Primary Sjogren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients.

OBJECTIVE: The aims of this study were to describe the clinical presentation of primary SS (pSS) in a large cohort of patients by assessing the prevalence of the patient subgroups at high risk for severe extraglandular manifestations and to explore the influence of the patients' serological profile on disease severity and on immunosuppressive drug utilization. METHODS: Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent serological markers for glandular and extraglandular disease manifestations were identified by logistic regression. RESULTS: The cohort included 1115 (1067 female, 48 male) pSS patients. Severe extraglandular manifestations were detectable in 15% of the patients and were represented by active synovitis (11%), axonal sensory-motor neuropathy (2%), severe leucocytopenia (14%), cutaneous vasculitis (6%) and non-Hodgkin's lymphoma (4.5%). We found that low C3/C4, hypergammaglobulinaemia, RF and cryoglobulinaemia were markers of severity for pSS. According to the number of serological variables, the patients were subdivided into three distinct groups: favourable (no serological markers), intermediate (one serological marker) and poor (two or more serological markers). In comparison with the other two patient groups, pSS patients presenting with two or more adverse determinants had a higher frequency of severe visceral disease complications and required more aggressive therapeutic interventions. CONCLUSION: This study confirmed that the prevalence of the pSS high-risk subset for severe systemic manifestations is ∼15%. Serological markers might help in the early identification of patients who are candidates to receive more aggressive treatments.

Outcome of pregnancy in Italian patients with primary Sjögren syndrome.

OBJECTIVE: To investigate pregnancy and fetal outcomes in patients with primary Sjögren syndrome (pSS). METHODS: An obstetric history of 36 women with established diagnosis of pSS at pregnancy was obtained from a multicenter cohort of 1075 patients. In a subgroup case-control analysis, 12 deliveries in patients with pSS were compared with 96 control deliveries. RESULTS: Thirty-six women (31 with anti-SSA/Ro and/or anti-SSB/La antibodies) with an established diagnosis of pSS had 45 pregnancies with the delivery of 40 newborns. Two miscarriages, 2 fetal deaths, and 1 induced abortion were recorded. Mean age at the first pregnancy was 33.9 years; mean number of pregnancies was 1.25; 18/40 (45%) cesarean births were delivered; mean pregnancy length was 38.5 weeks (range 32-43), with 6 preterm deliveries. The mean Apgar score at 5 min was 8.9, mean birthweight was 2920 g (range 826-4060 g). Congenital heart block (CHB) occurred in 2/40 (5%) newborns. The reported rate of breastfeeding for at least 1 month was 60.5%. In 4/40 pregnancies (10%) a flare of disease activity was observed within a year from delivery. In the case-control subgroup analysis, 12 deliveries were compared with 96 controls and no significant differences were found. CONCLUSION: Patients with pSS can have successful pregnancies, which might be followed by a mild relapse. CHB was the only cause of death for offspring of mothers with pSS.

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, Baker's 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 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.

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.

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.