Highlights
- Angioedema can become life-threatening; prompt diagnosis and tailored treatment are crucial.
- Advances in targeted therapies are revolutionizing the management of bradykinin-mediated angioedema.
Summary and Overview
Angioedema is sudden swelling of deeper skin and mucous membranes, often affecting the face, lips, tongue, and airway, with potential airway obstruction risks. It is classified into histamine-mediated, related to allergic reactions and responsive to antihistamines and epinephrine, and bradykinin-mediated types—including hereditary and drug-induced forms—that require different treatments. Accurate diagnosis is vital due to differing management strategies and risk of fatal outcomes. Recent advances in understanding the condition have led to targeted therapies improving patient care.
Pathophysiology and Classification
Angioedema results from increased vascular permeability caused by histamine or bradykinin. Histamine-mediated angioedema involves mast cell activation, often with hives, triggered by allergens or physical stimuli, and resolves within 1–2 days. Bradykinin-mediated angioedema involves dysregulation of the kallikrein-kinin system, causing prolonged, non-itchy swelling, often affecting the airway and gastrointestinal tract, and does not respond to standard allergy treatments.
Classification includes hereditary angioedema (HAE) with genetic causes, acquired angioedema (AAE) which can be histaminergic or non-histaminergic, and drug-induced forms like ACE inhibitor-associated angioedema. Differentiating histamine- from bradykinin-mediated types guides appropriate treatment.
Causes and Triggers
Histamine-mediated angioedema is caused by allergic reactions to foods, drugs, insect stings, or infections. Bradykinin-mediated angioedema arises from genetic mutations affecting C1-inhibitor function, drug effects (e.g., ACE inhibitors), or autoimmune processes. Idiopathic cases lack identifiable causes. Common triggers include allergens, medications, physical trauma, and hormonal factors. Avoiding known triggers is key in management.
Clinical Presentation and Diagnosis
Patients typically present with sudden, asymmetrical, nonpitting swelling of the skin or mucosa, often involving the face, airway, or gastrointestinal tract. Histamine-mediated forms often accompany hives and itching, while bradykinin-mediated forms do not. Airway swelling manifests as hoarseness, dysphagia, stridor, or respiratory distress and requires urgent evaluation. Fiberoptic laryngoscopy aids in assessing airway involvement.
Diagnosis relies on clinical history, symptom patterns, treatment response, and laboratory tests. Improvement with antihistamines and corticosteroids suggests histaminergic angioedema, while lack of response indicates bradykinin-mediated forms requiring further testing.
Emergency Management
The primary emergency goal is securing the airway. Histamine-mediated angioedema is treated with epinephrine, antihistamines, and corticosteroids. Bradykinin-mediated angioedema does not respond to these and requires C1-inhibitor concentrates, kallikrein inhibitors, or bradykinin receptor antagonists. Fiberoptic awake intubation is preferred for airway management; surgical airway access is necessary if intubation fails. Close monitoring for at least 24 hours is essential due to risk of delayed airway compromise.
Long-Term Management and Prevention
Long-term strategies focus on prophylaxis, especially for hereditary angioedema, using regular C1-inhibitor concentrate injections. Avoidance of triggers and discontinuation of offending drugs like ACE inhibitors are critical. Corticosteroids and antihistamines are ineffective for bradykinin-mediated forms. Patients with recurrent angioedema should have thorough evaluation and coordinated care involving specialists.
Prognosis and Complications
Prognosis depends on cause, severity, and treatment effectiveness. Airway obstruction is the most serious complication requiring prompt intervention. Recurrent cases may need prophylactic therapy to reduce attack frequency. While most histaminergic angioedema responds to standard treatments, bradykinin-mediated forms may require specialized therapies. Early recognition and management reduce morbidity and mortality.
Epidemiology
Angioedema can stem from hereditary, medication-induced, immune-related, or idiopathic causes. ACE inhibitor use is a common precipitant. Edema involving the oral cavity or oropharynx increases the risk of airway intervention. Symptoms like voice changes and stridor signal impending obstruction. Racial differences in ACE inhibitor-related angioedema risk exist but require further study.
Research and Emerging Therapies
Advances include higher-dose second-generation antihistamines for histamine-mediated angioedema and targeted treatments like C1-inhibitor concentrates and bradykinin receptor antagonists for bradykinin-mediated forms. Fresh frozen plasma is now less favored due to potential symptom worsening. Updated classifications and guidelines emphasize mechanism-based diagnosis and treatment. Ongoing research explores new pathways and therapies to further improve outcomes.
The content is provided by Jordan Fields, Scopewires
