Goran Radunovic

Diagnostic Value of Salivary Gland Ultrasonographic Scoring System in Primary Sjögren’s Syndrome: A Comparison with Scintigraphy and Biopsy

Objective. To compare an ultrasonographic (US) scoring system of salivary glands with scintigraphy and salivary gland biopsy, in order to evaluate its diagnostic value in primary Sjögren’s syndrome (SS). Methods. In 135 patients with suspected SS, the grades of 5 US measures of both parotid and submandibular salivary glands were scored (0–48 scale). Diagnosis of primary SS was established following the American-European Consensus Group criteria of 2002. The patients’ total scintigraphic score (0–12 scale) was determined and the histopathological changes of minor salivary glands graded. Area under the receiver-operating characteristic (ROC) curve was employed to evaluate the diagnostic value of the US scoring system. Results. Primary SS was diagnosed in 107 (79.2%) patients and the remaining 28 subjects (20.8%) constituted the control group. US changes of salivary glands were established in 98/107 patients with SS and in 14/28 controls. Mean US score was 26 in SS patients and 6 in controls. Through ROC curves, US arose as the best performer (0.95 ± 0.01), followed by scintigraphy (0.86 ± 0.31). Setting the cutoff score for US at 19 resulted in the best ratio of specificity (90.8%) to sensitivity (87.1%), while setting the cutoff scintigraphic score at 6 resulted in specificity of 86.1% and sensitivity of 67.1%. Among 70 patients with US score ≥ 19, a scintigraphic score > 6 was recorded in 54/70 (77.1%) and positive biopsy findings in 62/70 (88.5%) patients. Conclusion. We show high diagnostic accuracy of a novel US scoring system of salivary glands (0–48) in patients with primary SS comparable to invasive methods, i.e., scintigraphy and salivary gland biopsy.

Ultrasonography of major salivary glands could be an alternative tool to sialoscintigraphy in the American–European classification criteria for primary Sjögren's syndrome

OBJECTIVE To test the diagnostic accuracy of modified American-European classification criteria (AEC) for primary SS (pSS) by replacing sialoscintigraphy (sSC) with ultrasonography of the major salivary glands. METHODS One hundred and ninety subjects were evaluated for the diagnosis of pSS, including US of the salivary glands. We tested the diagnostic accuracy of the three different sets of five diagnostic criteria for pSS. Each set combined these four criteria (ocular symptoms, oral symptoms, Schirmer-I test and auto-SS-A antibody) and one of the following: US (US set), sSC (sSC set) or biopsy (Biopsy set). The area under the receiver operating characteristics curve (AUC-ROC) was used to evaluate the diagnostic accuracy of each set of criteria. RESULTS Out of 190 subjects examined, 140 subjects fulfilled the AEC for the diagnosis of pSS, whereas 50 subjects were classified as non-pSS subjects. US score was positive in 129 (92%), sSC in 123 (88%) and biopsy in 93 (66%) of 140 pSS patients. Among 140 patients with pSS, 88 (63%) patients fulfilled the criteria of the US set, 85 (61%) patients of the sSC set and 71 (51%) patients of the Biopsy set. None of the subjects from the non-pSS group fulfilled any of the sets of criteria. Diagnostic accuracy of each of the three sets of criteria was high and similar [AUC-ROC (s.e.) for the US set was 0.99 (0.00), followed by the sSC set at 0.98 (0.00) and the Biopsy set at 0.97 (0.00)]. CONCLUSION US finding of major salivary gland involvement could replace sSC in AEC for the diagnosis of pSS.

The role of Doppler ultrasound in rheumatic diseases

The use of Doppler techniques, including power, colour and spectral Doppler, has greatly increased in rheumatology in recent years. This is due to the ability of Doppler US (DUS) to detect pathological vascularization within joints and periarticular soft tissues, thereby demonstrating the presence of active inflammation, which has been reported to be correlated with the local neo-angiogenesis. In synovitis, DUS showed a high correlation with histological and MRI findings, thus it is considered a valid tool to detect pathological synovial vascularization. Moreover, it is more sensitive than clinical examination in detecting active joint inflammation and in the evaluation of response to treatment. In addition, DUS may be considered as a reference imaging modality in the assessment of enthesitis, MRI being not sensitive and histology not feasible. Moreover, it has been demonstrated to be able to detect changes in asymptomatic enthesis. In conclusion, DUS is a useful and sensitive tool in the evaluation and monitoring of active inflammation. Its widespread use in clinical rheumatological practice is recommended. The aim of this article is to review the current literature about the role of DUS in rheumatic diseases, analysing its validity, reliability and feasibility.

