Mariagrazia Modesti

The 6-joint ultrasonographic assessment: a valid, sensitive-to-change and feasible method for evaluating joint inflammation in RA

OBJECTIVE Musculoskeletal US can be useful in monitoring RA. It can be time-consuming and there is no consensus in defining the joints to evaluate. We assessed the validity, sensitivity to change and feasibility of a reduced 6-joint US score in patients with RA starting therapy with an anti-TNF agent. METHODS A group of consecutive RA patients starting etanercept were investigated. The patients underwent clinical evaluation, laboratory tests and US assessment at baseline and 3 months. A semi-quantitative score (0-3) was used to evaluate synovial effusion (SE), synovial proliferation (SP) and power Doppler (PD) signal in 12 joints. A process of data reduction, based on the frequency of synovial site involvement by US-SE, US-SP and US-PD signal, was conducted to investigate the validity of a 6-joint US assessment. RESULTS Forty-five RA patients were evaluated. A significant decrease in all clinical, serological and 12-joint US parameters was found at follow-up. A significant correlation between changes in the DAS-28 and changes in the US scores in the 12-joint assessment was observed at follow-up (P < 0.001). A reduced 6-joint US score was obtained, including wrist, second MCP and knee joints of both sides, detecting US-SE in 97.78% of patients, US-SP in 100% of patients and positive US-PD in 100% of patients. The 6-joint US score showed a highly significant correlation with changes in DAS-28 (P < 0.001). The 6-joint evaluation was quick and easy to do. CONCLUSION A 6-joint US assessment may be a valid, sensitive-to-change and feasible method for evaluating joint inflammation in RA.

Clinical and ultrasonography assessment of peripheral enthesitis in ankylosing spondylitis

OBJECTIVE The aim of this study was to compare clinical examination with power Doppler US (PDUS) in the detection of entheseal abnormalities in patients with AS. METHODS Thirty-six AS patients underwent clinical and PDUS examination of the following bilateral entheseal sites: common extensor tendon at its insertion at the lateral humeral epicondyle; gluteus tendons at their insertion at the greater trochanter; quadriceps tendon at its insertion at the superior pole of the patella; patellar tendon at its proximal insertion at the inferior pole of the patella; patellar tendon at its distal insertion at the tibial tuberosity; Achilles tendon at its insertion at the calcaneus; and plantar aponeuroses at its insertion at the calcaneus. RESULTS Clinical and PDUS examination revealed at least one abnormal enthesis in 23 (63.9%) and 35 (97.2%) AS patients, respectively. Furthermore, of 432 entheses examined in our 36 AS patients, 64 (14.8%) were considered abnormal by clinical examination and 192 (44.4%) by PDUS. US abnormalities most commonly found were enthesophytes (31.7%), calcifications (33.7%), thickening (29.8%) and hypoechogenicity (26.6%). We found erosions and PD signals in 9.7 and 6% of examined entheseal sites, respectively. The evidence of entheseal abnormalities by clinical examination has a poor likelihood ratio (LR) for the presence of US abnormalities with vascularization (LR = 1.61), without vascularization (LR = 1.24) or erosions (LR = 1.51) at all sites. CONCLUSIONS PDUS permits detection of structural and inflammatory abnormalities of the enthesis in AS and may complement the physical examination in order to better evaluate enthesitis.

The interobserver reliability of ultrasound in knee osteoarthritis

OBJECTIVE To assess the interobserver reliability between sonographers with different levels of experience in detecting inflammatory and structural damage abnormalities in patients with knee OA. METHODS After achieving consensus on definitions and scanning protocols, three ultrasonographers with different levels of experience in musculoskeletal US examined the knees of nine patients with OA. US examinations were conducted with independent blinded evaluations of inflammatory (joint effusion, synovial hypertrophy, power Doppler signal, Bakers cysts) and structural (osteophytes, cortical bone irregularities, femoral hyaline cartilage abnormalities, protrusion of the medial meniscus) lesions. All abnormalities were scored by applying a dichotomous scale (0-1). In addition, at each knee joint site global scores for joint inflammation, cortical bone abnormalities and cartilage damage were calculated by summing the single-lesion scores. Reliability was assessed using kappa (κ) coefficients. RESULTS Seventeen knees were examined. Inflammatory abnormalities were observed with moderate to very good agreement (κ = 0.55-0.88) between the observers. From fair to very good agreement (κ = 0.31-0.82) was registered between sonographers for structural damage lesions. The overall κ was 0.716 for junior and 0.571 for beginner sonographers comparing their findings with those of senior sonographers. CONCLUSION This represents the first ultrasonographic study focusing on the analysis of interobserver reliability between sonographers with different levels of experience in demonstrating inflammatory and structural abnormalities in knee OA. Globally, even considering some variable results that were mainly obtained by the evaluation of single components of bone involvement, US offered a reliable assessment of a wide set of abnormalities in knee OA.

