Several metabolic derangements and concomitant diseases have been suggested to be associated with DISH including obesity, increased waist circumference, hypertension, dyslipidaemia, diabetes mellitus (DM), hyperuricaemia, metabolic syndrome and an increased risk for cardiovascular diseases. Witnessing the present increase in lifespan, obesity, DM and metabolic syndrome in the Western population, the prevalence of DISH should be expected to rise. In order to increase the awareness for DISH, this review focuses on the extraspinal features of the condition.

Methods. Expression was determined using real-time PCR, production of RANK and RANKL by flow cytometry and that of OPG by ELISA. Modulation of these factors was determined upon treatment with IL-1β, TNF- and PGE₂. The functional consequences were examined following treatment with soluble RANKL or OPG-Fc (OPG without the heparin-binding domain).

Results. OPG, RANK and RANKL were expressed and produced by human chondrocytes. Membranous RANK was produced only by an OA chondrocyte subpopulation (29%) localized throughout the cartilage. The OPG/RANKL ratio was significantly (P = 0.05) reduced on the OA chondrocytes, whereas the RANK/RANKL ratio was significantly (P < 0.03) increased. OPG and membranous RANKL levels were significantly enhanced by IL-1β, TNF- and PGE₂, whereas membranous RANK was significantly increased only with IL-1β. Administration of soluble RANKL had no effect on the OA chondrocytes. However, addition of OPG-Fc significantly stimulated MMP-13 (P = 0.05) and protease-activated receptor-2 (PAR-2) (P < 0.04) production.

Conclusions. Our findings showed that human chondrocytes express and produce OPG, RANK and RANKL. OA chondrocyte treatment with catabolic factors pointed towards an increased biological effect of OPG. Interestingly, OPG appears to be involved in OA progression by increasing two catabolic factors involved in cartilage pathophysiology.

Methods. We quantified the mRNA expression of IL-17, -23, -27 and retinoic-acid-related orphan receptor (ROR)-, the regulator for the development and function of TH17, in the urinary sediment of 23 subjects with active lupus nephritis, 25 subjects with a history of lupus nephritis in remission, 30 SLE patients with no history of renal involvement and 8 healthy subjects.

Results. All three groups of lupus patients had a higher urinary expression of TH17-related cytokines than the controls. However, urinary expression of IL-17 and -27 was found to be inversely correlated with the SLEDAI score (r = –0.252 and –0.258, respectively; P < 0.05 for both). For patients with active lupus nephritis, the histological activity index of kidney biopsy was also found to be inversely correlated with the urinary expression of ROR- (r = –0.447; P = 0.032), IL-17 (r = –0.454; P = 0.029) and IL-23 (r = –0.455; P = 0.029). Urinary expression of IL-17, -23, -27 and ROR was also found to be inversely correlated with the urinary expression of IFN- and T-bet, the key transcription factor of type 1 Th cells. After 6 months of treatment, urinary IL-27 expression rose significantly in patients with complete response (from 2.07 ± 1.62 to 3.70 ± 1.69; P = 0.028) but remained unchanged in those with partial or no response (from 2.60 ± 1.87 to 2.52 ± 1.94; P = 0.9).

Conclusions. The urinary expression of TH17-related genes is increased in SLE patients. The degree of up-regulation, however, is inversely related to systemic and renal lupus activity, as well as urinary expression of TH1-related genes. Urinary expression of TH17-related genes increased again after successful immunosuppressive treatment of active disease. Our findings suggest a regulatory role of TH17-related cytokines in pathogenesis of lupus nephritis.

Methods. The ability of serum samples from 30 patients with SLE, 20 with non-SLE rheumatic diseases (RA, PsA, AS, SS) and 20 healthy controls to opsonize S. pneumoniae (strains D39 and Io11697) with C3b/iC3b was assessed using a standardized FACS technique and a FACSCalibur flow cytometer. Results were compared among the three groups using analysis of variance, followed by pairwise comparisons among groups using the Mann–Whitney U-test.

Results. The proportion of bacteria positive for C3b/iC3b was significantly lower in serum from patients with SLE (strain D39: 60.3% ± s.e.m. 2.87, strain Io11697: 55.3% ± 3.8) compared with healthy controls (strain D39: 70.6% ± 2.0, P = 0.01; strain Io11697: 67.8% ± 2.6; P = 0.05) and non-SLE rheumatic controls (strain D39: 69.8% ± 3.1; P = 0.03). For the patients with SLE, there was no association between C3b/iC3b deposition and serum complement levels or measurable classical pathway activity. C3b/iC3b deposition on S. pneumoniae was significantly lower in serum from SLE patients with a past history of pneumonia (n = 3) compared with those without (n = 27; P = 0.03).

Conclusions. Opsonization of S. pneumoniae with C3b/iC3b was significantly reduced in serum from patients with SLE compared with non-SLE rheumatic disease and healthy controls. Failure to appropriately activate the immune system via complement may contribute to the increased susceptibility of SLE subjects to infections, and may correlate with a risk of pneumonia in a subgroup of SLE patients.

Methods. The CTLA-4 CT60 (exon 4), +49 (exon 1) and –318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls.

Results. The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: ² = 10.965, P = 0.004; CT60: ² = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis.

Conclusion. This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV.

Methods. A prospective cross-sectional study of 288 patients with SLE were recruited from lupus clinics in Birmingham, UK. Resting transthoracic echocardiography was performed to estimate the pulmonary artery pressures and to assess cardiac morphology and function. PAH was defined as systolic pulmonary artery pressure (sPAP) >30 mmHg. We assessed potential risk factors such as the presence of lung disease, respiratory muscle weakness, autoantibodies, smoking, RP and APS.

Results. Of 288 patients who consented for participation, 283 patients were suitable for analysis. Twelve patients were found to have PAH with sPAP >30 mmHg. The range of sPAP in our PAH patients was 31–59 mmHg and three patients had sPAP >40 mmHg. The only significant risk factor for PAH was LAC (P = 0.005).

Conclusions. The point prevalence of PAH was 4.2% in our cohort of patients with SLE. Most of the PAH cases were found to be of mild severity (<40 mmHg). The significant association of LAC and presence of APS in PAH cases suggests that thrombosis may play an important role in PAH with SLE. This is important, as it is treatable.

Methods. Twenty-eight participants with SS and 37 controls were enrolled in a cohort-matched, prospective, cross-sectional study. Smell and taste thresholds were measured using standardized, validated tests. QoL was assessed by the Short Form 12 (SF-12).

Results. Smell threshold was reduced by 1 point (P = 0.002; 95% CI 0.35, 1.54) and taste threshold was reduced by 3.5 points (P < 0.001; 95% CI 1.80, 5.22) in the SS group compared with controls. The physical and mental components of SF-12 were reduced by 14.2 points (P < 0.001; 95% CI 9.47, 19.02) and 7.5 points (P = 0.002; 95% CI 2.97, 12.02), respectively, in the SS group compared with controls. Taste threshold was significantly correlated with both the physical (r = 0.48; P < 0.001) and the mental (r = 0.30; P = 0.015) components of SF-12. Smell threshold correlated with the physical (r = 0.457; P < 0.001), but not the mental component (r = 0.154; P = 0.222) of SF-12.

