Top

Published in:

Open Access 01-12-2018 | Research

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

Authors: Xavier Charest-Morin, Stephen Betschel, Rozita Borici-Mazi, Amin Kanani, Gina Lacuesta, Georges-Étienne Rivard, Eric Wagner, Susan Wasserman, Bill Yang, Christian Drouet

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2018

Abstract

Background

Hereditary 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.

Methods

The 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.

Results

C1-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.

Conclusion

This 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.

Charignon D, Späth P, Martin L, Drouet C. Icatibant, the bradykinin B2 receptor antagonist with target to the interconnected kinin systems. Expert Opin Pharmacother. 2012;13:2233–47.CrossRef

Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet. 2012;379:474–81.CrossRef

Hofman ZL, Relan A, Zeerleder S, Drouet C, Zuraw B, Hack CE. Angioedema attacks in patients with hereditary angioedema: local manifestations of a systemic activation process. J Allergy Clin Immunol. 2016;138:359–66.CrossRef

Zanichelli A, Magerl M, Longhurst H, Fabien V, Maurer M. Hereditary angioedema with C1 inhibitor deficiency: delay in diagnosis in Europe. Allergy Asthma. Clin Immunol. 2013;9(1):29. https://doi.org/10.1186/1710-1492-9-29.CrossRef

Schmaier AH. The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities. J Thromb Haemost. 2016;14:28–39.CrossRef

Schmaier AH. Plasma Prekallikrein: its role in hereditary angioedema and health and disease. Front Med. 2018;5:3. https://doi.org/10.3389/fmed.2018.00003.CrossRef

Weidmann H, Heikaus L, Long AT, Naudin C, Schlüter H, Renné T. The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity. Biochim Biophys Acta. 2017;1864(11 Pt B):2118–27. https://doi.org/10.3389/fmed.2018.00003.CrossRef

Defendi F, Charignon D, Ghannam A, Baroso R, Csopaki F, Allegret-Cadet M, Ponard D, Favier B, Cichon S, Nicolie B, Fain O, Martin L, Drouet C, National Reference Centre for Angioedema CREAK. Enzymatic assays for the diagnosis of bradykinin-dependent angioedema. PLoS ONE. 2013;8:e70140.CrossRef

Cicardi M, Aberer W, Banerji A, Bas M, Bernstein JA, Bork K, Caballero T, Farkas H, Grumach A, Kaplan AP, Riedl MA, Triggiani M, Zanichelli A, Zuraw B, HAWK under the patronage of EAACI (European Academy of Allergy and Clinical Immunology). Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69:602–16.CrossRef

10.

Gompels MM, Lock RJ, Morgan JE, Osborne J, Brown A, Virfo PF. A multicentre evaluation of the diagnostic efficency of serological investigations for c1 inhibitor deficiency. J Clin Pathol. 2002;55(2):145–7.CrossRef

11.

Giard C, Nicolie B, Drouet M, Lefebvre-Lacoeuille C, Le Sellin J, Bonneau JC, Maillard H, Rénier G, Cichon S, Ponard D, Martin L, Drouet C. Angio-oedema induced by oestrogen contraceptives is mediated by bradykinin and is frequently associated with urticaria. Dermatology. 2012;225:62–9.CrossRef

12.

Dessart P, Defendi F, Humeau H, Nicolie B, Sarre ME, Charignon D, Ponard D, Cichon S, Drouet C, Martin L. Distinct conditions support a novel classification for bradykinin-mediated angio-oedema. Dermatology. 2015;230:324–31.CrossRef

13.

Wagenaar-Bos IG, Drouet C, Aygören-Pursun E, Bork K, Bucher C, Bygum A, Farkas H, Fust G, Gregorek H, Hack CE, Hickey A, Joller-Jemelka HI, Kapusta M, Kreuz W, Longhurst H, Lopez-Trascasa M, Madalinski K, Naskalski J, Nieuwenhuys E, Ponard D, Truedsson L, Varga L, Nielsen EW, Wagner E, Zingale L, Cicardi M, van Ham SM. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations. J Immunol Methods. 2008;338(1–2):14–20. https://doi.org/10.1016/j.jim.2008.06.004.CrossRefPubMed

14.

Ghannam A, Sellier P, Defendi F, Favier B, Charignon D, López-Lera A, López-Trascasa M, Ponard D, Drouet C. C1 inhibitor function using contact-phase proteases as target: evaluation of an innovative assay. Allergy. 2015;70:1103–11.CrossRef

15.

Nielsen EW, Johansem HT, Straume B, Mollnes TE. Effect of time, temperature and additives on a functional assay of C1 inhibitor. J Immunol Methods. 1994;173:245–53.CrossRef

16.

