Federica Furini

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study.

AbstractAnti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.

Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study

OBJECTIVE Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynauds phenomenon, fever or mechanics hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. METHODS Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. RESULTS 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9-51) and 40 (24%) developed new accompanying features after 19months median (IQR 6-56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68-9.21, p=0.002). CONCLUSION Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.

Application of SLICC classification criteria in undifferentiated connective tissue disease and evolution in systemic lupus erythematosus: analysis of a large monocentric cohort with a long-term follow-up:

Objectives The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999–2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients who met the classification criteria proposed by Mosca et al. for UCTD, were analysed. The SLICC 2012 classification criteria for SLE were retrospectively applied to each patient at the time of the diagnosis (T0) and also periodically re-applied and compared to ACR 1997 criteria at three different time points in the follow-up. Results 329 patients were enrolled. According to inclusion criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively applying the SLE/SLICC criteria, 44 patients already satisfied this set of criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC criteria and 14 patients met the ACR criteria with a stable rate of progression to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL) positivity and serositis were the variables correlated to the evolution to SLE. Conclusions In our UCTD population, the application of SLICC classification criteria for SLE at disease onset allowed identification of a proportion of otherwise missed SLE cases; during follow-up, and compared with ACR criteria, SLICC criteria expanded the number of patients classifiable as SLE otherwise classified as UCTD.

Involvement of the Inconstant Bursa of the Fifth Metatarsophalangeal Joint in Psoriatic Arthritis: A Clinical and Ultrasonographic Study

Objective. To evaluate the involvement of the bursa located next to the head of the 5th metatarsal bone in patients with psoriatic arthritis (PsA) in comparison with the other seronegative spondyloarthritis (SpA). Methods. All patients with PsA seen during a period of 24 months were enrolled. The control group included healthy subjects and patients with the other SpA. All subjects underwent clinical and ultrasound (US) examination of the lateral surface of the 5th metatarsal. Results. 150 PsA patients (88 M; 62 F), 172 SpA (107 M; 65 F), and 95 healthy controls (58 M; 37 F) were evaluated. Based on clinical and US evaluation, bursitis was diagnosed in 17/150 (11.3%) PsA patients but in none of the SpA (P < 0.0001) and healthy (P = 0.0002) controls. In detecting bursitis, US was more sensitive than clinical examination, although the difference did not reach statistical significance (P = 0.09). Conclusion. The bursa of the 5th metatarsophalangeal joint appears to be involved in PsA more frequently than by chance. If confirmed by other studies, this finding could be considered as a distinctive clinical sign of PsA, useful for differential diagnosis with the other SpA. In asymptomatic patients, US proved to be more sensitive in the detection of bursitis.

FRI0384 Usefulness of Brain MRI in Early Lupus: How the Morphological Imaging Changes at Onset of the Disease and After Follow-Up

Background The prevalence of neuroimaging abnormalities is not defined in newly-diagnosed Systemic Lupus Erythematosus (SLE), especially in those patients without overt neuropsychiatric (NP) symptoms; furthermore the clinical significance of these alterations is not clear at all. Objectives To assess the prevalence of brain abnormalities found by Magnetic Resonance Imaging (MRI) in a monocentric cohort of patients with early SLE onset (within 12 months from diagnosis) with (NP-SLE) or without NP manifestations (SLE) and to assess if early abnormal neuroimaging findings could have a predictive role for lesion load progression or the occurrence of subsequent NP events. Methods We selected SLE patients, less than 55 years, diagnosed according to the 1997 ACR criteria, who underwent brain MRI examinations within 12 months since diagnosis and then repeated it in the following 24-36 months. Brain MRI results were considered as absence or presence of white matter hyperintensities (scoring 0-3 if focal lesions were respectively none, 1, 2-4 or >5) and also as absence or presence of atrophy (scoring 0-3 if atrophy was absent, light, moderate or severe) according to a modified semiquantitative scoring system proposed by Petri et al. Then we evaluated the appearance of each new NP event along a median follow up period of 42 months. Results We retrospectively evaluated 752 patients referred consecutively at our clinic dedicated to SLE in a period of 20 years (between 1995 and 2014); 46 patients met the criteria for inclusion in the study. The mean age of the whole studied population was 34 years (14-55 yrs), 93.5% female. Of these patients, 28 had at least 1 NP event at time of diagnosis (61%). Overall an abnormal MRI was reported in 21 patients (46%), especially in those with NP involvement (18 NP-SLE and 3 SLE, p=0,0023). At baseline median atrophy score and WMHI score were 0,15 and 1,02 respectively. After the first NP event all patients either increased their immunosuppressive therapy (steroid and/or cyclophosphamyde bolus) or added aspirin low dose or anticoagulant drugs. At the time of the second MRI, a lesion load progression or worsening was seen in 26% (12): 29% (8) of NPSLE and 22% (4) of SLE pts (p>0,05); in all SLE patients the first MRI was negative. Total and median (1,2) WMHI score worsened during FU, median score for atrophy doubled (0,28). Almost all (92%) worsened MRI were associated with positivity of antiphospholipid antibodies. Comparing patients with unchanged MRI to those with worsened MRI a new NP event was recorded in 5 pts versus 6 pts (p=0,02), for a total of 11 new NP episodes. Conclusions Imaging abnormalities are present in a high percentage of SLE individuals at onset of disease (46%). A basal neuroimaging evaluation in young patients with newly diagnosed SLE is recommended especially because the evolution of the neuroradiological pictures seems to be independent of the previous history. Serial assessment is extremely useful to compare with any further imaging finding. Although a predictive value for abnormal neuroimaging in new appearance of NP event has yet to be demonstrated we found that MRI worsening could predict the occurrence of new NP event during follow up. Disclosure of Interest None declared