Conclusions. Clinically important impairment of chemosensory perception occurred in the SS group compared with age- and gender-matched controls. Assessment using SF-12 suggests that this impairment contributed to the reduced health-related QoL that characterized these individuals.

Methods. ESPOIR is a French, multi-centric EA cohort. Four centres assessed the structural damage by both X-ray and US examination at baseline. X-rays of hands and feet were read first by the centre's local investigator (usual reading), then in the X-ray coordinating centre (central reading). Four trained examiners performed US blindly from clinical data to detect erosions on the second and fifth MCP (MCP2 and 5) and the fifth MTP (MTP5) joints bilaterally.

Results. Patients’ characteristics (n = 126) were: female 78%; mean age 50.3 years; disease duration 103 days; disease activity score on 28 joints 5; CRP level 22.7 mg/l; and 79.4% of the patients fulfilling RA ACR criteria. Twelve patients had missing data for X-rays. US revealed 42 (36.8%) patients with erosive disease, whereas radiography revealed only 30 (26%) with central reading and only 11% with usual reading. US missed erosive disease present in X-rays in 10 (8.8%) patients. Combined technique of both revealed 52 (45.6%) patients with erosive diseases. On the targeted joints, US detected erosion on 75 (11%) joints vs X-rays on only 11 (1.5%). Only three joints with erosion(s) detected on X-rays were missed on US. At baseline, the presence of PD activity was not associated with joint erosions.

Conclusions. US on six joints detected 1.4-fold more patients with erosions (3.3-fold more with the usual reading). In clinical practice, US combined with X-rays is of helpful diagnostic value in EA.

Methods. Twenty-nine patients with RA underwent USD examination of the wrist before and immediately after three interventions. The interventions were carried out on three separate days. The interventions were (i) isometric exercise of the muscles of the hand and forearm, (ii) heating and (iii) cooling of the hand. The amount of Doppler in the wrist joint was quantified by measuring the percentage of colour in the synovium—the colour fraction (CF). The CF values estimated before and after each intervention were compared to see if any intervention affected the amount of Doppler in the synovium.

Results. The CF decreased significantly after cooling of the hand (P = 0.018 and <0.0001). Despite being highly significant, the numerical decrease in CF was only modest, 0.78–1.33 percentage points. The other interventions did not affect the CF significantly, with P-values of 0.65 and 0.59 in the heating intervention and 0.49 in the exercise intervention.

Conclusions. Cooling of the hand should, if possible, be avoided before a USD examination of the wrist in patients with RA, because the amount of Doppler activity might be affected by low skin temperatures.

Methods. We review all Henoch–Schönlein cases published after 1969 with CNS dysfunction without severe hypertension and neuroimaging studies (n = 35), cranial or peripheral neuropathy (n = 15), both CNS and peripheral nervous system dysfunction without severe hypertension (n = 2) or nervous system dysfunction with severe hypertension (n = 2). Forty-four of the 54 patients were <20 years of age.

Results. In patients with CNS dysfunction without or with severe hypertension the following presentations were observed in decreasing order of frequency: altered level of consciousness, convulsions, focal neurological deficits, visual abnormalities and verbal disability. Imaging studies disclosed the following lesions: vascular lesions almost always involving two or more vessels, intracerebral haemorrhage, posterior subcortical oedema, diffuse brain oedema and thrombosis of the superior sagittal sinus. Following lesions were noted in the subjects with cranial or peripheral neuropathy without severe hypertension: peroneal neuropathy, peripheral facial palsy, Guillain–Barré syndrome, brachial plexopathy, posterior tibial nerve neuropathy, femoral neuropathy, ulnar neuropathy and mononeuritis multiplex. Persisting signs of either CNS (n = 9) or peripheral (n = 1) nervous system dysfunction were sometimes reported.

Conclusions. In Henoch–Schönlein syndrome, signs of nervous system dysfunction are uncommon but clinically relevant. This review helps clinicians managing Henoch–Schönlein syndrome with nervous system dysfunction.

Methods. Seventy patients with recent onset RA (median disease duration 106 days) were examined by US of the distal ulna, in addition to hand radiography [assessed by van der Heijde-modified Sharp score (vdHSS)] and MRI of the wrist [assessed by RA MRI scoring (RAMRIS) erosion score]. Twelve months later 58 patients were re-assessed.

Results. US detected erosions at the distal ulna in 11% of the patients at baseline and 24% at follow-up (the majority of erosions were at the ulnar side). Logistic regression analyses showed the presence of erosions at baseline to be associated with baseline RAMRIS erosion score (P < 0.001), and at follow-up to RAMRIS erosion score (P = 0.02) and vdHSS (P = 0.008).

Conclusions. A significant number of patients had US erosions at the distal ulna at baseline, with increased prevalence after 1 year. The US-detected erosions were associated with structural joint damage in hands assessed by both MRI and CR. US of the distal ulna could thus give useful clinical information.

Methods. Successive patients referred to the rheumatology clinic at St Vincent's University Hospital and Our Lady's Hospice were evaluated. Clinical assessments were undertaken at baseline and 3 months after commencing TNF- blockade. Fatigue was measured using an 11-point numeric rating scale (NRS). Sensitivity to change when compared with current core set outcome measures was determined by calculation of the standardized response mean (SRM). Multiple regression analysis was employed to determine the independent variance of fatigue scores relative to the core set.

Results. Forty-nine patients were evaluated. At baseline, mean (s.d.) fatigue scores were 6.7 ± 2.1. At 3 months, fatigue scores had fallen to 4.3 ± 2.6 (P < 0.001). Test–retest intraclass correlation coefficient for the NRS was 0.79 (P < 0.008). Fatigue was ranked third for relative sensitivity to change as shown by SRM: pain, 1.37; tender joint count (TJC), 1.09; fatigue, 0.92; swollen joint count (SJC), 0.86; HAQ, 0.82; CRP, 0.69; and patient global health (GH), 0.25. The relative independent variance in fatigue of 22% was higher than that of the core set: TJC, 20%; pain, 19%; SJC, 16%; GH, 8%; HAQ, 7%; and CRP, 8%.

Conclusions. This study demonstrates that measures of fatigue are reliable and sensitive to change, and should be considered for inclusion as a core outcome measure in RA.

Methods. A total of 158 subjects participated in the SLS. Data from the two treatment groups were combined for this analysis. We used five patient-reported anchors from the short form (SF)-36 instrument to assess MID for TDI—SF-36 transition question and four questions from SF-36 pertaining to walking on a flat surface or climbing stairs. On the SF-36 transition question, patients who rated as a little better or a little worse were defined as the MID subgroup. For other questions, patients who reported improvement from ‘Limited a lot’ to ‘Limited a little’ and ‘Limited a little’ to ‘No limit’ and vice versa were defined as the MID subgroup.

