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Background TNF-like weak inducer of apoptosis (TWEAK) regulates inflammation, angiogenesis and tissue remodeling. CD163 molecule, a scavenger receptor and marker of alternatively activated macrophages, modulates TWEAK activity through binding and internalization of TWEAK molecule. We have previously shown that, in a crossectional study, high serum concentrations of soluble CD163 (sCD163) and high CD163/TWEAK ratio were associated with lack of digital ulcers (DU) in patients with systemic sclerosis (SSc) [1]. Objectives To investigate whether serum levels of soluble CD163 (sCD163), soluble TWEAK (sTWEAK) or sCD163/sTWEAK ratio can predict clinical course of DU in patients with (SSc). Methods 50 patients fulfilling the ACR/EULAR classification criteria of SSc who were followed for at least 1 year were included. Serum levels of sCD163 and sTWEAK were measured using commercially available ELISA kits. Digital ulcers were defined as painful area of loss of tissue on the volar surface of fingertips or around the nail distal to the proximal interphalangeal digital crease, present at the time of assessment. In addition, evaluation of SSc patients included assessment of disease subset (diffuse/limited SSc), modified Rodnan skin score, the presence of interstitial lung disease, pulmonary hypertension, results of pulmonary function tests, echo-Doppler, autoantibody testing (anticentromere antibodies, anti-Scl-70 antibodies) and erythrocyte sedimentation rate. Results At baseline DU were present in 18 patients. During follow-up DU healed in 12 SSc patients and persisted in the remaining 6. In addition, 5 patients without DU at baseline developed new DU during follow-up. Because of relatively low numbers, patients with recurrent/persistent DU and those with new DU were analyzed together (n=11). In the remaining 27 patients DU were not found at any visit. There were no significant differences in baseline sCD163 levels between SSc patients in whom DU healed at follow-up, those with persisted/new DU or SSc patients without DU at any visit. In contrast, baseline serum levels of sTWEAK were significantly higher in SSc patients who subsequently experienced healing of DU compared with SSc patients with DU at follow-up and with SSc patients who never had DU (p In univariate analysis baseline DU, anticentromere antibodies (ACA) and sCD163/sTWEAK ratio were significantly associated with outcome of DU. In multivariate analysis including baseline DU, ACA and sCD163/sTWEAK ratio, baseline DUs were the strongest independent predictor of risk of DU at follow-up. Conclusions Our results suggest that CD163-TWEAK interactions might play a role in the development/healing of DU in SSc and indicate that sCD163–TWEAK serum ratio is a potential biomarker of peripheral vascular disease in SSc. References Arthritis Res Ther. 2013; Jun 24;15(3):R69. [Epub ahead of print] Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5343

Background CT-P13 is a biosimilar to innovator infliximab (INX) approved by the European Medicines Agency. From the PLANETRA, which is randomized, double-blind, active-controlled trial to assess efficacy and safety of CT-P13 in rheumatoid arthritis (RA) patients, therapeutic equivalence was demonstrated via the primary endpoint (ACR20 at Week30) 1 . Several secondary endpoints exist that can capture valuable information to the clinician. Objectives To compare efficacy via the DAS28, CDAI, and SDAI of CT-P13 and INX in patients with RA and effect of anti-drug antibody (ADA) on the clinical outcome measures. Methods In PLANETRA, 606 patients with RA were treated with either 3 mg/kg of CT-P13 or INX with methotrexate at usual schedule up to Week 54. Key secondary endpoints were CDAI, SDAI, and DAS28. ADA was measured at baseline and at Week 14, 30 and 54 by an electrochemiluminescent assay. Results The mean baseline DAS28 scores reflected high disease activity (DAS28-ESR, 6.7 vs 6.6; DAS28-CRP, 5.9 vs 5.8; CT-P13 vs INX). The mean change in DAS28-ESR over 54 weeks was -2.4 in both treatment groups. The baseline CDAI and SDAI scores were similar between treatment groups (mean CDAI, 40.7 vs 39.6; SDAI, 42.4 vs 41.4; CT-P13 vs INX, respectively). At week 54, CDAI decreased by -25.7 and -24.0 and SDAI decreased by -26.3 and -24.6 in the CT-P13 and INX groups, respectively. Statistically significant difference between groups was not shown in these assessments. The proportion of patients who become ADA positive was comparable between CT-P13 (52.3%) and INX (49.5%). More improvement on DAS28-ESR was shown in ADA negative subgroup than in ADA positive subgroup at Week 54, similarly in both treatment groups (CT-P13, -2.8 vs -2.1; INX, -2.7 vs -2.0). SDAI score decreased more in ADA negative subgroup than ADA positive subgroup up to Week 54 (CT-P13, -28.5 vs -24.3; INX, -26.7 vs -22.3). Similar trends were found in DAS28-CRP and CDAI at Week 54 (p 0.05), but different between ADA subgroups over time within each treatment group (p Conclusions These results demonstrate the efficacy of CT-P13 which is comparable to that of INX, based on various clinical outcome measures. The ADA development could diminish the clinical response achieved by infliximab, and the magnitude of influence was similar in both CT-P13 and INX treatment groups throughout the study. References Yoo D.H., et al. Ann Rheum Dis 2013;72:1613-20. Disclosure of Interest : D.-H. Yoo Grant/research support: CELLTRION, Inc., Consultant for: CELLTRION, Inc., Speakers bureau: CELLTRION, Inc., W. Park Grant/research support: CELLTRION, Inc., Consultant for: CELLTRION, Inc., Speakers bureau: CELLTRION, Inc., M. Brzosko Grant/research support: CELLTRION, Inc., P. Geher: None declared, D. Andersone Grant/research support: CELLTRION, Inc., J. Jaworski Grant/research support: CELLTRION, Inc., D. Rekalov Grant/research support: CELLTRION, Inc., B. Oparanov Grant/research support: CELLTRION, Inc., R. Kausiene Grant/research support: CELLTRION, Inc., C. Pacheco-Tena Grant/research support: CELLTRION, Inc., S. Lee Employee of: CELLTRION, Inc. DOI 10.1136/annrheumdis-2014-eular.3707

