Abstract
Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria. Recurrent angioedema without urticaria (AE) can be hereditary (HAE) and acquired (AAE), and several subtypes can be distinguished, although clinical presentation is quite similar in some of them. They present with subcutaneous and mucosal swellings, affecting extremities, face, genitals, bowels, and upper airways. AE is commonly misdiagnosed due to restricted access and availability of appropriate laboratorial tests. HAE with C1 inhibitor defect is associated with quantitative and/or functional deficiency. Although bradykinin-mediated disease results mainly from disturbance in the kallikrein–kinin system, traditionally complement evaluation has been used for diagnosis. Diagnosis is established by nephelometry, turbidimetry, or radial immunodiffusion for quantitative measurement of C1 inhibitor, and chromogenic assay or ELISA has been used for functional C1-INH analysis. Wrong handling of the samples can lead to misdiagnosis and, consequently, mistaken inappropriate approaches. Dried blood spot (DBS) tests have been used for decades in newborn screening for certain metabolic diseases, and there has been growing interest in their use for other congenital conditions. Recently, DBS is now proposed as an efficient tool to diagnose HAE with C1 inhibitor deficiency, and its use would improve the access to outbound areas and family members. Regarding HAE with normal C1 inhibitor, complement assays’ results are normal and the genetic sequencing of target genes, such as exon 9 of F12 and PLG, is the only available method. New methods to measure cleaved high-molecular-weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Validated biomarkers of kallikrein–kinin system activation could be helpful in differentiating mechanisms of angioedema. Our aim is to focus on the capability to differentiate histaminergic AE from bradykinin-mediated AE. In addition, we will describe the challenges developing specific tests like direct bradykinin measurements. The need for quality tests to improve the diagnosis is well represented by the variability of results in functional assays.
Highlights
Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria [1]
Specific mutations in factor XII gene (F12) emerged as the first biomarkers for a new subtype of hereditary angioedema (HAE)-nlC1-INH, the HAE with F12 gene mutation (HAE-F12), caused by mutations affecting a highly glycosylated region of factor XII encoded by the exon 9 of F12 [8,9,10]
idiopathic histaminergic acquired angioedema (AAE-IH) is a mast cell and histamine-dependent, in which patients respond to short-term steroid, and it may be distinguishable from the angioedema associated with chronic spontaneous urticaria by the relative absence of IgG antibody to the IgE receptor or with IgG anti-IgE [35]
Summary
Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria [1]. Idiopathic histaminergic acquired angioedema (AAE-IH) is the most common subtype of AE; the patients are responsive to antihistamines and the etiology is usually unknown [18, 19]. These patients probably do not share the main involvement of bradykinin, as well as a smaller group of patients with AAE idiopathic non-antihistaminergic (AAE-InH) [20]. An ultra-rare group of patients presents with acquired C1-INH deficiency (AAE-C1-INH) [21, 22] Another rare form of AAE is the angioedema exclusively induced by angiotensin-converting. Enzyme (ACE) inhibitors (AAE-ACEi), which affects less than 1% of patients taking this class of drug [23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