Results. The MID estimates for the TDI improvement and worsening ranged from 1.05 to 2.16 (mean score = 1.5) U and from –0.61 to –2.55 (mean score = –1.5) U, respectively. Change in this group was larger than that of the no-change group (mean score = 0.38 U). Patients who achieved the MID for improvement at 12 months had a greater improvement in their FVC% predicted (3.6%) compared with those who did not (–3.3%; P < 0.001).

Conclusion. A change (improvement/worsening) of 1.5 U in the TDI is the MID for SSc-related interstitial lung disease (SSc-ILD). This can aid in interpreting clinically important changes in breathlessness in SSc-ILD.

Methods. An inception cohort of 60 patients diagnosed with JDM from 1970 to 2006 was examined, median 16.8 (2.0–38.1) years after disease onset. Disease activity was measured by the disease activity score (DAS), organ damage by the myositis damage index (MDI) and physical function by the childhood or adult HAQ (CHAQ/HAQ). Medical records were reviewed for early disease variables at diagnosis, and 6 and 12 months post-diagnosis.

Results. Fifty-four (90%) patients had a cumulative MDI total score >=1 at follow-up (mean 4.2 ± 3.1). Damage occurred most frequently in cutaneous, muscular and skeletal domains (77, 65 and 57%, respectively). Early predictors of damage were DAS and MDI 6 months post-diagnosis (β = 0.334; P = 0.002 and 0.382, P < 0.001, respectively). Follow-up time also correlated with MDI (P = 0.010). Calcinosis, seen in 47% of the patients, was predicted by male gender [odds ratio (OR) 3.8; 95% CI 1.2, 12.1], and DAS 6 months post-diagnosis (OR 1.2; 95% CI 1.1, 1.4). The MDI score correlated with CHAQ/HAQ and DAS at follow-up (r_s = 0.355; P = 0.005 and 0.446, P < 0.001, respectively). The DAS decreased during the first-year post-diagnosis, whereas the MDI increased over time.

Conclusions. The majority of JDM patients had cumulative organ damage at follow-up, which was predicted by high disease activity and organ damage 6 months post-diagnosis.

Methods. SLE patients were recruited into this multi-centre cross-sectional study. At every assessment, data were collected on disease activity and therapy. Logistic regression was used to model an increase in therapy, as an indicator of active disease, by the Classic BILAG score in eight systems. As both indicate inactivity, scores of D and E were set to 0 and used as the baseline in the fitted model. The coefficients from the fitted model were used to determine the numerical values for Grades A, B and C. Different scoring schemes were then compared using receiver operating characteristic (ROC) curves. Validation analysis was performed using assessments from a single centre.

Results. There were 1510 assessments from 369 SLE patients. The currently used coding scheme (A = 9, B = 3, C = 1 and D/E = 0) did not fit the data well. The regression model suggested three possible numerical scoring schemes: (i) A = 11, B = 6, C = 1 and D/E = 0; (ii) A = 12, B = 6, C = 1 and D/E = 0; and (iii) A = 11, B = 7, C = 1 and D/E = 0. These schemes produced comparable ROC curves. Based on this, A = 12, B = 6, C = 1 and D/E = 0 seemed a reasonable and practical choice. The validation analysis suggested that although the A = 12, B = 6, C = 1 and D/E = 0 coding is still reasonable, a scheme with slightly less weighting for B, such as A = 12, B = 5, C = 1 and D/E = 0, may be more appropriate.

Conclusions. A reasonable additive numerical scoring scheme based on treatment decision for the Classic BILAG index is A = 12, B = 5, C = 1, D = 0 and E = 0.

Methods. ANAs were examined by IIF using HEp-2 cells as substrate in 2278 participants in the Cardiovascular Risk in Young Finns Study for whom detailed data on cardiovascular risk factors and markers of subclinical atherosclerosis (including brachial flow-mediated dilatation, carotid compliance and carotid intima-media thickness) were available.

Results. In multivariate analyses, adjusted for age, BMI, serum concentrations of CRP, triglycerides, high-density lipoprotein and low-density lipoprotein cholesterol, blood pressure and smoking habits, ANA positivity (titre > 160) was inversely associated (β = –0.145; P = 0.034) with carotid compliance in women.

Conclusions. Our results indicate that ANA positivity is associated with decreased carotid elasticity in women, suggesting that mechanisms resulting in ANA production may be involved in the development of early atherosclerosis.

Methods. RTX was used in 110 RA patients in six different Italian centres. The mean disease activity score on 28 joints (DAS28) was 6.4 ± 0.99 and the mean HAQ was 1.63 ± 0.68 at baseline. Thirty-two patients (29.1%) underwent RTX after the failure of DMARD therapy, 37 (33.6%) had failed or were intolerant to at least two anti-TNF agents, and 41 (37.3%) had failed or were intolerant to one anti-TNF agent. Univariate and multivariate analyses were performed.

Results. The number of previous anti-TNF agents (P = 0.043), HAQ (P = 0.023), RF positivity (P < 0.0001) and anti-cyclic citrullinated peptide (anti-CCP) positivity (P = 0.003) were associated with ACR response >=50 between month +4 and month +6 after starting RTX by univariate analysis. Multivariate analysis confirmed that a lower HAQ, a lower number of anti-TNF agents failed before RTX and RF positivity, but not anti-CCP positivity, were the selected variables associated with an ACR response >=50, with an accuracy of 84% of the model. Only RF positivity correlated with EULAR moderate to good response both in the univariate and in the multivariate analysis, with an accuracy of 79% of the model.

Conclusion. RF-positive rather than anti-CCP-positive RA patients with lower baseline disability and a lower number of previously failed TNF blockers may be the best candidates to RTX.

Methods. Cases were retrieved using hospital records and a serology database. All new cases of WG, MPA, CSS and PAN between 1997 and 2006 were included, provided they met pre-defined criteria, and were followed until 30 June 2008. The study area comprised two health care districts with a total population of 641 000. The standardized mortality ratio (SMR) was estimated using Swedish population data as a reference.

Results. A total of 140 (WG, 63; MPA 65; CSS 6; and PAN 6) cases (52% women) with a median age of 67.6 (range 20–96) years fulfilled the inclusion criteria. The annual incidence per million of the population (95% CI) was estimated to be 9.8 (7.4–12.2) for WG, 10.1 (7.7–12.6) for MPA and 0.9 (0–1.7) for both CSS and PAN. The highest incidence was found in patients aged >=75 years (79.1/million). The 1- and 5-year survival rates were 87.8 and 71.6% for all patients, but lower for MPA (80 and 55%) compared with WG (95 and 83%; P = 0.001), although the difference was not significant in the multivariate analysis. The SMR was 2.77 (95% CI 2.02, 3.71) for all patients.

