Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fluid, but not in serum.

OBJECTIVE: To evaluate ferritin concentration in serum and synovial fluid (SF) as a marker of activity of arthritis in comparison with C-reactive protein (CRP) and acute-phase serum amyloid A protein (A-SAA). METHODS: We determined the concentrations of ferritin, CRP and A-SAA in paired serum and SF in 34 rheumatoid arthritis (RA) and 21 osteoarthritis (OA) patients. The erythrocyte sedimentation rate (ESR) was also measured. RESULTS: The serum concentrations of ferritin, CRP and A-SAA were 93 +/- 76 (mean +/- SD) ng/ml, 4 +/- 5 mg/ml, 8 +/- 4 mg/ml in OA and 140 +/- 227, 59 +/- 34, 289 +/- 223 in RA, respectively. There was no significant difference in serum ferritin levels between OA and RA, and serum ferritin did not correlate with ESR, CRP or A-SAA. Both serum CRP and A-SAA levels were significantly higher in RA than in OA (p < 0.0001, p < 0.0001), and correlated with ESR in all arthritis (r = 0.658, p < 0.0001, r = 0.404, p < 0.01), respectively. Serum CRP levels correlated with A-SAA levels in serum (r = 0.727, p < 0.0001). In SF, the concentrations of ferritin, CRP and A-SAA in RA (421 +/- 307, 25 +/- 20 and 39 +/- 41) were significantly higher (p < 0.01, p < 0.0001, p < 0.001) than those in OA (202 +/- 220, 2 +/- 2 and 2 +/- 2), respectively. There were significant correlations among SF ferritin, CRP and A-SAA. CONCLUSION: Ferritin levels in SF but not in serum are significantly elevated in RA more than in OA, and ferritin correlated with CRP or A-SAA in SF, but not in serum. Higher levels of SF ferritin, as well as SF CRP and SF A-SAA, seem to reflect greater degrees of joints inflammation in RA and OA.     

Increased perivascular synovial membrane expression of myeloid-related proteins in psoriatic arthritis

OBJECTIVE: To analyze S-100 protein expression, in the form of myeloid-related protein 8 (MRP8), MRP14, and the heterodimer MRP8/MRP14, in psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients, and to determine the effect of methotrexate (MTX) on the MRP antigen expression in PsA patients. METHODS: Serum, synovial fluid (SF), and synovium (taken at arthroscopy) samples were obtained from PsA (before and after MTX treatment), RA, and SpA patients. Concentrations of MRP8/MRP14 in serum and SF were measured by enzyme-linked immunosorbent assay. Expression of MRP8, MRP14, and MRP8/MRP14 in synovium was determined by immunohistochemistry. RESULTS: MRP8, MRP14, and MRP8/MRP14 levels were increased in serum, SF, and synovium from PsA, RA, and SpA patients. In all 3 groups, paired samples of serum and SF showed significantly higher MRP8/MRP14 levels in SF (mean +/- SD 15310 +/- 16999 ng/ml [median 11400]) than in serum (908 +/- 679 ng/ml [median 695]) (P = 0.0001). MRP8/MRP14 levels in serum correlated with systemic parameters of disease activity (erythrocyte sedimentation rate [ESR] r = 0.55, P = 0.005; C-reactive protein [CRP] level r = 0.55, P = 0.005), whereas levels in SF correlated with local parameters of disease activity (white blood cell count r = 0.45, P = 0.01; acute-phase serum amyloid A level r = 0.32, P = 0.03). MRP expression was significantly higher in the synovial sublining layer (SLL) of PsA patients compared with RA and SpA patients. MRP antigens were predominantly expressed in perivascular areas of the SLL in PsA patients. Following MTX treatment, MRP expression in serum and synovium from PsA patients was significantly reduced. Serum levels of MRP were more sensitive to the effects of MTX than were the ESR, CRP, or clinical joint scores. CONCLUSION: MRP levels in serum and SF correlate with local and systemic inflammation and are equally increased in PsA, RA, and SpA patients. In contrast, MRP8, MRP14, and MRP8/MRP14 expression in the SLL of PsA patients is increased, particularly in perivascular regions, compared with that in RA and SpA patients, suggesting a central role of MRP proteins in transendothelial migration of leukocytes in PsA. Moreover, MRP expression is reduced following MTX treatment. MRP proteins may represent a novel therapeutic target in inflammatory arthritis.     