Craig T, Aygören-Pürsün E, Bork K, Bowen T, Boysen H, Farkas H, Grumach A, Katelaris CH, Lockey R, Longhurst H, Lumry W, Magerl M, Martinez-Saguer I, Ritchie B, Nast A, Pawankar R, Zuraw B, Maurer M. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012;5(12):182–99. https://doi.org/10.1097/wox.0b013e318279affa.CrossRefPubMedPubMedCentral

17.

Kay E, Pratt R, Waserman S, Waliul K, Hudecki P. Radial immunodiffusion method for evaluation of C1-esterase inhibitor function. J Allergy Clin Immunol. 2016;137(2):AB253. https://doi.org/10.1016/j.jaci.2015.12.911.CrossRef

18.

Wagner E, Sussman GD, Rivard GE. Personal communication; 2008 (unpublished).

19.

Li HH, Busse P, Lumry WR, Frazer-Abel A, Levy H, Steele T, Dayno J, Riedl M. Comparison of chromogenic and ELISA functional C1-inhibitor tests in diagnosing hereditary angioedema. J Allergy Clin Immunol Pract. 2015;3(2):200–5. https://doi.org/10.1016/j.jaip.2014.08.002.CrossRefPubMed

20.

Joseph K, Bains S, Tholanikunnel BG, Bygum A, Aabom A, Koch C, Farkas H, Varga L, Ghebrehiwet B, Kaplan AP. A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes. Allergy. 2015;70(1):115–9. https://doi.org/10.1111/all.12520.CrossRefPubMed

21.

Riedl MA, Lumry WR, Busse P, Levy H, Steele T, Dayno J, Li HH. Prevalence of hereditary angioedema in untested first-degree blood relatives of known subjects with hereditary angioedema. Allergy Asthma Proc. 2015;36(3):205–12. https://doi.org/10.2500/aap.2015.36.3833.CrossRef

22.

Zanichelli A, Arcoleo F, Barca MP, Borelli P, Bova M, Cancian M, Cicardi M, Cilliari E, De Carolis C, De Pasquale T, Del Corso I, Di Rocco PC, Guarino MD, Massaro I, Minale P, Rossi V, Triggiani M, Zanierato G, Zoli A. A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy. Orphanet J Rare Dis. 2015;10:11. https://doi.org/10.1186/s13023-015-0233-x.CrossRefPubMedPubMedCentral

23.

Martinez-Saguer I, Cicardi M, Suffritti C, Rusicke E, Aygören-Pürsün E, Stoll H, Rossmanith T, Feussner A, Kalina U, Kreuz W. Pharmacokinetics of plasma-derived C1 esterase inhibitor after subcutaneous versusintravenous administration in subjects with mild or moderate hereditary angioedema: the PASSION study. Transfusion. 2014;54(6):1552–61. https://doi.org/10.1111/trf.12501.CrossRefPubMed

24.

Nielsen EW, Johansen HT, Holt J, Mollnes TE. C1 inhibitor and diagnosis of hereditary angioedema in newborns. Pediatr Res. 1994;35(2):184–7.CrossRef

25.

Coppola L, Guastafierro S, Verrazzo G, Coppola A, De Lucia D, Tirelli A. C1 inhibitor infusion modifies platelet activity in hereditary angioedema patients. Arch Pathol Lab Med. 2002;126(7):842–5.PubMed

26.

Tarzi M, Hickey A, Forster T, Mohammadi M, Longhurst HJ. An evaluation of tests used for the diagnosis and monitoring of C1 inhibitor deficiency: normal serum C4 does not exclude hereditary angioedema. J Clin Exp Immunol. 2007;149(3):513–6. https://doi.org/10.1111/j.1365-2249.2007.03438.x.CrossRef

27.

Davis AE. C1 inhibitor and hereditary angioneurotic edema. Ann Rev Immuol. 1988;6:595–628.CrossRef

28.

Karim Y, Griffiths H, Deacock. Normal complement C4 values do not exclude hereditary angioedema. J Clin Pathol. 2004;57(2):213–4. https://doi.org/10.1136/jcp.2003.12021.CrossRefPubMedPubMedCentral

29.

Charignon D, Ghannam A, Ponard D, Drouet C. Hereditary C1 inhibitor deficiency is associated with high spontaneous amidase activity. Mol Immunol. 2017;85:120–2. https://doi.org/10.1016/j.molimm.2017.01.028 Epub 2017 Feb 20.CrossRefPubMed

30.