Background High resistance index (HRI), evaluated on the basis of Doppler spectrum of popliteal arteries, enables detection of subclinical changes in small vessels in systemic lupus erythematosus (SLE) patients. Objective To evaluate the association between decreased values of HRI in SLE patients and selected immunological parameters, the presence of markers of inflammation and classical risk factors for atherosclerosis and also selected clinical manifestations. Methods The investigation was performed in 76 patients with SLE (age 20-73 years). The mean course of the disease was 8.7 years. The coexistence of APS was confirmed in 17 patients (22.4%). The control group consisted of 30 healthy people. All the duplex Doppler examinations of popliteal arteries were performed with HDI 3500 (ATL) using 5- 12 MHz linear transducer under standardised conditions. We evaluated the presence of anti-endothelial antibodies (AECA) and profiles of anti-nuclear antibodies, anti-phospholipid antibodies (aPL) and anti-neutrophil cytoplasmic antibodies. We also analysed markers of inflammation (C-reactive protein, erythrocyte sedimentation rate and fibrinogen), classical risk factors for atherosclerosis (hypertension, hyperglycaemia, hyperlipidaemia, smoking and positive family history for cardiovascular disease) and clinical complications including cardiovascular and central nervous system manifestations, lupus nephritis, thromboembolic disorders and vasculitis. Statistical analysis was performed with chi 2 Yates, chi 2 Pearson, rank Spearman correlations tests. Logistic regression analysis and multivariate stepwise analysis were also done. All statistical analyses were performed with STATA 11. Results We found that HRI values in patients with SLE were significantly lower in comparison with the control group (p We have found no associations between decreased HRI values and the rest of analysed variables. Conclusions 1. HRI values are significantly decreased in SLE patients. 2. The coexistence of APS and the presence of aPL and AECA are risk factors for decreased HRI values in SLE patients. 3. There is a significant reverse relationship between HRI values and the duration of the disease and the presence of thromboembolic changes in SLE patients.

Background Objectives To compare plain radiographic and MRI findings in evaluation of non traumatic spinal fractures in patients with ankylosing spondylitis (AS), and to find correlation between spinal fractures and disease activity, age of patients, and disease duration. Methods 21 males and 2 females with AS, mean aged 49.8, were studied. Lateral radiographs and MRI examinations of lumbar, thoracic and cervical spine were performed in all patients. To detect vertebral body fractures with radiographs, the anterior, posterior and central heights of each vertebral body were measured. The ratio of each height to that of the two adjacent vertebrae, the ratio of the anterior height to the posterior height and of the central height to the posterior height were calculated. The subjects were considered to have fracture if any of these ratios was less than 0,85 for lumbar spine and less than 0,8 for thoracic and cervical spine. We assessed also the following indexes of disease activity: BASFI, BASDAI, BASG-t, BASG-6, BSMI. Results Total 25 fractures were found with the radiographic method: 7 fractures in lumbar spine, 15 in thoracic and 3 in cervical. The MRI examinations revealed total 51 fractures: 24 fractures in lumbar spine, 18 in thoracic and 9 in cervical. Out of 25 fractures detected by X-ray examination, MRI confirmed the site of fracture only in 10 (40%). Age of patients and disease duration correlated positively with total number of fractures, number of fractures in lumbar spine and number of fractures in thoracic detected by MRI. There was no such correlation for fractures detected by X-ray. Assessing indexes of disease activity we found positive correlation between BASFI, BASDAI, BASMI and total number of fractures and number of fractures in lumbar spine detected by MRI. Conclusion The significant difference between radiographic and MRI findings in detecting of vertebral fractures was found. The results suggest that plain X-rays cannot be considered as a sufficient method for detection vertebral fractures in patients with AS. MRI should be considered as the method of choice in revealing spinal fractures in AS patients. Disease activity may contribute in developing of non – traumatic spinal fractures in this group of patients.

