PhD Scientific Days 2018

Budapest, April 19–20, 2018

Genetic biomarkers and clinical significance of erythema marginatum in Hungarian patients with hereditary angioedema due to C1-inhibitor deficiency

Kőhalmi, Kinga Viktória

Kinga Viktória Kőhalmi1, Virág Menkő1, Nóra Veszeli1,2, Dorottya Csuka1, Lilian Varga1, Anastasios E. Germenis3 and Henriette Farkas1

1 Hungarian Angioedema Reference Center, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
2 MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary
3 Department of Immunology and Histocompatibility, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

Language of the presentation

Hungarian

Text of the abstract

Introduction: Hereditary angioedema (HAE) attacks in patients with HAE with C1-inhibitor deficiency (C1-INH-HAE) may be preceded by erythema marginatum (EM). EM can occur alone or accompany a HAE attack.

Aims and method: We assessed the prevalence of EM in C1-INH-HAE patients, using an Erythema Marginatum Questionnaire (EMQ). Furthermore, we explored possible associations among EM and different types of SERPING1 mutations, the carrier state of KLKB1-428G/A and F12-46C/T functional polymorphisms.

Results: According to the EMQ, 65/165 patients (39.4%; mean age: 38.4 years) from 43 families experienced EM during their lifetime; 39/65 (60%) were female. The distribution of EM by location was as follows: upper extremities 29.5%, chest 28%, back 18%, lower extremities 13%, abdomen 6.5%, and the face 5%. EM first appears at the age of 15.5 years on average. In 52% of patients, EM occurs as an isolated finding. On average, 7.5/10 EMs are followed by an HAE attack. Genetic analysis was done in 97 patients (mean age: 37.3 years) from 39 families. The different types of SERPING1 mutations were accompanied by EM in the following proportions: 73.3% of large defect, 67% of regulatory, 59% of frameshift, 56.3% of nonsense mutations; only 31.3% of patients with missense mutations had EM. With regard to the F12-46C/T polymorphism, 42.9% of heterozygous carriers, but 67.2% of ‘wild-type’ patients had EM. In case of the KLKB1-428G/A polymorphism, 73% of homozygous, 57.6% of heterozygous carriers had EM, while only 25% of ‘wild-type’ patients had EM.

Conclusion: EM manifests later than the onset of HAE attacks; it is characterized by female predominance. As 73% of EMs was followed by an HAE attack, early introduction of individualized therapy should be considered. Genetic predisposition is likely in EM and therefore, a predictive genetic pattern could be created by the analysis of further genes.

Data of the presenter

Doctoral School: Basic Medicine
Program: Vascular pathophisiology / atherosclerosis
Supervisor: Henriette Farkas
E-mail address: farkas.henriette@med.semmelweis-univ.hu

Disclosure of potential conflict of interest: This study was supported by ÚNKP-17-3-III-SE-13 New National Excellence Program of the Ministry of Human Capacities, National Scientific Research Fund (OTKA) 124557, and the Pharming Group NV.