Conclusions. The incidence of WG and MPA was equal in our district, but there was a difference in survival rates related to age and renal function. A progressive increase in age-specific incidence rates was observed.

Methods. For a mean of 41 months, 57 consecutive untreated patients with PMR were prospectively assessed for relapses/recurrences. This cohort represented all the patients diagnosed over a 18-month period in one Italian secondary referral centre. Clinical signs and symptoms as well as ESR and CRP were evaluated. US examination of the shoulders was performed in all 57 patients at diagnosis and after the onset of prednisone treatment (mean 24 ± 3 weeks). Power Doppler ultrasonography (PDUS) was performed in 24 patients. Shoulder sonograms were obtained according to standardized techniques.

Results. Prednisone therapy significantly reduced the frequency and the degree of subacromial/subdeltoid bursitis, long head biceps tenosynovitis and glenohumeral synovitis. At diagnosis, a positive PD signal was observed more frequently in the subacromial/subdeltoid bursae (33%). Prednisone therapy significantly reduced the frequency of patients with positive PD signal. Of the 44 patients in remission or with low disease activity at the time of the second US, 26 (59%) still had evidence of persistent inflammatory lesions. There was no association between the persistence of inflammation at US and relapses/recurrences; in contrast, a positive PD signal at diagnosis was significantly associated with the occurrence of relapses/recurrences at follow-up.

Conclusion. Subclinical inflammation detected by US persists in most PMR patients despite glucocorticoid treatment. PDUS may be useful to detect at diagnosis the patients with most active inflammation who have a higher risk of relapses/recurrences.

Methods. This multicentre study involved 354 patients with SSc, 245 with non-SSc CTDs and 102 healthy controls. ELISAs were used to detect anti-RNAP III antibody, anti-topo I antibody and ACA. The presence of anti-RNAP III antibody in selected serum samples was confirmed by immunoprecipitation (IP) assay.

Results. By ELISA, anti-RNAP III antibody was detected in 38 (10.7%) patients with SSc, 3 (1.2%) with non-SSc CTD and no healthy controls. The clinical specificity for SSc was excellent (98.8%), although a small number of false positives occurred. The sensitivity of the anti-topo I and ACA ELISAs for SSc was 59.9%, which increased to 68.2% without a reduction in specificity when the anti-RNAP III measurement was added. Clinical features associated with positivity for the anti-RNAP III antibody include dcSSc, a high total skin score and a trend towards high prevalence of renal crisis, consistent with previous studies that used an IP assay. Furthermore, on clinical severity scales, SSc patients with anti-RNAP III antibody scored highest for skin and renal involvement among patients subgrouped by the presence of individual SSc-related antibodies.

Conclusions. The measurement of anti-RNAP III antibody by ELISA is useful in routine clinical practice, because it helps diagnose SSc and identify a disease subset with severe skin and renal involvement.

Methods. Data from two large, randomized, controlled, double-blind trials in patients with early RA using adalimumab or infliximab+MTX or MTX alone were obtained and pooled. Composite disease activity indices were calculated at baseline and 1 year of treatment, and compared in groups of patients classified by quartiles of age with the highest age group comprising 61–82 years using analysis of variance or Kruskal–Wallis test.

Results. Across all age quartiles, improvement on MTX was similar with respect to changes of composite disease activity indices, assessment of physical function and X-ray progression. Likewise, TNFi+MTX had similar effects across all age groups, but the effects of the combination were more profound than those of MTX monotherapy. Also in 10% of the patients with the highest age, primarily septuagenarians, improvement was seen to a similar degree as in the younger ones.

Conclusions. Responsiveness of elderly patients with RA to MTX or TNFi+MTX is similar to that observed in patients of younger age.

Methods. RA synovial cells were cultured in the presence or absence of antibodies directed against IL-23p19 or -23R and -17. IL-23, -12, -17, and their receptors, and IL-6, -1β and TNF- were measured by ELISA and/or PCR.

Results. Small amounts of cell-associated IL-23 (median 110 pg/ml) were detected in RA synovial cultures, and found to be functional as IL-23R blockade resulting in a significant inhibition of TNF- (57%), IL-1β (51%) and IL-6 (30%). However, there was a considerable variability between individual patient samples, and anti-IL-23p19 was found to be considerably less effective. IL-17A protein was detected in ~40% of the supernatants and IL-17A blockade, in IL-17A-producing cultures, resulted in a small but significant inhibition of TNF- (38%), IL-1β (23%) and IL-6 (22%). Addition of recombinant IL-23 to cultures had a variable effect on the spontaneous production of endogenous IL-17A with enhancement observed in some but not all cultures, suggesting that either the low levels of endogenous IL-23 are sufficient to support cytokine production and/or that the relevant Th17 cells were not present.

Conclusions. These results suggest that although IL-23 may have pathogenic activity in a proportion of patients with late-stage RA, it is not abundantly produced in this inflammatory tissue, nor does it have a dominant role in all patient tissues analysed.

Methods. Plasma levels of the S100A4 protein were analysed in 40 anti-TNF- naive patients with active RA. Of the 40 patients, 25 were treated with adalimumab and monitored over time. The conformational form of S100A4 was analysed using size-exclusion gel chromatography. TNF- mRNA expression and protein synthesis were analysed by RT–PCR and ELISA, respectively.

Results. Baseline levels of S100A4 were significantly correlated with disease activity in RA patients (r = 0.41; P < 0.01). After 12 weeks of treatment with adalimumab, there was an obvious shift in the conformations of S100A4 from the multimeric to the dimeric forms, whereas the total levels of the S100A4 protein remained unchanged. This suggests that the bioactive (multimer) S100A4 may decline in response to successful treatment with adalimumab. In addition, we showed significant up-regulation of TNF- mRNA (P < 0.01), and protein release to the cell culture medium of monocytes stimulated with the S100A4 multimer compared with those treated with the dimer and to the unstimulated monocytes (P < 0.001).

Conclusions. This is the first study to show that the levels of the S100A4 protein are correlated with RA disease activity. Furthermore, only the bioactive form, but not the total amount of S100A4, decreases after successful TNF- blocking therapy in patients with RA. These data support an important role for the S100A4 multimer in the pathogenesis of RA.

Methods. We recruited 15 patients with dcSSc to take part in an open-label study using mycophenolate mofetil to treat their disease over a 12-month period. The primary outcome measure was the modified Rodnan skin score (mRSS), whereas secondary outcomes included the Medsger severity score, pulmonary function studies, 2D echocardiograms and the Short Form Health Survey (SF)-36 questionnaire.

Results. The mRSS significantly improved in those patients who tolerated the medication for >3 months (P < 0.0001), and there was a statistically significant improvement in the Medsger severity scores of the general (P = 0.05), peripheral vascular involvement (P = 0.05) and skin (P = 0.0003) scores. The SF-36 scores improved (P = 0.05) and the pulmonary function studies showed a trend towards improvement, though not of statistical significance. The mean pulmonary artery pressure by 2D echocardiography did not change.