Sir, Some cases of chronic urticaria, regarded so far as idiopathic, are in fact of autoimmune origin (1). Autoimmune thyroid disease (ATD) is characterized by the presence of anti-thyroid antibodies. Association of chronic urticaria and ATD is well known. Most studies have found a 15–30% prevalence of anti-thyroid antibodies in patients with chronic urticaria (2, 3). There have been some reports of successful treatment with L-thyroxine of either arthritis (4, 5) or autoimmune urticaria (1, 3) associated with ATD, as well as in euthyroid patients (3–5).

Cyclosporine (CS) is a widely used immunosuppressive drug. Its administration is related to multiple side- effects, most often gastrointestinal, renal impairment, hypertrichosis and hypertension (1). It can also contribute to neoplastic diseases of the skin (2, 3). Only one case of multiple angiomas related to CS has been reported in the literature (4). We describe here a 35-year-old man with psoriatic arthritis who developed haemangiomas on his upper and lower extremities in the course of CS treatment.CASE REpORtA 35-year-old man developed psoriatic arthritis 2 years after the onset of psoriasis. He was primarily treated with sulphasalazine, 1.0 g twice daily. After a flare-up of arthritis sulphasalazine was replaced with methotrexate, 17.5 mg weekly, and methylpredniso-lone, 5 mg daily. Due to insufficient response, CS was added in gradually increasing doses starting from 2.5mg/kg daily up to 4.0 mg/kg daily when remission of arthritis was achieved and this dose was used as the maintenance dose. During the treatment the patient developed gingival hyperplasia, which resolved after CS dose reduction to 3 mg/kg daily. three years after starting the treatment with CS the patient reported appearance of 2 nodules elevated above the surface of the skin, purple, hard and painless, 5 mm in diameter (Fig. 1). One was localized on his left fore-arm and the other on the right thigh. the former was surgically removed. Histological examination revealed a vascular lesion without any features of malignancy, con-sistent of haemangioma (Fig. 2). During the following 2 months another 8 new nodules (5 mm in diameter on average) appeared on the lower and upper extremities, sparing the head and the trunk. the one that was pre-sent previously grew to 8 mm. As the appearance of the lesions was supposed to be related to CS, this dose was reduced. It did not affect the growth of the lesion, and CS was finally discontinued. The exacerbation of arthritis was thereafter managed by increasing the dose of methylprednisolone and methotrexate. Within the following 3 months, only one new nodule appeared and the ones previously present did not grow. During the following 4 months the nodules got smaller and finally disappeared, leaving small depigmentation areas. In the meantime chest and abdominal imaging studies were performed showing no pathologies. Complete blood count, urinalysis, aminotransferases, creatinine and erythrocyte sedimentation rate were normal during the follow-up period. Since then the nodules have never reappeared and the patient has been well for over 2 years. He is currently treated with methotrexate, 15 mg weekly and methylprednisolone, 4 mg daily. DISCUSSIONCS has no mutagenic effect; however, due to its im-munosuppressive effect it may allow the growth of neoplastic cells (5). there are studies proving that CS has a significant influence on occurrence of skin malig-nancies (2, 3). Only one study has countered this (6). CS is known to cause non-malignant dermatological and

