From the Guidelines
Laboratory tests for angioedema should include complete blood count with differential, comprehensive metabolic panel, C4 level, C1 inhibitor level, and C1 inhibitor function, as these tests help differentiate between hereditary angioedema (HAE) and acquired forms, according to the most recent study 1. The diagnosis of angioedema involves a step-by-step approach to exclude various causes, including C1INH deficiency, medication-associated angioedema, and mast cell-mediated angioedema.
- The initial step involves excluding angioedema mimics and factitious angioedema, followed by obtaining a detailed family and medication history.
- The next step is to exclude C1INH deficiency by measuring C4, C1INH antigen, and C1INH function levels, as recommended by the study 1.
- If C1INH deficiency is excluded, the next step is to exclude medication-associated angioedema by stopping all possible drug culprits and observing for at least 1-3 months.
- A strong family history of recurrent angioedema may warrant targeted gene sequencing, as suggested by the study 1.
- The response to mast-cell targeted therapies, such as H1 antihistamines and montelukast, can help differentiate between mast cell-mediated and non-mast cell-mediated angioedema.
- The study 1 highlights the importance of early identification of patients with HAE, as optimal management depends on it.
- The most recent study 1 provides an updated international consensus paper on diagnosis, pathophysiology, and treatment of hereditary angioedema with normal C1 inhibitor, which is essential for guiding appropriate treatment strategies.
From the Research
Laboratory Tests for Angioedema
- Laboratory testing is essential for the diagnosis and differentiation of hereditary angioedema (HAE) and acquired angioedema (AAE) 2.
- The tests include measurement of C1INH levels and function, C1q levels, and testing for anti-C1INH autoantibodies 2, 3.
- For HAE, laboratory tests can differentiate between Type I and Type II, which is crucial for treatment options 2.
- Sample collection and handling are critical for functional assays, and serum samples must be collected, separated, and frozen at less than -60°C within 2 hours of the blood draw 2.
Types of Angioedema and Laboratory Diagnosis
- Hereditary angioedema with C1-inhibitor (C1-INH) deficiency Type I can be diagnosed by low C1-INH function and concentration 3.
- Hereditary angioedema with C1-inhibitor (C1-INH) deficiency Type II can be diagnosed by low C1-INH function, but normal or elevated C1-INH concentration 3.
- Acquired angioedema with C1-INH deficiency Type I is characterized by low C1-INH function and concentration, and low C1q concentration 3.
- Acquired angioedema with C1-INH deficiency Type II is characterized by low C1-INH function and concentration, low C1q concentration, and presence of autoantibodies against C1-INH 3.
Limitations of Laboratory Tests
- Currently, only five out of the nine different types of angioedema can be diagnosed by laboratory testing, and these occur only in a minority of the patient population 3.
- Diagnostic metrics are not available for idiopathic histaminergic acquired angioedema, idiopathic non-histaminergic acquired angioedema, acquired angioedema related to angiotensin-converting enzyme inhibitor, and hereditary angioedema of unknown origin 3.
- Complement testing can help exclude hereditary angioedema and acquired angioedema with C1-inhibitor deficiency, which is essential for establishing the diagnosis of acquired angioedema related to angiotensin-converting enzyme inhibitors 4.
Approach to Angioedema with Normal Laboratory Values
- When laboratory work-up is unrevealing, healthcare practitioners should consider subtypes such as hereditary angioedema with normal C1 inhibitor (HAE with normal C1INH), drug-induced angioedema, and idiopathic angioedema 5.
- A thorough medical and family history, clinical symptoms, and therapeutic response can aid in the diagnosis and management of these disorders 5.