The Role of Anti-Cyclic Cytrullinate Antibodies Testing in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disease, which leads to joint destruction and deformity and is often accompanied by systemic complications. It is generally considered an autoimmune disease characterized by several autoantibodies. The impressive advances made in understanding the biological mechanisms of RA have led to more focused, directed therapies that have joined, and in many cases overcome, more traditional treatments. Along the last decade, the so-called biological anti-TNF-alpha agents have been shown to reduce disease activity, to slow disease progression and to improve patients’ quality of life. The clear evidence that an early therapeutic intervention improves the overall outcome of the disease supports the importance of an early diagnosis. In the last years, several studies showed that anti-cyclic citrullinated peptide antibodies (anti-CCP) represent a sensitive and specific serologic marker for RA. Moreover, a large body of evidence has shown that anti-CCP may also serve as an early diagnostic and prognostic marker in RA. The aim of this article is to provide an overview of the current state of knowledge regarding anti-CCP focusing in particular on their clinical specificity and prognostic value in RA.

Subclinical synovitis in primary Sjögren’s syndrome: an ultrasonographic study

OBJECTIVES To evaluate, by musculoskeletal ultrasound (MSUS), articular involvement in primary SS (pSS) patients by analysing hand and wrist changes, and to correlate them with clinical evaluation and laboratory tests. METHODS Thirty-two pSS patients underwent clinical and laboratory examinations, including the SS Disease Damage Index (SSDDI) and the SS Disease Activity Index (SSDAI). MSUS was performed in all patients in both hands and wrists, evaluating the presence of inflammation within joints and periarticular tissues, and the existence of permanent joint damage. For synovial hypertrophy, joint effusion and Doppler signal findings, a semi-quantitative score (0-3) was used indicating the degree of involvement (0 = normal; 1 = mild change; 2 = moderate change; and 3 = severe change). For tenosynovitis and bone erosions, a dichotomous score (0 = absent and 1 = present) was applied. RESULTS Sonographic signs of synovitis of the radio-ulno-carpal joint were found in 17 (26.5%) out of 64 wrists. Wrist synovitis was found in 12 (37.5%) out of 32 patients. Ultrasonographic examination of the hand did not show significant changes. A statistically significant correlation was found between SSDDI score and the degree of sonographic signs of synovial proliferation in the wrist (P = 0.04). The correlation between the incidence of clinical involvement and the presence of pathological ultrasonographic findings was not significant. Patients with synovitis had a higher median age and higher median SSDDI (P = 0.004). CONCLUSIONS In pSS patients, MSUS may be considered a useful tool for detecting synovitis since articular involvement can often be silent but correlated with SSDDI.

SAT0207 Correlation of clinical, serologic and histologic findings in a large cohort of primary sjögren’s syndrome patients: A multicentric cross-sectional study