Background Involvement of heart in SS is estimated at 10-15%. Biomarker for heart failure and pulmonary artery hypertension (PAH) in the SS is NT-proBNP. Interleukin 6 is a proinflammatory cytokine, that participates in the pathogenesis of SS and heart damage. Objectives The aim of this study was to assess the relationship between RV and LV failure and their relation with the concentration of NT-proBNP and IL-6. Methods In study was enrolled 75 patients with SS aged 21 to 75 years. Control group consisted of 47 healthy subjects aged 21-77 years. Both groups were matched to the sex and age. Patients underwent echocardiography one and two dimension and Doppler analysis evaluating the selected parameters of the function of the left (LA, LVEDD, LVESD, IVSD, LVPW, IVRT, Mit E/A, LVEF, FS) and the right heart (RA, RVEDD, RVESD, RVH, Tr E/A, TAPS, ACT in the pulmonary artery, TRPG, MPA). In both groups was determined the level of NT-proBNP and IL-6 in serum. Ranges of reference values for NT-proBNP and IL-6 was determined on the basis of their concentrations in the control group. NT-proBNP concentrations were divided into three concentration ranges: normal, medium and high. Study was accepted by local ethical commission (BN-001/15/06 and BN-001/143/07). Results In patients with SS were found: 13.51% at the higher concentrations of NT-proBNP in the range of medium values, with 37.84% in the range of high value and in 38.33% of IL-6. The analysis backward step showed higher risk of elevated NT-proBNP concentrations in the range of high values (OR 31.11, 95% CI 7,89-1302,97, p=0.000) and IL-6 (OR 5.99, 95%CI 1,25-28,73 p=0.025) compared with the control. Echocardiographic study of the left heart in patients with SS was found increased dimension of: LA in 36%, LVEDD in 6.67%, LVESD in 24%, IVSD in 24%, LVPW in 34.67%, in 66.67% prolonged IVRT, in 40.28% reduced Mit E/A ratio, in 12% reduced LVEF and in 9.59% decreased FS. Higher risk of elevated NT-proBNP concentrations in the range of high value have been demonstrated in patients with enlarged LVEDD (OR 7.83, 95% CI 1,91-380,12, p=0.008) and LVESD (OR 4.47, 95% CI 1,91-380,12, p=0.027), and IL-6 in the reduced FS (OR 5.55, 95% CI 1,35-299,00, p=0.024). Assessing right heart were found increased size of:RA in 5.63%, RVEDD in 49.32%, RVESD in 27.78%, MPA in 6.94%, RVH in 15.07%, increased TRPG in 24.24%, in 9.72% reduced the ACT, in 16.67% reduced Tr E/a ratio and in 9.72% decreased TAPS. Higher risk of elevated NT-proBNP has been demonstrated in the medium values in patients with RVH (OR 7.91, 95% CI 1,33-47,22) and reduced Tr E/A ratio (OR 6.99, 95% CI 1,18-41,34), and IL-6 in the RVH (OR 5.55, 95% CI 1,35-299,00, p=0.024). Patients with SS demonstrated a higher risk of elevated NT-proBNP concentrations in the range of medium values and elevated levels of IL-6 (OR 21.01, 95% CI 2,02-218,56, p=0.011). Conclusions Echocardiography is very useful in assessment of LV and RV failure in patients with SS. In SS NT-proBNP and IL-6 may be early biomarkers of myocardial dysfunction, The association of NT-proBNP concentrations and IL-6 suggests an inflammatory background of myocardial damage in patients with SS. Disclosure of Interest None Declared