The Swedish early psoriatic arthritis register-- 2-year followup: a comparison with early rheumatoid arthritis

OBJECTIVE :Patients with symptoms and signs compatible with psoriatic arthritis (PsA), with or without psoriasis, have been documented in the Swedish Early Psoriatic Arthritis (SwePsA) register. Our aim was to find markers for disease progression and to evaluate treatments for PsA using these data. METHODS: Patients referred to rheumatology outpatient clinics within 2 years of onset were assessed on inclusion and at followup 2 years later. Data collection was performed according to the program for SwePsA, and classification was as described by Moll and Wright and the ClASsification Criteria for Psoriatic ARthritis (CASPAR). Remission was recorded if the patient had no tender or swollen joints and if erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within the reference range. Patients with early rheumatoid arthritis (RA) recruited from the Swedish Early Rheumatoid Arthritis Register (Ramona) provided comparison data. RESULTS: One hundred thirty-five patients with PsA according to CASPAR were assessed; 44% were classified as having mono/oligoarthritis and 47% as polyarthritis. Two patients (1%) were in remission initially, and 23 (17%) at followup. Patients with polyarticular disease had the highest inflammatory activity, measured by swollen and tender joint counts, ESR, Health Assessment Questionnaire, and self-assessment by visual analog scale of pain and global disease activity. Dactylitis was associated with radiological findings. Compared with RA patients, they had significantly lower CRP, ESR, and number of swollen joints (p = 0.0003, p = 0.0026, p = 0.0380, respectively) at inclusion, but equal numbers of tender joints and self-assessment of pain and disease activity. CONCLUSION: About half the patients had polyarthritis and the other half had mono/oligoarthritis at followup after 2 years. Patients with polyarthritis had the highest inflammatory activity. Apart from ESR, CRP, and swollen joint count, there were no significant differences in activity between RA and polyarticular PsA.     

High sensitivity C-reactive protein as a disease activity marker in rheumatoid arthritis

OBJECTIVE: To elucidate the potential contribution of high sensitivity C-reactive protein (hs-CRP) testing in the assessment of disease activity in rheumatoid arthritis (RA). METHODS: We recorded clinical and psychological variables, the hs-CRP, and erythrocyte sedimentation rate (ESR) in 146 consecutive patients with RA. We analyzed the associations between the ESR and hs-CRP versus the other recorded variables. RESULTS: The median (interquartile range) ESR (mm/h) and hs-CRP (mg/l) were 15 (7-36) and 5 (2.3-13.9), respectively. Thirty-two (22%) patients had an hs-CRP < 2 mg/l, 61 (42%) an hs-CRP of 2-8 mg/l and 53 (36%) an hs-CRP > 8 mg/l. In patients with an hs-CRP of 2-8 mg/l, the swollen joint counts and the physician disease activity scales were higher, and remission rates were lower than in patients with an hs-CRP of < 2 mg/l. The hs-CRP was consistently more closely associated with disease activity, depression, and helplessness than was the ESR. CONCLUSION: High sensitivity CRP testing reveals systemic inflammation that is generally not detectable with routine CRP assays and that is associated with disease activity in RA.     

S100 proteins calprotectin and S100A12 are related to radiographic changes rather than disease activity in psoriatic arthritis with low disease activity

OBJECTIVE: To investigate serum levels of calprotectin (S100A8/S100A9) and S100A12 as markers of disease activity or distinct clinical or radiographic features in patients with psoriatic arthritis (PsA). METHODS: Serum levels of calprotectin and S100A12, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were determined in 119 patients with PsA. Correlations to clinical variables were calculated, and subgroups of patients were compared. RESULTS: The correlations to clinical disease activity measures were stronger for CRP than for ESR and calprotectin. In the regression analysis, calprotectin was identified as an independently associated factor for presence of peripheral radiographic features of arthritis (OR 1.33, 95% CI 1.01-1.76). S100A12 levels were also elevated in those with peripheral radiographic features (p = 0.036), but did not correlate with clinical variables of disease activity. CONCLUSION: Calprotectin and S100A12 do not perform better than traditional biomarkers of disease activity in PsA, but were associated with presence of peripheral radiographic features in this cross-sectional study. The patients' low level of disease activity may have led to underestimation of the associations between any biomarker and disease measures.     

