Hereditary angioedema classification: Expanding knowledge by genotyping and endotyping.

Area of Science:

• Immunology
• Genetics
• Vascular Biology

Background:

• Hereditary angioedema (HAE) is a group of genetic disorders characterized by recurrent swelling due to increased vascular permeability, primarily mediated by bradykinin.
• HAE presents diagnostic challenges, leading to underdiagnosis, delayed treatment, and significant morbidity and mortality, with untreated laryngeal angioedema carrying a 25-40% mortality rate.
• There is a critical need to increase awareness of HAE and its warning signs, potentially aided by mnemonics like H4AE.

Purpose of the Study:

• To comprehensively review the clinical, laboratory, and physiopathological features of documented HAE subtypes.
• To advocate for an improved classification system for HAE based on endotypes, integrating current knowledge of angioedema pathophysiology.
• To provide a framework for advancing the understanding and classification of HAE.

Main Methods:

• Comprehensive literature review of clinical, laboratory, and physiopathological data for HAE subtypes.
• Analysis of existing HAE classification systems and pathophysiological mechanisms.
• Synthesis of information to propose an endotype-based classification framework.

Main Results:

• Detailed review of HAE subtypes, highlighting diagnostic challenges and severe manifestations.
• Identification of bradykinin as a key mediator of increased vascular permeability in HAE.
• Development of a proposed endotype-based classification for HAE.

Conclusions:

• An endotype-based classification offers a clear and applicable framework for HAE.
• Improved classification can enhance disease understanding and guide therapeutic advancements.
• Increased awareness and accurate diagnosis are vital for managing HAE and reducing mortality.