In this episode, Dr. Thomas Buttgereit welcomes Dr. Alexis Bocquet from the French National Center for Angioedema in Grenoble to discuss one of the most challenging forms of drug-induced angioedema — ACE inhibitor–induced angioedema.
They discuss
🔹 Why are ACE inhibitors among the most prescribed cardiovascular drugs worldwide?
🔹 How can physicians distinguish bradykinin-mediated from mast-cell-mediated angioedema?
🔹 What are the key risk factors for developing ACE inhibitor–induced angioedema?
🔹 How can the new diagnostic core support clinicians in practice?
Dr. Bocquet shares findings from a French multicenter study conducted in Grenoble and Réunion Island, where he and his colleagues identified four clinical criteria that accurately differentiate ACE inhibitor–induced angioedema from other forms. He also explains the score they developed — a five-point tool that predicts diagnosis with more than 90% accuracy — and offers practical advice on treatment, including when to use icatibant or C1 inhibitor concentrate in acute care.
Join us for a scientifically rich and practical conversation on how to diagnose and manage one of the most life-threatening but underrecognized types of angioedema.
Key Learnings from the Epesode:
ACE inhibitors are widely used for heart failure, hypertension, and kidney protection but can rarely cause bradykinin-mediated angioedema.
The pathophysiology involves inhibition of bradykinin degradation, leading to increased vascular permeability and swelling.
Risk factors include age over 65, female sex, African or Afro-Caribbean ethnicity, concomitant use of NSAIDs, smoking, cardiovascular comorbidities, and genetic variants in bradykinin receptor B2 or aminopeptidase N.
In a French bicenter study (Grenoble & Réunion Island, 2019–2022), 126 patients were evaluated for angioedema without hives; 49 were confirmed as ACE inhibitor–induced, and 44 as mast cell-mediated.
The four diagnostic factors identified were:
No relapse after discontinuation of ACE inhibitor
Attack duration longer than 24 hours
Hospitalization in intensive care
Fewer than three previous angioedema attacks
These factors formed the five-point score:
0–2 points → Likely mast cell angioedema
4–5 points → >90% probability of ACE inhibitor–induced angioedema
Persistent angioedema after stopping ACE inhibitors usually indicates mast- cell-mediated angioedema or CSU, not ACE inhibitor–induced angioedema.
Genetic testing may help rule out hereditary angioedema with normal C1 inhibitor.
Tranexamic acid shows little benefit in ACE inhibitor–induced angioedema.
Treatment recommendations:
Icatibant is first-line off-label therapy with rapid efficacy.
C1 inhibitor concentrate is an effective alternative.
Both are off-label but justified in life-threatening upper-airway cases.
The team plans a national prospective validation of the diagnostic Score for ACE inhibitor-induced anigoedema across France in 2025.
Chapters:
00:00 Introduction to ACE Inhibitor Induced Angioedema
03:31 Understanding ACE Inhibitors and Their Benefits
06:00 Pathophysiology and Risk Factors of Angioedema
09:02 Research Insights from CRIAC and Study Design
11:30 Clinical Features and Diagnosis of Angioedema
14:01 Proposed Diagnostic Score for Angioedema
16:40 Treatment Options for ACE Inhibitor Induced Angioedema
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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 Challenges
02:48 Understanding Angioedema: Types and Diagnosis
07:13 Treatment Approaches for Angioedema
12:22 Patient Experiences and Impact of Angioedema
15:35 Prophylactic Treatments and Future Directions
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In this episode, Thomas welcomes Dr. Riccardo Senter, allergist at the University Hospital of Padova and member of the ITACA Network, to discuss the impact of COVID-19 on patients with bradykinin-mediated angioedema — including both hereditary and acquired C1 inhibitor deficiency forms.
They discuss:
🔹 How did COVID-19 affect angioedema severity, hospitalization rates, and recovery?
🔹 What does new data from the pan-Italian ITACA registry reveal about patient outcomes?
🔹 How do hereditary and acquired angioedema differ in their response to coronavirus infection?
