Angiotensin-converting enzyme inhibitor-induced angioedema: Proposal for a diagnostic score

Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema (AE-ACEI) may be life-threatening, and the treatment should therefore be discontinued. However, patients taking ACEI may also have mast cell-mediated angioedema (AE-MC). Differentiating between AE-ACEI and AE-MC in patients taking ACEI is sometimes difficult. We propose to identify the factors associated with the diagnosis of AE-ACEI in patients.

A multicenter retrospective study was carried out at Grenoble Alpes University Hospital and University Hospital of La Réunion. All patients referred for suspected diagnosis of AE-ACEI were included in the study between January 2019 and January 2022. The final diagnosis was made by the expert physician after a minimum follow-up of 1 year and after a biological work-up ruling other bradykinin-mediated angioedema.

A total of 93 patients were analyzed, 49 with a final diagnosis of AE-ACEI and 44 with a diagnosis of AE-MC. Multivariate analysis identified 4 factors associated with the final diagnosis of AE-ACEI: number of AE between the introduction of ACEI and the consultation ≤3 (OR: 7.93 [1.60-50.7], p = 0.017) (1 point), duration of AE strictly greater than 24 h regardless of the treatments administered (OR: 8.41[2.07-44.5], p < 0.01) (1 point), hospitalization in intensive care unit (OR: 7.14[1.19-50.0], p = 0.045) (1 point) and no recurrence of AE after stopping ACEI, regardless of the delay (OR: 16.7[3.37-125], p < 0.01) (2 points).This five-point diagnostic score (AUC: 0.85 [0.75-0.95]) identifies patients with a low probability of AE-ACEI when the score is 0-2 (sensitivity: 0.93, specificity: 0.35) and a high probability when it is between 4 and 5 (sensitivity: 0.53, specificity: 0.97).

After a consultation in an angioedema expert center, the diagnosis of AE-ACEI has been excluded in almost half the patients. We identified a five-point score that could help in the diagnosis of AE-ACEI and in the decision to contraindicate the use of ACE inhibitors for life.