Background Psoriatic arthritis (PsA) is a progressive chronic inflammatory disease which affects both the axial and peripheral joints and often causes patient impairment; patients function and health-related quality of life could be compromised. Following the introduction of anti tumor necrosis factor-α (TNFα) agents in the treatment of active spondyloarthritis, several aspects including disease activity, spinal mobility, peripheral arthritis and enthesitis as well as quality of-life have improved considerably. Objectives The aim of this study was to evaluate the long-term efficacy of adalimumab and etanercept treatment in clinical practice in PsA patients and to assess the percentage of patients with progressive lengthening of therapy interval administration in the event of optimal treatment response. Methods A retrospective study was carried out on 127 PsA outpatients receiving adalimumab and etanercept treatment over a 4 year period (March 2003-October 2012) attending the Rheumatology Unit, University of Padua. Age, sex, onset age, disease and therapy duration were evaluated. The therapy efficacy was determined using the Bath Ankylosing Spondylitis Activity Score (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Health Assessment Questionnaire (HAQ), DAS28, the patient global assessment, the pain global assessment, the erytrocite sedimentation rate (ESR) and C-reactive protein (CRP). The percentage of patients in whom therapy interval administration was prolonged was also evaluated. Results One hundred twenty-seven patients (79 male 62.2 %; median age 50.14±11.81 yrs; mean disease duration 11.9±8.35 yrs; mean follow-up 52.3±24.92 months) were treated with etanercept and adalimumab (respectively 48.8% and 51.2%). Average baseline and of treatment values were: BASDAI 51.05±22.30 vs BASDAI 26.70±19.55 (p<0.0001); BASFI 34.25±23.74 vs BASFI 16.85±10.51 (p<0.0001); HAQ 0.72±0.60 vs HAQ 0.36±0.22 (p<0.0001); DAS 28 3.10±1.22 vs DAS 28 2.17±0.92 (p<0.0001); patient global assessment 47.20±23.20 vs 26.11±18.23 (p<0.0001); patient pain assessment 41.09±21.44 vs 25.83±18.29 (p<0.0001); ESR 26.90±20.31 mm/1^h vs ESR 13.76±11.71 mm/1^h (p<0.0001); CPR 10.35±8.36 mg/l vs CPR 2.82±1.82 mg/l (p<0.0001). It was possible to extend the interval between injections in 54 (42.5%) of the patients whose responds to therapy was satisfactory, after a mean treatment of 11.84±5.69 months, with adalimumab and etanercept respectively 15.7% and 26.8%. The mean interval obtained was 3.05 weeks in adalimumab and 2.26 weeks in etanercept. Conclusions A clinical, functional and bioumoral improvement was observed in both patients treated with adalimumab as well as etanercept. Treatment with anti-TNFα agents provokes a satisfactory prolonged, clinical response. It was possible to extend the interval between injections in a high percentage of PsA patients. Disclosure of Interest None Declared
Background Erosive osteoarthritis of the hand (EHOA) is believed to be a subset of HOA targeting interphalangeal (IP) joints and characterised by an abrupt onset, marked pain and functional impairment, inflammatory symptoms and signs, and a worse outcome than non-erosive HOA. Despite these characteristic features, it is still unclear if erosions are found only in predisposed patients or are a consequence of an inflammatory phase occurring in any patient with HOA. Some studies suggest that patients with EHOA share HLA or non-HLA genetic predisposition, in particular associated with a genomic region containing the interleukin (IL)-1β 5810 single nucleotide polymorphism. This would support the hypothesis the IL-1 has a role in the pathogenesis of this severe phenotype of HOA. Objectives This study was designed to assess the hypothesis that patients with EHOA share a different phenotype from those with non-EHOA. Thus, we investigated if synovial fluid (SF) levels of proinflammatory interleukin (IL)s and metalloproteinase (MMP)-3 from patients with knee OA presenting a concomitant EHOA were different from those with non-EHOA. Methods In consecutive patients with knee effusions due to OA (ACR criteria), SF was aspirated and subsequently analysed for the presence of crystals and leukocyte (WBC) counts; the remaining SF was stored at -80°C. Patients with crystals of any type and with other concomitant known arthropathies were excluded from the study. Thus, a total of 100 patients were enrolled and underwent hand X-rays which were subsequently