Polymorphisms of the eNOS gene are associated with disease activity in rheumatoid arthritis

Nitric oxide (NO) is a mediator in autoimmune responses and thus involved in the pathogenesis of a variety of rheumatic diseases. Genetic factors that influence the expression of the enzyme endothelial nitric oxide synthase (eNOS) that catalyzes NO synthesis are important for the control of NO level and consequently its activity. We have analyzed three functionally relevant polymorphisms of eNOS gene: T-786C, G894T and VNTR (4a/b), to investigate whether they are predisposing factors in pathogenesis of RA in Serbian population and to evaluate their role in clinical manifestations of RA. We performed genotyping of 196 patients with RA and the control group of 132 healthy individuals from Serbian population, using PCR and polymerase chain reaction–restriction fragment length polymorphism methods. Disease activity was prospectively assessed using number of tender joints, number of swollen joints and 28-joints disease activity score (DAS28). There were no differences between the patients and control groups in the genotypes and alleles frequencies of the three analyzed SNPs. Our results showed statistically significant differences in all three analyzed parameters of disease severity between 786TT/786CT and 786CC genotypes and between 894GG/894GT and 894TT genotypes. In the case of 4a/b polymorphism, carriers of minor allele had significantly lower DAS28 values. In conclusion, our results do not support the implication of analyzed eNOS gene polymorphisms in susceptibility to RA but associate them with the disease activity and give assumption that minor alleles are indicators of better clinical course.

Matrix Metalloproteinases-3 Baseline Serum Levels in Early Rheumatoid Arthritis Patients Without Initial Radiographic Changes: A Two Year Ultrasonographic Study

Objective: To investigate the association of high baseline serum levels of metalloproteinases-3 (MMP-3) with structural damage to hand and feet joints, assessed by ultrasonography (US), in patients with early, treatment-naïve rheumatoid arthritis (RA), without initial X-ray-visible erosions, during 24 months follow-up. Methods: Sixty-three early RA (European League Against Rheumatism/American College of Rheumatology 2010), disease-modifying anti-rheumatic drugs/glucocorticoid naïve patients (mean age 53.4 ± 14.1) with symptom duration ≤12 months, had baseline serum levels of MMP-3 tested. OMERACT US group definition was used to detect the presence, as well as longitudinal diameter of erosions by US at study entry and after 24 months, at the level of wrists, metacarpophalangeal (MCP2/MCP5) joints of both hands, and fifth metatarsophalangeal joints. Results: Complete data were collected from 52 out of 63 patients. High baseline serum levels of MMP-3 (MMP-3-positive) were found in 46/63 patients. 122 bone erosions in total (1.9 bone erosions/patients) were detected by US at baseline visit and 213 erosions (4.3/patients) after 24 months. MMP-3 positive patients had significantly higher total number of erosions than MMP-3-negative (p = 0.039) and higher increase in size of bone erosions in the feet but not in the hand joints after follow-up (OR 4.82 [1.23–18.9], p = 0.024; OR 1.17 [0.320–4.26], p = 0.816 respectively). Conclusion: After 2 years of follow-up, US assessment showed a higher number of new bone erosions in MMP-3-positive compared to MMP-3-negative patients with early RA and no visible initial radiographic changes. High baseline levels of MMP-3 predict significantly higher structural damage progression at the level of feet, but not at the level of hand joints.

