In this episode of the GA²LEN (Global Allergy and Asthma Excellence Network) Podcast on Everything Urticaria, Professor Torsten Zuberbier speaks with Professor Michihiro Hide from Hiroshima, Japan — a pioneer in urticaria research — about an unexpected connection between dermatology and mathematics.
The discuss:
🔹 Why do urticaria wheals form distinct shapes — round, annular, or geographic?
🔹 What controls how long a wheal lasts before fading?
🔹 Can mathematical formulas help explain the biology of hives?
🔹 What could this mean for diagnosis and treatment in the future?
Professor Hide shares how a collaboration with a mathematician led to the creation of a computational model that simulates wheal formation in silico, revealing five recurring urticaria patterns that correspond to clinical types such as cholinergic or chronic spontaneous urticaria. Together, the two professors explore how mast cells, basophils, endothelial cells, and coagulation factors interact through feedback loops to create (and stop) a wheal — and how this model could reshape our understanding of urticaria’s pathophysiology and treatment.
Key Learnings from the Episode
Urticaria’s shapes and lifespans can be mathematically modeled using Turing-inspired reaction-diffusion formulas.
Five recurring patterns of wheals emerged from simulations, mirroring real-world urticaria morphology.
Basophil-driven small dots (e.g., cholinergic urticaria) differ mechanistically from mast-cell-driven geographic wheals.
Wheals persist longer than histamine-only reactions, implying sustained mast-cell activation.
Urticaria develops through three stages — initiation, expansion, and resolution — governed by positive and negative feedback.
Understanding the inhibitory phase that stops mast-cell activation is a key future research frontier.
Mathematical modeling could help visualize and predict disease activity, opening paths for personalized therapy.
Collaboration between clinicians and mathematicians may lead to a new diagnostic and research paradigm in chronic urticaria.
Chapters
00:00 Introduction to Urticaria Research
02:03 Exploring the Mechanisms of Urticaria
06:25 Mathematical Approaches to Urticaria
10:30 Patterns and Predictions in Urticaria
15:37 Understanding Treatment Responses
19:07 Future Directions in Urticaria Research
Press release
https://www.eurekalert.org/news-releases/1009793
References
1. Seirin-Lee S, et al. A single reaction-diffusion equation for. the multifarious eruptions of urticaria. PLOS Computational Biology. 2020;16(1):e1007590
2. Seirin-LeeS, et al. Mathematical-based morphological classification of skin eruptions corresponding to the pathophysiological state of chronic spontaneous urticaria.Communications Medicine. 2023;3(1):171.
3. Seirin-Lee S, et al. Pathophysiological Mechanisms of the Onset, Development, and Disappearance Phases of Skin Eruptions in Chronic Spontaneous Urticaria, Bulletin of Mathematical Biology. 2025; 87, 1
Michihiro Hide has receivedlecture and/or consultation fees from Japan Tobacco, Kaken, Kyorin, KyowaKirin, Meiji Seiyaku, Mitsubishi Tanabe, Nippon Zoki, Novartis, Sanofi, Taiho,Teikoku and Yuhan.
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In this episode, Prof. Torsten Zuberbier (Global Allergy and Asthma Excellence Network President) welcomes Prof. Petra Staubach, urticaria expert from Germany, to talk about Urticaria Day (UDAY) — held each year on October 1st — and why awareness is just as important as science.
They discuss:
🔹 Why do we need a dedicated awareness day for urticaria?
🔹 What is the true burden of urticaria on patients and families?
🔹 How can physicians and patients improve communication and advocacy?
🔹 What do the new 2025 urticaria guidelines mean for treatment worldwide?
Together, they highlight the unmet needs of urticaria patients, the role of patient organizations, and the importance of empowering patients to speak openly about their burden. The discussion also previews the new treatment options in the 2025 guideline, including biosimilars of omalizumab, dupilumab, and remibrutinib.
Join us for this inspiring episode on why urticaria is a serious disease that deserves global awareness — and how new therapies and guidelines are changing the future.
Key Learnings from the Episode:
Urticaria Day (UDAY) has been celebrated since 2014 to raise global awareness about the seriousness of urticaria.
Despite perceptions of being “just hives,” urticaria causes major quality-of-life impairment: sleep disruption, depression, social isolation, and stigma.
84% of patients feel embarrassed to be seen with wheals or angioedema.
Urticaria affects people of all ages, from children to the elderly, with equal burden.