🔹 What role do patient registries and research networks play in supporting rare disease care?
Dr. Senter presents survey data from 15 Italian centers, detailing age, sex, disease severity, and COVID-19 outcomes for 52 angioedema patients treated in early 2021. He explains the differences between hereditary and acquired forms, why registries like ITACA are crucial for building robust knowledge, and how collaboration supports better care for rare disease patients.
Join us for an insightful discussion on the realities of COVID-19 in angioedema patients — and how international research efforts can drive advancements in diagnosis, management, and patient support.
Key Learnings from the Episode:
COVID-19 did not lead to increased mortality in angioedema patients; no deaths occurred in the surveyed group.
8% of hereditary angioedema patients had severe COVID-19 requiring hospitalization, but all recovered.
Acquired angioedema patients, despite older age, did not experience severe COVID-19 or complications.
The ITACA network enabled collecting robust data across many centers, highlighting the role of registries in rare disease research.
The distinction between hereditary (genetic deficiency) and acquired (secondary to other diseases like lymphoma) C1 inhibitor deficiency is crucial for clinicians and patients.
Collaborative networks and standardized registries improve care and understanding of rare angioedema forms during pandemics.
Chapters
00:00 Introduction to Angioedema and COVID-19
03:35 Understanding HAE and Acquired Angioedema
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In this episode, Thomas welcomes Dr. Mar Guilarte, allergist at Hospital Universitari Vall d’Hebron in Barcelona, to explore an often overlooked topic in HAE care: prodromal signs — the early symptoms that may signal an HAE attack.
They discuss:
🔹 What are prodromal signs, and how common are they in HAE patients?
🔹 Do patients treat their attacks differently based on these signs?
🔹 How do UK and Spanish patients compare in their treatment decisions?
🔹 Could biomarkers help us distinguish true HAE prodromes?
Dr. Guilarte shares findings from her recent research, conducted with HAE patient groups in the UK and Spain, and discusses how early treatment can shorten attack duration and severity. She also explains how signs like erythema marginatum, abdominal discomfort, irritability, and fatigue vary across patients — and why clear definitions, education, and better diagnostic tools are urgently needed.
Join us for a thought-provoking discussion on the complexity of HAE prodromes — and how understanding them better can help optimize treatment and outcomes.
Key Learnings from the Episode:
Prodromes are early signs or symptoms that precede HAE attacks — up to 60–80% of patients report them.
Common prodromal symptoms include erythema marginatum, bloating, nausea, abdominal discomfort, irritability, and fatigue.
Each patient tends to have consistent prodromes, which can help predict attacks, though subjective symptoms vary widely.
Spanish patients tend to treat later than UK patients, possibly due to less specialist guidance or medication access.
Treating attacks early reduces duration and severity, but definitions of “early” vary — especially with injectable medications.
Oral on-demand therapies may encourage earlier intervention, as they’re easier to carry and administer.
Not all prodromes lead to attacks, and the severity of a prodrome does not always predict the severity of the attack.
There is a need for biomarkers to help determine whether a prodrome will be followed by an actual HAE attack.
Erythema marginatum is the only objective prodrome, but can be confused with urticaria, leading to misdiagnosis.
Education of both patients and physicians is critical to recognizing and acting on prodromal signs.
Chapters
00:00 Introduction to Angioedema and Prodromal Signs
03:13 Understanding Prodromal Signs in HAE
04:04 Research Findings on Prodromal Signs
05:37 Common Prodromal Signs Reported by Patients
07:11 Comparative Analysis of Patient Responses
08:43 The Importance of Early Treatment
09:00 Challenges in Defining Early Treatment
11:23 Unanswered Questions in Prodromal Research
13:25 Differentiating Erythema Marginatum and Angioedema
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In this episode, host Thomas Buttgereit speaks with Dr. Francisco Contreras, pediatric allergist and head of the Angioedema Clinic at the National Institute of Pediatrics in Mexico City, about the current challenges and progress in treating hereditary angioedema (HAE) in Mexico.
