AB1112\u2005DIAGNOSTIC DELAY AND DAMAGE OF POLISH ADULT PATIENTS AFFECTED BY HEREDITARY AUTOINFLAMMATORY SYNDROMES

Abstract

Background Autoinflammatory diseases (AIDs) cover a spectrum of diseases, which lead to chronic or recurrent inflammation caused by activation of the innate immune system, typically in the absence of high titre autoantibodies.1 The most common monogenic AIDs are cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF) and tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS). In hereditary AIDs, chronic and recurrent inflammation can lead to both acute disease and irreversible damage.2 Objectives To describe irreversible damage and diagnostic delay of AID in Polish adult patients (age≥18). Methods We rewieved the records of 11 Caucasian (2 women, 9 men) and one female patient with Middle Eastern ancestry followed in our center from Aug 2012 to Jan 2019. We analysed demographic features, diagnostic delay, previous diagnosis and organ damage3. Results Eleven patients had documented variant mutation and AID diagnosis (6-TRAPS, 4-CAPS, 1-FMF). One patient with AA amyloidosis had negative genetic results. The mean age of the patients at the time of disease onset was 9,1 years (0,1- 37) and 33 years (16-62) at diagnosis, In all Caucasian patients diagnosis was established after the age of 18. Previous diagnosis was: JIA (2), AOSD (2), UCTD (4), vasculitis (1), seronegative RA (1), FMF (3 finaly confirmed TRAPS) and allergy (3). Prior treatment included GCS (12/12), cDMARDS (7), antimalarials (6), colchcine (4), bDMARDS: tocilizumab-1, etanercept-2, adalimumab-1, CYC (2).After diagnosis 11 patients received IL-1 inhibitor, ankinra, Only one, 62 year old woman with TRAPS, did not need biological treatment. Only 3 TRAPS patients were free from damage accrual. We documented following damage categories: renal/amyloidosis (5 male cases), developmental (3 growth retardation), ear (severe hearing loss -3 CAPS cases). CINCA male patient at age 29 had multiple organ damage: neurological (epilepsy), severe hearing loss, severe ocular involvement (including optic nerve athrophy), joint restriction and deformity leading to complete physical disability. One FMF woman was adviced elective abortion, one MWS had miscarriage. Two of 3 women had history of malignancy (one: breast cancer and ovarian cancer, and another thyroid cancer). No any mental retardation occured. During follow up 2 male patients with extensive amyloidosis died despite anakinra treatment. Conclusion AID are misdiagnosed and have high risk of damage. We advocate the need for efforts in order to increase awarness of AID to reduce the diagnostic delay. The frequency of malignancy in AID should be addressed in future international collaborative studies. References [1] Masters SL, et al. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009;27:621–68. [2] Federici S, et al. Evidence-based provisional clinical classification criteria for autoinflammatory periodic fevers. Ann Rheumatic Dis 2015;74:799–805. [3] ter Haar NM, et al. Development of the autoinfammatory disease damage index. Ann Rheum Dis 2017;76:821–830 Disclosure of Interests None declared