Physicians often underestimate disease control compared to patient perception, creating a communication gap.
Patient honesty and empowerment are crucial: patients should describe the real impact of disease to their doctors.
Patient organizations help bridge gaps, provide support, and increase awareness globally — but many countries still lack them.
The 2025 urticaria guideline will emphasize:
Early up-dosing of antihistamines (don’t wait months if ineffective).
Omalizumab remains the global standard, now also with biosimilars.
Dupilumab (already used in asthma/atopic dermatitis) and Remibrutinib (oral BTK inhibitor) enter the treatment landscape.
Flexibility: co-administration with cyclosporine, consideration of costs, and tailoring to patient burden.
The key message: Stay flexible, treat early, and adapt care to the patient’s real needs.
Awareness & advocacy matter: urticaria’s burden is as high as ischemic heart disease — it must be taken seriously by society and healthcare systems.
Chapters
00:00 Introduction to Urticaria Awareness
02:32 The Importance of Urticaria Day
05:16 Understanding the Burden of Urticaria
07:58 Communication Between Patients and Physicians
10:59 Future Treatment Options for Urticaria
14:05 Conclusion and Call to Action
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In this episode, Sophia Neisinger welcomes Dr. Melba Muñoz, head of the Chronic Inducible Urticaria Program in Berlin, to discuss symptomatic dermographism (SD), the most common form of inducible urticaria.
They discuss:
🔹 What exactly is symptomatic dermographism, and why is it so burdensome for patients?
🔹 How common is SD, and what did the latest international prevalence study reveal?
🔹 How can tools like the FricTest help diagnose and assess SD?
🔹 Which treatments are available today—and which exciting therapies are on the horizon?
Dr. Muñoz shares insights on the challenges SD patients face in daily life, the importance of proper diagnosis, and why new therapies in clinical trials may soon change the landscape of treatment. She also highlights the need for awareness among both physicians and patients to reduce diagnostic delays and improve care.
Join us for this engaging conversation on how better diagnostics, treatment options, and awareness can transform the lives of SD patients.
Key Learnings from the Episode
Definition: Symptomatic dermographism is a form of inducible urticaria where scratching or stroking on the skin leads to wheals, redness, and itch.
Prevalence: International data suggest approximately 4% of the population may be affected, making it surprisingly common.
Impact: Even daily activities like wearing clothes or combing hair can trigger symptoms, causing significant quality-of-life impairment.
Diagnosis: The FricTest is a standardized tool to diagnose and measure SD activity, more reliable than ad-hoc methods like using a pen.
Overlap: Around 30–40% of SD patients also present with chronic spontaneous urticaria (CSU).
Treatment today: Only antihistamines are licensed; omalizumab may be used off-label (or in-label if CSU is present).
Future therapies: Anti-KIT antibodies (barzolvolimab, briquilumab), oral KIT inhibitors, and BTK inhibitors (remibrutinib) show great promise.
Diagnostic delays: Many SD patients experience long delays, partly due to lack of awareness and the perception that symptoms are "normal."
Patient-reported tools: The Urticaria Control Test (UCT) and the new SD-Qual scale are validated instruments for assessing disease control and quality of life.
Awareness: Education for general practitioners and patients is key, as many still use antihistamines incorrectly (on demand instead of regularly).
Chapters
00:00 Introduction to Symptomatic Demographism
02:53 Understanding Symptomatic Demographism
04:49 Prevalence and Diagnosis of SD
06:54 Diagnostic Tools for SD
09:16 Treatment Options for SD
13:52 Challenges in Diagnosis and Awareness
18:40 Patient-Reported Outcomes and Future Directions
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In this episode, Prof. Torsten Zuberbier welcomes Dr. Larissa Brandão, pediatric allergist from the Federal University of São Paulo, Brazil, to talk about chronic urticaria in children — a condition that is often misunderstood and underdiagnosed.
🔹 When does chronic urticaria typically begin in kids?
🔹 What role do infections or allergens, play?
🔹 Which treatments are available in public healthcare?
🔹 How do cold urticaria and cholinergic urticaria show up in warm climates?
Dr. Brandão shares her clinical experience from Brazil, where many children with chronic urticaria also suffer from comorbidities like asthma and allergic rhinitis. She explains how treatment responses differ from adults and discusses the impact of restricted access to second-generation antihistamines.
