From the Guidelines
Hereditary angioedema can be diagnosed through specific blood tests that measure the levels and function of proteins involved in the complement system, including C4 complement levels, C1 inhibitor (C1-INH) antigen levels, and C1 inhibitor functional assays, as recommended by the most recent international consensus paper on diagnosis, pathophysiology, and treatment 1.
Diagnosis of Hereditary Angioedema
The primary tests for diagnosing hereditary angioedema include:
- C4 complement levels: A low C4 level is typically the first screening test, as it's abnormal in about 95% of HAE patients during attacks and often between attacks as well.
- C1 inhibitor (C1-INH) antigen levels: If C4 is low, further testing should include C1-INH antigen levels.
- C1 inhibitor functional assays: Functional activity of C1-INH should also be assessed.
Types of Hereditary Angioedema
There are different types of HAE, including:
- Type 1 HAE: Shows low C1-INH antigen levels.
- Type 2 HAE: Shows normal or elevated C1-INH antigen but reduced function.
- Type 3 HAE (normal C1-INH): May require genetic testing for factor XII mutations or other pathogenic variants, as suggested by recent studies 1.
Importance of Early Diagnosis
Early diagnosis is crucial as it allows for appropriate preventive treatment and emergency care planning, significantly reducing morbidity and mortality associated with this potentially life-threatening condition. Testing should be performed when the patient is not experiencing an acute attack for baseline levels, and repeated during an attack if initial results are inconclusive. Family members of diagnosed patients should also be tested due to the autosomal dominant inheritance pattern, as emphasized in recent guidelines 1.
Additional Considerations
A detailed family history for evidence of recurrent angioedema or a diagnosis of HAE in other family members is essential in all patients with recurrent angioedema, and genetic screening for pathogenic variants may be necessary in some cases 1. Furthermore, a short course of a bradykinin B2 receptor antagonist or another approved HAE on-demand treatment may be considered to support the diagnosis of bradykinin-mediated angioedema 1.
From the Research
Hereditary Angioedema Test
- Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene 2.
- The clinical presentation of HAE varies between patients, but it usually presents with nonpitting angioedema and occasionally abdominal pain 2.
- Laboratory testing shows abnormal levels of C1-INH and high levels of bradykinin, and C4 and D-dimer levels can also be monitored if an acute HAE attack is suspected 2.
Diagnosis and Treatment
- Diagnosis of HAE can be challenging, especially for HAE with normal C1 esterase inhibitor (HAE-nl-C1-INH), and pharmacologic management is not well defined 3.
- A patient history and family history of angioedema are important for diagnosis, and a genetic mutational analysis may be helpful 3.
- Treatment options for HAE include plasma-derived C1 inhibitor (C1-INH) concentrates, bradykinin B2 receptor antagonists, and recombinant human C1-INH for acute attacks 4.
- Prophylactic treatment options include attenuated androgens, antifibrinolytics, and plasma-derived C1-INH concentrates 5, 6, 4.
Prophylaxis Treatment Strategies
- Routine long-term prophylaxis with either attenuated androgens or C1-esterase inhibitor has been shown to reduce the frequency and severity of HAE attacks 6.
- A stepwise approach is suggested for suspected HAE-nl-C1-INH, including investigating the possibility of response to histaminergic and/or mast cell-targeting treatments, and following HAE type I and II treatment guidelines if necessary 3.
- Response to medications approved for HAE types I/II provides compelling support for a high clinical suspicion of HAE-nl-C1-INH 3.