From the Guidelines
The workup for hereditary angioedema (HAE) should begin with measuring C4 levels, which are typically low during and between attacks, as recommended by the Journal of Allergy and Clinical Immunology 1. The diagnosis of HAE depends on early identification of patients, and optimal management relies on distinguishing between different types of HAE, including type I and type II, which can be diagnosed based on laboratory findings, such as low C1INH antigenic and functional levels for type I, and normal C1INH antigenic levels but decreased C1INH functional levels for type II 1. Some key points to consider in the workup include:
- Measuring C1 inhibitor (C1-INH) levels and function if C4 is low
- Documenting clinical symptoms, including frequency, severity, and location of swelling episodes, as well as any triggers or family history
- Laboratory testing should ideally be performed during an acute attack and confirmed when the patient is asymptomatic
- Differential diagnosis should rule out acquired angioedema, which can present similarly but typically occurs later in life and may be associated with underlying lymphoproliferative or autoimmune disorders
- Referring patients to an immunologist or allergist with expertise in HAE for long-term management, which may include on-demand treatment for acute attacks and prophylactic therapy for those with frequent or severe episodes, as recommended by consensus US (HAEA) and international (HAWK, iCAALL) guidelines 1. It's also important to note that epinephrine, corticosteroids, and antihistamines are not efficacious and are not recommended for the treatment of HAE, and that management of HAE attacks can involve symptomatic treatment based on the region of body swelling, as well as the use of fresh frozen plasma, C1INH replacement, or short-term, high-dose anabolic androgen therapy for short-term prophylaxis 1.
From the Research
Hereditary Angioedema Workup
- Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene, affecting 1/50,000 people worldwide 2.
- There are three main types of HAE: type I, type II, and type III, with type I being the most common and characterized by a deficiency in C1-INH 2.
- Laboratory testing for HAE shows abnormal levels of C1-INH and high levels of bradykinin, with C4 and D-dimer levels also being monitored if an acute HAE attack is suspected 2.
Diagnosis and Clinical Presentation
- The clinical presentation of HAE varies between patients, but it usually presents with nonpitting angioedema and occasionally abdominal pain 2.
- Young children are typically asymptomatic, with symptoms usually appearing in the early 20s 2.
- Symptoms can arise as a result of stress, infection, or trauma 2.
Treatment and Management
- Acute treatment of HAE can include IV infusions of C1-INH, receptor antagonists, and kallikrein inhibitors 2.
- Short- and long-term prophylaxis can also be administered to patients with HAE, with first-line therapies for long-term prophylaxis including IV infusion of C1-INH 2.
- A comprehensive management plan for HAE should include access to an expert physician, ongoing patient education, access to effective treatment options, and coordination of care and management of treatment logistics 3.
- Prophylactic treatment options for HAE include attenuated androgens and nanofiltered C1 INH (C1 INH-nf), with each patient having unique needs based on the nature and frequency of past attacks, proximity to a medical center, occupation, and the patient's wishes 4.
Emerging Management Options
- Several novel therapies have completed phase III trials in the US, including plasma-derived C1-INH replacement therapies, a recombinant C1-INH replacement therapy, a kallikrein inhibitor, and a bradykinin-2-receptor antagonist 5.
- Replacement therapy with partly purified C1 inhibitor has been shown to be effective in treating acute episodes of angioedema 6.