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The diagnosis of anaphylaxis can be tricky, especially in the absence of known triggers and when other conditions, such as urticaria and asthma, mimic aspects of the reaction. Biomarkers can help to identify this deadly condition promptly. But only histamine and tryptase have been extensively studied.
Tryptase is the most frequently used biomarker for diagnosing anaphylaxis, but it is not the most reliable in minimizing false-positive or negative results. A more accurate approach to using tryptase requires clinicians to have the patient’s baseline level on hand, according to a new systematic review published in The Journal of Allergy and Clinical Immunology.
“There are so many other biomarkers that could maybe help us diagnose anaphylaxis with better accuracy,” said Roy Khalaf, MD, a resident in the Faculty of Medicine at McGill University in Montreal, Quebec, Canada, and a lead author of the study.
Khalaf and his colleagues analyzed 28 studies published over a 20-year period starting in 2004 on biomarkers of anaphylaxis, with a sample of more than 18,000 patients, 3329 of whom had confirmed anaphylaxis. While tryptase was the most studied biomarker, its ability to correctly identify patients who have the disease, or sensitivity, was suboptimal at 0.49. However, its specificity, or ability to identify those who did not have the disease, was 0.82. When a baseline level of tryptase was compared with a level drawn during anaphylaxis, the sensitivity improved to 0.78. Many patients do not have their baseline levels unless they have seen an allergist.
One study indicated that combining histamine with tryptase boosted the sensitivity to 0.93. Histamine alone showed higher sensitivity (0.76) but lower specificity (0.69). The use of histamine is also limited by its short half-life of about 15 minutes.
One study in the review of a rarely used biomarker, platelet-activating factor (PAF), showed great promise (sensitivity, 100%), but Khalaf said more data are needed before the test can be used clinically. Limited data on PAF acetylhydrolase and urinary prostaglandin D2 were available.
Urinary prostaglandin D2 has shown promise, but “there may be practical challenges in obtaining urine samples from patients experiencing life-threatening reactions,” Khalaf and his colleagues wrote.
Inflammatory chemicals like tryptase and prostaglandins are triggered by a reaction caused by allergens or environmental factors like exercise. These mediators can cause vasodilation, smooth muscle contraction, and increased vascular permeability, resulting in bronchoconstriction, airway swelling, and death. If found early, anaphylaxis can be reversed with the use of epinephrine.
“If you already have a confirmed diagnosis of anaphylaxis, you can anticipate the next reaction and act appropriately,” Khalaf told Medscape Medical News.
Establishing a definitive diagnosis is instrumental to preventing another occurrence. Khalaf said he hopes more clinicians, especially in emergency settings, will test for biomarkers to confirm anaphylaxis, especially in diagnostically challenging situations or when a clinician is unfamiliar with the condition. Patients with anaphylaxis must be monitored for a few hours after the event to prevent a flare-up of the condition.
Patients with confirmed anaphylaxis should also receive a prescription for an epinephrine auto-injector. Clinicians should also make a referral to an allergist to determine triggers, especially considering epinephrine auto-injectors can be costly, said Jason Caldwell, DO, an allergy and immunology specialist at the Medical University of South Carolina in Charleston, South Carolina. Additionally, allergists routinely order biomarker tests.
While tryptase and histamine are readily available, the other biomarkers are largely only accessible in urban hospital settings, Caldwell said. Tryptase sensitivity is enhanced when a clinician knows baseline levels, but few patients have this information when they arrive at the emergency department. Primary care clinicians and pediatricians generally do not order these tests for patients with allergies who have not had the reaction.
With more comprehensive studies, researchers could establish protocols and improve patient outcomes, Khalaf said.
Clinicians also need new biomarkers because those currently available do not cover every trigger, Caldwell said.
“We are still not capturing all anaphylactic cases with the biomarkers we currently use,” he said.
The authors of the review reported no relevant financial disclosures.
Vivien Fellegi, MD, is a freelance medical writer and a retired family medicine physician.
