FRI0568 THE USE OF NEXT GENERATION SEQUENCING PANEL IN UNDIFFERENTIATED AUTOINFLAMMATORY DISEASES IDENTIFY A SEPARATE SUBSET OF COLCHICINE-RESPONDER RECURRENT FEVERS DISTINCT FROM PFAPA SYNDROME
Authors: Riccardo Papa, Marta Rusmini, Stefano Volpi, Roberta Caorsi, Paolo Picco, Alice Grossi, Francesco Caroli, Francesca Bovis, Valeria Musso, Laura Obici, Cinzia Castana, Angelo Ravelli, Marielle E van Gijn, Isabella Ceccherini, Marco Gattorno
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The number of monogenic innate immune system disorders classified as systemic autoinflammatory diseases (SAID) has increased during the recent years. However, more than 70% of patients with clinical manifestations of SAID not achieved a molecular diagnosis, thus getting into the so-called undifferentiated or undefined SAID (uSAID). <h3>Objectives</h3> The aim of the present study is to characterize a subgroup of patients with recurrent fever episodes distinct to PFAPA that turned out to be negative to a large 41-gene NGS panel. <h3>Methods</h3> We designed an NGS panel including 41 genes clustered in seven subpanels. <h3>Results</h3> Fifty patients were enrolled in the study. 34 patients (72%) displayed recurrent fevers and sixteen presented a chronic inflammatory disease course. A total of 100 gene variants were found (mean 2 per patient; range 0-6). Mutations with a sure or possible diagnostic impact were detected in five patients (10%). Differently from PFAPA syndrome (table), genetically negative patients with recurrent fevers presented episodes that lasted on average of six days (P&lt;0.0001). Abdominal pain and limb pain were the most common symptoms. The classic PFAPA triad (pharingotonsillitis, aphthosis and cervical lymphadenopathy) was less frequently reported (P&lt;0.0001) while skin rash and arthritis were more frequent (P&lt;0.0001). Eighteen patients were exclusively treated with steroid on demand with a high response rate (94%). In 18 patients, colchicine treatment was used with an overall complete or partial response of 78%. <h3>Conclusion</h3> Even with a low molecular diagnostics rate, an NGS-based approach is able to provide a final diagnosis in a proportion of uSAID patients. It also allows the identification of a subgroup of genetically negative patients with recurrent fever responding to steroid on demand and colchicine. <h3>References</h3> [1] Rusmini M, et al. Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases. Ann Rheum Dis. 2016Aug;75(8):1550-7. <h3>Disclosure of Interests</h3> Riccardo Papa: None declared, Marta Rusmini: None declared, Stefano Volpi: None declared, Roberta Caorsi: None declared, Paolo Picco: None declared, Alice Grossi: None declared, Francesco Caroli: None declared, Francesca Bovis: None declared, Valeria Musso: None declared, Laura Obici: None declared, Cinzia Castana: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson &amp; Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson &amp; Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson &amp; Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Marielle E van Gijn: None declared, Isabella Ceccherini: None declared, Marco Gattorno Grant/research support from: MG has received unrestricted grants from Sobi and Novartis