Bone mineral density in children with juvenile idiopathic arthritis after one year of treatment with etanercept

Introduction/Objective Juvenile idiopathic arthritis (JIA) is the most frequent chronic inflammatory, rheumatic disease of childhood, associated with disturbance of bone mineral metabolism, which develops gradually and progressively, and if untreated eventually leads to osteoporosis in adulthood. The aim of our study was to evaluate bone mineral density (BMD) in patients with JIA treated with etanercept over a period of one year. Methods The prospective cohort study included 94 JIA patients (66 female, 28 male), their median age being 14.77 years. BMD was measured by dual-energy X-ray absorptiometry on the lumbar spine. Disease activity was assessed using the American College of Rheumatology Pedi 50 criteria. Results After one year of treatment with etanercept, we found a statistically significant increment in all osteodensitometry variables (p < 0.001). Annual enhancement for the whole group was as follows: bone mineral content 15.8%, BMD 7.2%, BMDvol 4.2%. Z-score improved from -0.86 to -0.58 SD at the last visit, but decreased in rheumatoid factor-positive polyarthritis patients. Patients with systemic JIA had the lowest Z-score. Z-score correlated with functional disability level. BMD was lower in the group treated with glucocorticoids. Conclusion Our results showed significant improvement of bone mineral density in children with JIA after one year of treatment with etanercept. Rheumatoid factor-positive and systemic JIA subtypes and treatment with glucocorticoids are the risk factors for impairing bone mineral metabolism.

AB0243 The Importance of Biomarkers (RF, ACPA and MMP-3) Serum Levels of Rheumatoid Arthritis (RA) in Prediction Bone Erosions in Patients with Early RA and No Visible Radiographic Structural Damages-An Echosonographic Study

Background Rheumatoid factor (RF) and autoantibodies against citrullinated peptides/proteins (ACPA) has been recognized as an important predictor of more severe structural joint damage. Baseline matrix metalloproteinases 3 (MMP-3) serum levels were described as a predictor for the development of joint erosions.Ultrasonography is more sensitive than X-ray in detecting erosions in RA. Objectives to assess the importance of the RF, ACPA and MMP-3 serum levels in prediction of hands and feet bone erosions, detected by ultrasound (US) examination, in patients with early rheumatoid arthritis, without structural damage visible on X-ray. Methods A group of 65 patients (56 female, mean age 53.8±14.6 yrs.) with early RA (Eular/ACR 2010 classification criteria) and ≤1 year duration, (mean duration 3.8 month), were enrolled in the cross sectional clinical study. All patients had been disease-modifying anti-rheumatic drug (DMARDs) and glicocorticoid therapy naïve and had no visible structural damage on hands and feet X-ray. The serological markers of RA were measured: RF (normal concentration<16 U/ml), ACPA (normal concentration<20 IU/ml) and total MMP-3 (normal cut-off range for females: 18–60 ng/ml and males: 24–120 ng/ml). The levels above normal were reted as positive. Ultrasound examination of both hand (wrist, MCP2, MCP5 joints) and MTP5 joints was performed by Esaote My Lab 70 machine using 18 MHz linear probe. Findings of bone erosion were determined according to OMERACT US group definition. Collected data were analyzed in SPSS 16 system. Results Joint bone erosions were found in 59 (90.8%) pts. by US examination. Forty-two (64.6%) pts. were RF positive (mean concentration 88.8±108.2). The mean 2.1 vs.1.6 US bone erosions were detected in RF positive in comparison to RF negative pts. respectively. Forty-six (70.7%) pts. were ACPA positive (mean concentration 467.0±454.4) with mean bone erosions 1.9 vs.1.8 bone erosions in ACPA negative pts. Forty-six out of 63 (73.0%) pts were MMP-3 positive (mean concentration 185.1±241.0) with mean bone erosions 2.1 vs.1.5 bone erosions in MMP-3 negative pts. The 0.500 value of the area under the ROC curve is found for RF, 0.443 for ACPA and 0.627 value for MMP-3. The 75.4% sensitivity, 67% specificity (cut of 99.2 ng/ml) of MMP-3, 71.9% sensitivity, 50% specificity (cut of 232 IU/ml) of ACPA and 66.7% sensitivity, 67% specificity (cut of 79.5 U/ml) of RF were established in predicting US bone erosion. Conclusions Early RA patients with no visible structural damages on X-ray, and increased RF, ACPA and MMP-3 serum levels had higher number of bone erosions assessed by US. Baseline MMP-3 serum levels had the highest sensitivity in predicting joint bone erosions assessed by ultrasound examination. Disclosure of Interest None declared