Laboratory findings in psoriatic arthritis

Psoriatic arthritis (PsA) has been classically defined as an inflammatory arthritis associated with psoriasis. However, in comparison with other relevant inflammatory arthropathies, in which a definite diagnosis is frequently possible only by means of laboratory investigations, in PsA true laboratory diagnostic markers are lacking. Some markers are utilised more to differentiate other diseases than to characterise PsA. For example in polyarticular PsA, which may be in some cases indistinguishable from RA, the rheumatoid factor (RF) or the more specific and recently introduced antibodies to cyclic citrullinated peptides (anti-CCP), may be useful to better identify RA. However, RF was found in 5% to 13% of patients with PsA, and anti-CCP may be observed in almost similar percentage. The determination of ESR and/or CRP is frequently disappointing in PsA, since they are both elevated in only half of the patients with PsA. However, ESR and/or CRP are included in the most utilised response criteria for RA, such as ACR and DAS, and, in addition are also considered reliable in the assessment of PsA. Furthermore, elevated levels of ESR have been proposed as one of the best predictors of damage progression and, in addition, a low ESR seems protective, while an ESR >15 mm/h is one of the factors associated with an increased mortality in PsA. The synovial fluid (SF) effusion is much higher in PsA, in comparison with other arthropathies. When available, SF analysis may offer additive information useful for the diagnosis, such as the increased number of leukocytes, which underlines the inflammatory nature of the effusion even in a patient with normal serum levels of acute phase response. We found that elevated IL-1 levels in SF of patients with early disease (<6 months), may be predictive of an evolution in polyarticular form at follow-up. This observation is in keeping with the crucial role that inflammatory cytokines play in PsA, probably related to a genetic predisposition. The recent introduction in PsA of anti-TNF-alpha agents and the demonstration of their efficacy in the management of many clinical disease expressions including peripheral arthropathy, axial involvement, enthesopathy and skin manifestations, have stimulated the research also in the field of the possible laboratory markers.     

A comparative evaluation of quality of life and life satisfaction in patients with psoriatic and rheumatoid arthritis

Both rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have a negative impact on patients’ quality of life (QOL). The aim of this study was to compare QOL and life satisfaction in patients with RA and PsA. Forty patients with PsA, 40 patients with RA, and 40 healthy control subjects were included in the study. Demographic data and clinical characteristics including age, sex, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), peripheral pain assessed by visual analog scale (VAS) and Larsen scores of hand X-rays were recorded. Nottingham Health Profile (NHP) was used to evaluate QOL, and Life satisfaction index (LSI) was used to measure psychological well-being in both groups. The demographic data of the subjects were similar between the groups. The scores of all NHP subscales were significantly higher and the scores of LSI were significantly lower in PsA and RA patients than in control subjects. The inflammation markers including ESR, CRP, pain by VAS and Larsen scores were found to be significantly higher in RA patients. The scores of LSI were similar between the groups. Although the scores of physical domains of NHP (pain and physical disability) were statistically higher in RA patients (p<0.05), the scores of psychosocial subgroups of NHP were similar between RA and PsA patients (p>0.05). Both PsA and RA patients had disturbed QoL and decreased life satisfaction. In conclusion, peripheral joint damage, inflammation, and physical disability are significantly greater in RA but psychosocial reflection of QOL and life satisfaction are the same for both groups which can be explained by the additional impact of skin disease in patients with PsA.     