They discuss:
🔹 Why is HAE still underdiagnosed in Mexico?
🔹 What testing and treatments are currently available?
🔹 How is access influenced by Mexico’s divided healthcare system?
🔹 What can help improve HAE care for children and rural patients?
Dr. Contreras shares his frontline experience treating pediatric patients with HAE and outlines the systemic barriers — from limited awareness among physicians to inconsistent access to diagnostic testing and long-term therapies. He also discusses how national registries, physician training, and patient advocacy are shaping the future of HAE care across Mexico.
Join us for an honest, informative conversation about improving rare disease care in resource-diverse settings.
Key Learnings from the Episode:
HAE is significantly underdiagnosed in Mexico, with only 14–21% of estimated pediatric cases identified.
Lack of awareness among general physicians is a major barrier — even though lab tests (C4, C1 inhibitor) are available in urban centers.
Specialized testing is often limited to private or large public hospitals, delaying diagnosis for rural and underserved patients.
Pharmaceutical industry partnerships help provide diagnostic support and access to genetic testing.
Available treatments include:
C1 inhibitor (plasma-derived) for on-demand and prophylaxis
Icatibant for acute attacks
Limited access to newer therapies, especially for long-term prophylaxis
Mexico’s fragmented healthcare system affects treatment availability — with different access across social security, military, private, and public services.
Off-label treatment is required for pediatric HAE patients with normal C1 inhibitor and confirmed mutations.
Childhood obesity complicates dosing, as adult doses are sometimes needed in children with higher body weight.
Patient advocacy organizations are playing a growing role in awareness and support.
Registries and awareness campaigns are underway to improve diagnosis and physician education.
Dr. Contreras and colleagues aim to establish the first ACARE center in Mexico, boosting access and research.
Early diagnosis and collaborative care are essential to improving patient outcomes and quality of life.
Chapters
00:00 Introduction to HAE and Guest Background
03:17 Current Situation of HAE in Mexico
05:35 Challenges in Diagnosis and Treatment
08:02 Available Treatments for HAE
09:47 Access and Prescription Challenges
12:28 Patient Advocacy and Future Improvements
14:10 Final Thoughts and Collaboration
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In this episode, Thomas welcomes Dr. Sabine Altrichter, urticaria expert and physician at Kepler University Hospital in Linz, Austria, to discuss a fascinating and underrecognized condition: cholinergic urticaria — especially in patients who also experience angioedema.
They discuss:
🔹 What makes cholinergic urticaria different from other urticaria types?
🔹 Why do some patients develop angioedema in addition to wheals?
🔹 How can we distinguish between cholinergic urticaria and exercise-induced anaphylaxis?
🔹 What are current and emerging treatment options? Dr. Altrichter shares insights from clinical research and experience, including findings that show nearly half of cholinergic urticaria patients may develop angioedema.
She explains the two main subtypes — allergy-related and sweat gland-related — and what this means for diagnosis and treatment. The discussion also covers new treatment options like anti-IgE therapies, mast cell-depleting agents, and drugs in the clinical pipeline like remibrutinib. Join us for a practical and engaging conversation on how to better diagnose and manage this unique condition.
Key Learnings from the Episode:
Cholinergic urticaria is triggered by body heating (e.g., exercise, sauna, passive warmth), leading to small, itchy wheals.
Nearly 50% of patients also experience angioedema, often around the eyes or lips, indicating more severe disease.
Patients with angioedema tend to have longer-lasting and more intense symptoms than those without.
Two subtypes are emerging: one IgE/allergy-related and another with sweat gland dysfunction.
Angioedema in cholinergic urticaria is not typically life-threatening, but may be accompanied by mild systemic symptoms.
Provocation testing (e.g., exercise or stair running) helps confirm diagnosis.
Antihistamines are first-line, but often insufficient in patients with angioedema.
Omalizumab (anti-IgE) is effective in about two-thirds of patients.
Mast cell-depleting therapies and remibrutinib are promising treatments in development.