Conclusions. In this prospective open-label study of mycophenolate mofetil for the treatment of dcSSc, we observed significant improvements in skin scores, peripheral vascular involvement and patient-perceived health status. Pulmonary function studies did not worsen as expected, but instead showed a trend towards improvement. Controlled trials are needed to further investigate this trend for improved pulmonary function studies.

Methods. Two cohorts of consecutive patients with RA seen at outpatient clinics in Malmö, Sweden, were started in 1978 (n = 148) and 1995 (n = 161) and compared with the corresponding background population. Patients were followed for 8 years, and fatal and non-fatal cardiovascular first events were identified using two national registers, hospital discharge and cause of death. Standardized morbidity ratio (SMoR) and standardized mortality ratio (SMR), adjusted for age and sex were calculated.

Results. Sex distribution, age at disease onset and disease duration were similar in both groups. The 1995 cohort was more extensively treated with DMARDs and had less disease activity and disability. Total cardiovascular morbidity was increased in the 1978 cohort (SMoR 158; 95% CI 111, 225) as well as in the 1995 cohort (SMoR 168; 95% CI 118, 232). This was mainly due to an increased risk of coronary artery disease. Overall mortality was elevated in the 1978 cohort but not in the 1995 cohort. There was no change in cardiovascular excess mortality (SMR 175; 95% CI 100, 284; and 172; 100, 276 for the two cohorts, respectively).

Conclusions. There were similar elevations in the incidence of cardiovascular comorbidity in RA patients, identified two decades apart compared with the general population, in spite of more extensive treatment and reduced disease severity in the more recent cohort.

Methods. We recruited RA patients without overt arterial disease aged 40–65 years, attending hospital rheumatology outpatient clinics. Standardized research nurse assessment included blood pressure (BP), pulse wave analysis (PWA, SphygmoCor), BMI, fasting blood sample (lipids, glucose, RF and ESR), patient questionnaire (smoking, alcohol, diet, exercise, family history of premature coronary heart disease and Stanford HAQ), current medication and medical record review. Cumulative inflammatory burden was measured as ESR area-under-the-curve (ESR-years) extracted from medical records. Arterial stiffness was measured using PWA [aortic augmentation index (AIX@75)]. Multiple linear regression was used to adjust for age, sex and nine other cardiovascular risk factors.

Results. We recruited 114 RA patients (mean age 54 years, female 81%, current DMARD 90%, current NSAID 70%, ACR criteria 56%) comprising 1040 RA person-years. Cholesterol, glucose and BMI were similar in women and men. Women had a longer duration of arthritis (10 vs 7 years) and were more likely to be seropositive (85 vs 71%). BP, smoking and alcohol consumption were lower for women. On fully adjusted analysis, an increase of 100 ESR-years was associated with an increase in AIX@75 of 0.51 (95% CI 0.13, 0.88). On fully adjusted analysis restricted to women the increase was 0.43 (95% CI 0.01, 0.85).

Conclusions. In RA patients free of overt arterial disease, a dose–response relationship exists between cumulative inflammatory burden and arterial stiffness. This relationship is independent of established CV risk factors.

Methods. Twenty-four RA synovial samples were analysed by gene expression oligonucleotide microarrays. Expression levels of TREM-1 mRNA in murine CIA paws were determined by quantitative PCR (qPCR). TREM-1 protein expression was detected by immunohistochemistry in five RA synovial samples and two OA synovial samples. TREM-1-positive cells from five RA synovial tissues were analysed by FACS staining to determine the cell type. Activation of TREM-1 was tested in five RA synovial samples. Soluble TREM-1 was measured in serum from 32 RA patients.

Results. The expression of TREM-1 mRNA was found to increase 6.5-fold in RA synovial samples, whereas it was increased 132-fold in CIA paws. Increased numbers of TREM-1-positive cells were seen in RA synovium sections and these cells co-expressed CD14. Using a TREM-1-activating cross-linking antibody in RA synovial cultures, multiple pro-inflammatory cytokines were induced. The average amount of soluble TREM-1 in plasma from RA patients was found to be higher than that in plasma from healthy volunteers.

Conclusions. These findings suggest that the presence of high levels of functionally active TREM-1 in RA synovium may contribute to the development or maintenance of RA, or both. Inhibiting TREM-1 activity may, therefore, have a therapeutic effect on RA. High levels of soluble TREM-1 in the plasma of RA patients compared with healthy volunteers may indicate disease activity.

Methods. We conducted a random effect meta-analysis on the association of the A/A genotype (the recessive effect), the A/A + A/G genotype (the dominant effect) and the A allele of the TNF- –308 and –238 polymorphisms with AS.

Results. Eight studies, consisting of seven European studies and one Latin American study, were included in this meta-analysis. Any association between AS and the TNF- –308 A allele was not found [odds ratio (OR) = 0.911; 95% CI 0.512, 1.286; P = 0.636; I² = 73.8]. There was also no association of the TNF- –308 AA and AA+AG genotypes with AS. Meta-analysis of the TNF- –238 polymorphisms showed no association with AS (OR for A allele = 0.930; 95% CI 0.498, 1.737; P = 0.821; I² = 71.6). Subgroup analysis by ethnicity and HLA-B27 positivity did not change the results for the association of the TNF- –308 and –238 polymorphisms with AS.

Conclusions. This meta-analysis including 2247 subjects has shown that there is a lack of association of the TNF- –308 A/G and –238 A/G polymorphisms with AS.

Methods. Unrelated 750 RA patients and individually matched 750 healthy controls were genotyped for single nucleotide polymorphism (SNP), rs11889341, in STAT4, which tags the susceptibility haplotype. Association analyses were performed on the whole data set and on sex subsets. Significant relationships were determined between clinical variables and rs11889341 for each disease subtype in the studied groups.

Results. There was no evidence of a significant association between rs11889341 and RA. The heterozygous CT genotype was associated with RA in female group [P = 0.027; odds ratio (OR) 1.31; 95% CI 1.03, 1.65]. No association was found in male group and in any subsets of RA based on sex, RF and anti-cyclic citrullinated peptide (anti-CCP) antibody. However, in the Han Chinese population with RA disease, we observed a significantly decreased frequency of the minor T allele and TT genotype in the RF-positive subgroup compared with RF-negative subgroup (T allele: P = 0.024; OR 0.73; 95% CI 0.56, 0.95; TT genotype P = 0.013; OR 0.49; 95% CI 0.28, 0.86).

Conclusion. The STAT4 RA-susceptibility haplotype identified in other previously reported populations has not been replicated in the Han Chinese population with individually matched case–control study design. It is associated only with the presence of RF in the Han Chinese population with RA disease.