Background LITHE was a 2-y, randomised, double-blind, placebo-controlled study of TCZ in pts with moderate to severe RA who were inadequate responders to methotrexate (MTX) with an additional 3 y of open-label extension. Objectives To report radiographic, efficacy and safety data in RA pts treated with TCZ in LITHE at 5 y of follow up. Methods In LITHE, 1190 pts were randomised (1:1:1) to receive TCZ (4 mg/kg [TCZ4] or 8 mg/kg [TCZ8]) or placebo every 4 wks + MTX (10-25 mg/wk). Mean duration of RA at study entry was 8.96 to 9.43 y in the 3 arms. Pts could receive rescue with TCZ from wk 16; after wk 52, pts could switch to open-label TCZ8. Radiographs were analysed by Genant-modified Total Sharp Score (GmTSS) at baseline (BL) and at wks 52, 104, 152, 200 and 260 by original randomised group. Pts with at least BL, wk 104 and post-wk 104 radiographs were included in the analysis; linear extrapolation was used to impute any additional missing time points. Signs and symptoms and safety data were pooled for all pts who received ≥1 dose of TCZ (All TCZ) with data presented from the first dose of TCZ. LOCF was used for missing tender and swollen joint counts; no imputation was used for missing HAQ-DI score, CRP, ESR and VAS assessments. The proportions of pts who maintained an ACR20/50/70, DAS28-ESR, EULAR or HAQ-DI response consecutively for ≥24 wks at any time point during the study were summarised (Table). Results 1149 pts received ≥1 dose of TCZ with 4379.6 pt-y (PY) of exposure, and 34% received 5 y of treatment (All TCZ). Mean duration in the All TCZ population was 3.81 y with half the pts participating for ≥4.69 y. Radiographic data were assessed in 803 pts: 545 initially assigned to TCZ and 258 initially assigned to placebo. The mean change in GmTSS over 5 y showed a 56% greater inhibition of joint damage in pts randomised to TCZ vs those initially randomised to placebo, with greatest APR in y 1 (Table). 53% of TCZ pts had no progression (GmTSS≤0) during the 5 y vs 35% of placebo pts (placebo pts might have switched to TCZ as early as wk 16). Clinical benefit was maintained, as measured by maintenance of ACR response, DAS28-ESR remission and EULAR good/moderate response (Table). Overall rates/100PY of serious adverse events and serious infections were 11.67 and 3.42, respectively. The safety profile at 5 y was similar to that observed at 2 y.1 Image/graph Conclusions During long-term treatment, TCZ + MTX continued to inhibit radiographic progression. Improvements in signs and symptoms and in physical function were maintained with continued TCZ treatment. The safety profile of TCZ at 5 y was similar to that previously observed.1 References Ann Rheum Dis 2010;69(suppl 3):387 Disclosure of Interest J. Kremer Grant/research support from: Genentech, Consultant for: Genentech, A.-M. Halland: None Declared, M. Brzosko: None Declared, R. Burgos-Vargas Grant/research support from: Abbott, Consultant for: Abbott, BMS, Janssen, Pfizer, Roche, Speakers bureau: Abbott, BMS, Janssen, Pfizer, Roche, C. Mela Employee of: Roche, E. Vernon Employee of: Roche, R. Fleischmann Grant/research support from: Abbott, Amgen, Janssen, UCB, BMS, Roche, Genentech, Lexicon, Sanofi Aventis, Lilly, MSD, Pfizer, Regeneron, Consultant for: Abbott, Amgen, Janssen, UCB, BMS, Roche, Genentech, Lexicon, Sanofi Aventis, Lilly, MSD, Pfizer, Regeneron

Background Nature of SS promotes the development of multiple organ dysfunction and metabolic disorders that are responsible for high mortality. Male gender, subtype dcSSc, the occurrence of aScl-70 and impaired LV systolic function are known risk factors for mortality in SS. Search for new risk factors for death in the SS can improve the prognosis in these patients. Objectives The aim of this study was to demonstrate whether there is a connection between death of SS patients with selected clinical features, serological, and biochemical parameters in the study group. Methods In the study was enrolled 75 SS patients aged 21-75 years treated in the Department of Rheumatology and Internal Medicine of PAM and Rheumatology Outpatient in Szczecin in the years 2004-2010. In the study group six patients died that represent 8.02% of participants. An analysis of the variables that characterize the patients taking into account: sex, SS subtype, duration of disease and Raynaud’s syndrome, NYHA functional classification, interstitial lung disease, cardiovascular diseases (hypertension, ischemic heart disease), nephropathy, and diabetes. The analysis also included: occurrence in patients with SS some autoantibodies (ANA, aScl-70, ACA, AECA), the concentration of acute phase proteins (ESR, fibrinogen, CRP, IL-6), lipid disorders, homocysteine and echocardiographic parameters of dysfunction of systolic and diastolic right and left ventricular hypertrophy. Study was accepted by local ethical commission (BN-001/15/06 and BN-001/143/07). Results Analysis of Causes of Death of Patients with SS Revealed significant associations between: male sex (OR 15.00, 95% CI 2,36-95,47 p=0.004), and dcSSc type of disease (OR 19.50, 95 4,72-913,36% CI, p=0.000), and presence of aScl antibodies (OR 10.32, 95% CI 2,54-485,36, p=0.003) and Stage III of the NYHA (OR 78; 64, 95% CI 2,30-2690,19, p=0.015), and elevated ESR (OR 7.40, 95% CI 1,83-349,32 p=0.001;), and elevated serum level of fibrinogen (OR 42.75, 95% CI 9,82-1998,05 p=0.000;), and elevated serum level of IL-6 (OR 10.88, 95% CI 2,62-528,12, p=0.002), and elevated serum level of Homocysteine (OR 15.18, 95% CI 1,22-205,11 p=0.035;), and lower LVEF (OR 10.99, 95% CI 1,02-118,53 p=0.048) and RVH (OR 16.22, 95% CI 1,40-187,32, p=0.026). Sensitivity and specificity were calculated for each factor of death. It was shown that the highest sensitivity and specificity for risks of death shows: subtype dcSSc (sensitivity 100%, specificity 76, 47%), ESR (sensitivity 100%, specificity 55.22%) and fibrinogen (sensitivity 100%, specificity 76, 47%). However, left ventricular ejection fraction (sensitivity 50%, specificity 91.80%) and homocysteine level (sensitivity 50%, specificity 91.18%) in patients in the study group is characterized by the lowest sensitivity and high specificity. Conclusions 1. Risk factors for death in studied patients with SS are: male gender, subtype dsSSc, aScl, NYHA III degree, accelerated ESR, elevated levels of IL-6, fibrinogen and homocysteine, lower ejection fraction and left ventricular hypertrophy, right ventricle hypertrophy. 2. Among risk factors the highest sensitivity and specificity for mortality show: subtype dcSSc, ESR and fibrinogen concentration, whereas left ventricular ejection fraction and the levels of homocysteine have a lowest sensitivity and high specificity. Disclosure of Interest None Declared