Join us for a practical and global look at what it takes to recognize, treat, and support children with chronic urticaria — especially in resource-limited settings.
Key Learnings from the Episode
Chronic urticaria in children typically begins around age 7–8, with chronic spontaneous urticaria (CSU) being the most common subtype.
In Brazil is the most common chronic inducible form; cold urticaria and cholinergic urticaria are also present but less frequent.
Cold triggers in Brazil include ice cream, cold drinks, pools, and beaches — not ambient winter weather.
Pediatric CSU patients often have comorbid atopic conditions, especially asthma and allergic rhinitis.
Children tend to respond better than adults to standard or up-dosed second-generation antihistamines, but fatigue can be a common side effect.
Loratadine is the only antihistamine widely available through Brazil’s public health system; desloratadine, bilastine, or fexofenadine are often unaffordable.
Liver function monitoring is used for kids on high-dose loratadine.
Omalizumab is rarely needed, but effective in more severe pediatric cases — especially those with comorbid asthma.
Dupilumab is now licensed in Brazil for CSU in children aged 12+, and early reports show benefits for patients with both asthma and urticaria.
Pseudoallergen-triggered symptoms (e.g. from candy, dyes, preservatives) are observed, and short-term elimination diets are used diagnostically.
Cold urticaria can cause anaphylaxis, especially in pools — and adrenaline auto-injectors are recommended for high-risk children.
Counseling on safety, including family education about temperature triggers, is essential for cold urticaria management.
Brazilian UCARE centers use social media and in-clinic education to raise awareness and prepare for Urticaria Day (October 1) each year.
Chapters
00:00 Introduction to Urticaria in Children
01:46 Understanding Chronic Urticaria in Children
03:33 Infections and Chronic Urticaria
05:13 Allergic Comorbidities in Children
06:27 Treatment Algorithms for Chronic Urticaria
08:32 Dietary Influences on Urticaria
12:09 Cold Urticaria and Safety Concerns
15:13 Advancements in Urticaria Treatment
17:30 Advocacy and Awareness for Urticaria
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In this episode, Prof. Torsten Zuberbier welcomes Prof. Gil Yosipovitch, world-renowned itch researcher and dermatologist at the University of Miami, for an in-depth discussion on the science of itch in urticaria, and why histamine isn’t the full story.
They discuss:
🔹 Why do antihistamines fail in up to 40% of urticaria patients?
🔹 What is MRGPRX2, and why is it such a promising target for future treatments?
🔹 How do pain and itch differ neurologically — and why is itch harder to ignore?
🔹 What role do topical steroids, JAK inhibitors, and GABAergic drugs play?
Prof. Yosipovitch shares clinical and research insights on chronic itch mechanisms, highlighting how mast cells, nerves, cytokines, and ion channels interact to drive symptoms. The episode also explores why scratching can feel pleasurable, what makes urticaria itch unique, and how new therapies could revolutionize care.
Join us for a cutting-edge conversation on the future of urticaria treatment — and why individualized care is the most powerful approach of all.
Key Learnings from the Episode
Chronic urticaria itch is not purely histaminergic — up to 40% of patients don’t respond to antihistamines, indicating other mechanisms.
MRGPRX2 is a key non-histaminergic itch receptor found on mast cells and possibly nerve fibers — and is overexpressed in many itch disorders.
Scratching itch activates pleasure centers in the brain, but urticaria patients scratch less deeply than those with atopic dermatitis.
Cold and heat don’t always inhibit itch — responses vary across diseases and individuals, involving channels like TRPM8.
Steroids and JAK inhibitors modulate both histaminergic and non-histaminergic itch pathways.
Long-term steroid use is still widespread, especially in the US — but leads to serious comorbidities.
Gabapentin and SNRIs like mirtazapine are valid add-on options in selected chronic itch patients.
New biologics and mast cell-targeting drugs (like CKIT inhibitors) are on the horizon and may transform treatment.
Each patient is unique — clinicians must move beyond dogma and adjust treatments to the individual, not just the guideline.
Chapters
00:00 Understanding Itch: The Science Behind Chronic Pruritus
03:02 The Role of MRGPRX2 in Itch Mechanisms
05:53 Pain vs. Itch: Exploring the Neural Pathways
09:03 Individual Patient Experiences: The Complexity of Itch
11:48 Treatment Approaches: Antihistamines and Beyond
15:11 Emerging Therapies: The Future of Itch Management
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In this episode, Dr. Sophia Neisinger welcomes Prof. Emek Kocatürk, leading urticaria researcher and UCARE expert from Istanbul, to explore the gender-specific aspects of chronic urticaria, with a special focus on pregnancy.
