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Unnecessary Abdominal Surgeries in Attacks of Hereditary Angioedema with Normal C1 Inhibitor

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Abstract

Hereditary angioedema (HAE) is an autosomal dominant disease mostly due to the deficiency of C1 inhibitor (C1-INH). HAE with normal C1-INH was first described in 2000 and associated with mutations in the coagulation factor XII in 2006. Both diseases are associated with high bradykinin production, resulting in increased vascular permeability. Gastrointestinal edema due to HAE can be misdiagnosed as acute abdomen and unnecessary surgical procedures may be performed. The present study evaluates the prevalence of surgical procedures and/or acute abdomen in HAE patients with the coagulation factor XII mutation. It is a retrospective study where patients were diagnosed with recurrent angioedema without urticaria, normal C1-INH levels, and positive family history of angioedema. All patients were evaluated for the known mutations located at exon 9 of the F12 gene. Medical records were evaluated and questionnaires were applied to 52 patients with normal C1-INH levels (age range 13–76 years; 47/52, 90.38% women; 5/52, 9.61% men). F12 mutation was present in 32/52 patients (61.5%). Acute abdominal pain was diagnosed in 16/52 (30.76%) patients, appendicitis in 9/16 (56.2%), and undetermined diagnosis in 7/16 (43.7%). Among patients diagnosed with acute abdominal pain, 13/16 (81.2%) underwent surgery and 3/16 (18.7%) improved without surgical intervention. We conclude that many HAE patients with coagulation factor XII mutation were misdiagnosed with acute abdomen and subjected to unnecessary invasive procedures. It is critical to disseminate information about this rare mutation in patients with otherwise normal C1-INH activity, in order to speed up diagnosis and avoid misconduct.

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Abbreviations

HAE:

hereditary angioedema

C1-INH:

C1 inhibitor

C1-INH-HAE:

HAE with C1-INH defect

nC1-INH-HAE:

HAE with normal C1-INH;

U-HAE:

HAE with unknown mutation

FXII-HAE:

HAE with F12 gene mutation

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Funding

MG-received a grant from National Council for Scientific and Technological Development (CNPq) (113924/2019-4); ASG: awarded productivity grant from National Council for Scientific and Technological Development (CNPq) (308556/2018-6). CLV: received grants from CNPq (407714/2018-9) and FAPESP (2015/25494-1).

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Authors and Affiliations

  1. Faculdade de Medicina, Centro Universitario Saude ABC, Santo Andre, Sao Paulo, SP, Brazil

    Marcel Gutierrez & Anete S. Grumach

  2. Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, San Diego, USA

    Camila L. Veronez

  3. Research Service, San Diego Veterans Affairs Healthcare, San Diego, USA

    Camila L. Veronez

  4. Serviço de Imunologia. Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

    Solange O Rodrigues Valle & Maria Luiza Oliva Alonso

  5. Private Allergy and Immunology Clinic, Belo Horizonte, MG, Brazil

    Rozana Fátima Gonçalves

  6. Ribeirão Preto School of Medicine, University of São Paulo, Ribeirao Preto, SP, Brazil

    Mariana Paes Leme Ferriani, Adriana S. Moreno & L. Karla Arruda

  7. Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, SP, Brazil

    Marcelo Vivolo Aun & Pedro Giavina-Bianchi

  8. Albert Einstein School of Medicine, Faculdade Israelita de Ciências da Saúde, Sao Paulo, SP, Brazil

    Marcelo Vivolo Aun

  9. Department of Biophysics, Federal University of São Paulo, Sao Paulo, Brazil

    Joao B. Pesquero

Authors
  1. Marcel Gutierrez
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  2. Camila L. Veronez
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  3. Solange O Rodrigues Valle
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  4. Rozana Fátima Gonçalves
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  5. Mariana Paes Leme Ferriani
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  6. Adriana S. Moreno
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  7. L. Karla Arruda
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  8. Marcelo Vivolo Aun
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  9. Pedro Giavina-Bianchi
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  10. Maria Luiza Oliva Alonso
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  11. Joao B. Pesquero
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  12. Anete S. Grumach
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Contributions

Conception: MG, CV, ASG. Acquisition of data: all authors. Analysis of data: MG, CV, ASG. Approved the manuscript: all authors.

Corresponding author

Correspondence to Anete S. Grumach.

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Ethical Approval

The protocol was approved by the ethical committee of Centro Universitario Saude ABC (CAAE 36889514.8.0000.0082).

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The authors declare that they have no conflict of interest.

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Gutierrez, M., Veronez, C.L., Rodrigues Valle, S.O. et al. Unnecessary Abdominal Surgeries in Attacks of Hereditary Angioedema with Normal C1 Inhibitor. Clinic Rev Allerg Immunol 61, 60–65 (2021). https://doi.org/10.1007/s12016-021-08852-7

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  • DOI: https://doi.org/10.1007/s12016-021-08852-7

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