Julia Martínez-Barrio

Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and which joints should be assessed?

To investigate the sensitivity for detecting subclinical synovitis of different reduced joint ultrasound (US) assessment models as compared with a comprehensive US assessment in rheumatoid arthritis (RA) patients in clinical remission.

Predictive value of Doppler ultrasound-detected synovitis in relation to failed tapering of biologic therapy in patients with rheumatoid arthritis

OBJECTIVE To investigate the predictive value of synovitis detected by Doppler US in relation to failed tapering of biologic therapy (BT) in RA patients in sustained clinical remission. METHODS A total of 77 RA patients (52 women, 25 men) in sustained clinical remission, treated with a stable dosage of BT were prospectively recruited. BT was tapered according to an agreed strategy implemented in clinical practice (i.e. increasing the interval between doses for s.c. BT and reducing the dose for i.v. BT). BT tapering failure was assessed at 6 and 12 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy and synovial power Doppler signal (i.e. Doppler synovitis) was performed at baseline by a rheumatologist blinded to clinical and laboratory data. Hand and foot radiographs were obtained at baseline and at 12-month follow-up. RESULTS Of the 77 patients, 46 (59.7%) were on s.c. BT and 31 (40.3%) on i.v. BT. At 12 months, 35 patients (45.5%) presented BT tapering failure, 23 of them (29.9% of all patients) in the first 6 months of BT tapering. In logistic regression analysis, the baseline DAS28 and the global score of Doppler synovitis were identified as independent predictors of BT tapering failure at 12 and 6 months. The presence of Doppler synovitis was the strongest predictor for BT tapering failure. No patient showed radiographic progression. CONCLUSION Our results suggest that the presence of Doppler-detected synovitis may predict BT tapering failure in RA patients in sustained clinical remission.

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.

Structural damage in rheumatoid arthritis: comparison between tendon damage evaluated by ultrasound and radiographic damage

OBJECTIVE To compare structural damage assessed by conventional radiography and tendon damage assessed by musculoskeletal US (MSUS) at wrist and ankle in RA patients. METHODS We evaluated 72 consecutive patients [56 (77.8%) females] with RA. The MSUS evaluation consisted in a B-mode examination of bilateral extensor carpi ulnaris and tibialis posterior tendons. Tendon damage was defined and scored according to OMERACT. A total score for the tendon damage score (TDS) was calculated by summing the grades for each tendon. For the radiographic evaluations we used the van der Heijde score; a total radiographic score (RTS) was calculated by summing a bone erosion score (ERS) and a joint space narrowing score (JSNS). RESULTS We evaluated 288 tendons. The mean (s.d.) of TDS was 2.3 (1.8). Fifty-four (75%) patients presented tendon damage of at least one tendon. From all evaluated tendons, 134 (46.5%) had no tendon damage, 146 (50.7%) had grade 1 and 8 (2.8%) had grade 2 tendon damage. The mean (s.d.) for RTS was 91.4 (97), for ERS was 47.3 (61.9) and for JSNS was 44.1 (37.2). We found a significant correlation between disease duration and both TDS and RTS (r = 0.413 and r = 0.560, respectively; P < 0.0001). We found a good significant correlation between TDS and all variables of radiographic structural damage (RTS, r = 0.65; ERS, r = 0.637; JSNS, r = 0.618; P < 0.001). CONCLUSION The MSUS assessment of only four tendons can be an additional feasible method to assess structural damage in RA patients.

SAT0509 Clinical and Serological Profile of Children with Positive SSA-Ro/SSB-La Antibodies

Background Several studies have shown the relationship between anti-SSA-Ro/SSB-La antibodies and Systemic Lupus Erythematosus (SLE), Sjögren Syndrome (SS) and other autoimmune diseases in adult population. However, the expression of these autoantibodies and clinical correlation in juvenile patients is poorly described. Objectives To characterize the clinical and serological profile and primary rheumatic diseases in pediatric patients with positive anti-SSA-Ro and/or anti-SSB-La antibodies. Methods The data was obtained from a long term prospective cohort of patients under age 18 diagnosed with rheumatic diseases in a tertiary hospital in Spain. Demographic, clinical, and laboratory data were collected from 1986 to 2010. Patients were divided into 2 groups: anti-SSA-Ro/SSB-La positive and anti-SSA-Ro/SSB-La negative. Results A total of 187 patients were tested for anti Extractable Nuclear Antigens (ENA), with a following mean time of 11 years. Mean age at disease onset was 12.6 years and 77% were female. Fifty-four (28.9%) anti-SSA-Ro/SSB-La positive subjects were compared against 133 (71.1%) anti-SSA-Ro/SSB-La negative subjects. Among positive cases, 13 (24.1%) patients were double-positive for anti-SSA-Ro and anti-SSB-La, 51 (94.4%) were positive for anti-SSA-Ro and 3 (5.5%) were single-positive for anti-SSB-La. The anti-SSA-Ro/SSB-La antibodies were found less frequently (p=0.003) in the overlapping syndromes, and more frequently in SLE (p=0.007). In addition rheumatoid factor (p<0.001), anti-Sm (p<0.001) and anti-RNP (p<0.001) were frequently co-expressed with anti-SSA-Ro/SSB-La antibodies. Finally the anti-SSA-Ro/SSB-La positive group presented more hematological and skin manifestations than the negative group (p<0.05). Conclusions Similarly to adults, we observed a relationship between anti-SSA-Ro/SSB-La antibodies and SLE in pediatric patients. However a low proportion of childhood primary SS exists in our anti-SSA-Ro/SSB-La positive cases. This could be explained by underdiagnoses related to the atypical clinical presentation of SS in pediatric population. Single-positive anti-SSB-La patients are uncommon, the clinical significance of this serological result remains uncertain in children. References Rheumatol Int (2014) 34:1123–1127. Disclosure of Interest None declared

