A. Lo Monaco

Multicentric reticulohistiocytosis: a rare cause of erosive arthropathy of the distal interphalangeal finger joints

Background: Multicentric reticulohistiocytosis (MRH) is a rare systemic disease, presenting with typical skin abnormalities and erosive polyarthritis, which is often associated with malignancy. Case report: A case of MRH arthropathy, in which the typical nodular skin manifestation of the disease was absent, is described in a patient with a past history of breast cancer and no evidence of recurrent or new malignancy. Results: Careful clinical and roentgenological evaluation disclosed important clues to differentiate this condition from other more common distal interphalangeal arthritides—namely, osteoarthritis and its “erosive” variant, rheumatoid arthritis, psoriatic arthritis, tophaceous gout, dialysis related hand arthropathy, and from the rarer fibroblastic rheumatism, all of which can be mimicked by MRH. Histopathology showed the characteristic histiocytic and multinucleated giant cell infiltrate with ground glass cytoplasm, and immunohistochemical analysis showed markers evocative of a monocyte/macrophage origin of MRH.

Hearing Loss Evaluation of Sjogren's Syndrome Using Distortion Product Otoacoustic Emissions

Sjögrens syndrome (SS) is a cell-mediated immune disorder primarily affecting the exocrine glands and hearing loss may be the first otological manifestation of this autoimmune disease. In order to assess the degree of sensorineural hearing loss in SS, 22 female patients were examined by means of standard audiometric tests (pure-tone audiometry, acoustic reflexes and impedance testing) and using distortion product otoacoustic emissions (DPOAEs). The results indicated that only 36.3% of the patients had mild sensorineural hearing loss. Hearing level and distortion product threshold estimates were found to be significantly correlated. No relationship was found between the duration of the disease and the DPOAE and hearing threshold variables. The data suggest that SS may not directly cause sensorineural hearing loss.

AB0419 Frequency of disease flare and study of the cd4+cd25+highcd127low/- cell populations after discontinuation of anti-tnfΑ therapy in patients with rheumatoid arthritisin persistent remission

Background Rheumatoid arthritis (RA) patients in a prolonged remission status represent a population whose future management has yet to be established. Treg cell function in patients with active RA is assumed to be impaired, a trend that seems to be reversed by TNFalpha antagonist therapy (aTNF). Theoretically a deeper remission may be represented by an immunological resetting of immune system, a condition which could enable to consider the possibility of a drug-free remission. Objectives To evaluate the incidence of disease flare after cessation of aTNF in pts in remission together with reconstitution of the CD4 +CD25highCD127low/- Tcell subset respect to those patients in the same remission status with persistent low CD4 +CD25highCD127low/-Tcell population, assuming the Treg populations as a markers of deep remission allowing a better selection of those patients at low-risk of flare after aTNF withdrawal. Methods inclusion criteria: patients with RA (>18 years) fulfilling the 1987 ACR classification criteria treated with aTNF and synthetic DMARDs for at least 12 months, in remission (DAS28 <2.6/DAS44 <1.6)>6 months, without glucocorticosteroid. Exclusion criteria:<18 years, glucocorticosteroids within the three months before; another inflammatory disease other than RA; ongoing infections. Intervention: aTNF drug withdrawal with continuation of DMARDs previously associated (MTX or LFN); a 24 months of follow up was performed. Serial clinical and instrumental evaluation, blood sampling and radiographs have been performed according to the scheduled protocol. Treg population and several cytokines/chemokines/growth factors were analysed (Human Cytokine/Chemokine Panel I, Millipore). Results 23 patients were included, mean age 53 years (SD 12.3), 68% RF +, 52% ACPA +, DAS28 medium 1.41 (SD 0.48); average duration of illness 9.62 years (SD ±5.73). During the 24 month post-suspension follow-up, for a total of 267 person-months, 11 patients presented a flare, for a flare rate of 3.74/100 person-months (CI95% 1.79–6.88). The average observed exacerbation time from aTNF withdrawal was 14.6 months (SD ±9.32). None statistical predictive value of Treg levels regarding disease outcome after aTNF withdrawal was observed IIR (95% CI) 1.38 (0.82–2.30). None significant correlation among cytokines concentrations and disease status/Treg levels was observed. A correlation was observed between the presence of a synovitis with PD1+* at the baseline and the loss of remission [HR 7.062 (1.64–30.41, p 0.009);*higher values were exclusion criteria]. All 3 patients with positive US (PD1) who had flare-up were asymptomatic at baseline. Conclusions 47.8% of pts maintained aTNF-induced remission at 24 months continuing only sDMARDs therapy (MTX). Only in 1 case reintroduction of Adalimumab did not allow to regain clinical remission, which was obtained using another therapeutic target (anti-CTL4). The presence of a residual synovitis, although mild (PD1), was correlated with the risk of exacerbation. Further results will be discussed. Reference [1] Kawashiri, et al. J Rheumatol2011;38(12):2517–21. Acknowledgements Study financed with funds from the Emilia-Romagna Region deriving from the ”Alessandro Liberati” young researchers in the framework of the. Region-University research program 2013 Disclosure of Interest None declared