Increased perivascular synovial membrane expression of myeloid‐related proteins in psoriatic arthritis

Objective

To analyze S‐100 protein expression, in the form of myeloid‐related protein 8 (MRP8), MRP14, and the heterodimer MRP8/MRP14, in psoriatic arthritis (PsA) patients compared with rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients, and to determine the effect of methotrexate (MTX) on the MRP antigen expression in PsA patients.

Methods

Serum, synovial fluid (SF), and synovium (taken at arthroscopy) samples were obtained from PsA (before and after MTX treatment), RA, and SpA patients. Concentrations of MRP8/MRP14 in serum and SF were measured by enzyme‐linked immunosorbent assay. Expression of MRP8, MRP14, and MRP8/MRP14 in synovium was determined by immunohistochemistry.

Results

MRP8, MRP14, and MRP8/MRP14 levels were increased in serum, SF, and synovium from PsA, RA, and SpA patients. In all 3 groups, paired samples of serum and SF showed significantly higher MRP8/MRP14 levels in SF (mean ± SD 15,310 ± 16,999 ng/ml [median 11,400]) than in serum (908 ± 679 ng/ml [median 695]) (P = 0.0001). MRP8/MRP14 levels in serum correlated with systemic parameters of disease activity (erythrocyte sedimentation rate [ESR] r = 0.55, P = 0.005; C‐reactive protein [CRP] level r = 0.55, P = 0.005), whereas levels in SF correlated with local parameters of disease activity (white blood cell count r = 0.45, P = 0.01; acute‐phase serum amyloid A level r = 0.32, P = 0.03). MRP expression was significantly higher in the synovial sublining layer (SLL) of PsA patients compared with RA and SpA patients. MRP antigens were predominantly expressed in perivascular areas of the SLL in PsA patients. Following MTX treatment, MRP expression in serum and synovium from PsA patients was significantly reduced. Serum levels of MRP were more sensitive to the effects of MTX than were the ESR, CRP, or clinical joint scores.

Conclusion

MRP levels in serum and SF correlate with local and systemic inflammation and are equally increased in PsA, RA, and SpA patients. In contrast, MRP8, MRP14, and MRP8/MRP14 expression in the SLL of PsA patients is increased, particularly in perivascular regions, compared with that in RA and SpA patients, suggesting a central role of MRP proteins in transendothelial migration of leukocytes in PsA. Moreover, MRP expression is reduced following MTX treatment. MRP proteins may represent a novel therapeutic target in inflammatory arthritis.

     

Healthcare and burden of disease in psoriatic arthritis. A comparison with rheumatoid arthritis and ankylosing spondylitis

OBJECTIVE: To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists. METHODS: Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished. RESULTS: We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose < 7.5 mg. CONCLUSION: Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.     

Increased ferritin response in adult Still's disease: specificity and relationship to outcome

BACKGROUND: The disproportionate ferritin response encountered in some patients with adult Still's disease (ASD) may reflect a fundamental aspect in the pathophysiology of ASD. METHODS: An observational case-control study of 22 ASD patients followed for 63 months. Baseline laboratory data were compared with age- and gender-matched controls with new-onset rheumatoid arthritis (RA). Serum levels of ferritin and C-reactive protein (CRP) and the ferritin/CRP ratio were related to clinical outcome in ASD through nonparametric statistical analyses. RESULTS: Compared to RA patients, haemoglobin levels were lower (11.8 vs. 13.5 g/dL; p = 0.009) and leucocyte counts (17.1 vs. 8.6 10(9)/mL; p<0.001), erythrocyte sedimentation rate (ESR) (84 vs. 38 mm; p = 0.001), CRP (154 vs. 27 mg/L; p<0.001), aspartate aminotransferase (ASAT) (52 vs. 23 U/l; p = 0.004), serum ferritin (8750 vs. 62 microg/L; p<0.001) and ferritin/CRP ratios (9.7 vs. 1.7; p<0.001) were higher in ASD patients at baseline. Six patients (27%) achieved sustained remission (monocyclic disease), while 16 patients (73%) developed chronic disease (progressive in 27%, relapsing/remitting in 46%). The levels of ESR and CRP or other baseline variables were not associated with outcome. However, baseline serum ferritin was significantly higher in ASD patients with chronic disease (p = 0.04), while a cut-off of five times the normal upper level (NUL) was 100% sensitive and 60% specific for predicting chronic disease. CONCLUSION: An exaggerated ferritin response with levels>5 times the NUL and high ferritin/CRP ratios is useful for distinguishing between ASD and RA patients. Ferritin levels>5 times the NUL are also associated with a chronic disease course.     

