Angioedema is a distressing condition, mainly studied in specialized care. With only one survey-based study estimating a 7.4% lifetime prevalence 1, the true occurrence in the general population remains unclear. Differentiating between subtypes (mast cell-mediated, bradykinin-mediated, angiotensin-converting enzyme inhibitors (ACEI) induced) is crucial for appropriate treatment, yet at first presentation this is often challenging. In primary care, distinguishing laboratory tests are rarely performed and management is typically pragmatic, starting with antihistamines and discontinuing ACEI when used 2, 3. While ACEIs are a well-known cause 2, their contribution in individual cases remains uncertain since there is no diagnostic test to confirm ACEI causality. In the Netherlands, all citizens are initially managed by their general practitioner (GP), making primary care data suitable to study angioedema in the general population. We investigated angioedema prevalence, disease course and its relation to ACEI usage in a representative Dutch GP population using the Julius General Practitioner Network database (N = ±450,000) 4. All patients registered with angioedema between 2010 and 2020 were selected, excluding patients with concomitant urticaria (n = 179). As mechanistic subtypes of angioedema are typically not distinguished in primary care, no such distinction was made. All angioedema-related contacts (including emergency department presentations), prescriptions for angioedema, and ACEI were analyzed. Angioedema was diagnosed in 951 patients (59.7% females; mean age 44 years), with an annual point prevalence of 0.04%–0.06% for angioedema for which patients sought care from their GP (Table 1). While 49% (n = 465) had a single angioedema-related contact, 51% (n = 486) had multiple contacts (median 3 2–6) over a median of 39 4–153 weeks of angioedema-related follow-up. The latter group more often received prophylactic antihistamine treatment (64% vs. 47%, p < 0.001) and prednisolone/epinephrine (34% vs. 19%, p < 0.001), suggesting more frequent and/or severe disease compared to those with one contact and reflecting primary care management. ACEI were prescribed to 273 angioedema patients (29%). We analyzed 208 patients with angioedema onset and ACEI prescription initiated ≥ 2 years before data lock to analyze its impact on angioedema-related care. Of these, 38% (n = 80/208) continued ACEI and 15% (n = 32/208) initiated ACEI after angioedema onset (Figure 1). Interestingly, patients who continued ACEI despite angioedema had a median of one angioedema-related contact and short follow-up (< 1 week), not more than patients who discontinued ACEI directly (n = 75/208) or delayed (n = 21/208, Figure 1), suggesting that ACEI continuation did not increase angioedema-related healthcare use in these patients. Among patients initiating ACEI after angioedema onset, 9% (n = 19/208) received their first ACEI after their final angioedema consultation, with fewer angioedema-related consultations and shorter follow-up compared to patients who discontinued before (n = 7/208) or continued after the final angioedema consultation (n = 6/208, Figure 1), indicating that prior angioedema may not always be a contraindication for ACEI treatment. Altogether, among 208 ACEI users, 38% initiated ACEI before angioedema onset and continued it, and 9% initiated ACEIs despite prior angioedema, accounting for 47% who remained on ACEI without further angioedema-related care, reflecting a different underlying cause. Nevertheless, ACEI-induced angioedema warrants careful consideration due to potential airway obstruction 5. In our study, 10% (n = 21/208) received a final ACEI after angioedema onset and discontinued before the last angioedema-related contact. These patients had significantly more angioedema-related contacts, longer follow-up, and more prednisolone/epinephrine prescriptions than those who discontinued directly or continued despite it (Figure 1), suggesting more severe angioedema, leading to discontinuation. This study was limited to GP-recorded data, without information on specialist referrals or self-managed symptoms, possibly leading to underestimation of the point prevalence and incomplete capture of the recurrence of angioedema after ACEI continuation. In conclusion, this large population-based study presented a point prevalence of 0.04%–0.06% for angioedema managed in primary care, with a short and mild course in half of patients. Notably, 47% of ACEI users continued or initiated treatment despite angioedema, with minimal further angioedema-related care recorded. Given the absence of a diagnostic test to confirm ACEI causality, our findings suggest that a tailored approach to ACEI management, considering angioedema timing and severity, and cardiovascular benefit, may be worth considering in primary care. The authors have nothing to report. A.C.K.: None, in relation to this work. A.C.K. received institutional sponsoring for research or consultancy from: ALK, Thermofisher, Nutricia/Danone, DBV technologies, Novartis, EUROIMMUN, Stallergenes Greer. H.R. received institutional sponsoring for Research, consultancy or speakers fee outside the submitted work from Pharming and Novartis Pharma, Sanofi, Third Harmonic Bio, Abbvie, Leo Pharma. J.M.P.A.R. carried out clinical trials for AbbVie, Celgene, Almirall, and Janssen and has received speaking fees/attended advisory boards from Zoetis, AbbVie, Janssen, BMS, Almirall, LEO Pharma, Novartis, UCB and Eli Lilly and reimbursement for attending or chairing a symposium from Janssen, Pfizer, Celgene and AbbVie. All funding is not personal but goes to the independent research fund of the department of dermatology of Radboudumc Nijmegen, the Netherlands. I.A.M.G., N.B.-B., R.S., and S.A. have no conflicts of interest to disclose. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Soegiharto et al. (Mon,) studied this question.