AB0595 Descriptive Analysis of A Single Center Series of 23 Patients with Positive PM-SCL Antibody

Background PM-Scl antibodies (abs) belong to the group of myositis-associated antibodies and typically determine a nucleolar or speckled pattern on immunofluorescence. These abs found in patients (pts) with Scleromyositis and, less frequently, in isolated forms of Systemic sclerosis (SSc), Polymyositis (PM) and Dermatomyositis (DM). In SSc pts PM-Scl +, pulmonary involvement seems less severe, while they show more frequent arthritis. Raynauds phenomenon (RP), digital ulcers (DU) and gastroesophageal involvement appear to be less frequently expressed. In myositis the association with esophageal and lung involvement is well known. Objectives To characterize demographic and clinical features of a single center series of PM-Scl positive patients. Methods Sera from 48 SSc and 60 idiopathic inflammatory myophaties (MII) attending local outpatient clinic, detected with EUROIMMUNE Myositis Profile 4 kit, were tested to search PM-ScL antibodies. Demographic, laboratory and clinical data (RP, arthritis, DU, muscular involvement, disphagia) were retrospectively retrieved from available clinical charts. The presence of interstitial lung disease (ILD), was evaluated by HRCT (measured by using score of Goh for the extension) and functional respiratory testing (FVC and DLCO). Severe ILD was defined by: Goh score of>20 and FVC and DLCO <75%. Results 23 Pts (18 F) resulted positive for PM-Scl. The mean age was 60.5±9.4 years and the mean disease duration was 145.9± 76.3 months. 1 patient had negative ANA, 1 showed ANA anticentromere and 1 dot pattern; the remaining 20 patients (86,9%) were ANA+ showing nucleolar pattern. By applying available formal classification criteria 5 (21.7%) pts were diagnosed as DM, 2 (8.7%) as DM amyopathic, 3 (13.05%) as overlap Scleromyositis, 3 (13.05%) as PM, 1 (4.4%) as cancer associated PM, 9 (39.1%) as SSc (2 diffuse, limited 6, intermediate 1). 13 (56.5%) pts had no evidence of cytopathic muscle involvement (defined as normal CPK, myoglobin and LDH). 5 pts (21.7%) presented a Goh score >20, 1 FVC <75%, and 7 (30.4%) DLCO <75%. 4 pts presented arthritis. 14 (60.8%) had RP, 6 (26%) DU, 8 (34.8%), dysphagia (see images 1). When compared with patients with SSc and MII negative for PM-Scl, MII PM-Scl + pts did not show significant greater risk of developing ILD (Goh>20)dysphagia or minor muscle involvement. SSc PM-Scl + pts seem to have a greater risk of developing arthritis and DU than their corresponding SSc PM-Scl negative pts (p<0.05) while no differences did emerged about ILD (Goh>20) and dysphagia. Conclusions The role of PM-Scl as a risk factor for ILD in MII pts is not confirmed, but should be considered the positivity in the control group of Jo1, representing per se a major risk factor for this complication (image 2). For patients with SSc is confirmed the role of PM-Scl as a risk factor for arthritis and digital ulcers but not for ILD. References Long-term out come of patients with polymiositis/dermatomyositis and anti PM/Scl antibody. Marie et al. Journal of Dermatology 2010; 162(2): 337–44 Disclosure of Interest None declared