Diagnostic usefulness of synovial vascular morphology in chronic arthritis. A systematic survey of 100 cases

OBJECTIVES: To assess the diagnostic usefulness of the systematic analysis of synovial vascular morphology in various inflammatory, early, and longstanding arthropathies, and to examine the validity of the vascular patterns in predicting the evolution of a group of patients with undifferentiated arthritis (UA). METHODS: One hundred patients who underwent rheumatologic arthroscopy of a symptomatic joint (85 knees, 11 wrists, 3 elbows, 1 metacarpophalangeal joint) were evaluated. The same observer, blinded to patient diagnosis, analyzed the video recordings of the arthroscopies. Vascular morphology was classified into 3 patterns: straight, tortuous, and mixed. RESULTS: Eighty-one patients had inflammatory arthritis: 35 rheumatoid arthritis (RA), 16 psoriatic arthritis (PsA), 13 spondyloarthropathies (SpA), and 17 UA. Forty-nine percent of patients with RA had a straight pattern, 28% a mixed, and 23% a tortuous one. The sensitivity rate of the straight pattern for RA was 77% and the specificity rate was 70%. Seventy-six percent of RA patients with a straight pattern were rheumatoid factor positive (RF+) against 25% of RA patients with a tortuous pattern. The odds ratio for RA associated to straight compared with tortuous pattern was 57.3 (95% confidence interval, 6.6 to 499.5; P <.001). Patients with PsA and SpA shared the same pattern and were analyzed as 1 group. Ninety-three percent of patients with PsA/SpA had a tortuous pattern, 4% a straight pattern, and 3% a mixed pattern. The sensitivity rate of the tortuous pattern for PsA/SpA was 61% and the specificity rate was 95%. During 2 years of follow-up, 6 of 17 patients with UA were definitely diagnosed: 4 RA (2 RF+ and straight pattern; 2 with a tortuous pattern, 1 with RF+ and HLA-B27+); 1 SpA and 1 PsA, both with a tortuous pattern. No differences in vascular patterns were observed according to disease duration. Our results indicate that vascular patterns are not modified by disease modifying antirheumatic drug (DMARD) treatment. The other 19 patients had osteoarthritis (n = 8) and calcium pyrophosphate dihydrate crystal deposition disease (n = 11) and their predominant vascular pattern was tortuous-like. CONCLUSIONS: Arthroscopic assessment of synovial vascular changes in chronic arthritis may be of diagnostic and pathogenetic interest, although differences between published studies suggest a need for consensus in evaluating vascular patterns. A straight pattern is strongly associated with RF + RA whereas a tortuous pattern is generally associated with PsA or SpA; these associations are independent of disease duration. The vascular pattern likely does not change qualitatively with DMARD therapy. The application of this technique to the diagnosis or prognosis of patients with UA may be a complementary tool for the treatment of these patients, but larger, prospective studies are necessary to confirm this hypothesis.     

Increased Ed-B fibronectin plasma levels in spondyloarthropathies: comparison with rheumatoid arthritis patients and a healthy population.