Methods. We analysed data from 4238 RA cases and 1811 controls, for which genotypes were available at all five loci.

Results. Statistical analysis identified eight high-risk combinations conferring an odds ratio >6 compared with carriage of no susceptibility variants and, interestingly, 10% population controls carried a combination conferring high risk. All high-risk combinations included SE, and all but one contained PTPN22. Statistical modelling showed that a model containing only these two loci could achieve comparable sensitivity and specificity to a model including all five. Furthermore, replacing SE (which requires full subtyping at the HLA-DRB1 gene) with DRB1*1/4/10 carriage resulted in little further loss of information (correlation coefficient between models = 0.93).

Conclusions. This represents the first exploration of the viability of population screening for RA and identifies several high-risk genetic combinations. However, given the population incidence of RA, genetic screening based on these loci alone is neither sufficiently sensitive nor specific at the current time.

Methods. DNA samples of 200 BD patients [59 Caucasians, 139 Middle Easterns (MEs) of Arab descent and 2 Asians] and 520 healthy controls (444 Caucasians and 76 MEs) were genotyped using a Taqman assay.

Results. Both the Arg702Trp and Leu1007fs (frameshift) variants were significantly less frequently present among BD patients compared with healthy controls (0.5 vs 5.8%; P < 1.10^–5 and 0.0 vs 1.8%; P < 0.007, respectively). In the Caucasian subpopulation, Arg702Trp was significantly less frequent in the BD group as compared with the controls (P = 0.04); whereas in the ME subpopulation, a trend was observed (P < 0.06).

Conclusions. Of the three CD-associated single nucleotide polymorphisms, one of the variant NOD2 alleles, was found to be present significantly less in Caucasian BD patients.

Methods. A total of 1000 patients with a confirmed diagnosis of AS under the clinical care of 10 specialist rheumatology centres across the UK were invited to participate in a study evaluating a new quality of life measure. Patients completed a questionnaire, which also included questions relating to the impact of AS on their sexual relationships, sociodemographic and clinical characteristics.

Results. Six hundred and twelve (64%) patients took part in the study. The majority were male (71.6%), mean age 50.8 ± 12.2 years, mean diagnosed disease duration 17.3 ± 11.7 years and mean symptom duration 23 ± 18.6 years. Of those who responded to the question on sexual relationships (n = 552), 210 (38.0%) reported that their sexual relationships were affected ‘moderately’, ‘quite a bit’ or ‘extremely’ by their AS. Males reported greater sexual problems with increasing age. Poor function [odds ratio (OR) 3.64; 95% CI 1.92, 6.87], depression (OR 2.03; 95% CI 1.21, 3.41), greater disease activity (OR 2.10; 95% CI 1.01, 4.40), unemployment (OR 1.99; 95% CI 1.16, 3.40) and poor self-efficacy (OR 1.25; 95% CI 1.09, 1.43) were independently associated with a greater impact on patients’ sexual relationships.

Conclusion. AS has a substantial impact on patients’ sexual relationships. Management of AS and its impact on sexual relationships should be directed not only towards physical outcomes such as disease activity and physical function, but also take into consideration the psychological state of the patient.

Methods. We enrolled 33 consecutive SSc patients (mean age 54 ± 13 years, 30 females) in the Rheumatology Clinic of the University of Pisa. We assessed ULCs and chest HRCT within 1 week independently in all the patients. ULC score was obtained by summing the number of lung comets on the anterior and posterior chest. Pulmonary fibrosis was quantified by HRCT with a previously described 30-point Warrick score.

Results. Presence of ULCs (defined as a total number more than 10) was observed in 17 (51%) SSc patients. Mean ULC score was 37 ± 50, higher in the diffuse than in the limited form (73 ± 66 vs 21 ± 35; P < 0.05). A significant positive linear correlation was found between ULCs and Warrick scores (r = 0.72; P < 0.001).

Conclusions. ULCs are often found in SSc, are more frequent in the diffuse than the limited form and are reasonably well correlated with HRCT-derived assessment of lung fibrosis. They represent a simple, bedside, radiation-free hallmark of pulmonary fibrosis of potential diagnostic and prognostic value.

Methods. Eighty-four (59 males and 25 females) patients with BS with mainly skin mucosa disease and a history of recurrent OU for >=1 year were studied. When they had at least two OUs with a total diameter of >=4 mm, they were randomly allocated to (i) 2000 IFN- IU/day, (ii) 1000 IFN- IU/day and (iii) placebo groups. Subjects were monitored weekly over an initial 4 weeks and bi-weekly for an additional 8 weeks of treatment. OU were counted and measured at each study visit. The primary efficacy end point was the difference in the total ulcer burden at Week 0 compared with that at Week 12.

Results. Out of the 84 patients enrolled, 72 completed the trial. There were no statistically significant differences between the treatment arms in terms of the primary endpoint.

Conclusions. Low-dose natural human IFN- did not have beneficial effects on reducing the total ulcer burden among BS patients from Turkey. The study also showed that counting the number of ulcers rather than measuring the size would be adequate in future studies.

Trial registration. ClinicalTrials.gov, NCT00483184, http://www.clinicaltrials.gov/ct2/results?term=NCT00483184

Methods. Mexican and Texan SLE patients (fulfilling ACR criteria) participating in separate longitudinal outcome studies were evaluated. Texan patients were randomly chosen to match total disease duration with the Mexican patients. Cross-sectional data for the Mexican patients were obtained by a US-trained investigator who had previously participated in data collection for the cohort to which the Texan patients belonged. Socio-economic and -demographic characteristics, clinical characteristics, disease activity (with SLAM-Revised), damage accrual (with SLICC/ACR Damage Index) and self-reported function (with Short Form-36) were compared between the two groups.

Results. Seventy Mexican patients were matched with either one or two Texan patients (n = 94) for a total of 164 patients. Mexican patients were younger. In age-adjusted analyses, the Mexican patients were more educated, had better health-related quality of life and overall less systemic SLE manifestations. Mexican patients were exposed more frequently to AZA.

Conclusions. Texan patients had more severe disease than the Mexican patients. In multivariable analyses, Texan Hispanic ethnicity was significantly associated with high disease activity, but significance was not reached for damage. The discrepant findings observed between these two Hispanic groups of SLE patients may reflect socio-economic or biological factors. Given the global phenomenon of immigration, rheumatologists should be aware of the overall course and outcome of immigrant SLE patients if undesirable outcomes are to be prevented.

Methods. One hundred and eighty-three early RA patients were included in the study during 1985–89. Mean ± s.d. of age at onset was 51.4 ± 12.4 years, and mean duration of symptoms before inclusion 12 ± 7 months; 64% were women. The patients were followed annually. Assessment of hand deformities was standardized. Hand mobility was measured by signals of functional impairment (SOFI), disability by HAQ and hand HAQ, disease activity by ESR and radiographic changes by the Larsen method.