SAT0630 Sensitivity and Specificity 99mTc-Pertechnetate Hand Perfusion Scintigraphy in Patients with Raynaud's Phenomenon

Objectives The aim of this study was to assess sensitivity and specificity of 99mTc-pertechnetate hand perfusion scintigraphy in patients with Raynauds phenomenon (RP). Methods The study population consisted of 10 healthy individuals (mean age 57 years), 18 patients with primary RP (mean age 48 years) and 25 patients with secondary RP within systemic sclerosis (SSc) (mean age 54 years). Gamma-camera dynamic first-pass study during the first 60 sec and a static scintigraphy after 5 min were recorded following a bolus injection of 99mTc-pertechnetate via a cubital vein. Regions of interest were drawn on the summed images around the fingers and the palmar region. The fingers-to-palm ratios were then calculated from the total counts inside these regions of interest separately for each hand. Results The mean fingers-to-palm ratio for dynamic study (blood flow) was 0,58±0,19 for the healthy group, 0,45±0,18 for the primary RP and 0,43±0,21 for the SSc patients. The mean fingers-to-palm ratio for static study (blood pool) was 0,44±0.06 for the healthy group, 0,42±0,06 for the primary RP and 0,36±0,07 for the SSc patients. Analysis of variance showed these differences to be significant (p=0.039 from blood flow and p=0,004 from blood pool). The receiver operating characteristic curve showed sensitivity of 80% and a specificity of 60% when using cutoff values of 0.40 for blood flow and sensitivity of 72% and a specificity of 73% when using cutoff values of 0.40 for blood pool. Conclusions Our method is able to differentiate between patients with normal and those with abnormal microcirculation of the hands. Dynamic study separates the healthy subjects from patients with RP, while static study separating primary from secondary RP. References Csiki Z, Galuska L, Garai I, Szabό N, Varga J, András C, Zeher M. Raynauds syndrome: comparison of late and early onset forms using hand perfusion scintigraphy. Rheumatol Int. 2006 Sep;26(11):1014-8. Csiki Z, Garai I, Varga J, Szücs G, Galajda Z, András C, Zeher M, Galuska L. Microcirculation of the fingers in Raynauds syndrome: (99m)Tc-DTPA imaging. Nuklearmedizin. 2005 Feb;44(1):29-32. Disclosure of Interest None declared

AB0317 Do Cigarette Smoking Patients Have More Severe Early Rheumatoid Arthritis

Background Smoking in association with genetic factor can facilitate production of auto antibodies against citrullinated peptide and lead rheumatoid arthritis (RA) development (1). Objectives To investigate the influence of cigarette smoking on severity of early rheumatoid arthritis. Methods The 63 (85.7% female) early RA patients, mean age of 53.79±14.1 yrs. were enrolled in prospective observational study. All pts fulfilled EULAR/ACR 2010 criteria for diagnosis of early RA, had disease duration ≤12 months (in average 3.6 months) and have been without structural changes on radiography of hands and foot. Patients were treatment naïve for disease modifying anti-rheumatic drugs (DMARDs) and steroids. RA activity was assessed by the 28-joint disease activity score (DAS28-ESR) and bone erosions of hands and feet estimated by echosonography at the baseline, when early RA diagnosis was established and after 6 months of MTX (15 mg per week) therapy. Ultrasound examination was done by ESAOTE My Lab70 machine using 8-18 MHz linear probe according to OMERACT recommendations. The severity of smoking was estimated by pack/year: light (smoking ≤5 pack/yrs); moderate (5-20 pack/yrs) and heavy (≥20 pack/yrs), Anova statistical method was performed in data processing. Results The total 33 (52.4%) early RA pts had never smoked, 11 (17.4%) pts. had stopped smoking at list 2 years before early RA onset. Nineteen (30.2%) pts. were current smokers. Three (4.8%) pts were a light-smokers, thirteen (20.6%) pts. were a moderate-smokers and three (4.8%) pts were a heavy smokers. Initially, there was no statistical difference between group of RA non-smokers, light-smokers, moderate or heavy-smokers pts regarding value of DAS28 score (mean value: 5.7; 6.5; 5.2; 6.1 respectively, p=0.387) and number of echo erosions (mean value: 2.4; 1.7; 2.3; 3.3 respectively, p=0.814). The group of moderate and heavy-smokers had statistically significant less decrease in DAS28 score than non-smokers and light-smokers (mean value: 0.9; 0.9; 1.7; 3.2 respectively, p<0.05) after 6 months of treatment. However, there was no statistically significant difference between heavy-smokers and moderate-smokers in comparison to non-smokers and light-smokers in increasing number of new echo erosions (mean value: 1.7; 0.2; 0.3; 1.0 respectively, p>0.05) after six months of therapy with MTX. Conclusions After 6 months of MTX 15 mg/week treatment of sixty-three patients with early rheumatoid arthritis, non-smokers and light-smokers had significantly higher decrease of DAS28 score in comparison with group of moderate and heavy smokers. Number of new erosions observed by ultrasound was not significantly different between these groups. References Klareskog L, Stolt P, Lundberg K et al. Smoking May Trigger HLA–DR (Shared Epitope)–Restricted Immune Reactionsto Autoantigens Modified by Citrullination, Arthritis & Rheumatism 2006; 54 (1): 38–46. Disclosure of Interest None declared

