In this episode of All Things Angioedema, Dr. Thomas Buttgereit speaks with Dr. Mark Kačar from Slovenia about the practical, clinical, and organizational steps required to establish a dedicated angioedema center within the ACARE network. Drawing from Mark’s unique experience of helping build angioedema services in multiple countries, the conversation offers valuable insights for clinicians worldwide. 

They discuss:

🔹 Why are specialized angioedema centers essential for optimal patient care? 
🔹 What clinical expertise, diagnostics, and infrastructure are truly required? 
🔹 Which ACARE criteria are most challenging for smaller or emerging centers? 
🔹 How can education, registries, and collaboration strengthen national care pathways? 

Dr. Kačar shares lessons from Slovenia’s healthcare system, where centralized expertise is key for managing rare and complex diseases like angioedema. He discusses the importance of clinical experience, multidisciplinary teamwork, access to diagnostics and genetics, patient education initiatives, and the realities of meeting ACARE requirements. Together, they highlight how international collaboration, training fellowships, and strong doctor–patient relationships form the foundation of sustainable centersof excellence in angioedema care. 

Key Learnings from the Episode:

Dedicated angioedema centers improve care by centralizing expertise and experience for rare diseases. 

Small countries such as Slowenia benefit from national referral structures rather than fragmented outpatient care. 

ACARE certification requires fulfillment of 32 defined criteria, many embedded in daily clinical practice. 

Key challenges include staffing specialized nurses, participation in registries, and access to clinical trials. 

Strong diagnostic capabilities, including complement studies and genetics, are essential. 

Training experiences at established centers accelerate knowledge transfer and best practices. 

Patient education events and collaboration with international patient organizations enhance care quality. 

Building an ACARE center is a gradual process driven by teamwork, commitment, and global networking. 

Chapters:

00:00 Introduction to Angioedema and ACARE

01:39 Mark's Journey in Allergy and Immunology

05:06 Importance of a Dedicated Angioedema Center

07:56 Experiences from Charité and Clinical Insights

11:16 Challenges in Establishing the Center

16:11 Patient Education and Resources

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In this episode of All Things Angioedema, Thomas Buttgereit speaks with Dr. Vesna Trajkova, dermatologist and researcher from Skopje, North Macedonia, about the clinical relevance of angioedema in chronic spontaneous urticaria (CSU) and what its presence reveals about disease severity and underlying mechanisms. 

They discuss:

🔹 How common is angioedema in patients with CSU? 
🔹 Is angioedema linked to more severe or longer-lasting disease? 
🔹 What is the role of autoimmunity and autologous serum skin testing? 
🔹 How should these findings influence everyday clinical practice? 

Dr. Trajkova presents data from her recent study showing that 70% of CSU patients experience angioedema, with the vast majority occurring in those with severe disease. The discussion highlights associations between angioedema, higher disease activity, longer disease duration, and autoimmune markers, emphasizing that angioedema should nobe viewed as a minor accompanying symptom. Together, they explore how recognizing angioedema as a clinically meaningful marker can improve risk stratification, monitoring, and treatment decisions in CSU. 

Key Learnings from the Episode:

Angioedema is highly prevalent in CSU, affecting around 70% of patients the CSU population investigated in the study.

The presence of angioedema is strongly associated with severe CSU, occurring in over 80% of severe cases.

CSU patients with angioedema tend to have a longer disease duration, indicating a higher cumulative burden.

Autoimmune markers and comorbid autoimmune diseases are more frequent in CSU patients with angioedema.

Autologous serum skin test positivity shows a trend toward higher angioedema prevalence, supporting an autoimmune component.

Angioedema does not merely coexist with CSU but acts as a marker of disease severity and complexity.

Routine CSU assessment should actively include angioedema evaluation, not just wheals and itch.

Recognizing angioedema can help guide earlier treatment escalation and closer follow-up in clinical practice.

Chapters:

00:00 Introduction to Angioedema and CSU

02:30 Guest Introduction: Vesna Trejkova

04:50 Research Rationale and Study Overview

10:34 Key Findings on Angioedema in CSU

13:15 Study Limitations and Future Directions

15:32 Clinical Implications of Research Findings

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In this episode, Dr. Thomas Buttgereit welcomes Mats de Lange, medical doctor and PhD candidate at Amsterdam UMC, to discuss one of the rarest and most challenging forms of angioedema – acquired angioedema (AAE) due to C1 inhibitor deficiency (AAE-C1INH). 

They discuss

🔹 What causes AAE, and how does it differ from hereditary angioedema? 
🔹 Why is treatment still off-label for most patients? 
🔹 What did the Amsterdam investigator-initiated trial reveal about Deucrictibant, a new bradykinin B2 receptor antagonist? 
🔹 How could this research pave the way for the first approved AAE therapy? 

Mats de Lange shares insights from his team’s investigator-initiated trial on the long-term use of Deucrictibant, showing remarkable results – three out of four patients remained attack-free for 20 months. The discussion also highlights the unique challenges of studying such an ultra-rare condition and the hope for future phase III trials. 

Join us as we explore how collaborative research and patient participation are advancing the field of bradykinin-mediated angioedema. 

Key Learnings from the Episode:

Acquired angioedema (AAE) is an extremely rare disorder caused by C1 inhibitor deficiency. Patients often have underlying hematologic diseases, making trials complex. Deucrictibant showed strong efficacy and safety in an investigator-initiated trial. All participants became attack-free during treatment, without major adverse events. Off-label access remains a challenge – approved therapies are urgently needed. Future multi-center studies and regulatory approval could transform patient care.

Chapters

00:00 Introduction to Angioedema and Guest Introduction

03:06 Understanding Acquired Angioedema due to C1 Inhibitor Deficiency

06:05 Current Treatment Landscape and Challenges

07:16 Investigator-Initiated Trials and Droycriptiband

11:05 Trial Design and Patient Characteristics

11:52 Promising Results from the Trial

13:06 Key Learnings and Future Directions

15:44 Next Steps in Research and Treatment Approval

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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:

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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