Background Although primary Sjögren’s syndrome (pSS) is often a benign condition some patients develop systemic features. Identifying independent risk factors for pSS different clinical phenotypes would provide useful insights into patients’ assessment. Objectives to describe the clinical presentation of pSS in a large cohort of patients and to identify independent risk factors for severe disease manifestations. Methods Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent risk factors for disease manifestations were identified by logistic regression. Results The cohort included 1115 (1067 F:48M) pSS patients with a mean age of 51.6±13.8 yrs at diagnosis and 57.5±13.7 yrs at inclusion in the study (mean follow-up=5.8±6.5 yrs). Anti-Ro/SSA and anti-La SSB were detected in the 68% and 37% of the cases. Xerostomia (92%), xerophtalmia (94%) and articular involvement (61%) were the most commonly detected clinical manifestations. Salivary gland enlargement was detected in 346/1115 (31%) pSS patients while 475/1115 (42%) developed systemic extra-glandular involvement. Moderate to severe leukopenia (28%), peripheral arthritis (11%) and sensory-motor neuropathy (1.8%) were the most severe disease extra-glandular manifestations requiring immunosuppressive drugs. Independent risk factors for leukopenia were Raynaud’s phenomenon (RP) (p=0.008), low C3 (p=0.001), hypergammaglobulinemia (p=0.0006) and cryoglobulinemia (p=0.01). Arthritis was associated to RP (p=0.005) while sensory-motor neuropathy to purpura (p<0.0001), low C4 (p<0.0001) and cryoglobulinemia (p<0.0001). From the analysis, low C3/C4, hypergammaglobulinemia and cryoglobulinemia emerged as prognostic adverse laboratory abnormalities. Table 1 summarises patients’ clinical presentation according to the number of the laboratory abnormalities detected (“group A” = no abnormalities, “group B” =1 and “group C” ≥2 abnormalities). No factors 1 factor ≥2 factors p-value n=469 n=427 n=219 p-value Salivary gland enlargement 106 (22.6%) 150 (35.2%) 90 (41.1%) 0.000 Purpura 15 (3.2%) 35 (8.3%) 56 (25.7%) 0.000 Kidney 2 (0.4%) 12 (2.8%) 10 (4.6%) 0.001 Haematological manifestations 88 (19%) 152 (35.6%) 118 (54%) 0.000 Lung 20 (4.3%) 21 (4.9%) 19 (8.7%) 0.05 Peripheral nervous system 21 (4.5%) 18 (4.2%) 20 (9.1%) 0.01 Lymphoma 9 (1.9%) 10 (2.3%) 31 (14.2%) 0.000 Anti-Ro/SSA 239 (51.5%) 336 (79.4%) 187 (85.4%) 0.000 Anti-La/SSB 96 (20.7%) 200 (47.3%) 114 (52.1%) 0.000 Rheumatoid Factor 158 (36.3%) 264 (66%) 160 (73.7%) 0.000 Focus score ≥1 240 (77.9%) 226 (82.2%) 111 (88.8%) 0.03 Glucocorticoids 168 (36.3%) 166 (39.1%) 104 (47.9%) 0.01 Immunosuppressive drugs 42 (9.3%) 62 (14.7%) 69 (30.1%) 0.0001 Conclusions This study described the presentation of pSS in a large cohort of patients allowing us to identify independent risk factors which might help to predict the signs and symptoms of the disease. Patients with laboratory signs of B-cell hyperactivation should be more closely monitored since they may be at higher risk of severe extra-glandular involvement. Disclosure of Interest None Declared

Nucleosome accumulation and reduction of C-reactive protein are associated with the generation of anti-nuclear antibodies in patients with rheumatoid arthritis treated with adalimumab, but not with etanercept

During the last decade, three tumour necrosis factor (TNF)α antagonists have been approved for the treatment of moderate to severe rheumatoid arthritis (RA).1 These new drugs, while extremely powerful, can induce puzzling biological phenomena such as the production of autoantibodies whose extent seems to vary accordingly to the drug used.2,3 A dysregulation of apoptosis with exposition of nuclear antigens and consequent rapid (within hours) accumulation of nucleosomes has been evoked to explain autoantibody occurrence in patients treated with infliximab.4 In addition (or in alternative) to an increased release of nuclear antigens, a defect in clearance mechanisms can play a role in the generation of autoantibodies.5 We studied autoantibody profiles (anti-nuclear antibody (ANA), anti-double stranded …

SAT0212 Pregnancy and fetal outcome in patients with an established diagnosis of primary sjögren’s syndrome