Differentiating from exercise-induced anaphylaxis is key: the latter causes more unpredictable and systemic reactions.
Ongoing trials may reshape how we treat both mild and severe forms of the disease.
Chapters
00:00 Introduction to Chronic Inducible Urticaria
03:03 Understanding Cholinergic Urticaria
04:57 Angioedema and Its Connection to Cholinergic Urticaria
07:23 Subtypes of Cholinergic Urticaria
08:17 Mechanisms Behind Cholinergic Urticaria
09:56 Diagnosis of Cholinergic Urticaria
11:17 Treatment Options for Cholinergic Urticaria
13:10 Differentiating from Exercise-Induced Anaphylaxis
14:34 Future Treatments and Research
16:41 Mast Cell Depletion and Its Implications
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In this episode, Thomas welcomes Felix Aulenbacher, a bioinformatician and statistician from ACARE Berlin, to discuss the role of data science, machine learning, and artificial intelligence (AI) in angioedema research.
They discuss:
🔹 How does data analysis help classify different types of angioedema?
🔹 What role do AI and machine learning play in identifying disease patterns?
🔹 How does the "10 Questions" tool assist in diagnosing angioedema?
🔹 How is AI revolutionizing medical research, and what are its limitations?
Felix shares insights on the intersection of bioinformatics and medicine, the challenges of medical data analysis, and how AI is transforming the field of angioedema research.
Key Learnings from the Episode
Bioinformatics plays a crucial role in medical research, analyzing large datasets to uncover hidden patterns in diseases.
Data standardization is essential—poorly formatted data can make analysis difficult and lead to incorrect conclusions.
Machine learning models like Random Forest help classify different types of angioedema based on patient questionnaires.
The "10 Questions" tool has been developed to quickly differentiate different types of angioedema including HAE, mast cell-mediated angioedema, and drug-induced angioedema.
AI can enhance data analysis, but it requires careful validation—incorrect use can lead to misinformation.
ChatGPT and AI tools assist with coding and data analysis, but human oversight is still essential.
AIDUOS, a ChatGPT-based tool, has been developed for urticaria research, relying on verified medical publications.
AI is not a threat to data analysts, but professionals must adapt to its evolving capabilities.
Chapters
00:00 Introduction to Angioedema and Bioinformatics
02:20 Felix's Journey into Bioinformatics
04:26 The Role of Data Management in Medical Research
06:54 Statistical Methods and Their Applications
09:21 Machine Learning in Angioedema Research
11:43 The Impact of AI on Data Analysis
14:05 Future of Data Management and AI in Medicine
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In this episode, Thomas welcomes Dr. Fernanda Minafra, allergist and immunologist at the Federal University of Minas Gerais, Brazil, to discuss one of the most concerning aspects of hereditary angioedema (HAE): mortality.
They discuss:
🔹 How often do HAE-related deaths occur?
🔹 Why is undiagnosed HAE a major risk factor?
🔹 What do global studies say about mortality rates?
🔹 What can be done to reduce HAE deaths worldwide?
Dr. Minafra shares insights from her research, including a systematic review on HAE-related deaths and a study on mortality rates in Brazil. She highlights the urgent need for better diagnosis, access to treatment, and public health policies to prevent avoidable deaths.
Join us for this crucial discussion on why early diagnosis and proper treatment are key to saving lives.
Key Learnings from the Episode
HAE-related deaths are often caused by asphyxiation due to laryngeal angioedema.
HAE mortality rates remain high in many parts of the world, especially in developing countries.
A systematic review found that 1 in 20 HAE patients has died from asphyxia.
Undiagnosed patients are at much higher risk of fatal outcomes.
Many death certificates fail to properly identify HAE as the cause of death.
HAE patients who die from asphyxiation typically lose 20 years of life expectancy.
Access to diagnostic tests and effective treatments is essential for preventing deaths.
Global collaboration through ACARE centers is needed to improve mortality data collection and patient outcomes.
