title: Association of celiac disease and hereditary angioedema due to C1-inhibitor deficiency. Screening patients with hereditary angioedema for celiac disease: is it worth the effort?
abstract: OBJECTIVE
  Hereditary angioedema due to C1-inhibitor deficiency is a life-threatening condition, which manifests as edematous attacks involving subcutaneous tissues and/or the upper airway/gastrointestinal mucosa. Celiac disease is a gluten-sensitive small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. Both hereditary angioedema and celiac disease may present with abdominal symptoms. Our aim was to study the occurrence of celiac disease in the hereditary angioedema population, as well as to analyze the clinical course of cases with both diseases.
  
  
  METHODS
  One hundred and twenty-eight patients with hereditary angioedema were screened for celiac disease, using serological methods [antiendomysial antibodies-immunoglobulin A (IgA), antiendomysial antibodies-IgG and tissue transglutaminase-IgA, tissue transglutaminase-IgG]. Clinical data of a child with hereditary angioedema and celiac disease diagnosed earlier were added to the dataset to be analyzed. Thus, the total number of patients was 129, comprising 107 adults and 22 pediatric patients. In patients with celiac disease, molecular genetics analysis (human leukocyte antigen-DQA1, human leukocyte antigen-DQB1) was carried out along with the introduction of a gluten-free diet and regular follow-up.
  
  
  RESULTS
  Four out of the 22 children were diagnosed with celiac disease in our hereditary angioedema population. The prevalence of celiac disease among our pediatric patients with hereditary angioedema (22 children) was higher than in the general population (18.1 vs. 1.2%). Switching from the wheat starch-containing tranexamic acid product to danazol and introducing a gluten-free diet mitigated abdominal symptoms of hereditary angioedema.
  
  
  CONCLUSIONS
  Similarities between the symptoms of hereditary angioedema and celiac disease may cause difficulties in differential diagnosis, as well as in choosing the appropriate therapy. In our opinion, screening hereditary angioedema patients for celiac disease is warranted if abdominal attacks or neurological symptoms persist despite adequate management. Complement testing is recommended whenever abdominal symptoms persist despite the histological and serological remission of gluten-sensitive enteropathy after the introduction of a gluten-free diet.
authors.affiliation: Semmelweis University, 3rd Department of Internal Medicine, Central Laboratory, Budapest, Hungary.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Csuka
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kelemen
authors.forename: Ibolya
authors.initials: I
authors.lastname: Czaller
authors.forename: Katalin
authors.initials: K
authors.lastname: Molnár
authors.forename: George
authors.initials: G
authors.lastname: Füst
authors.forename: Lilian
authors.initials: L
authors.lastname: Varga
authors.forename: Katalin
authors.initials: K
authors.lastname: Rajczy
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Szabó
authors.forename: Kata
authors.initials: K
authors.lastname: Miklós
authors.forename: András
authors.initials: A
authors.lastname: Bors
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D002446:Celiac Disease / Q000175:diagnosis* / Q000178:diet therapy / Q000453:epidemiology / Q000276:immunology; D002648:Child; D015331:Cohort Studies; D015897:Comorbidity; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency*; D050718:Complement C1 Inhibitor Protein; D003613:Danazol / Q000627:therapeutic use; D055050:Diet, Gluten-Free; D005260:Female; D056829:Hereditary Angioedema Types I and II / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008403:Mass Screening / Q000191:economics / Q000379:methods*; D008875:Middle Aged; D015995:Prevalence; D011503:Transglutaminases / Q000097:blood / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C469952:SERPING1 protein, human; D011503:Transglutaminases; D003613:Danazol