Results. One hundred and eight (59%) patients developed at least one hand deformity during the study time. The majority occurred during the first years. After 10 years, the rate of ulnar deviation, button hole deformity and swan neck deformity was 44, 24 and 23.5%, respectively. The deformity group showed significantly higher disease activity during the first 5 years, and significantly more hand impairment, more disability and more severe radiographic changes throughout the study. Presence of a deformity after 1 year increased the risk of developing a Larsen score above median after 5 years. Odds ratio (95% CI) was 2.1 (1.023, 4.385).

Conclusions. More than half of the patients in this early RA cohort had developed hand deformities after 10 years. Most deformities occurred during the first year of the disease. Presence of hand deformities had an impact on daily life function and added useful prognostic information, being an early sign of a more severe disease.

Methods. This is a prospective observational study of two independent cohorts. The derivation cohort included 590 patients recruited from seven hospitals between March 1999 and March 2000. The validation cohort included 339 patients recruited from six hospitals between September 2003 and September 2004. Socio-demographic and clinical data were collected for the participants, all of whom completed the WOMAC before hip replacement and 6 months later. Univariate and Regression Trees, by classification and regression trees (CART), analyses were performed in the derivation cohort. The decision trees derived in the derivation cohort were validated in the validation cohort.

Results. Main variables that predicted change in the WOMAC pain and functional limitation domains were pre-intervention pain or functional limitation and the application of non-surgical treatments. CART analysis showed that when pre-intervention pain was classified as minor, or WOMAC pain or functional limitation scores were <=40, there was an odds ratio of 0.076 (95% CI 0.031, 0.185) of having an expected gain after THR in the WOMAC pain domain of >30 or >25 in the WOMAC functional limitation domain.

Conclusions. A simple decision tree based on WOMAC outcomes can help to determine the appropriate application of THR. It could also be used to evaluate clinical practice or for quality control.

Methods. A retrospective chart review was performed in patients with JLS who had been treated with MMF after the failure of a combination of MTX and corticosteroids for at least 4 months, or whose JLS had concomitant severe extracutaneous manifestations. Outcome was assessed through clinical examination and thermography. Adverse events were recorded.

Results. Ten patients (six females and four males) were enrolled in the study. JLS clinical subtypes were deep morphoea (two patients with disabling pansclerotic morphoea), generalized morphoea (three patients), linear scleroderma (five patients) affecting the limbs in two and face in three patients (en coup de sabre). The age at onset of disease was 8 (range 2–16) years, and the disease duration at the time of treatment with MMF was 18 (range 8–62) months. All MMF-treated patients experienced clinical improvement that allowed withdrawal or reduction of doses of corticosteroids and MTX. Over a follow-up of 27 (range 6–36) months, mild abdominal discomfort was reported in only one patient.

Conclusions. MMF appears to be effective in arresting disease progression in severe or MTX-refractory JLS and is generally well tolerated. Further controlled studies are needed to confirm these data.

Methods. All the patients and controls underwent clinical examination, X-ray and ultrasonography (US) evaluations of the hands and wrists. Forty-five SSc patients all of whom satisfied the ACR criteria and 45 controls—15 patients with RA, 15 patients with FM syndrome and 15 healthy subjects were assessed. US was performed by a General Electric Logiq-5 PRO using a 7-12 MHz linear array transducer.

Results. Joint effusion was found in 22 (49%) SSc patients; synovial proliferation in 19 (42%), which was associated with a power Doppler signal in 11 of them; marginal bone erosions in 5 (11%); joint space narrowing in 8 (18%); periarticular calcinosis in 12 (27%); and osteophytosis in 26 (59%). In SSc patients, the prevalence of synovitis as detected by US (i.e. effusion and/or synovial proliferation) was found to be significantly higher than that found by clinical examination (i.e. tenderness and/or swelling) (26 vs 15 out of 45 cases; P = 0.03). US indicated a significantly higher number of joints with osteophytes than X-rays (59 vs 27%; P < 0.005).

Conclusions. Our study depicts the main sonographic abnormalities of the SSc hand. Using US, we found an unexpectedly high prevalence of joint pathology in SSc without clinically involved hands. The clinical usefulness of US in the assessment of SSc articular involvement either in clinical practice or in therapeutic trials is yet to be defined.

Methods. One hundred and forty-eight RA patients with no previous history of cardiovascular disease (CVD) had their augmentation index corrected for a heart rate of 75 beats per minute (AIx@75), and parameters of RA disease activity and CV risk measured. Forty-seven patients were then treated with either MTX (n = 21) or etanercept (ETAN) (n = 26), and assessments were repeated at 2 and 4 months.

Results. Patients with high CRP (>10 mg/l) showed significantly higher mean AIx@75 than those with low CRP (<=10 mg/l) (33 ± 8 vs 30 ± 8%; P = 0.033). On regression analysis, log₁₀ CRP (β = 0.298; P = 0.002), gender (β = 0.257; P = 0.007), BMI (β = –0.292; P = 0.004), diastolic blood pressure (β = 0.260; P = 0.009) and age (β = 0.194; P = 0.046) were independently associated with AIx@75. Treatment with ETAN (35 ± 9, 32.5 ± 1 and 32.5 ± 8%; P = 0.025) but not MTX (31 ± 1, 31 ± 1 and 31 ± 1%; P = 0.971) attenuated the AIx@75 significantly from baseline to Visits 2 and 3.

Conclusions. Systemic inflammation (CRP) is an independent predictor of arterial stiffness and pulse wave reflection in patients with RA. ETAN but not MTX therapy reduces arterial stiffness and pulse wave reflection and may thus improve CV morbidity in RA.

Methods. The national identification numbers of all 220 living Icelanders in Reykjavik known to have PsA were linked with the genealogy database. RRs for developing PsA were estimated in first-degree relatives (FDRs) to fifth-degree relatives of PsA cases. The kinship coefficient (KC) for PsA was also calculated. The control populations were 1000 and 10 000 sets of matched Icelandic subjects for each proband, respectively.

Results. FDRs to fourth-degree relatives of patients with PsA had RRs of 39, 12, 3.6 and 2.3, respectively (all P-values < 0.0001), reflecting a strong genetic component, whereas the fifth-degree relatives had an RR of 1.2 (P = 0.236). KCs of 5.0, 3.4, 1.7, 1.3, 1.0, 0.8 and 0.7 were observed for the first seven excluded meioses (all P-values < 0.0001), confirming the familial risk.

Conclusions. Patients with PsA in Reykjavik, Iceland, are significantly more related to each other than to randomly sampled control subjects. This is in agreement with previous reports, but the present study examines the inheritance in more distantly related individuals. These findings indicate that in addition to a strong and complex genetic component in PsA, there is an important environmental contribution.