Chapters
00:00 Introduction to Angioedema and Mortality
03:13 Understanding Hereditary Angioedema (HAE) and Its Risks
05:34 Research Insights on Mortality in HAE
08:21 Findings from Brazil: A Closer Look at HAE Deaths
10:47 The Impact of Diagnosis and Treatment on HAE Mortality
13:41 Current Status and Future Directions in HAE Research
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In this episode, Thomas welcomes Dr. Jane Wong from Queen Mary Hospital, Hong Kong, to discuss a groundbreaking method for diagnosing hereditary angioedema (HAE) in regions with limited laboratory access. Traditional tests like complement C4, C1 inhibitor levels and C1 inhibitor function are crucial but not widely available in many parts of the world, delaying diagnosis and treatment.
They discuss:
🔹 What is dried blood spot (DBS) testing?
🔹 How does DBS compare to conventional lab tests?
🔹 Can DBS be used for large-scale screening and family testing?
🔹 What are the limitations and future applications of DBS?
Join us for an in-depth discussion on how this simple, cost-effective method can revolutionize HAE diagnosis and patient care worldwide.
Key Learnings from the Episode:
Traditional HAE testing (C4, C1 inhibitor levels and function) is limited in many regions, delaying diagnosis and treatment.
Dried blood spot (DBS) testing offers a reliable, cost-effective alternative, requiring only a few drops of blood.
DBS showed strong correlation with conventional lab results, making it a promising screening tool.
DBS allows for easy at-home or community-based sample collection, overcoming logistical barriers.
DBS can be used for family screening, identifying undiagnosed relatives in high-risk groups.
The method is stable and easy to transport, requiring minimal laboratory infrastructure.
More extensive studies are needed to validate DBS for broader population screening.
Future applications may include genetic testing for HAE with normal C1 inhibitor cases.
Chapters
00:00 Introduction to HAE and Diagnostic Challenges
03:12 Conventional Testing Methods for HAE
05:44 Exploring Alternative Diagnostic Methods
08:25 Validation of the Dried Blood Spot Method
10:40 Family Screening and Community Engagement
13:29 Limitations and Future Directions
16:07 The Future of HAE Diagnostics in Asia-Pacific
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In this episode, Dr. Thomas Buttgereit speaks with Dr. Adil Adatia about the latest findings on hereditary angioedema (HAE) in Canada, focusing on the challenges in diagnosing and treating patients with normal C1 inhibitor levels. They explore the differences between well-known genetic variants, discuss the average diagnostic delay of over 10 years, and examine treatment approaches, including long-term prophylaxis and the role of estrogen as a trigger. Additionally, they highlight the need for standardized guidelines in diagnosing and managing this condition to better treatment response.
Key Learnings from the Episode
The average diagnostic delay for hereditary angioedema with normal C1 inhibitor levels exceeds 10 years in Canada.
Patients with normal C1 inhibitor function often experience different triggers, with estrogen and stress being more prominent compared to other angioedema variants.
A significant heterogeneous group of patients exists, where genetic mutations have yet to be identified.
Many patients require multiple long-term prophylaxis treatments, indicating a more severe disease course.
Genetic testing has historically been limited, but recent efforts are increasing its role in diagnosis.
The lack of standardized diagnostic criteria across Canada makes it difficult to classify and treat patients uniformly.
Insurance coverage for treatments like omalizumab varies by province and county, making access to care inconsistent.
There is a need for clear definitions of treatment trials and treatment failures to improve clinical decision-making.
Chapters
00:00 Introduction to HAE and the Guest
02:27 Understanding HAE with Normal C1 Inhibitor
05:30 Diagnostic Challenges and Delays
08:21 Comparative Analysis of HAE Types
11:32 Limitations of Current Research
14:34 Treatment Responses and Variability
17:16 Conclusion and Future Directions
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What comorbidities are seen in people with HAE? Dr Linda Sundler Björkman joins Dr Thomas Buttgereit to discuss her research on comorbidities in HAE, including methodology, key findings, and the need for further research.
Disclosure statement: Unrestricted research grant from CSL Behring. Honorars from Takeda, Biocryst and CSL Behring.
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