AB0623 Psychological Profile of Patients with Sjogren's Syndrome – Associations with Disease Activity

Background Psychological profiles of patients with Sjogrens syndrome (SS) can influence severity of symptoms of dryness, pain, fatigue and fibromyalgia. We assume that treatment of the disease manifestations can be improved when the psychological heterogeneity of patients is taken into account. Objectives To determine the spectrum of psychological features in SS patients and to assess the association of psychological profiles with disease activity. Methods Seventy patients with confirmed SS by AECG criteria (mean age 51,3 years, mean disease duration 4.7 years) and thirty-two healthy controls (mean age 50.3 years) participated in our study. All participants were females who provided written informed consent. The disease activity was measured by EULAR SS disease activity index (ESSDAI). All participants filled the self-reported questionnaire which addresses demographic characteristics (age, educational level, occupational status, residence and comorbidity). The second part consisted of the NEO Personality Inventory-Revised (NEO-PI-R) - a 240-item measure of the Big Five personality profiles: Neuroticism (N), Extraversion (E), Openness to Experience (O), Agreeableness (A) and Conscientiousness C. Items are answered on a 5-point Likert scale, ranging from strong disagreement to strong agreement. Level of scores for each personality dimensions graded according to 5-point scale, ranging from very low to very high. Statistical analysis was performed by SPSS software (version 16.0). Data were examined by t-tests, λ2 test, Fishers exact tests, ANOVA and Spearmans ρ correlation. A p-value <0.05 was considered significant. Results The mean value ESSDAI score was 4.30±3.70. Comorbidity was similar in both groups (p>0.05). Scores N were significantly higher in SS patients than in healthy controls (95.4 and 79.8, respectively, p=0.001). This N scores in SS group correlates negatively with disease duration (ρ=-0.30, p=0.01). Control group had significantly higher E (107.8) and O (99.7) scores than SS group (93.0 and 99.7 respectively, p=0.00). Scores C were higher in SS patients than in control group (129.4 and 121.9), but differences were not statistically significant (p=0.06). Scores A were quite similar in both groups (p>0.05). The differences between groups were not statistically significant for psychological profiles and age, educational levels, occupational status (ANOVA, p>0.05). Scores A in SS group were significantly higher in urban population (p=0.03). Several psychological profiles were significantly related with some domens of ESSDAI (hematological, pulmo, peripheral nervous system), p<0.05. Conclusions Our patients with SS had neurotic psychological profile and probably have increased risk to develop different mental disorders. The level of neuroticism was higher at the onset of the disease. Compared with healthy controls, SS patients are more introverted and conservative, less opened and similarly agreeable and conscientious to healthy controls. Correlation of certain psychological profiles of SS patients and disease activity is questionable. Disclosure of Interest None declared