The diagnosis of hereditary angioedema with C1 inhibitor deficiency: a survey of Canadian physicians and laboratories

Abstract

BackgroundHereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease resulting in random and unpredictable attacks of swelling. The swelling in C1-INH-HAE is a result of impaired regulation of bradykinin production. The fact that the array of tests needed to diagnose HAE is not always available to the treating physicians is challenging for them and their patients.MethodsThe data for this article were extracted from two distinct surveys. The first survey was conducted among HAE treating physicians and aimed to determine the availability and utilization of the various assays performed to help the diagnosis of C1-INH-HAE. The second survey was conducted with the various laboratories across Canada that performs the assays used in the diagnosis of HAE. The aim of this survey was to determine the availability and profile of the various assays used in the diagnosis of C1-INH-HAE in Canada, thereby ultimately bringing a rational basis for the biological testing.ResultsC1-INH functional assay was widely available in Canada (93%), but was only offered by a small numbers of hospitals meaning that there could be longer delays in the analysis of these samples that may explain why the physicians expressed a lower level of confidence in this assay (59%). Antigenic C1-INH was available to the vast majority of the physicians treating C1-INH-HAE (93%) and was considered reliable by 96% of the respondents. Antigenic C4 was found available to all Canadian physicians and, although with limited specificity, was considered very reliable by all the participants. This study revealed that 81% of physicians were able to order the antigenic C1q and the confidence in this assay was moderate (70%). Concerning genetic testing, the survey revealed that most of the CHAEN members never had to or couldn’t order this test.ConclusionThis study highlights the need for improved education and knowledge exchange, about biological assays available to Canadian physicians and their performance in proper diagnosis of C1-INH-HAE to improve confidence and access to relevant tests.

Biomarkers in Hereditary Angioedema

“…Functional C1-INH (fC1-INH, C1-INH activity) plasma levels are considered a reference test in the diagnosis of HAE due to C1-INH deficiency (C1-INH-HAE), particularly of type 2 [14,[18][19][20]. However, there have been some concerns in relation to this test, including variability due to sample handling and time of storage or an increase in its levels in the course of inflammation and infection [21][22][23]. In addition, different types of assays may yield divergent results [19,24].…”

The multifactorial impact of receiving a hereditary angioedema diagnosis

“… 58 Direct costs include the cost of medical care, including medication, medical visits, supportive care, and travel. For example, as genetic testing for HAE is often not routinely conducted and may not always be available to a patient's primary care physician, 36 , 60 patients often search and pay for genetic tests themselves. Some patients may also decline any additional genetic testing if no mutations are identified in their SERPING1 gene for financial reasons, which can create difficulties in obtaining future insurance coverage for any long-term treatments.…”

Paveldima angioedema: patogenezė, diagnostika ir genetinės konsultacijos vaidmuo klinikinėje praktikoje

“…C3 koncentracija paprastai yra normali, todėl PAE diagnostikai šis tyrimas netikslingas [8]. Jaunesniems nei [39,40]. Be to, C4 koncentracija paprastai pasiekia suaugusiųjų lygį nuo 2-3 metų amžiaus [41].…”

“…Taip pat tais atvejais, jei C4 bei C1-INH kiekis ir aktyvumas yra normalūs, galima įtarti PAE-nC1-INH, tuomet diagnozei patvirtinti reikalingas XII faktoriaus (F12), angiopoetino-1 (ANGPT1), plazminogeno (PLG) genų tyrimas [43]. Kaip minėta, vaikams iki vienerių metų C1-INH nustatymas nėra patikimas diagnozuojant PAE [40], todėl genetinis tyrimas tikslingas nustatant PAE diagnozę vaikams, ypač tais atvejais, kai biocheminiai tyrimai neinformatyvūs ir žinoma tiksli tėvams rasta mutacija [6,41,44,45]. Genetiniai tyrimai taip pat gali būti tikslingi siekiant suteikti pacientui genetinę konsultaciją, kai įtariamas gonadų mozaicizmas [20].…”