They discuss:
🔹 Why do more women than men suffer from chronic urticaria?
🔹 How does pregnancy affect urticaria symptoms and treatment response?
🔹 What medications are safe during pregnancy and breastfeeding?
🔹 How should physicians approach treatment decisions with female patients?
Prof. Kocatürk shares key insights from the PREG-CU study, involving over 300 pregnant CSU patients, and explains why half of them improve during pregnancy. She outlines practical treatment guidelines for antihistamines and omalizumab use during pregnancy and breastfeeding, discusses estrogen’s inflammatory role, and gives tips for shared decision-making in clinical care.
Join us for an important and empowering episode that sheds light on female-specific urticaria challenges and how to manage them with evidence-based confidence.
Key Learnings from the Episode
70% of CSU patients are female, pointing to hormonal and autoimmune factors in disease susceptibility.
Female CSU patients suffer more: more angioedema, systemic symptoms, worse disease control, and more comorbidities like asthma, thyroid disease, and depression.
The PREG-CU study showed that 50% of CSU patients improve during pregnancy, offering hope to women planning to conceive.
Exacerbations during pregnancy are common and linked to worse pregnancy outcomes if untreated.
Antihistamines (especially cetirizine, loratadine) are safe in pregnancy; second-generation agents are preferred.
Omalizumab is safe in pregnancy and lactation, particularly starting in the second trimester.
Antihistamines can be safely continued and even up-dosed during breastfeeding.
Keeping CSU under control during and after pregnancy is essential for maternal well-being and newborn bonding.
Shared decision-making and good counseling reduce fear and improve patient experience.
Digital tools, registries like CURE and CARE, and collaborative research are key to improving care for women with urticaria.
Chapters
00:00 Understanding Chronic Urticaria: A Female Predominance
06:20 Pregnancy and Chronic Urticaria: What to Expect
11:36 Managing Urticaria During Pregnancy and Lactation
17:18 Fun Facts and Closing Thoughts
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In this episode, Prof. Torsten Zuberbier calls up Dr. Hanna Bonnekoh, dermatologist and researcher at Charité Berlin, to dive into the complexities of cold-induced urticaria—particularly rare and familial forms that challenge current diagnostics and treatments.
They discuss:
🔹 What makes wind-induced cold urticaria so difficult to diagnose?
🔹 How can physicians distinguish between histamine- and IL-1-mediated disease?
🔹 What role do biologics like omalizumab and dupilumab play in treatment?
🔹 Why are IL-1 blockers crucial in autoinflammatory syndromes like Muckle-Wells-syndrome?
Dr. Bonnekoh shares her clinical perspective on diagnostic tools like the TempTest, the pathophysiology behind cold urticaria variants, and how novel therapies like anti-CKIT antibodies are shaping the future of care. She also emphasizes the importance of family history, wheal morphology, and systemic symptoms when evaluating patients with atypical urticaria.
Join us for a deep dive into cold urticaria phenotypes, treatment strategies, and the call for more research and global registry data to support patients worldwide.
Key Learnings from the Episode
Cold urticaria includes rare phenotypes, such as wind-induced and familial forms, often undetectable by standard tests.
The TempTest is useful for threshold diagnosis, but not all cold urticaria types respond.
Histamine-mediated urticaria may respond to antihistamines or omalizumab, while IL-1-mediated types (e.g., Muckle-Wells) require immunomodulatory therapy.
IL-1 plays a key role in autoinflammation; identifying its overproduction is crucial in diagnosis.
CRP and ESR are easy, accessible lab markers to differentiate urticaria types.
New biologics like anti-CKIT antibodies (e.g., barzolvolimab) are promising in depleting mast cells.
Wheal appearance, duration, and sensations (itch vs. burn) help guide subtype classification.
Cold-induced cholinergic urticaria is an emerging phenotype needing further research.
Global registries like CURE are key to improving care for rare urticaria types.