OBJECTIVE: To determine, for the first time, plasma levels of general fibronectin (Fn) and two spliced isoforms, Ed-A and Ed-B, in patients with spondyloarthropathy (SpA) in comparison with rheumatoid arthritis (RA) patients and healthy volunteers (HV). METHODS: Plasmas (EDTA) as well as clinical data, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected in two groups of 10 patients fulfilling the European Spondylarthropathy Study Group criteria for SpA or the 1987 American College of Rheumatology criteria for RA. Plasmas of 21 blood donors served as controls. Plasma levels of Fns were determined by using an in-house immunocapture ELISA, using monoclonal antibodies (MAbs) against general Fn and its isoforms. RESULTS: Total Fn plasma levels were significantly higher in the SpA group (mean+/-S.D.=1387+/-569 mg/l) than in the RA group (684+/-196 mg/l; P=0.02) and in HV (303+/-211 mg/l; P<0.0001). Ed-A Fn levels appeared higher in SpA (23+/-10.4 mg/l) and RA (32.5+/-16.5 mg/l) groups than in the HV group (2.8+/-0.9 mg/l; P=0.0003 and P<0.0001, respectively), without a significant difference between SpA and RA groups. Ed-B Fn levels were higher in SpA (6.9+/-2.1 mg/l) than in RA (3.2+/-1.9 mg/l; P=0. 02) and HV (1.1+/-0.8 mg/l; P=0.0003) groups. No significant correlation was observed in SpA patients between each Fn level and clinical activity, ESR or CRP levels. CONCLUSIONS: This study showed an increase in plasma levels of Fn and Ed-B Fn in SpA patients compared with RA patients and HV, which could not be attributed solely to systemic inflammation. It may be hypothesized that Ed-A and Ed-B Fn might reflect local turnover in inflamed tissues, and that Ed-B Fn might be particularly involved in the musculoskeletal inflammatory process of SpA.     

Patient-reported outcomes better discriminate active treatment from placebo in randomized controlled trials in rheumatoid arthritis

BACKGROUND: Recent randomized controlled trials (RCTs) in rheumatoid arthritis (RA) have used patient- and physician-reported outcomes, ESR and/or CRP as components of ACR response criteria to assess efficacy. OBJECTIVES: Mean changes from baseline in patient- and physician-reported outcome measures, ESR and CRP were compared in two RCTs in patients with active RA. Comparisons between active and placebo treatment used mean percentage improvements and standard effect sizes (SESs). RESULTS: In both protocols, patient-reported assessments of disease activity, pain and physical function reflected little or no improvement with placebo, best discriminating between active and placebo therapy, as did ESR and CRP. CONCLUSION: Improvements in signs and symptoms of active RA in placebo RCTs appear to be best reflected by patient-reported measures of physical function, as long as reported changes in global assessments of disease activity and/or pain reflect similar benefit. Patient-reported outcome measures should be considered objective; treatment-associated changes are congruent with measures of inflammation, and appear less susceptible to the placebo response.     

Renal abnormalities in a population of patients with psoriatic arthritis.

OBJECTIVE: To investigate the prevalence of and to identify predictive factors for renal abnormalities in patients with psoriatic arthritis (PsA). METHODS: 73 patients with PsA were consecutively examined by laboratory analyses and clinically for joint manifestations. Renal function was estimated by creatinine clearance and urinary albumin. RESULTS: 17 (23.3%) of the patients had renal abnormalities as defined by creatinine clearance below the lower cut off of normal distribution (mean - 2 SD) and/or urinary excretion of albumin more than 25 mg/24 h. These patients were significantly older at the time of the study, older at joint disease onset, had longer skin disease duration, increased serum levels of beta2-microglobulin, and higher incidence of increased ESR and/or CRP levels. Increased ESR/CRP levels had significantly predictive value in multivariate analysis. CONCLUSIONS: In this study subclinical renal abnormalities was a prevalent finding. Predictive factor was inflammatory activity measured by laboratory variables. There were no predisposing effects of NSAID or DMARD therapy.     

Evaluation of red blood cell distribution width in patients with psoriatic arthritis