SAT0170 Bdmards Mono vs Combo Therapy in Rheumatoid Arthritis. Analysis of A Rheumatological Single Tertiary Center Real-Life Experience

Background Despite adavantages of biological combo therapy over biological mono for RA treatement and the limited approval of biologics as monotherapy (etanercept, adalimumab, certolizumab, tocilizumab), real life registries data revealed that approximately one-third of patients taking biologic agents are using them as monotherapy. Objectives To assess the prevalence of bDMARDs use as monotherapy (bDMARDs-mono) in a cohort of RA patients treated with bDMARDs attending a tertiary rheumatological center.To characterize the clinical profile of these patients, and to investigate factors related to monotherapy. Methods All patients with Rheumatoid Arthritis attending our center and receiving bDMARDs up to 31th january 2015 were retrospectively analyzed. Demographic, and clinical characteristics of each patient were recorded: age, gender, disease duration, drugs history and clinical disease activity (DAS28) at last visit. Results 341 RA patients receiving bDMARDS were included. F 160, M 123, mean age 59.98 ±12.54, disease duration 178.69±101.81 months. 197 patients were taking bDMARD as first line bio-therapy, 144 had been previously treated with one or more bDMARDs. 52% (n=179) of patients were receving bDMARD-mono with a mean disease duration 187.4±125.1 month; 48% (n=162) were bDMARDs-combo, 65% of them with MTX; mean disease duration 168.9±42.4 m. Biologic agents used as mono or combo are shown in table 1. 32% of bDMARDs-mono had discontinued csDMARDs before starting biological therapy, 68% after an average 50,4 months after starting bDMARDs (p<0.001). The most common reasons for discontinuing csDMARDs were toxicity (55% of cases), with significant difference between those who stopped before and after starting bDMARDs (66% vs 48% respectively, p<0,02). 11% of patients discontinue csDMARDs because of nonspecific bad tolerance, 9% for inefficacy, 11% for others unspecified reasons. 25 patients (14%) on bDMARDs-mono stopped csDMARDs for clinical remission. Overall, 57% of RA patients were in clinical remission (DAS28 PCR <2.6) at the time of the inclusion in the study, without significant differece between the two groups (bDMARDs-mono vs combo). The use of bDMARDs-mono was more frequently observed in those patients with disease duration longer than 10 years (p<0,0001). Conclusions Biologic monotherapy for managing RA is widely used in our clinical practice especially in patients with long term disease. The proportion of patients (1/3) who start bDMARD-mono is quite similar to that reported in literature. On the other hand, most of patients arrive to bDMARDs-mono after starting biologic agent as the result of csDMARD witdrawal due to AE or intollerance to DMARDs and to a lesser extent because achieving good control of the disease since patients preference is strongly oriented to csDMARD discontinuation rather than bDMARDs withdrawal or tapering. References Emery P, et al. Ann Rheum Dis 2013:Dec:72 (12):1897–904. Disclosure of Interest None declared

SAT0310 Overlap Syndrome Systemic Sclerosis-Rheumatoid Arthritis and Pulmonary Involvement: Description of A Monocentric Series