Chapters
00:00 Introduction to Cold-Induced Problems
03:29 Understanding Atypical Cold Urticaria
06:23 Treatment Options for Cold Urticaria
09:12 Exploring Rare Forms of Cold Urticaria
11:53 The Role of Interleukin-1 in Cold Urticaria
14:40 Differential Diagnosis in Cold Urticaria
17:15 Research and Future Directions in Cold Urticaria
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In this episode, Prof. Dr. Torsten Zuberbier (GA²LEN) welcomes Dr. Sophia Neisinger to discuss CRUSE, a digital health tool for chronic spontaneous urticaria (CSU). CRUSE is a free, globally available self-evaluation app that helps patients track their symptoms and provides valuable research data to improve urticaria care.
They discuss:
📊 How CRUSE helps patients track their CSU symptoms daily.
🔬 How anonymized CRUSE data is shaping global urticaria research.
📢 The importance of continuous data input—even on good days.
💊 Treatment disparities worldwide & the fight against long-term corticosteroid use.
📡 Upcoming developments, including smartwatch & wearable integration.
Join us as we explore how CRUSE is making a difference for patients, physicians, and researchers worldwide!
Key Learnings from the Episode:
CRUSE is a free, validated self-evaluation app for CSU patients, helping track their disease and treatment effectiveness.
Daily symptom tracking is crucial, even when patients feel well, to improve research insights.
CRUSE data reveals treatment disparities worldwide, with some countries lacking access to second-line treatments.
Systemic corticosteroids are still overused, despite their severe side effects, highlighting the need for better awareness and alternative treatments.
CRUSE allows patients to share their symptom data with their physicians, improving personalized treatment decisions.
The app is continuously evolving, with new features like improved reports and future integration with smartwatches and wearables.
CRUSE is expanding globally, with North Macedonia being the next country to adopt the platform.
Physicians and researchers can use CRUSE for studies, making it a valuable tool for small-scale trials and real-world data collection.
Chapters
00:00 Introduction to CRUISE and Its Purpose
03:18 Data Collection and Patient Engagement
05:47 Global Insights from CRUISE Data
08:52 Future Developments and Enhancements
11:35 Awareness and Advocacy for Urticaria
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In this episode, Prof. Torsten Zuberbier (Charité Berlin, GA²LEN) welcomes Dr. Stefan Frischbutter, senior researcher at the Institute of Allergy in Berlin, to explore the fascinating world of mast cells and urticaria.
They discuss:
🔬 The critical role of mast cells in immune responses and skin conditions like urticaria.
💡 How temperature, autoantibodies, and nerves can trigger mast cell activation.
🦠 Different types of mast cell activation: IgE, IgG autoantibodies & pseudo-allergens.
🧪 New research techniques to study mast cells and identify better treatments.
💊 How eosinophils, neutrophils & T-cells influence chronic urticaria severity.
📢 The latest advances in urticaria treatment and why biopsies could guide therapy.
Join us for an insightful discussion on the immune system’s “orchestrators” and how scientific discoveries are shaping the future of urticaria treatment!
Key Learnings from the epsiode:
Mast cells act as immune response directors, responding to heat, cold, allergens, stress, and autoantibodies.
Urticaria has multiple causes, including IgE and IgG autoantibodies, pseudo-allergen receptors (MRGPRX2), and nerve signals.
Not all urticaria cases are histamine-driven—other immune cells like eosinophils and neutrophils play a major role.
Chronic spontaneous urticaria patients often have autoantibodies targeting mast cells, making treatment challenging.
Taking a skin biopsy at the right time (after a wheal disappears) can reveal immune cell involvement and guide personalized treatments.
New research techniques, like mast cell activation tests and ex-vivo skin models, help identify triggers and potential treatments.
Different immune cells require different treatments, and eosinophil/neutrophil-driven urticaria may need specialized drugs.
Exciting future treatments are emerging, and ongoing research will provide better-targeted therapies for urticaria patients.
Chapters
00:00 Introduction to Mast Cells and Their Importance
02:50 Understanding Urticaria and Its Triggers
05:55 Mast Cell Activation Mechanisms
08:30 The Role of Other Immune Cells in Urticaria
11:30 Clinical Implications and Biopsy Timing
14:08 Research Advances and Future Directions
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What steps can be taken to manage solar urticaria? Professor Torsten Zuberbier and Dr Lea Kiefer examine solar urticaria, discussing the role of skin type, management strategies, and treatment methods.
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Professor Torsten Zuberbier welcomes Dr Luis Ensina to discuss essential information for people with urticaria, highlighting the benefits of keeping a diary before medical appointments and how using patient-reported outcome tools can help doctors understand their condition better.
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