Methods. Prospective unblinded randomized multicentre controlled 1-year trial in which 65 patients with early (<6 months) and active [disease activity score (DAS28_ESR) >5.1] RA were assigned to Group 1 (32 patients): MTX (0.3 mg/kg/week, maximum of 20 mg/week, without escalating dose regimen) or to Group 2 (33 patients): initial combination therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low DAS (DAS28_ESR <3.2).

Results. From Week 12 until Week 52, seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy (P = 0.28). The 1-year area under the curve (AUC) of DAS28 was lower in Group 2 owing to an initial better response. The total intake of anti-TNF- and the mean increase in total modified Sharp score was similar in the two groups.

Conclusions. Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF- treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX.

Methods. Gene expression was determined by quantitative RT–PCR and immunohistochemistry, and gene regulation by electro mobility shift assay and chromatin immunoprecipitation. Functional assays on migration and differentiation were done after cell treatment and transfection.

Results. DCC was shown to be specifically up-regulated in OA compared with normal chondrocytes in vitro and in vivo. Promoter analysis and transfection studies showed that the up-regulation of DCC in OA chondrocytes may be mediated by the transcription factors Sox9 and AP-2. Netrin-1, the ligand of DCC, was revealed to induce the migration of OA chondrocytes specifically. Expression of DCC in healthy chondrocytes by transient transfection significantly induced cell migration and chemotaxis to Netrin-1. DCC expression had no influence on cell differentiation; however, induction of MMP1 and -3 expression was observed.

Conclusion. Strong differential expression of DCC in OA compared with normal chondrocytes hints of a possible role of DCC in the pathophysiology of OA. The strong impact of the DCC receptor on cellular mobility of chondrocytes in vitro suggests a major relevance of migratory activities in physiological and pathological conditions of cartilage. However, definite proof of chondrocyte movements in vivo still has to be established.

Methods. The study consisted of two visits. At Visit 1, a plain radiograph of the ‘index joint’ was obtained. The ‘index joint’ was defined as a joint that has had the most acute attacks of gout historically. The index joint plain radiograph had to be free of erosive damage in order for the subject to qualify for Visit 2. At Visit 2, the subject had an MRI with contrast and an US of the index joint. Each subject also had an MRI and US of an ‘asymptomatic joint’. The ‘asymptomatic joint’ was defined as a joint that had never experienced an acute attack of gout (determined by standard protocol). The primary endpoint was erosive changes on the MRI and/or US of the index joint. Secondary endpoints included erosive changes on the asymptomatic joint as well as bone marrow oedema (BME) (on MRI), synovial pannus (SP), soft tissue tophi (STT) or oedema (STE) on either the index or asymptomatic joint.

Results. Twenty-seven subjects (26 males; 1 female) completed both visits. Their average age and disease duration were 55.1 years (range 21–75 years) and 6.8 years (range 0.25–25 years), respectively. The subjects’ average serum uric acid level over the past 5 years was 8.09 mg/dl (range 4.1–12.8 mg/dl); their average on the day of Visit 1 was 7.96 mg/dl (range 4.6–13.9 mg/dl). The first MTP was the most common index joint (17) followed by the ankle (5), mid-tarsal (2), knee (2) and wrist (1). The knee was the most common asymptomatic joint (21) followed by the wrist (3), MTP (2) and ankle (1). All subjects had both MRIs; one subject refused the US. Out of 27 subjects, 15 (56%) had erosions on MRI of their index joint (P < 0.0001); only 1 subject (4%) had erosions identified in the index joint by US (P = NS). Regarding the secondary endpoints on the index joint, the MRI detected SP (13), BME (4), STE (3) and STT (0); the US detected SP (1), STT (1) and STE (0). Regarding the MRI of the asymptomatic joint, positive findings included SP (3), BME (3), STE (2) and erosions (1). There were no positive findings by US in the asymptomatic joint.

Conclusions. A large percentage of patients with gout and normal plain radiographs have occult destructive arthropathy that is only detected by advanced imaging such as MRI and/or US. However, MRI appears to be much more sensitive than US at detecting these findings.

Methods. Rabbit cells from NP and AF were isolated and their phenotype was compared with that of AC by real-time PCR analysis of type I (COL1A1), II (COL2A1) and V (COL5A1) collagens, aggrecan transcript (AGC1), matrix Gla protein (MGP) and Htra serine peptidase 1 (Htra1).

Results. Transcript analysis indicated that despite certain similarities, IVD cells exhibit distinct COL2A1/COL1A1 and COL2A1/AGC1 ratios as compared with AC. The expression pattern of COL5A1, MGP and Htra1 makes it possible to define a phenotypic signature for NP and AF cells.

Conclusions. Our study shows that NP and AF cells exhibit a clearly distinguishable phenotype from that of AC. Type V collagen, MGP and HtrA1 could greatly help to discriminate among NP, AF and AC cells.

Methods. We analysed charts of six patients treated in an open-label safety trial and seven additional patients treated with infliximab on a compassionate care basis for uncontrolled SLE organ inflammation.

Results. Out of nine patients with lupus nephritis, six had a long-term response after four infusions of infliximab in combination with AZA, lasting for up to 5 years. All five patients with lupus arthritis responded, but this response did not last for >2 months after the last infusion. One additional patient had a long-lasting improvement in SLE interstitial lung disease. No symptoms suggestive of infliximab-induced SLE flares occurred in any patients. Short-term treatment appeared relatively safe, but one patient developed deep-vein thrombosis and several infections. Under long-term therapy, two patients had life-threatening or fatal events, namely CNS lymphoma and Legionella pneumonia. Retreatment and treatment without concomitant immunosuppression led to drug reactions.

Conclusions. Short-term therapy with four infusions of infliximab in combination with AZA was relatively safe, and had remarkable long-term efficacy for lupus nephritis and, potentially, also interstitial lung disease. Long-term therapy with infliximab, however, was associated with severe adverse events in two out of three SLE patients, which may have been provoked by infliximab and/or by their long-standing refractory SLE and previous therapies.

Methods. We looked for patients who presented with signs and symptoms not typical for FMF but carried MEFV mutations. We also searched for reports about similar conditions in the English medical literature, and we surveyed the website ‘Infevers’ for MEFV mutations defined as associated with ‘atypical FMF’.

Results. We encountered three patients carrying MEFV mutations who presented with distinct clinical presentations not typical of FMF. We identified additional reports about MEFV-related non-FMF disease entities such as palindromic rheumatism. By screening the ‘Infevers’ website, we further disclosed 13 cases with MEFV mutations that were defined as ‘atypical FMF’ and 4 cases categorized as ‘recurrent arthritis’.

Conclusions. These findings suggest that the MEFV gene is associated with clinical conditions other than FMF. Changing our concept regarding the MEFV gene and its link to such clinical phenotypes may call for a higher awareness of the existence of additional autoinflammatory diseases. Furthermore, a correct diagnosis of these MEFV gene mutation-associated syndromes will justify a therapeutic trial with colchicine, thereby relieving suffering of many patients who up to now have been misdiagnosed.