TNF Receptor–Associated Periodic Syndrome: An Analysis of a Slovakian Cohort of TRAPS Patients
Branislav Slenker1
, Peter Banovcin1, Katarina Hrubiskova2, Veronika Vargova4, Anna Bobcakova1,3,4,5, Dusana Gensor1, Eva Malicherova Jurkova1, Daniela Kapustova1, Lenka Kapustova1,4,5, Adam Markocsy1,4,5, Otilia Petrovicova1,5, Milos Jesenak1,3,4,5
1Department of Paediatrics, National Centre for Periodic Fever Syndromes, Comenius University Bratislava Jessenius Faculty of Medicine in Martin, University Teaching Hospital Martin, Martin, Slovak Republic
25th Department of Internal Medicine, Centre for Periodic Fever Syndromes, Comenius University Bratislava Faculty of Medicine, University Hospital, Bratislava, Slovak Republic
3Department of Paediatrics and Adolescent Medicine, Pavol Jozef Safarik University Faculty of Medicine, Children Faculty Hospital, Kosice, Slovak Republic
4Department of Pulmonology and Phthisiology, National Centre for Periodic Fever Syndromes, Jessenius Faculty of Medicine Martin, Comenius University Bratislava, University Teaching Hospital Martin, Martin, Slovak Republic
5Institute of Clinical Immunology and Medical Genetics, Jessenius Faculty of Medicine Martin, Comenius University Bratislava, University Teaching Hospital Martin, Martin, Slovak Republic
Keywords: Interleukin-1 inhibition, periodic fever syndromes, TRAPS, TNFRSF1A gene, systemic autoinflammatory diseases
Abstract
Background/Aims: Tumor necrosis factor receptor–associated periodic syndrome (TRAPS) is an autosomal dominant systemic autoinflammatory disease caused by mutations in the TNFRSF1A gene. The clinical presentation of TRAPS is heterogeneous, which can complicate its diagnosis. This study aimed to characterize the clinical and genetic features of patients with TRAPS diagnosed and treated in Slovakia, as well as to evaluate their therapeutic response to canakinumab.
Materials and Methods: A retrospective analysis of clinical data from the Slovak national database of patients with periodic fever syndromes was performed, including 7 TRAPS patients diagnosed between 2019 and 2022 in Slovakia. These data were compared with findings from available cohorts from Europe, China, and Japan.
Results: All 7 patients were female, with a median age at clinical disease onset of 6 years (range: 8 months to 30 years); 1 patient had adult-onset disease. The most frequent symptoms were recurrent episodes of fever (6/7), skin rash (6/7), arthralgia (6/7), myalgia (5/7), abdominal pain (4/7), chest pain (4/7), and general fatigue (4/7). Notably, 1 patient exhibited central nervous system (CNS) involvement manifesting as seizures and aseptic CNS inflammation. Genetic analysis identified 4 variants in TNFRSF1A, including the N145S variant (also referred to as N116S), a variant only rarely reported in the literature. Treatment with canakinumab resulted in a significant reduction in flare frequency and decreases in inflammatory markers.
Conclusion: This study underscores the phenotypic diversity of TRAPS, as shown by the identification of the rare TNFRSF1A N145S variant and a case with CNS involvement. The estimated prevalence of TRAPS in Slovakia is approximately 1 : 780 000, and the clinical features of these patients are comparable to those reported in European cohorts. Furthermore, the favorable therapeutic response to canakinumab supports its potential as an effective treatment option for TRAPS.
Cite this article as: Slenker B, Banovcin P, Hrubiskova K, et al. TNF receptor–associated periodic syndrome: An analysis of a Slovakian cohort of TRAPS patients. Arch Rheumatol. 2025;40(3):288-298.
This study was approved by the Ethics Committee of the Jessenius Faculty of Medicine, Comenius University in Bratislava (Approval No.: EK UNM 77/2022; Date: 7 December 2022)
Written informed consent was obtained from all patients and their parents who agreed to take part in the study
Externally peer-reviewed.
Concept – B.S., P.B., K.H., V.V., D.G., M.J.; Design – B.S., M.J., K.H., V.V.; Supervision – P.B., M.J., A.M., A.B.; Resources – B.S., P.B., M.J., K.H., V.V.; Materials – B.S., K.H., M.J.; Data Collection and/or Processing – B.S., M.J., V.V., A.B., D.K., L.K., A.M.; Analysis and/or Interpretation – B.S., P.B., K.H., V.V., A.B., D.G., E.J.M., A.M., O.P., M.J.; Literature Search – B.S., K.H., E.J.M., D.K., D.G., A.M., M.J.; Writing Manuscript – B.S., K.H., V.V., A.B., D.G., E.J.M., D.K., L.K., A.M., O.P., M.J.; Critical Review – B.S., P.B., K.H., V.V., A.B., D.G., L.K., A.M., M.J.
The authors have no conflicts of interest to declare.
This publication has been produced with the support of the Integrated Infrastructure Operational Program for the project: Systemic Public Research Infrastructure – Biobank for Cancer and Rare Diseases, ITMS: 313011AFG5, co-financed by the European Regional Development Fund. This work was also supported by the Comenius University Grant No. US/158/2023 and Excellent Grant of Comenius University No. US/3133/2024.
The data that support the findings of this study are available on request from the corresponding author.