Introduction Systemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. CD163 is a scavenger receptor which affects inflammatory response and may contribute to connective tissue remodelling. It has recently been demonstrated that CD163 can bind and neutralize the TNF-like weak inducer of apoptosis (TWEAK), a multifunctional cytokine which regulates inflammation, angiogenesis and tissue remodelling. We aimed to investigate the relationships between serum levels of soluble CD163 (sCD163) and soluble TWEAK (sTWEAK) in relation to disease manifestations in SSc patients. Methods This study included 89 patients with SSc who had not received immunosuppressive drugs or steroids for at least 6 months and 48 age- and sex-matched healthy controls (HC) from four European centres. Serum concentrations of sTWEAK and sCD163 were measured using commercially available ELISA kits. Results The mean serum concentrations of sTWEAK were comparable between SSc patients (mean +/- SD: 270 +/- 171 pg/mL) and HC (294 +/- 147pg/mL, P >0.05). Concentration of sCD163 and sCD163/sTWEAK ratio were significantly greater in SSc patients (984 +/- 420 ng/mL and 4837 +/- 3103, respectively) as compared to HC (823 +/- 331 ng/mL and 3115 +/- 1346 respectively, P mean +2SD of HC) were both associated with a lower risk of digital ulcers in SSc patients (OR, 95%CI: 0.09; 0.01, 0.71, and 0.17; 0.06, 0.51, respectively). Accordingly, patients without digital ulcers had a significantly higher sCD163 concentration and sCD163/sTWEAK ratio as compared to SSc patients with digital ulcers (P

Background Rheumatoid arthritis (RA) is a disease of the connective tissue, in the course of which the occurrence of symmetrical peripheral joints arthritis is the main symptom. It may lead to irreversible destruction of musculoskeletal system. Matrix metalloproteinase-3 (MMP-3) is a proteolytic enzyme which participates in the destruction of cartilage and bone, also in the course of active RA. As such it might be a sensitive marker of bone and cartilage tissue destruction also in an early stage of the disease. It could be also helpful in identifying patients at high risk of the osteolytic lesions occurrence. Objectives The aim of this study was to assess the relationship of MMP-3 concentration with already recognized clinical and laboratory markers of RA activity in order to evaluate its potential role in monitoring the RA activity. Methods 34 consecutive patients with established RA from the outpatient clinic were qualified for the study (all meeting the 2010 EULAR/ACR criteria). All of them consented to the study. Each patient was evaluated for concentration of MMP-3 (Aesculis DF MMP-3) and CRP together with routine monitoring blood tests. They were also asked to evaluate their disease activity on VAS scale. Peripheral joints of were examined for presence of tenderness and effusion, and assessed using ultrasound. The ultrasonographic assessment included gray scale and power Doppler mode examinations of radiocarpal, midcarpal, distal radioulnar joints of both wrists, also metacarpophalangeal and metatarsophalangeal joints in 0 – 3 grading scales for synovitis. The 1-6. compartments of the wrists extensors were assessed for tenosynovitis. The ultrasonographer was blinded to the results of physical examination and laboratory tests of the patients. The Disease Activity Score 28 was calculated for every patient. There were 24 patients with increased concentration of MMP-3 (mean age 55,1 yrs) who constituted the studied group while the ones with normal MMP-3 concentration created a control group (mean age 51,1 yrs). Mann-Whitney test, Kruskal-Wallis test, χ2Pearson’s test with Yates’s correction and logistic regression model were performed for statistical evaluation of the results. Results High concentration of MMP-3 was associated with joint swelling (p=0,041), presence of extraarticular symptoms of RA (p=0,034) and also with increased values of CRP (p=0,038). The increased MMP-3 levels were also significantly related to abnormalities shown on ultrasonography of the wrists, i.e. synovial overgrowth of the wrist joints shown in gray scale ultrasonographic assessment (p=0,019) and to active tenosynovitis (both in gray scale and in power Doppler mode) within any of the 6 compartments of wrist extensors (p=0,017). Conclusions The study demonstrated that MMP-3 levels are significantly associated with clinical, laboratory and also with ultrasonographic features of RA activity. High concentration of MMP-3 seems to reflect high activity of RA, so it might be considered as a reliable laboratory marker of the disease, what warrants further studies on bigger populations. Disclosure of Interest None Declared

