Kounis syndrome describes acute coronary syndrome (ACS) triggered by allergic reactions through mast cell activation. Although typically linked with anaphylaxis, ACS events related to mild or subclinical allergic responses may remain unrecognized. A prospective observational study published in Scientific Reports assessed immune markers and autonomic nervous system activity to characterize allergy-associated ACS occurring without anaphylactic manifestations.

Among 375 patients treated for ACS between April 2022 and March 2024, 49 were prospectively enrolled for detailed evaluation. Patients were categorized as non–allergy-associated ACS (ACS-NA; n = 32) or allergy-associated ACS (ACS-AL; n = 17). The ACS-AL group included patients without anaphylaxis (ACS-AL[nonA]; n = 11) and those with anaphylaxis (ACS-AL[withA]; n = 6).

Allergic status was assessed, and serum immunoglobulin E (IgE) and plasma histamine levels were measured at ACS onset. Autonomic nervous system activity was evaluated using heart rate variability parameters obtained from 24-hour ambulatory monitoring within one week after percutaneous coronary intervention.

Both ACS-AL subgroups showed significantly higher IgE and histamine levels than the ACS-NA group (P<0.05), with overlapping distributions. Heart rate variability analysis demonstrated higher LF/HF ratios and reduced daytime HF components in ACS-AL groups, indicating sympathetic predominance. 

Allergy-associated ACS without anaphylaxis was characterized by immune activation and autonomic imbalance. Combined assessment of IgE, histamine, and HRV parameters may aid recognition of this phenotype.