Aim of the workTo evaluate the red blood cell distribution width (RDW) values in psoriatic arthritis (PsA) patients and to study the relationship between these values and disease activation.Patients and methodsForty seven patients with PsA and 56 age- and sex matched healthy controls were included in this study. Laboratory test results of both groups were retrospectively collected from medical records; these included levels for white blood cell count, hemoglobin, platelet, RDW, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity score (DAS28) was used to evaluate disease activity.ResultsThe study comprised 47 PsA patients (32 females and 15 males) (F:M 2.1:1) with a mean age of 39.2 ± 9.9 (20–54) years and mean disease duration was 3.3 ± 1.94 (1–8) years. 39 (83%) patients were receiving monotherapy, 8 (17%) were receiving combined therapy. The RDW values were significantly higher when comparing active disease period (16 ± 3.9) of PsA patients versus inactive disease period (14.2 ± 1.04) and controls (14.03 ± 1.2) (p < 0.001). Otherwise, no significant differences were found when comparing inactive disease period of PsA patients versus controls (p = 0.18). RDW values of active disease period of PsA patients significantly correlated with ESR (r = 0.57, p < 0.001), CRP (r = 0.4, p = 0.006) and DAS28 (r = 0.42, p = 0.003).ConclusionsIncreased RDW is associated with active disease period of PsA patients. RDW seems to be a surrogate marker of the inflammation, like CRP and ESR. It is included in the complete blood count thus its measurement does not need any additional costs. RDW may be a potential marker to evaluate disease activity of PsA.     

Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis

Our aim was to determine whether C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) is more appropriate in measuring disease activity in ankylosing spondylitis (AS). We studied 191 consecutive outpatients with AS in The Netherlands, France, and Belgium. Patients were attending secondary and tertiary referral centers. The external criterion for disease activity was: physician and patient assessment of disease activity on a visual analog scale (VAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In each measure we defined 3 levels of disease activity: no activity, ambiguous activity, and definite disease activity. The patients with AS (modified New York criteria) were divided into 2 groups: those with spinal involvement only (n=149) and those who also had peripheral arthritis and/or inflammatory bowel disease (IBD) (n=42). For each criterion of disease activity, the patients with no activity and with definite activity were included in receiver operator curves and used to determine cutoff values with the highest sensitivity and specificity. We also calculated Spearman correlations. The median CRP and ESR were 16 mg/l and 13 mm/h, respectively, in the spinal group and 25 mg/l and 21 mm/h, respectively, in the peripheral/IBD group. In both groups the Spearman correlation coefficients between CRP and ESR were around 0.50. There was moderate to poor correlation between CRP, ESR, and the 3 disease activity variables (0.06-0.48). Sensitivity for both ESR and CRP was 100% for physician assessment and between 44 and 78% for patient assessment of disease activity and the BASDAI, while specificity was between 44 and 84% for all disease activity measures. The positive predictive values of CRP and ESR in our setting were low (0.15-0.69). We conclude that neither CRP nor ESR is superior to assess disease activity.     

类风湿关节炎患者抗环瓜氨酸肽抗体与人类白细胞抗原-DR4等位基因相关性研究

目的 研究类风湿关节炎(RA)及未分类关节炎(痛)(UA)患者抗环瓜氨酸肽(CCP)抗体与人类白细胞抗原(HLA)-DR4等位基因相关性.方法 对91例RA患者,46例UA患者,35名健康志愿者,均为浙江汉族人,应用酶联免疫吸附试验(ELISA)法检测血清抗CCP抗体,序列特异性引物聚合酶链反应(PCR-SSP)检测HLA-DR4等位基因.结果 RA组、UA组HLA-DR4阳性率分别为47.2%、45.6%,均以DRB1*0405为主,分别为25.3%、23.9%.RA组、UA组患者的抗CCP抗体与HLA-DR4具有相关性(r=613,0.703,P＜0.01).与HLA-DRB1*0405具有弱相关性(r=0.304,P＜0.01;r=0.333,P＜0.05). 2组HLA-DR4阳性患者抗CCP抗体水平明显高于HLA-DR4阴性患者,差异有统计学意义(P＜0.01).抗CCP抗体、HLA-DR4均阳性患者红细胞沉降率(ESR)、C反应蛋白(CRP)、血小板水平明显升高,晨僵时间延长,关节肿胀度积分升高,与二者阴性患者比较,差异有统计学意义(P＜0.05或P＜0.01).对UA组患者3个月后随访,抗CCP抗体、HLA-DR4在早期RA的阳性率为94.7%(18/19).结论 抗CCP抗体与HLADR4、DRB1*0405相关;抗CCP抗体、HLA-DR4均阳性反映了RA病情活动性;联合检测抗CCP抗体、HLA-DR4或DRB1*0405有助于RA早期诊断;抗CCP抗体可能在HLA-DR4等遗传因素参与下介导了RA发病.     