Background SAPHO syndrome is an uncommon but recognized subgroup of psoriatic arthritis and is characterized by dermatological symptoms such as palmo-plantar pulstulosis and acne and osteoarticular symptoms. Radiographic assessment belongs to the diagnostic procedures of SAPHO syndrome although the present of them doesn’t belong to diagnostic criteria. Objectives To compare usefulness different methods of imaging of sterno-clavicular joints in SAPHO syndrome Methods We studied 15 patients (14 female, 1 male) with confirmed diagnosis of SAPHO syndrome. 14 patients had palmo-plantar pustulosis, 1 patient had severe acne. All of patients had pain and swelling of sterno-clavicular joints. Mean age of patients was 50,4±12,1 years, mean disease duration was 2,9 ± years. All of patients underwent bone scintigraphy, routine x-ray and computed tomography (CT) of sterno-clavicular joints. Results Increased tracer uptake on bone scintigraphy was found in 13(86,7%) of patients. In 9 of them in sterno-clavicular joints, in 4 – in sacroiliac joints and in 2 – in peripheral joints. Routine x-ray assessment of sterno-clavicular joints presented abnormalities in 4(26,7%) patients. These were: clavicle enlargement (1 patient), erosions with hyperostosis (1 patient), irregular calcifications (1 patient), irregular surface of clavicles (1 patient). Computed tomography of sterno-clavicular joints presented abnormalities in 6(40%) patients. These were: erosions (4 patients), hyperostosis (3 patients) and geodes (1 patients). All of patients with abnormal result in CT had increased tracer uptake on bone scintigraphy. Four of them had abnormal result on routine x-ray. Two of them had no changes on routine x-ray. Conclusions In patients with SAPHO syndrome routine x-ray in not sensitive and seems not necessary in diagnostic procedures. CT assessment is more sensitive in this group of patients. Bone scintigraphy is very sensitive but it could be nonspecific. References Przepiera-Bedzak H, Brzosko I, Flicinski J, Samborski W, Brzosko M: SAPHO syndrome – Clinical features. Pol Arch Med Wewn2006 116(6): 1172-7. Colina M, Govoni M, Orzincolo C, Trotta F: Clinical and radiological evolution of synovitis, acne, pulstulosis, hyperostosis and osteitis syndrome: a single center study of a cohort of 71 subjects. Arthritis Rheum 2009; 61(6): 813-21. Salles M, Olive A, Perez-Andres R, Holgado S, Mateo L, Riera E, Tena X: The SAPHO syndrome: a clinical and imaging study. Clin Rheumatol 2011; 30: 245-9. Disclosure of Interest None Declared

Renal clear cell carcinomas represent about 3% of all visceral cancers and account for approximately 85% of renal cancers in adults. Environmental and genetic factors are involved in the development of renal cancer. Although to date there are 19 hereditary syndromes described in which renal cell cancer may occur, only four syndromes with an unequivocal genetic predisposition to renal cell carcinoma have been identified: VHL syndrome (mutations in the VHL gene), hereditary clear cell carcinoma (translocations t(3:8), t(2:3)), hereditary papillary carcinoma (mutations in the MET protooncogene) and tuberous sclerosis (mutations in the TSC1 and TSC2 genes). Little is known genetically about the other forms of familial renal cell cancer. Since there is a growing awareness about the necessity of early intervention, clinical criteria have been developed that aid in the identification of hereditary forms of renal cancer. The aim of the current study was to identify minimal inclusion criteria so that nuclear pedigree families can be ascertained for risk assessment and/or kidney tumour screening. The results reveal that inclusion features described herein, such as (a) renal clear cell cancer diagnosed before 55 years of age, and (b) renal clear cell cancer and gastric cancer or lung cancer among first degree relatives, are useful in identifying suspected hereditary clear cell renal cancer patients.

