{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:44:52Z","timestamp":1790747092042,"version":"4.1.0"},"reference-count":39,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2024,10,20]]},"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Familial Mediterranean fever (FMF) is a genetic disease leading to recurrent episodes of inflammation. Two pathogenic variants are required for classical disease, but the disease can occur in heterozygous patients. Patients are treated continuously with colchicine to prevent amyloid A (AA) amyloidosis, including heterozygous patients who display a moderate form of FMF and rarely develop AA amyloidosis. The need for lifelong colchicine treatment in heterozygous FMF is therefore controversial. We aimed to characterise genotype-specific levels of inflammatory biomarkers, and to focus on heterozygous patients who discontinued colchicine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>All patients with FMF from the European databases AIDnet and JIRcohort who received colchicine during follow-up were included. Demographics, C reactive protein (CRP), serum amyloid A (SAA), S100A8\/A9 and S100A12 levels, leucocyte and neutrophil counts were extracted. Visits were classified as active, subclinical or inactive according to symptoms, CRP and SAA levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Data from 747 patients were extracted (233 homozygous, 201 compound heterozygous, 224 heterozygous patients, 49 heterozygous with one class III variant and 40 compound heterozygous with two class III variants). During active visits, all biomarker levels were higher compared with inactive visits (p&lt;0.001). Heterozygous patients showed lower levels of CRP, SAA, S100A8\/A9 and S100A12 during inactive and subclinical visits than patients with two class IV-V variants. Colchicine was discontinued in 52 heterozygous patients and reintroduced in 23 of them (44%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>S100A8\/A9 and S100A12 proteins are biomarkers that can be used to assess disease activity. Heterozygous patients have lower levels of inflammatory biomarkers and some of them can sustainably discontinue colchicine treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-004677","type":"journal-article","created":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T13:05:36Z","timestamp":1732453536000},"page":"e004677","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Inflammatory biomarker analysis confirms reduced disease severity in heterozygous patients with familial Mediterranean fever"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9767-2262","authenticated-orcid":false,"given":"In\u00e8s","family":"Elhani","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Hospital Centre Versailles, Le Chesnay, France"},{"name":"Department of Internal Medicine, H\u00f4pital Tenon, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Backes","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology and Immunology, University Medicine, Albert-Schweitzer-Campus 1, Munster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2404-9397","authenticated-orcid":false,"given":"Tilmann","family":"Kallinich","sequence":"additional","affiliation":[{"name":"Pediatric Pneumology and Immunology, Charite Medical Faculty Berlin, Berlin, Germany"},{"name":"Charit\u00e9 University Medicine Berlin, Social Pediatric Center, Berlin, Germany"},{"name":"German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayane","family":"Amaryan","sequence":"additional","affiliation":[{"name":"National Pediatrics Center for Familial Mediterranean Fever, \"Arabkir\" Medical Complex-Institute of Child and Adolescent Health, Yerevan, Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-5332","authenticated-orcid":false,"given":"Alexandre","family":"Belot","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Rheumatology and Dermatology, Centre Hospitalier Universitaire de Lyon, Lyon, France"},{"name":"Innate Immunity in Infectious and Autoimmune Diseases, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Berendes","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology, Children's Hospital St. Marien, Landshut, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Witten\/Herdecke University, Witten, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Dressler","sequence":"additional","affiliation":[{"name":"Kinderklinik, Medizinische Hochschule Hannover, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1946-3916","authenticated-orcid":false,"given":"Dirk","family":"Foell","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology and Immunology, University Medicine, Albert-Schweitzer-Campus 1, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"F\u00fchner","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology and Immunology, University Medicine, Albert-Schweitzer-Campus 1, Munster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnd","family":"Giese","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Marienhospital Herne Medical Center of Ruhr University Bochum, Herne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claas","family":"Hinze","sequence":"additional","affiliation":[{"name":"Pediatric Rheumatology and Immunology, University Medicine, Albert-Schweitzer-Campus 1, Munster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Lisa","family":"Hitzegrad","sequence":"additional","affiliation":[{"name":"Charit\u00e9 University Medicine Berlin, Social Pediatric Center, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Horneff","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Asklepios Hospital Group, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Jansson","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology and Immunology, Department of Pediatrics, University Hospital of Munich, Munchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2954-5755","authenticated-orcid":false,"given":"Jens","family":"Klotsche","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, German Rheumatism Research Center Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Lainka","sequence":"additional","affiliation":[{"name":"Department of Paediatrics II, University Hospital Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Niehues","sequence":"additional","affiliation":[{"name":"Helios Klinikum Krefeld, Center of Pediatrics and Youth Medicine, Krefeld, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad","family":"Oommen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology, Division of Pediatric Rheumatology, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes-Peter","family":"Haas","sequence":"additional","affiliation":[{"name":"German Center for Pediatric and adolescent Rheumatology, Hospital Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Rietschel","sequence":"additional","affiliation":[{"name":"Kinder- und Jugendrheumatologie, Clementine Children's Hospital\u2014Dr Christ'sche Foundation, Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Theodoropoulo","sequence":"additional","affiliation":[{"name":"D\u00e9partement Femme-M\u00e8re-Enfant (DFME), Unit\u00e9 Romande d'Immuno-rhumatologie P\u00e9diatrique (URIRP), CHUV, University of Lausanne, Lausanne, 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