Hereditary angioedema (HAE) is a rare, autosomal dominant genetic disorder characterized by recurrent, unpredictable, and potentially life-threatening episodes of swelling.¹ At the EAACI Hong Kong Allergy School 2025, leading global experts offered a comprehensive international perspective on HAE—highlighting a paradigm shift in treatment goals to long-term prophylaxis (LTP) in high-resource countries, and the pressing challenges of underdiagnosis and limited access to treatment in resource-limited settings.^1-3 The future of HAE care hinges on bridging this profound global disparity through international collaboration, patient advocacy, and equitable access to diagnostics and transformative therapies.²

Dr. Hilary Longhurst, Associate Professor of Immunology from Auckland University in New Zealand, and Professor Constance Katelaris from Western Sydney University in Australia, underscored the profound burden of HAE.^1,3 Beyond the life-threatening risk of asphyxiation, HAE inflicts significant psychological distress.³ Patients often grapple with anxiety over future attacks, depression, and the fear of passing the condition to their children.³ Their quality of life (QoL) is severely compromised, with levels comparable to those experienced during rheumatoid arthritis or moderate migraine episodes.¹ The disease also often leads to absenteeism—averaging 20 days per year—and impedes career progression in over half of HAE patients.³ Understanding this burden has led to a dramatic transformation in the management of HAE over the past two decades.¹ Historically, the primary focus was on preventing fatal laryngeal attacks and alleviating acute pain.¹ Today, in well-resourced regions, the treatment paradigm has shifted toward complete disease control.¹ Thanks to the advent of highly effective therapies, the new standard of care aims for zero attacks and normalization of QoL in all dimensions.³ LTP is being increasingly recognized as the strategy capable of achieving these ambitious goals.³

Modern LTP therapies for HAE are designed to correct the underlying pathophysiology: a deficiency in C1 inhibitor that leads to dysregulated activity of the contact pathway and overproduction of bradykinin, the key mediator of swelling.¹ Traditional LTP approaches include agents like the monoclonal antibody lanadelumab, which inhibits kallikrein, a critical enzyme in bradykinin production.³ Garadacimab, a monoclonal antibody that inhibits activated Factor XIIa, has been shown to dramatically reduce the mean monthly attack rate from 3.07 to 0.27, and an unprecedented 61.5% of patients became completely attack-free.³ Investigational CRISPR-based therapy aims to provide a “functional cure” by knocking out the KLKB1 gene in the liver, thereby reducing prekallikrein production.³ Early results have shown profound and sustained improvements in QoL after a single dose.³ As for acute attacks, early treatment is critical to reduce their duration and severity.¹ Options like intravenous C1 inhibitor and subcutaneous icatibant (a bradykinin B2 receptor antagonist) remain the mainstays of acute management.¹

While advanced therapies are transforming life with HAE in high-resource regions, a starkly different reality persists in many parts of Asia.² Dr. Ankur Jindal of Manipal Hospitals, India, highlighted the significant challenges faced in diagnosing and managing HAE in countries with limited resources and low awareness.² Despite similar global prevalence, over 95% of patients in countries like India and China remain undiagnosed.² This stems from limited access to diagnostic tools such as C1 inhibitor functional assays, a lack of specialized centers, and low awareness among physicians, leading to years of diagnostic delay.² Even when diagnosed, treatment options are often outdated or inaccessible.² First-line therapies are frequently unavailable or unaffordable, leaving clinicians to depend on older, off-label treatments like fresh frozen plasma, androgens, and tranexamic acid—despite their side effects.² LTP offers the potential for complete disease control and normalized QoL, but access remains a major barrier due to high costs in these regions.^2,3

In summary, the “vicious cycle” of underdiagnosis is a persistent challenge. Low detection rates reduce commercial interest and government investment, which in turn sustains limited awareness and access.² Breaking this cycle requires coordinated efforts—regional guidelines, better physician education, active case finding, and stronger patient advocacy.² Clinicians should recognize the value of modern therapies to effectively advocate with regulators and payers.^2,3 The ultimate goal is to free patients from the burden of HAE—a vision increasingly within reach thanks to highly effective long-term prophylactic options that can truly normalize life for HAE patients.^2,3

Below are highlights consolidated from the panel discussion session: 

1. How can we improve the diagnosis rate for HAE? 
   
   A multi-faceted approach is needed. Medical education for students and practicing physicians is critical to raise awareness. In Japan, adding HAE to the national medical exam was highly effective. Public education and patient stories also play a key role. Clinically, a simple rule is to test the C4 level in any patient with angioedema without wheals who responds poorly to standard treatments like adrenaline and antihistamines. 
    
2. Can on-demand treatment like icatibant replace LTP? 
   No. While on-demand treatment is effective for acute attacks, it cannot replace LTP. It does not alleviate the significant psychological burden and constant fear of the next attack. Effective LTP is crucial for normalizing a patient's quality of life by removing this fear. 
    
3. What is the impact of HAE on mental health? 
   
   The impact is significant, with high rates of anxiety and depression reported among patients. The constant threat of attacks creates a heavy psychological burden. Providing access to psychological support is important, but effective prophylactic treatment is the most powerful intervention, as it directly addresses the root cause of this anxiety. 
    
4. Why is the cost of HAE treatment so high and what can be done? 
   HAE medications are high-cost drugs, particularly C1 inhibitors, which are complex blood products. This creates significant barriers to care, with access varying globally. In Hong Kong, treatments are now fully subsidized, while in other regions, patients often pay out-of-pocket. Advocacy and negotiation between governments and pharmaceutical companies are essential to improve access and affordability. Economic analyses showing that effective treatment is less expensive than hospitalization have successfully persuaded payers to provide coverage.