Clonal expansion of CD4+CD28- T cells is a characteristic finding in patients with rheumatoid arthritis (RA). Expanded CD4+ clonotypes are present in the peripheral blood, infiltrate into the joints, and persist for years. CD4+CD28- T cells are oligoclonal lymphocytes that are rare in healthy individuals but are found in high percentages in patients with chronic inflammatory diseases. The size of the peripheral blood CD4+CD28- T-cell compartment was determined in 42 patients with RA and 24 healthy subjects by two-color FACS analysis. The frequency of CD4+CD28- T cells was significantly higher in RA patients than in healthy subjects. Additionally, the number of these cells was significantly higher in patients with extra-articular manifestations and advanced joint destruction than in patients with limited joint manifestations. The results suggest that the frequency of CD4+CD28- T cells may be a marker correlating with extra-articular manifestations and joint involvement.

Monogenic autoinflammatory diseases (AIDs, formerly known as hereditary periodic fever syndromes) cover a spectrum of diseases which lead to chronic or recurrent inflammation caused by activation of the innate immune system. The most common monogenic AID is familial Mediterranean fever. Monogenic autoinflammatory diseases are generally considered intracellular signalling defects. Some stereotypical knowledge may be misleading; e.g. monogenic AIDs are not exclusively found in children, family history is often negative, fever frequently is not a leading manifestation and frequency of attacks in adults is usually variable. Lack of genetic confirmation should not stop anti-inflammatory ex juvantibus therapy. The pattern of tissue injury in AIDs is basically different from that observed in autoimmunity. There is no autoaggression against organ-specific antigens, but substantial damage (amyloidosis, cachexia, premature cardiovascular disease) is secondary to long-lasting inflammation. The Polish national programme of anti-interleukin 1 treatment opens new possibilities for the treatment. However, monogenic AIDs are frequently misdiagnosed and more awareness is needed.

Introduction Angiogenesis is involved in the pathogenesis of arthritis. Objectives The aim of the study was to assess the serum levels of selected angiogenic cytokines and their association with clinical presentation in patients with psoriatic arthritis (PsA) and SAPHO syndrome. Patients and methods We studied 98 patients: 80 with PsA and 18 with SAPHO syndrome. The following data were recorded: age, sex, disease duration, joint involvement, type of psoriasis, nail involvement, and treatment. The following indices used to assess the activity of PsA and SAPHO were measured: PASI, BASDAI, BASFI, BASMI, BASG, and VAS pain. We determined erythrocyte sedimentation rate, C‑reactive protein (CRP), and platelet count. The serum levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic and acidic fibroblast growth factors (FGFb and FGFa) were determined using an enzyme‑linked immunosorbent assay. Results In patients with PsA, VEGF levels were positively correlated with CRP (P = 0.04), BASFI (P = 0.03), and disease duration (P = 0.007). No differences were found between patients with and without nail psoriasis in the VEGF or EGF levels (P = 0.32 and P = 0.85, respectively). There were no differences between patients with the peripheral and axial forms of arthritis in VEGF or EGF levels (P = 0.56 and P = 0.28, respectively). No significant correlations were observed between EGF and FGF levels and clinical presentation in patients with PsA. In patients with SAPHO, no significant correlations were found between angiogenic cytokine levels and clinical presentation. Conclusions Our data suggest a role of VEGF in the pathogenesis of PsA. Further studies are required to better understand the role of angiogenic cytokines in PsA.

Early diagnosis of subclinical atherosclerosis can be established using noninvasive imaging techniques, which enable to assess atherosclerotic lesions at different stages of their development, from endo‑ thelial dysfunction, through morpho logical lesions in the arteries, to advanced atherosclerotic plaques. Given high risk of accelerated development of atherosclerotic lesions in patients with systemic lupus erythematosus (SLE), these techniques should be incorporated in routine diagnostic evaluation in this population. Cardiovascular risk factors in patients with SLE differ significantly from those observed in the general population. Chronic inflammation and the presence of auto antibodies play the key role, while classic risk factors are less important. Subclinical atherosclerotic lesions can be detected in 30% to 40% of the SLE patients. The occurrence of severe symptoms in the cardiovascular and central nervous systems can be caused by such lesions. Recent data indicate that the main causes of death in this patient group represent cardiovascular complications. Early identification of patients in the risk group allows to implement appropriate prophylactic and therapeutic procedures.

ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV.In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry.LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease.Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.