Osteoarthritis and its management - Epidemiology, nutritional aspects and environmental factors

Osteoarthritis (OA) is the most prevalent chronic rheumatic diseases worldwide, with a strong impact on individual and population health. OA is a clinically heterogeneous disease presenting with different clinical phenotypes recognising systemic and local risk factors. The pathogenesis is multifactorial including constitutive features of the joint, non-modifiable and modifiable risk factors. Epidemiological studies highlight the link between metabolic syndrome and OA and the effect of interplay between immunological and metabolic processes is getting increasing emphasis because of to the discovery that metabolic syndrome is implicated in OA pathogenesis and progression. In addition, recent findings suggest a potential role of dietary factors in susceptibility and progression of OA. In this review, we summarise the most robust evidence on epidemiology and classical risk factors OA, also exploring the most recent evidence on metabolic changes and Mediterranean diet for OA as a possible target to impact on the natural history of the disease.

The UltraSound-CLinical ARthritis Activity (US-CLARA) index: Properties of a new composite disease activity index for rheumatoid arthritis

OBJECTIVE To assess validity, responsiveness and interpretability of the UltraSound-CLinical ARthritis Activity (US-CLARA) index in patients with rheumatoid arthritis (RA). METHODS In this longitudinal study were involved RA patients starting treatment with abatacept. Subjects were followed along three visits in the first 6 months of therapy and underwent a comprehensive clinimetric evaluation. Validity was explored correlating the baseline scores and the cumulative inflammatory burden of the US-CLARA with the other composite indices applied. Sensitivity to change was assessed after 6 months of treatment in terms of internal and external responsiveness. Interpretability was defined in terms of determination of cutoffs against external criteria for remission (REM), low disease activity (LDA), moderate disease activity (MDA), and high disease activity (HDA) of SDAI. RESULTS One-hundred and thirty patients completed the study. VALIDITY moderate correlations were observed between US-CLARA and both DAS28-CRP and DAS28-ESR. Higher correlations were also found between US-CLARA and both SDAI and CDAI scores. Responsiveness: internal responsiveness was wide, with SRM and ES ranging from 0.91 to 1.51. US-CLARA responsiveness was similar to that of DAS28, SDAI, or CDAI. Similarly, the area under ROC curve (AUC-ROC) of US-CLARA gives identical results. The AUC of cumulative inflammatory burden, calculated during the 6-months follow-up of all combinations were highly correlated (p < 0.0001). Interpretability: cutoff values for REM, US-CLARA <2.0; for LDA, 2.0 ≤US-CLARA <3; for MDA, 3 ≤US-CLARA ≤4.8; for HDA, US-CLARA >4.8. CONCLUSION The US-CLARA is valid and sensitive tool to assess disease activity in RA.

AB0448 Use of denosumab in patients with systemic lupus erythematosus: a real life multi-centric experience

