Diagnostic certainty after investigation of perioperative hypersensitivity: a retrospective cohort analysis

Perioperative hypersensitivity is uniquely challenging to investigate, with multiple differential diagnoses, poor validation of routinely available tests, and highly restricted access to the gold standard of provocation testing. Collectively, these limitations can result in diagnostic uncertainty, exposing patients to the risk of future reactions and potentially harmful avoidance of safe drugs. We therefore sought to systematically evaluate diagnostic certainty among a large cohort of patients investigated for suspected perioperative hypersensitivity reactions.

We conducted a retrospective cohort analysis of adult patients referred to the Yorkshire Perioperative Hypersensitivity Reactions clinic, UK, between January 2012 and March 2025. A five-point scoring system was used to define diagnostic certainty, with one point each for more than two clinical features suggestive of hypersensitivity, drug administered within 15 min of reaction, mast cell tryptase rise, positive skin test, and other causal drugs excluded.

Among 565 patients, 407 (72%) were confirmed to have suffered a hypersensitivity reaction to a culprit drug. Within this group, 116 (29%) achieved the highest score for diagnostic certainty (5/5), whereas the remaining 291 (71%) received a less certain diagnosis. Uncertainty typically resulted from absence of a confirmed mast cell tryptase rise or lack of congruent skin tests.

Limitations in the investigative pathway of suspected perioperative hypersensitivity result in diagnostic uncertainty for a substantial proportion of patients. This uncertainty is a source of potential harm. Further research is required to determine how the diagnostic pathway for this patient group can be improved.