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