Gelatinase expression and activity in the synovium and skin of patients with erosive psoriatic arthritis

OBJECTIVE: Matrix metalloproteinases (MMP), especially the gelatinases (MMP2, MMP9), have been implicated in several features of inflammatory arthritis including angiogenesis and bone erosions. We examined the expression and activity of the gelatinases and their regulators in psoriatic skin and synovium using tissue immunohistochemistry and a sensitive tissue based zymographic technique. METHODS: Lesional and perilesional skin biopsies and synovial samples obtained by closed needle biopsy from 15 patients with erosive psoriatic arthritis (PsA) were analyzed by immunohistochemistry for the expression of the gelatinases and their regulators, tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1, TIMP-2) and membrane type metalloproteinases (MTI-MMP. MT2-MMP), using immunohistochemistry. Synovial tissue from 8 patients with erosive rheumatoid arthritis (RA) was used as a comparison. MMP tissue expression was quantified by 2 blinded independent observers. Immunohistochemical data are reported as the mean percentage positive cells per total nucleated cells in 10 high power fields +/- SD. Functional activity of the gelatinases was measured using a sensitive tissue based zymography technique and corrected for protein content. Zymography data are presented as ng/mg +/- SE. RESULTS: MMP expression was greater in the synovial lining layer (LL) than in the synovial sublining layer (SL) in both PsA and RA tissue for most MMP except collagenase I (MMPI), which was equally distributed between the LL and SL. Expression of MMP or their regulators did not differ between PsA synovial membrane (SM) and RA SM in LL. Moreover, although latent gelatinase A (MMP2) staining in PsA SM was equivalent to RA SM, increased gelatinase A activity was found in PsA SM over RA SM using zymography L82.4 (SD 62.8) vs 10.1 (SD 1.7); p = 0.02]. Compared to PsA SM, lesional skin had lower levels of MT1-MMP (MMP14) (1.4 +/- 1.7 vs 15.7 +/- 8.4; p = 0.009) and MT2-MMP (MMP15) (12.1 +/- 8.7 vs 21.6 +/- 9.9; p = 0.001). CONCLUSION: We characterized the expression and activity of gelatinases in PsA and demonstrate that gelatinase activity in SM of PsA patients with erosive disease is comparable to if not greater than that in RA synovium.     

Measurement of disease activity in psoriatic arthritis. Extended report

OBJECTIVE: To determine whether activity indices, generally accepted in rheumatoid arthritis (RA) are useful and valid to measure disease activity in psoriatic arthritis (PsA) patients with peripheral arthritis. METHODS: 38 PsA patients were studied before and after a one year DMARD treatment. Extended and reduced tender and swollen joint counts, Ritchie articular index, Health Assessment Questionnaire HAQ) score, erythrocyte sedimentation rate (ESR) morning stiffness, the patient's and the assessor's global assessment (PGA and AGA) were recorded. Disease activity scores, EULAR, ACR and Clegg improvement criteria were calculated. RESULTS: All indices correlated well before and after treatment with AGA (r > 0.337, p < 0.042), except morning stiffness and tender joint counts. After treatment, PGA correlated well only with the 68 and 28 tender joint counts, ESR and HAQ (r > 0.340, p < 0.05). The response to DMARD treatment was well characterized with the changes in the number of tender and swollen joint counts, and DAS4, DAS3, DAS28. The changes correlated with the PGA and AGA. The level of agreement between Clegg and the EULAR improvement criteria with both extended and reduced joint count was comparable (p < 0.01). CONCLUSION: The well-known activity indices generally accepted in RA, as tender and swollen joint count, DAS3, DAS4, DAS28, are useful and valid indices measuring arthritis activity in PsA with peripheral arthritis. The correlation between Clegg and EULAR improvement classification indices were similar. Both seemed to characterize changes authenticated during DMARD treatment.