Background Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. It affects mainly population from Mediterranean origin and is associated with MEFV exon 10 mutations. FMF is characterized by short and recurrent attacks of fever, abdominal or thoracic pain that lasts less than three days [1]. Several studies reported that FMF diagnosis may be missed or delayed even in countries with a high prevalence of the disease such Turkey and Israel but real causes explaining diagnostic delay in FMF are not totally elucidated.

Objectives Our aim was to study a large cohort of European FMF patients to identify the frequency and associated factors of diagnosis delay.

Methods Clinical data were extracted from the Juvenile Inflammatory Rheumatism (JIR)- cohort. All FMF patients fulfilled Livneh Criteria and had a sequencing of MEFV exon 10 available [2]. We defined FMF-diagnostic delay (d-FMF) as a duration between the onset of the symptoms and FMF diagnosis of more than 10 years.

Results We enrolled 960 FMF patients; delayed diagnosis (d-FMF) was noted in 20% of patients (n=200) whereas 80% of other patients (FMF) (n=760) had the diagnosis made within the 10 years from the onset of symptoms. d-FMF patients were significantly older than other FMF with a median age of 46.4 years old versus 15.5 (p < 0.0001). Concerning women, the percentage of d-FMF was higher than other FMF patients (56% versus 47%, p=0.03).

Regarding the clinical presentation during FMF attacks, the difference was not statistically significant on abdominal pain, musculoskeletal symptoms and chest pain. Only, erysipelas-like erythema was more frequently observed among d-FMF patients (33% versus 22%, p=0.0003). The percentage of patients with one or two pathogenic MEFV mutation was not different between d-FMF and other FMF patients. AA amyloidosis was significantly more frequent in d-FMF than FMF (10 % versus 2.6 %, p< 0.0001). As well, d-FMF patients received significantly more biotherapy compared to other FMF (18% versus 3.8%, p<0.0001).

Conclusion Twenty percent of FMF patients were misdiagnosed before being officially diagnosed as FMF with significantly more women; this could be linked to the differential diagnosis of abdominal attacks with period pains, as frequently reported be women patients. Another clinical feature is erysipelas-like erythema which seems not be known as a pathognomonic symptom of FMF by all practitioners; this finding was previously reported in Israel and Turkey were the disease is however highly prevalent [4,5].

In conclusion, FMF delay is still significantly high nowadays. To our knowledge, our study is the first cohort study to investigate diagnostic wandering and the factors associated with long diagnostic wandering in a large European cohort. Education and better communication on this disease to patients and practitioners could be fruitful to improve FMF earlier diagnosis.

References [1]Savey L, Grateau G, Georgin-Lavialle S. Fièvre méditerranéenne familiale en 2020. Néphrologie & Thérapeutique 2021;17:S119–25. doi:10.1016/j.nephro.2020.02.013

[2]Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial mediterranean fever. Arthritis & Rheumatism 1997;40:1879–85. doi:10.1002/art.1780401023

[3]Lidar M, Tokov I, Chetrit A, et al. Diagnosis delay in familial Mediterranean fever (FMF): social and gender gaps disclosed. Clin Exp Rheumatol 2005;23:357–63.

Acknowledgements Investigators:

Joke Dehoorne, Pascal Pillet et Olivier Richer, Etienne Merlin, Gilles Kaplanski, Carine Wouters, Samuel Ardois, Claire Ballot, Isabel Bolt, Achille Aouba, Andreas Woerner, Florence Uettwiller, Charlotte Rebelle, Daniela Kaiser, Gerad Berthet, Catherine Barbier, Helmut Wittkowski, Federica Vanoni, Jurgen Brunner, Brigitte Bader-Meunier, Léa Savey, Gilles Grateau.

Disclosure of Interests None Declared.