Objectives To investigate pregnancy and fetal outcome in patients with an established diagnosis of primary Sjögren’s syndrome (pSS) Methods The clinical charts of 1073 women with pSS from four rheumatology centres were retrospectively evaluated. When a pregnancy has occurred after pSS diagnosis, the patient was personally interviewed to obtain more detailed information regarding obstetric history; obstetric clinical charts were reviewed as well. Results Patients’ mean age was 59 yr (17-89), mean age at diagnosis 51,4 yr; 138/1073 (12,8%) were diagnosed before 35 yr. Thirty-five women (31 with anti-SSA/Ro and/or anti-SSA/La antibodies) with an established diagnosis of pSS had 44 pregnancies which ended with the delivery of 39 newborns. Two miscarriages, 2 fetal death and one induced abortion were recorded. Mean age at the latest pregnancy was 34,6 yr (range 29-44), mean number of pregnancy 1,25 (1-3); 17/39 cesarean sections were performed, mean pregnancy length was 38,5 week (range 32-43) with 6 preterm delivery. The mean Apgar score at 5 minute was 8,9 (range 5-10), mean birth weight was 2934 mg (range 826-4060). Congenital heart block (CHB) occurred in 2 newborns of 31 mothers with anti-SSA and/or SSB antibodies (6,45%), with fatal outcome. Other 2 infants had cardial incontinence and a mild interatrial defect, respectively. During pregnancy one patient presented thrombocytopenia and another palpable purpura. In 4/39 pregnancies (10,2%) a flare of disease activity was observed (arthralgia/arthritis and central nervous system involvement) within a year from delivery. Conclusions Even if pSS generally starts after menopause, it can appear during the childbearing age. pSS can have successful pregnancies, which might be followed by a mild relapse. CHB is a fearful complication for women with anti-SSA/Ro and or anti-SSB/La antibodies. Disclosure of Interest None Declared

THU0192 Myositis in primary sjægren’s syndrome: Data from a multicenter cohort

Background Although muscle pain is relatively frequent in primary Sjogren Syndrome (pSS), a frank myositis is rare and reported only in 2.5-11% of patients. The most frequent symptoms are muscular weakness and myalgias and diagnosis is based on clinical, laboratory and histologic evaluation. Objectives To describe the prevalence and course of myositis in a multicenter cohort of patients with pSS. Methods Clinical and laboratory data from patients with a diagnosis of pSS were retrospectively collected. The clinical charts of patients with symptoms and/or signs of inflammatory myositis were carefully reviewed. Results One thousand one hundred seventy patients with pSS (52M, 1118 F, mean age 57.3 years; range 17–89 years) were considered. Mean age at diagnosis was 51±14 years and the mean follow up from diagnosis was 5.6 years (range 0–42 years). Ten female patients (0.85%) presented invalidating muscular weakness in the upper and lower limbs and/or severe myalgias. In 8/10 patients an increase of Creatine Phosphokinase (CK) serum level was present. A possible iatrogenic effect was excluded; in one case myositis started under statin therapy but didn’t disappear after drug discontinuation. In the 10 patients, mean age at pSS diagnosis was 47.4 years (range 14–68), while mean age of myositis diagnosis was 50.6 years (range 23–69). In six out of ten, muscular and sicca symptoms had occurred together at onset. Diagnosis of myositis was supported by clinical evidences and by the presence of increased CK serum levels. In 7/10 patients muscle biopsy was performed. In all biopsies signs of inflammation were present. In 1/7 patients (14.2%) the biopsy was typical of an inclusion body myositis, while in the remaining cases histological aspects of Dermatomyositis and Polymyositis (PM) were detected. Eight out of ten patients presented at least three criteria for inflammatory myopathy (according to Bohan and Peter criteria, 1975) suggesting a possible diagnosis of a true overlap syndrome. In one of these patients serum anti Jo-1 and anti RNP antibodies were detected. Six patients (60%) were successfully treated with DMARDs, while four (40%) did not respond. Thus, two were treated with IvIg, one showing complete remission of myositis, and the remaining two non-responder patients were treated with Rituximab, one showing complete remission. Conclusions Our retrospective study shows a lower prevalence of myositis in pSS than previously reported. Muscle involvement can occasionally represent the first symptom at disease onset. An overlap syndrome with inflammatory myopathies, above all PM, should be considered. Different therapeutic approaches can be used: DMARDs are effective in the majority of the patients, while IvIg and Rituximab may represent an available alternative therapeutic options in non-responder patients. Disclosure of Interest None Declared

Nuclear factor-kappa B (NF-kappaB) inducing kinase is preferentially expressed in rheumatoid arthritis synovial tissue containing ectopic lymphoid neogenesis

In approximately 30% of patients with rheumatoid arthritis (RA), synovial inflammation is characterised by ectopic lymphoid neogenesis (ELN) resulting in ‘germinal centre-like’ structures that contain dendritic cells (DC) and aggregates of B and T cells. This process does not define a specific disease subset and also occurs in other types of chronic inflammation. Nuclear factor-kappaB (NF-kappaB) transcription factors are not only essential for the expression of proinflammatory cytokines, but also induce regulatory circuits. These regulatory properties are thought …