Hereditary angioedema with C1-inhibitor deficiency: a retrospective study of 194 patients

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Abstract

BACKGROUND: Hereditary angioedema due to C1-inhibitor deficiency is a rare disease caused by deficiency and/or low functional activity of C1-inhibitor. The main symptom of hereditary angioedema is recurrent angioedema in various localizations, which can lead to temporary incapacity or even death.

AIM: To study the features of the clinical course of the disease in patients with hereditary angioedema from the registry of the National Research Center (NRC) “Institute of Immunology” of the FMBA of Russia, identify the predictors of life-threatening angioedema and the need for long-term therapy, and compare the features of the course of the disease in different groups of patients.

MATERIALS AND METHODS: A total of 194 patients from NRC Institute of Immunology FMBA of Russia registry from 124 unrelated families with a diagnosis of hereditary angioedema with C1-inhibitor deficiency, confirmed in accordance with accepted diagnostic standards, were enrolled in the retrospective descriptive study.

RESULTS: Overall, 194 patients were included in the analysis (70% female and 30% male). The mean age of patients was 35±17 years. Moreover, 89% and 11% of patients had hereditary angioedema types I and II, respectively. The mean age of clinical onset was 11±9 years. Ninety-eight percent of participants had a history of at least one episode of peripheral angioedema, 86% experienced abdominal attacks, 86% experienced facial swellings, and 49% experienced laryngeal attacks. The mean diagnostic delay was 17.5±11.24 years. The older the patient is, the more possible laryngeal attacks (p <0.001), facial and neck swellings (p <0.001), and abdominal attacks are (p=0.031). No significant differences in clinical features were noted between men and women.

CONCLUSIONS: There is a problem of a long diagnostic delay of hereditary angioedema in Russia. As a consequence of the study, we have identified a number of warning criteria of hereditary angioedema: the presence of a family history, a combination of recurrent angioedema and abdominal attacks, and the onset of angioedema and/or abdominal attacks in early childhood. The existence of such criteria will make it possible to optimize the diagnosis of hereditary angioedema. Moreover, we have identified the risk factors for the development of life-threatening angioedema: the patient’s age (the older the patient, the higher the risk) and a history of angioedema of the face and neck.

About the authors

Irina A. Manto

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Author for correspondence.
Email: irina.manto@yandex.ru
ORCID iD: 0000-0001-6432-394X
SPIN-code: 7944-5159

MD, Research Associate

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Elena A. Latysheva

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia; Pirogov Russian National Research Medical University

Email: ealat@mail.ru
ORCID iD: 0000-0002-1606-205X
SPIN-code: 2063-7973

MD, Dr. Sci. (Med.), Leading Research Associate

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; Moscow

Daria O. Timoshenko

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Email: d.o.timoshenko@gmail.com
ORCID iD: 0000-0002-7585-1390
SPIN-code: 2714-0906

Post graduate student, MD

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Yulia A. Gornostaeva

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Email: ygornost@yandex.ru
SPIN-code: 8191-5590

MD, Cand. Sci. (Med.), Senior Research Associate

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Aristitsa M. Kostinova

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Email: aristica_kostino@mail.ru
ORCID iD: 0000-0002-0584-2376
SPIN-code: 2922-5274

MD

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Ekaterina N. Medunitsyna

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia; Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: medunitsyna.kate@yandex.ru
ORCID iD: 0000-0002-7872-6261

MD, Cand. Sci. (Med.), Senior Research Associate

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; Moscow

Tatyana N. Myasnikova

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Email: t_miasnikova@mail.ru
ORCID iD: 0000-0001-8491-195X
SPIN-code: 4684-3112

MD, Cand. Sci. (Med.), Senior Research Associate

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Tatyana S. Romanova

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Email: ts_romanova@mail.ru
ORCID iD: 0000-0003-3350-3811
SPIN-code: 8027-8625

MD, Cand. Sci. (Med.)

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Nailya Kh. Setdikova

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia; Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: nh.setdikova@nrcii.ru
ORCID iD: 0000-0003-2587-7928
SPIN-code: 6339-6945

MD, Dr. Sci. (Med.), Leading Research Associate

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; Moscow

Evgeniy A. Frolov

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Email: frolovevgeny@rambler.ru
ORCID iD: 0000-0002-0800-5960
SPIN-code: 5963-4062

MD

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Olga V. Shubina

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia

Email: shubina15@mail.ru
SPIN-code: 9010-4704

MD, Cand. Sci. (Med.)

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522

Tatiana V. Latysheva

National Research Center ― Institute of Immunology Federal Medical-Biological Agency of Russia; Moscow State University of Medicine and Dentistry named after A.I. Evdokimov

Email: tvlat@mail.ru
ORCID iD: 0000-0003-1508-0640
SPIN-code: 8929-7644

head of the Immunopathology and Intensive Care Department, MD, Dr. Sci. (Med.), Professor, PhD

Russian Federation, 24, Kashirskoye shosse, Moscow, 115522; Moscow

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Supplementary files

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2. Fig. 5. The dynamics of the increase in the number of patients with hereditary angioedema with C1-inhibitor deficiency, observed at the Institute of Immunology.

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3. Fig. 1. Age of symptoms onset (n=181).

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4. Fig. 2. Diagnostic delay of HAE types I and II (n=181).

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5. Fig. 3. Dependence of clinical symptoms on age.

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6. Fig. 4. The presence of laryngeal angioedema in patients in different age groups.

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