suspect cases that had confirmatory laboratory evidence but no clinical information.
Confirmed cases were classified based on symptomatic severity, including anaphylaxis, hives/swelling/cutaneous itching, or gastrointestinal symptoms only.
There were 305 patients (40.3%) who recalled a tick bite before the onset of symptoms, and 71.2% of these patients had confirmed alpha-gal syndrome, making up 53.8% of the confirmed case population.
Male sex, known tick bite, white ethnicity, and anaphylaxis were associated with confirmed alpha-gal syndrome.
As awareness of alpha-gal syndrome grew among patients and providers between 2013 and 2022, the researchers said, so did testing, which increased from eight tests sent in 2013 to 185 tests sent in 2021.
But despite these increases, the mean annual proportion of confirmed cases remained stable at 0.59 cases per test sent for the full study period. The proportion of positive test results remained stable during the study period as well.
Median concentrations of sIgE varied across age ranges without any clear associations, the researchers continued. The most common symptom was urticaria and hives among all tested patients (57.2%), confirmed cases (58.2%) and non-cases (56%).
Patients aged 30 to 49 years, however, most often experienced abdominal pain. Also, 26.4% (n = 108) of confirmed cases and 15.5% (n = 63) of non-cases reported anaphylaxis. Males overall had higher median sIgE concentrations than women across all three symptom phenotypes:
- anaphylaxis: 5.35 kU/L (95% CI, 1.56-14.1) for men and 4.72 kU/L (95% CI, 1.04-15.85) for women;
- urticaria/angioedema/itching: 3.52 kU/L (95% CI, 1.15-17.6) for men and 2.64 kU/L (95% CI, 0.93-13.68) for women; and
- gastrointestinal symptoms only: 1.9 kU/L (95% CI, 0.6-7.12) for men and 1.6 kU/L (0.61-7.98) for women.
The researchers further noted a possible trend toward increases in alpha-gal sIgE levels with age across all three phenotypes. Overall median concentrations of alpha-gal sIgE included:
- anaphylaxis: 5.35 kU/L (95% CI, 1.24-15.6);
- urticaria/angioedema: 3.18 kU/L (95% CI, 1.1-14.9);
- gastrointestinal symptoms only: 1.66 kU/L (95% CI, 0.6-7.9).
Based on these results, the researchers said, alpha-gal sIgE concentration and severity may be related, whereas other factors may be involved in the overt presentation of symptoms once sensitization to alpha-gal has occurred.
Additionally, the researchers said, patients with urticaria/angioedema/itching were more likely to be in the group with negative tests, indicating that urticaria symptoms may not be a specific indicator of alpha-gal syndrome.
The researchers also said these findings indicate that providers are correctly homing in on key features of alpha-gal syndrome, whereas other clinical scenarios such as urticaria and angioedema may resemble alpha-gal syndrome enough to prompt testing.
By using an alpha-gal case definition, the researchers concluded, they found increasing incidence of confirmed alpha-gal cases in middle Tennessee while awareness of the disease was increasing as well.
Perspective
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One significant finding is that the proportion of tests sent leading to a “confirmed” diagnosis was stable (50% to 60%) over the previous years. It is just that testing is becoming more frequent. To me, this suggests we are increasing awareness of a condition that has probably been present for a long time, and we are picking it up more now because of awareness and because we are testing more for it.
However, I do not think that the gender and race findings are really that significant, as I think they are simply based on the population tested and indications. Also, the speculation or hypothesis that a higher IgE level for alpha-gal may be associated with more severe reactions is intriguing, but I do not think this study is enough to support that notion at all.
Overall, these findings are in line with our experience and what is seen in the literature in general. They show that tick bites are the part of the history that probably is most indicative of alpha-gal allergy rather than the demographics of the patient or the symptoms on presentation.
Continuing to increase knowledge about the condition so we test the correct people is probably the best message from this study. For example, the authors show that testing someone for recurrent hives probably does not have very high yields in diagnosing alpha-gal allergy. Rather, taking a good history regarding food triggers (if any) and the timing of symptoms after ingestion, as well as using a history of tick-bite exposure, are probably the most important things in predicting whether the patient is likely to have alpha-gal allergy.
Finally, regarding epidemiology, in a perfect world, we would have a national registry and have challenge-proven diagnosis to really understand the epidemiology of alpha-gal allergy.
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