What is the recommended workup and treatment for a patient with angioedema?

From the Guidelines

The recommended workup for angioedema begins with a thorough history and physical examination to determine the type and potential triggers, as outlined in the most recent guidelines from 2022 1. For hereditary angioedema (HAE), laboratory tests should include C4 levels, C1 inhibitor levels, and C1 inhibitor function. For acquired or allergic angioedema, consider complete blood count, tryptase levels, and specific IgE testing if an allergic trigger is suspected. Some key points to consider in the workup include:

• Recurrent unexplained fever, joint/bone pain, or malaise may suggest an autoinflammatory disease
• Average wheal duration > 24h may indicate chronic spontaneous urticaria or another condition
• A history of ACE inhibitor treatment or remission after stopping the medication can help diagnose ACE inhibitor-induced angioedema Treatment depends on the type and severity. For acute episodes with airway involvement, secure the airway first, which may require intubation in severe cases. For bradykinin-mediated angioedema (including HAE), first-line treatments include C1 inhibitor concentrates (Berinert, Cinryze) at 20 units/kg IV, icatibant (Firazyr) 30 mg subcutaneously, or ecallantide (Kalbitor) 30 mg subcutaneously, as supported by recent studies 1. For histamine-mediated angioedema, administer epinephrine 0.3-0.5 mg IM for severe reactions, followed by antihistamines (diphenhydramine 25-50 mg IV/PO or cetirizine 10 mg PO) and corticosteroids (prednisone 40-60 mg PO or methylprednisolone 125 mg IV). Long-term prophylaxis for HAE includes lanadelumab (Takhzyro) 300 mg subcutaneously every 2 weeks, berotralstat (Orladeyo) 150 mg PO daily, or danazol 200 mg PO twice daily. Patients with recurrent angioedema should be educated about trigger avoidance, carry emergency medications, and have a clear action plan. The pathophysiology of angioedema involves either mast cell degranulation with histamine release (allergic) or bradykinin pathway dysregulation (hereditary or ACE inhibitor-induced), which explains the different treatment approaches, as discussed in previous studies 1.

From the FDA Drug Label

The safety and efficacy of KALBITOR to treat acute attacks of hereditary angioedema in adolescents and adults were evaluated in 2 randomized, double-blind, placebo-controlled trials (EDEMA4 and EDEMA3) in 168 patients with HAE Patients having an attack of hereditary angioedema, at any anatomic location, with at least 1 moderate or severe symptom, were treated with 30 mg subcutaneous KALBITOR or placebo.

The recommended workup for a patient with angioedema is not explicitly stated in the provided drug labels. However, the treatment for acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older is KALBITOR (ecallantide), as indicated in the drug label 2 and 2. Key points to consider in the treatment of HAE include:

• Dosing: 30 mg subcutaneous KALBITOR
• Patient selection: Patients with HAE, 12 years of age and older, with at least 1 moderate or severe symptom
• Efficacy endpoints: Mean Symptom Complex Severity (MSCS) score and Treatment Outcome Score (TOS)

From the Research

Recommended Workup for Angioedema

• The workup for angioedema should include an assessment of the patient's medical history, physical examination, and laboratory tests to determine the underlying cause of the condition 3.
• The patient's history should include questions about medication use, particularly angiotensin-converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs), as these are common causes of angioedema 3, 4.
• Laboratory tests may include measurements of C1 esterase inhibitor levels to distinguish between hereditary and acquired angioedema 5, 6.

Treatment of Angioedema

• The treatment of angioedema depends on the underlying cause and may include antihistamines, corticosteroids, and epinephrine for histaminergic angioedema 3.
• For non-histaminergic angioedema, such as that caused by ACE inhibitors, treatment options may include fresh frozen plasma, C1 esterase inhibitor, icatibant, and ecallantide 4, 5, 6.
• In severe cases of angioedema, securing the airway is the most important intervention, followed by administration of pharmacologic interventions based on disease pathology 7.

Specific Treatment Options

• Icatibant, C1 esterase inhibitor, and fresh frozen plasma have been shown to be effective in treating acute attacks of ACE inhibitor-induced angioedema and idiopathic angioedema 4, 5, 6.
• Omalizumab, tranexamic acid, and C1 esterase inhibitor may be effective for prophylactic treatment of idiopathic angioedema and angioedema with wheals 6.
• Novel pharmacologic agents, such as icatibant and ecallantide, have recently become available for the acute treatment of angioedema syndromes 7.