Background Systemic autoinflammatory diseases (SAID) are characterized by inappropriate activation of the innate immune system and include not only monogenic periodic fever syndromes but also multifactorial conditions. As SAID are rare and represent a diagnostic challenge, a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients. Objective To describe the organization of our multidisciplinary SAID clinic and to characterize our clinical experience, highlighting the benefits of multidisciplinary team management. Methods Our SAID clinic takes place monthly and is managed by pediatric rheumatologists closely collaborating with pediatricians specialized in infectious diseases and immunodeficiencies and one medical geneticist. Patients’ data are systematically incorporated in the Rheumatic Diseases Portuguese Register (Reuma.pt). Biological samples are stored in a biobank. We describe our clinical experience based on SAID patients registered into Reuma.pt/SAID between July 2011 and June 2020. Results We have registered 176 patients, with a median age of disease onset of 3.1 ± 4.4 years and median age at disease diagnosis of 4.7 ± 4.0 years. Most patients were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome (PFAPA) (n=133), 20 with undefined SAID (uSAID) and 13 with monogenic SAID, including familial Mediterranean fever (FMF) (n=5), tumor necrosis factor receptor-associated periodic syndrome (TRAPS) (n=1), cryopyrin-associated periodic disease (CAPS) (n=1), and hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD) (n=2). A genetic test was performed in 31 patients (18%), and in 26% of these a mutation responsible for the phenotype was found. Thirty-four patients (19%) achieved remission. Conclusion FMF was the most common monogenic SAID and the percentage of patients with an identified causal mutation was low. A structured electronic clinical record coupled with a biobank and a multidisciplinary approach are crucial to ensure successful diagnosis and adequate follow-up of these patients.

BackgroundSystemic autoinflammatory diseases (SAIDs) are rare inherited disorders characterized by periodic or chronic multisystemic inflammation. The diagnosis is based on typical phenotypes and often supported by genetic testing. However, a distinct diagnosis cannot be met in half of these patients, being classified as undefined SAIDs (uSAIDs) [1].ObjectivesTo analyse the clinical and genetic characteristics of a portuguese cohort of uSAID.MethodsPatients followed up in 2 SAIDs clinics with recurrent or persistent episodes of systemic inflammation associated with serum acute phase reactants elevation who do not meet the PRINTO diagnosis criteria for any well-defined SAIDs [2] were classified as having uSAID. Patients who do not have any pathogenic gene mutation or have 1 variant of uncertain significance of a gene related to a well-known autosomal dominant SAID were included, as well as patients with pending genetic analysis. Categorical variables are described as frequencies and percentages and continuous variables as median (IQR1, IQR3).ResultsThis study included 24 patients, of which 12 (50.0%) were female and 12 (50.0%) were male. The median age at disease onset was 2.4 (IQR: 1.4, 8.2) years old, the median age at diagnosis was 6.5 (IQR: 2.4, 9.9) years old and the median time of disease duration was 6.8 (IQR: 9, 12.4) years. The majority of the patients (n=14, 58.3%) had episodes of recurrent systemic inflammation lasting 2 to 5 days. Two patients exhibited persistent inflammation. Regarding patients with recurrent inflammation, 10 (41.7%) had more than 12 episodes per year, 7 (29.2%) had 2 to 6 episodes per year and 4 (16.6%) had 7 to 12 episodes per year. The remaining patient had an episode every 2 years. In 13 (54.2%) the intercritical interval was regular, with a median of 21 days. Besides fever, the most commonly reported clinical manifestations were mucocutaneous lesions (n=24) including mouth ulcers (n=11), abdominal pain (n=12), lymphadenopathy (n=10) and arthralgia (n=10). C-reactive protein was elevated in all patients during attacks, erythrocyte rate sedimentation in 20 (83.3%) and amyloid A protein in 10 (41.7%). In 14 (63.6%) patients, acute phase reactants normalized during the intercritical phase. Genetic analysis was performed in 22 patients of this cohort – 8 patients were found to have a variant of uncertain significance in genes associated with hereditary SAIDs or mutations in genes that are not known to be associated with SAIDs and results are pending in the remaining 4. The most frequently used therapy was oral steroids (n=18, 75.0%) and half of these patients were treated with a single dose of 1 mg/kg of oral prednisolone on demand with shortening/resolution of the episode in 8 patients. Colchicine was used in 14 patients decreasing the number of episodes in 9 (64.2%). Anakinra led to complete remission in 3 of the 5 treated patients. Two patients were treated with canakinumab achieving complete remission. Infliximab, in association with azathioprine, resulted in disease remission in the only patient in which this therapy was used. None of the 3 patients submitted to tonsillectomy achieved remission.ConclusionSimilarly to other uSAIDs’ cohorts, mucocutaneus manifestations, abdominal pain and arthralgia were frequently reported. A third exhibited acute phase reactants elevation in the intercritical phase. Most of our patients had a favourable response to colchicine and IL-1 inhibitors. It is worth noting the high frequency of mouth ulcers, lymphadenopathy and pharyngitis and the high response rate to oral steroids and colchicine. These features resemble PFAPA syndrome, highlighting the challenges in the differential diagnosis of both conditions.References[1] Krainer J, Siebenhandl S, Weinhäusel A. Systemic autoinflammatory diseases. J Autoimmun. 2020 May 1; 109: 102421[2] Gattorno M, Hofer M, Federici S for the Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO), et alClassification criteria for autoinflammatory recurrent feversAnnals of the Rheumatic Diseases2019;78:1025-1032Acknowledgements:NIL.Disclosure of InterestsNone Declared.