Background the overlap syndrome Systemic sclerosis-rheumatoid arthritis (SSc-RA) is characterized by the presence in the same patient of clinical and laboratory features that meet the classification criteria for both diseases. The current literature shows how that lung involvement is more frequent and severe in SSc-RA than in SSc alone [1]. Objectives to describe the frequency of clinically significant interstitial lung disease (ILD), determining the reduction of the forced vital capacity (FVC) or the alveolar-capillary diffusion of carbon monoxide (DLCO) in a group of 25 patients with SSc-RA compared to a control group of 570 patients with SSc alone. Methods data were retrieved from a database and from medical records of patients followed at the outpatient clinic dedicated to SSc of the Rheumatology Unit of S. Anna Hospital, Ferrara. All patients fulfilled the classification criteria for SSc (ACR 1980 and LeRoy 2001) and RA (1987). For both groups (SSc and SSc-RA) the following seroimmunologic data were assessed: anticentromere antibodies (ACA), anti topoisomerase 1 (Scl 70), rheumatoid factor (RF) and anti-citrulline (ACPA). Pulmonary involvement was assessed by high-resolution chest CT scan using the score of Warrick, and spirometry including DLCO. A cut-off of Warricks score able to detect patients with ILD has been identified by the application of a regression curve between the total score at HRCT and spirometry data (FVC and/or DLCO <75% as predicted); the analysis identified a value>10 able to alter lung function. Results in the SSc control group FR was available in 38% of cases and ACPA only in 8.9% RF and ACPA were available in all 25 SSc-RA patients. Positivity for both FR and ACCP was detected in 23 SSc-RA patients whilst 2 were seronegative. ILD was more frequent in SSc-RA group compared to SSc (76% VS 33%, p<0.05, OR 6.43). The SSc-RA/ACA + group presented a higher frequency of ILD than in SSc/ACA + (54.5% VS 21.7%, p<0.05, OR 4:33) as if the known protective role of the ACA for the development of ILD was less relevant in SSc-RA. In the SSc group, the positivity of the RF seems to be associated with the risk of developing ILD only in patients ACA/Scl 70 negative (72% vs. 28%, p<0.05, OR 6.3). Due to missing data it was not possible to perform the analysis for the ACPA in SSc group. Conclusions an increased risk of ILD in SSc-RA compared to SSc was confirmed. In SSc-RA group, ACA seems to lose its role as a “protective” factor against the possible development of pulmonary fibrosis. If this information is confirmed, in SSc-RA patients, despite their ACA positivity, it could justify a more “tight” clinical-instrumental follow-up, to detect lung involvement early and to monitor its evolution. References Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity. Szücs G, Szekanecz Z, Zilahi E et al. Rheumatology (Oxford). 2007 Jun;46(6):989-93 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5137

THU0395 Adult Onset Still's Disease: A Multicenter Retrospective Cohort Study of 233 Italian Patients

Background Adult onset Stills disease (AOSD) is a rare rheumatic disease with an estimated prevalence of less than 1 case per 100,000 population. The diagnosis is difficult and is often delayed due to the lack of specific diagnostic tests and the need to rule out other pathological entities. Objectives To describe the clinical characteristics of a multicenter Italian case series of patients with AOSD. Methods 14 Italian University Hospital centers participated in the study. A standardized medical record containing clinical data, laboratory investigations, disease patterns and the different therapies has been sent to all participating centers. Each center collected data retrospectively. Results In the first wave of data collection, from March to May 2013, 233 patients were included with AOSD according to Yamaguchi criteria (125 males, 53.6%, mean age at onset: 40.2±16.2 years, time between onset and diagnosis: 242±650 days). The most frequent manifestations at onset were: arthralgia (93.0%), fever (92.6%), leukocytosis (89.0%), typical rash (67.7%), sore throat (61.8%), lymphadenopathy/splenomegaly (60.4%), increased liver enzymes (53.5%). In 56.4% of patients ferritin was increased more than 5 times the normal threshold. Fever intensity was recorded up to 41 ° C (mean 39.1±0.7), with a single daily peak in 27.3% of cases and 2 peaks in 51.9% of cases. The average duration of febrile episodes was 10.3 days with variable interval between episodes (average 3.2 days). Based on clinical evolution the disease was classified polycyclic systemic in 40.8%, chronic articular polycyclicin 30.7%, systemic monocyclic in 23.9% and chronic articular monocyclic in 4.6%. In 21.9% of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biological drugs have been shown to be effective. 56 cycles of biological drugs were used in 51 patients: anakinra in 22 cases, etanercept in 15 cases, infliximab in 8 cases, adalimumab in 7 cases, rituximab in 3 cases, tocilizumab in 2 cases, abatacept and golimumab in 1 case each (anti- TNFalpha 52.5%, 37.3% anakinra, other 10.2%). Conclusions This study presents the largest Italian multicentre series of AOSD patients. The main clinical and laboratory characteristics are in line with those reported in the literature. In more than 20% of patients biologics are the only drugs that allow to control the disease. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5300