Salivary gland ultrasound is linked to the autoimmunity profile in patients with primary Sjögren’s syndrome:

Objective Salivary gland ultrasound (SGU) is a reliable technique for assessing the salivary glands in patients with primary Sjögren’s syndrome (pSS). The aim of this study was to elucidate the relationship between SGU findings and autoimmunity in patients with pSS. Methods Patients with pSS underwent an SGU assessment. The patients were classified into three groups according to their autoimmunity profile: the complete positive group (positive rheumatoid factor, antinuclear antibodies, and anti-Ro/anti-La antibodies), the partial seropositive group (positivity of at least one autoantibody but not all), and the seronegative group. Results In total, 93 patients were evaluated. Eighty-six (92.5%) were female, and their median age was 49.5 years. The median disease duration was 12.3 years. Pathological SGU findings were present in 32 (34.4%) patients [25 of 36 (78.1%) in the complete positive group and 7 of 44 (21.9%) in the partial positive group]. Patients with pathological SGU findings had a shorter disease duration and slightly higher European League Against Rheumatism Sjögren’s syndrome disease activity index. Conclusions The autoimmunity profile and pathological SGU findings are strongly associated with each other in patients with pSS. However, the disease duration does not seem to be related to pathological SGU findings.

FRI0260 Survival, causes of death and mortality risk factors in systemic sclerosis

Background Among the rheumatic diseases, Systemic Sclerosis (SSc) stands out as a severely incapacitating and life-threatening disease. Objectives To analize the causes of death, survival and risk factors for mortality in SSc patients. Methods Demographic, clinical, immunological and mortality data were obtained from a long term prospective cohort of SSc patients recruited between 1986 and 2011 in the Rheumatology Department of Gregorio Marañon Hospital in Madrid, Spain. Patients were divided into 4 groups: limited SSc, diffuse SSc, SSc in overlap and SSc in mixed connective tissue disease (SSc-MCTD). ANOVA, Kruskal-Wallis or χ2 tests were used to identify differences among groups; Kaplan-Meier and Mantel-Haenszel (log-rank) analysis were used to estimate survival, and Cox proportional hazards regression analysis was used to identify factors associated with mortality. Results A total of 137 patients were included, of whom 122 (89%) were women. Mean age at diagnosis was 43±17.7 years, and the mean follow-up time was 15.2 years. A global mortality of 34 (24.8%) cases was observed: 8 related to cardiac involvement, 8 to serious infections, 7 to pulmonary involvement, 6 to neoplasms, 2 to renal involvement and 3 to other causes. Survival rates from disease onset were 96, 90, 75 and 50% at 5, 10, 20 and 30 years, respectively. Limited SSc and SSc-MCTD show a significantly (p=0.002) higher survival mean time (33.7 years) when compared to diffuse and overlap variants (22.4 years). Poorer survival is associated with interstitial lung disease, pulmonary arterial hypertension, severe infections, cardiac involvement, chronic kidney disease, and Anti-Ro antibodies (see table 1). Independent prognostic factors for mortality were interstitial lung disease (HR 6.8, CI 95% 1.5-30, p=0.012), pulmonary arterial hypertension (HR 5.6, CI 95% 1.2-26.9, p=0.032), and Anti-Ro antibodies (HR 3.9, CI 95% 1.5-9.8, p=0.004). Table 1. Risk factors related to mortality. Univariate and multivariate analysis Factors Dead (%) Alive (%) HR (95% CI) p* Diffuse SSc 47.1 26.2 3.4 (1.1-10.2) 0.031 SSc in Overlap 20.6 6.8 3.9 (1.1-14.2) 0.032 Severe Infections 64.7 21.4 3.6 (1.7-7.4) <0.001 Interstitial lung disease‡ 84.4 50 3.3 (1.2-8.5) 0.016 Pulmonary arterial hypertension‡ 17.6 4.9 3.1 (1.2-7.5) 0.014 Cardiac Involvement 61.8 16.5 2.8 (1.4-5.9) 0.004 Chronic kidney disease 20.6 2.9 3.2 (1.3-7.9) 0.011 Anti-Ro‡ 39.3 16.3 3.2 (1.5-7.2) 0.004 Anti-Ro 52KDa 28.6 15.1 2.5 (1.1-5.9) 0.03 Anti-Ro 60KDa 14.3 5.8 2.4 (0.8-7.1) 0.118 SSc: Systemic Sclerosis. *Univariant Cox proportional hazards regression analysis. ‡Independent risk factors for mortality. Conclusions A 20-year survival was seen in more than 70% of SSc patients. The main causes of death are cardiac involvement, severe infections and pulmonary manifestations. Diffuse SSc, SSc-MCTD, interstitial lung disease, pulmonary arterial hypertension, severe infections, cardiac involvement, chronic kidney disease, and Anti-Ro antibodies are the main risk factors for mortality. Disclosure of Interest None Declared