Background The occurrence of osteoporosis (OP) and fragility fractures (FF) is a frequent comorbidity in patients with systemic lupus erythematosus (SLE), mainly due to the concomitant presence of many risks factors for secondary osteoporosis (drugs, gender, concomitant diseases). The use of corticosteroids (CS) increases the risk of osteoporosis induced by corticosteroid (GIOP) and FF [1]. Denosumab is monoclonal antibody that binds to RANKL, inhibiting osteoclast formation and activation, used for both male and women OP to prevent FFx [2,3]. Previous RCT [2] reported a numerically higher serious adverse events of infections in the denosumab users. In particular severe skin infections were significantly more frequent [4]. The possible increase in infection risk might be a concern in subjects treated with CS. The use of denosumab in SLE with GIOP patients is recently reported in 17 cases within a RCT [5]. Anyway, no data regarding the tolerability and disease activity during therapy were reported Objectives Our aim was to analyze the prevalence, the tolerability, and relevant changes in disease activity or damage in a cohort of SLE patients treated with denosumab Methods among all SLE patients currently followed in two referral Center we selected the ones that received at least one dose of denosumab. Clinical, serological manifestations, concomitant diseases and therapies were collected from clinical charts. Damage index (SDI), activity index (SLEDAI-2K) were calculated when denosumab was introduced (first cycle) and at the last evaluation (last cycle). For statistical analysis Chi-squared test or Fisher exact test was used Results Among 793 patients in our cohorts, 21 (2.6%) were treated with denosumab. Demographic data reported a female prevalence (19 cases,90%), mean age at onset of 38±12years, mean duration of disease of 28±10years and mean follow-up of 21±7.8years; most frequent manifestations were arthritis (90%), cutaneous (67%) and neurological (67%). All patients were still treated with CS (mean duration of 25±6.8 years) with a daily dose of 8.5±3.5mg/day. Other risk factors for OP were present in the majority of them: drugs (anticoagulants in 6pts, cyclosporin in 3 and antiepileptic in 2), chronic kidney disease (CKD) (4pts), hypovitaminosis D (15pts), anorexia, celiac disease and hemochromatosis (1pt, each). Indication for denosumab was OP with FFx in 17 cases: denosumab was used for a new FF during biphosphonates or after teriparatide. In the other 4 the indication was primary prevention with contraindications at the use of biphosphonates for concomitant severe CKD. Mean duration therapy was 4 cycles (range 1–8): data regarding disease activity, damage and adverse events are reported in table 1. No new FFx developed in any of the included patients at the last evaluation available. Conclusions In our cohorts denosumab is still used in few selected patients. However it could be considered as a valid option in GIOP patients because it was globally well tolerated and in our cohort its efficacy in the prevention of new fragility fractures was confirmed References Gudbjornsson, et al. Ann Rheum Dis 2002;61,32–36. Cummings SR et al. N Eng J Med 2009; 61:756–65. Austin M et al. J Bone Miner Res 2012;27:687–93. Watts NB, Osteoporos Int 2012;23:327–37. Mok CC, et al. Bone 2015;75:222–8. 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

FRI0385 UCTD and Progression to SLE. Analysis of a Wide Monocentric Cohort with a Long Follow-Up

Background The term undifferentiated connective tissue diseases (UCTD) has been widely used to identify conditions not fulfilling classification criteria for a defined connective tissue diseases (CTD). Recently the introduction of new classification criteria for different CTD allowed to take a significant step forward for their early identification and for a more reliable diagnosis of UCTD. Objectives To analyze the clinical and serological characteristics of a large cohort of patients (pts) with UCTD and to evaluate: the incidence of Systemic Lupus Erythematosus (SLE) defined according two different “set” of classification criteria for lupus, ACR 1997 and SLICC 2012, in a time frame of 15 years (1999-2013); to analyse clinical and serological data comparing pts affected by stable UCTD to UCTD evolved to SLE. Methods A cohort of pts referred to our clinic dedicated to UCTD, who met the classification criteria proposed by Mosca et al. [1], were retrospectively analyzed. The pts with a median follow-up less than one year were excluded. Clinical and serological assessment was performed at the time of diagnosis (T0) and at 3 different time points indicated as T1 (time interval between the first and third year), T2 (between the third and fifth year) and T3 (from the fifth to the tenth year). The classification criteria for SLE, ACR 1997 and SLICC 2012, were applied to each patient at time T0, T1, T2 and T3. Results 329 pts were enrolled. An observation period up to T1 was recorded for the entire sample, up to T2 for 273 pts and 206 pts had completed the follow-up to T3. At T0 no pts met SLE/ACR criteria (according to inclusion criteria of study), whilst 44 pts met SLE/SLICC criteria: 41 females (F, 93.2%) and 3 males (M), mean age 40.1±14 years. Overall, at the end of the observation period, the SLE/SLICC criteria were cumulatively observed in 67 pts (20.4%), while 14 pts met the ACR criteria. In 12 pts both sets of criteria were satisfied. At the end of follow-up, 260 pts did not meet any set of classification criteria (UCTD stable, 79% of the whole population, 253 F and 7 M, mean age 53.6±15.5 years). During the follow-up the rate of progression to SLE was stable over the years, with a number of switch to SLE constant even after 5 years of diagnosis of UCTD. A peak rate of new cases was observed at T3 where five new cases of SLE/ACR (2.4%) and 7 cases of SLE/SLICC (3.4%) were recorded. The baseline clinical and serological characteristics of pts with stable UCTD were compared to pts evolved in SLE. Acute or subacute skin rash (p 0.02), serositis (p 0.03) and the presence of antiphospholipid antibodies (p 0.02) were the variables correlated with the progression to SLE/SLICC. Acute or subacute skin rash (p 0.001) and the presence of antiphospholipid antibodies (p 0.03) were the variables correlated with the evolution to SLE/ACR. Conclusions From our study in a cohort of UCTD pts the application of the new set of SLICC classification criteria for SLE, compared with the old ACR criteria, would not seem to have contributed significantly in terms of predictability of the evolution towards lupus, but certainly they expanded the number of pts classified as SLE at onset of the disease allowing a certain diagnosis in a greater number of pts who would otherwise be classified as UCTD. References Mosca M et al. Clin Exp Rheumatol 1999;17:615-620. Disclosure of Interest None declared