When C1 Is Normal: Managing Rare Bradykinin-Mediated Angioedema

In this episode, Dr. Thomas Buttgereit welcomes Dr. Efrem Eren, immunologist and allergy specialist from the University of Southampton, to discuss practical approaches to diagnosing and treating patients with recurrent angioedema, especially those with normal C1 inhibitor values. They discuss:🔹 How can physicians distinguish histamine- vs. bradykinin-mediated angioedema?  🔹 Why do some patients develop angioedema years after starting ACE inhibitors?  🔹 How can icatibant be used not only as treatment but also as a diagnostic tool?  🔹 What options exist for long-term prophylaxis when standard therapies fail? Dr. Eren shares his clinical framework for approaching difficult cases, including the value of patient education, treatment trials with tranexamic acid or omalizumab, and the growing role of icatibant and kallikrein inhibitors. He also highlights a moving patient story that demonstrates the life-changing impact of correct diagnosis and targeted therapy. Join us for this insightful discussion on how to navigate diagnostic uncertainty, choose treatment strategies, and improve patient outcomes in rare forms of angioedema. Key Learnings from the Episode:Categorization is key: Angioedema can often be grouped into histamine-mediated, mast-cell–bradykinin–mediated, or bradykinin-mediated causes. Diagnostic limitations: Laboratory tools are scarce; bradykinin measurement is not routinely available. Diagnosis often relies on clinical features and treatment response. ACE inhibitor angioedema can appear years after therapy initiation, often requiring a “second hit” to trigger. Treatment trials help guide diagnosis: High-dose antihistamines → mast-cell mediated Steroid responsiveness → mast-cell involvement Omalizumab → effective in some mast-cell angioedema cases Icatibant → valuable for suspected bradykinin-mediated angioedema (also used diagnostically) Tranexamic acid can be effective for some patients with angioedema linked to mast cells. C1 inhibitor concentrate is ineffective in patients with normal C1 levels and function. Patient burden is high, including anxiety, frequent hospital admissions, and restrictions in daily life. Case story: A teenager with unexplained recurrent angioedema gained her independence and normal life back after diagnosis and treatment with icatibant and kallikrein inhibition. Prophylaxis: Kallikrein inhibitors like berotralstat can be used in select patients; responses are typically evaluated over at least 3 months. Objective evidence (photos, symptom scores) is essential for diagnosis and evaluating treatment response. Chapters:00:00 Introduction to Angioedema and Its Challenges02:48 Understanding Angioedema: Types and Diagnosis07:13 Treatment Approaches for Angioedema12:22 Patient Experiences and Impact of Angioedema15:35 Prophylactic Treatments and Future DirectionsDo you have suggestions for future episodes? Please provide feedback and offer your suggestions for future topics and expert selection here.Feedback form ATA: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://forms.office.com/e/ZWxx3D4Cmr⁠⁠