Cicardi M, Zanichelli A. Acquired angioedema. Allergy Asthma. Clin Immunol. 2010;6(1):14. https://doi.org/10.1186/1710-1492-6-14.CrossRef

31.

Jesus AA, Campos LM, Liphaus BL, Carneiro-Sampaio M, Mangueira CL, Rosseto EA, Silva CA, Scheinberg M. Anti-C1q, anti-chromatin/nucleosome, and anti-dsDNA antibodies in juvenile systemic lupus erythematosus patients. Rev Bras Reumatol. 2012;52(6):976–81.CrossRef

32.

Nilsson B, Ekdahl KN. Complement diagnostics: concepts, indications and practical guidelines. Clin Dev Immunol. 2012;2012:962702. https://doi.org/10.1155/2012/962702.CrossRefPubMedPubMedCentral

33.

Alexander RL. Comparisons of radial immunodiffusion and laser nephelometry for quantitating serum proteins. Clin Chem. 1980;26(2):314–7.PubMed

34.

Roumenina LT, Sène D, Radanova M, Blouin J, Halbwachs-Mecarelli L, Dragon-Durey MA, Fridman WH, Fremeaux-Bacchi V. Functional complement C1q abnormality leads to impaired immune complexes and apoptotic cell clearance. J Immunol. 2011;187(8):4369–73. https://doi.org/10.4049/jimmunol.1101749.CrossRefPubMed

35.

Loules G, Zamanakou M, Parsopoulou F, Vatsiou S, Psarros F, Csuka D, Porebski G, Obtulowicz K, Valrieva A, Staevska M, Lopez-Lera A, Lopez-Trascasa M, Moldovan D, Magerl M, Maurer M, Speletas M, Farkas H, Germenis AE. Targeted next-generation sequencing for the molecular diagnosis of hereditary angioedema due to C1-inhibitor deficiency. Gene. 2018;667:76–82. https://doi.org/10.1016/j.gene.2018.05.029.CrossRefPubMed

36.

Drouet C, Desormeaux A, Robillard J, Ponard D, Bouillet L, Martin L, Kanny G, Moneret-Vautrin D-A, Bosson J-L, Quesada J-L, Lopez-Trascasa M, Adam A. Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P. J Allergy Clin Immunol. 2008;121(2):429–33.CrossRef

37.

Charignon D, Ghannam A, Defendi F, Ponard D, Monnier N, López Trascasa M, Launay D, Caballero T, Djenouhat K, Fain O, Cichon S, Martin L, Drouet C. Hereditary angioedema with F12 mutation: factors modifying the clinical phenotype. Allergy. 2014;69:1659–65.CrossRef

38.

Baroso R, Sellier P, Defendi F, Charignon D, Ghannam A, Habib M, Drouet C, Favier B. Kininogen cleavage assay: diagnostic assistance for kinin-mediated angioedema conditions. PLoS ONE. 2016;11:e0163958.CrossRef

39.

Robillard J, Gauvin F, Molinaro G, Leduc L, Adam A, Rivard GE. The syndrome of amniotic fluid embolism: a potential contribution of bradykinin. Am J Obstet Gynecol. 2005;193:1508–12.CrossRef

40.

Beaudouin E, Defendi F, Picaud J, Drouet C, Ponard D, Moneret-Vautrin DA. Iatrogenic angioedema associated with ACEi, sitagliptin, and deficiency of 3 enzymes catabolizing bradykinin. Eur Ann Allergy Clin Immunol. 2014;46:119–22.PubMed

Title: The diagnosis of hereditary angioedema with C1 inhibitor deficiency: a survey of Canadian physicians and laboratories
Authors: Xavier Charest-Morin
Stephen Betschel
Rozita Borici-Mazi
Amin Kanani
Gina Lacuesta
Georges-Étienne Rivard
Eric Wagner
Susan Wasserman
Bill Yang
Christian Drouet
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Allergy, Asthma & Clinical Immunology / Issue 1/2018
Electronic ISSN: 1710-1492
DOI: https://doi.org/10.1186/s13223-018-0307-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2018

Preliminary study on chronic granulomatous disease in Sri Lanka

Common allergies in urban adolescents and their relationships with asthma control and healthcare utilization

Effect of artemisinin and neurectomy of pterygoid canal in ovalbumin-induced allergic rhinitis mouse model

Review of cold-induced urticaria characteristics, diagnosis and management in a Western Canadian allergy practice

Effects of nasal dilator strips on subjective measures of sleep in subjects with chronic nocturnal nasal congestion: a randomized, placebo-controlled trial

Airway reversibility in asthma and phenotypes of Th2-biomarkers, lung function and disease control