examined for the presence of subchondral erosions in the interphalangeal joints. In all SF from patients with erosions of the hand and in 20 consecutive patients without erosions, levels of IL-1β, IL-6, IL-8 and MMP-3 were determined. Statistical analysis was performed with the Mann- Whitney nonparametric test and the Spearman test for correlations. Results Sixteen out of 100 patients (16%, 11 females, mean age 61.69±7.14), with knee OA had at least one erosion according to X-rays. Serum MMP- 3 levels were higher in EHOA patients with respect to non-EHOA (15.63±3.46 ng/ml vs 10.81±1.71 ng/ml) and the MMP-3 levels were correlated with disease duration (p<0.05; r=0.38) only in the EHOA patients. Significant correlation was found in cytokine levels, particularly in IL-1β (p<0.0001; r=0.91), IL-6 (p<0.05; r=0.53), MMP-3 (p=0.0006; r=0.76) in EHOA patients Conclusions High levels of cytokines, only in Knee OA patients with EHOA, could suggest that this particular form of OA have a genetic predisposition for the disease and these patients may present a more severe form of general OA Disclosure of Interest None Declared
We studied the impact of hypertension along with traditional and new cardiovascular risk factors on the structural and functional properties of arteries in psoriatic arthritis (PsA) patients. We examined 42 PsA subjects (aged 51±9 years) stratified according to hypertensive status (19 normotensive, PsA-NT and 23 hypertensives, PsA-HT). Thirty-eight normotensive subjects (C-NT) and 23 hypertensives (C-HT) comparable by age and sex served as controls. Mean carotid intima-media thickness (mean-IMT) and mean of the maximum IMT (M-Max) were evaluated by ultrasound in carotid artery segment bilaterally. Post-occlusion flow-mediated dilation (FMD) of the brachial artery was evaluated by ultrasonography. These parameters were correlated with risk factors, markers of inflammation and disease activity. Values of mean-IMT were higher in both groups of PsA patients compared with C-NT (0.68 mm in PsA-NT and 0.75 mm in PsA-HT versus 0.61 mm in C-NT). PsA-HT displayed higher M-Max (0.95 mm) versus both C-HT (0.71 mm) and PsA-NT (0.79 mm). FMD was impaired in PsA subjects compared with C-NT (5.7% in PsA-NT and 6.0% PsA-HT versus 9.3% in C-NT), whereas there was no difference among PsA-HT, PsA-NT, and C-HT groups. Values of carotid IMT were directly related to tumor necrosis factor (TNF)-α, osteoprotegerin (OPG), blood pressure and lipid profile levels. FMD showed an inverse relationship with TNF-α and blood pressure, but no correlation with lipids. In conclusion, PsA per se implies a pro-atherogenic remodeling, which is enhanced by the hypertensive status. TNF-α and OPG may have an independent role in the development of such vascular damage.
"Infection relapse in spondyloarthritis treated with biological drugs: a single-centre study." Scandinavian Journal of Rheumatology, 41(6), pp. 490–491
Churg–Strauss syndrome (CSS) is a rare, systemic, necrotizing vasculitis of small vessels that occurs in subjects with a background of asthma, allergic rhinitis, and/or nasal polyps (1). Lungs, ski...
Background Osteoarthritis (OA) is the most common joint disease and the knee is frequently involved. OA is characterized by a progressive loss of articular cartilage, osteophyte formation, thickening of the subchondral bone, but as well as some signs of intraarticular inflammation with synovitis. Multiple factors such as mechanical factors, genetics and aging are involved in the pathogenesis of OA. However there is still some debate about the role of inflammation in pathogenetic mechanisms of OA (1). Only a few studies have recently recognized the potential role of calcium crystals (CC) in synovial inflammation and in OA progression (2-4). The most common CC in OA are calcium pyrophosphate dihydrate (CPP) and basic calcium phosphate (BCP), including hydroxyapatite, octacalcium and tricalcium phosphate. Several studies demonstrated that CC occur in up to 60% of SF in OA patients. Although it is difficult to identify CC in SF of OA, the relationship between pathogenetic mechanisms or disease progression and the presence of CC is very interesting. Recognition of CPP, which range in length from 2-20 μm, is a relatively simple procedure. Nevertheless they are not always released in a uniform manner and it is not simple to detect them even when the most sensitive methods are been used in. Due to their sub-microscopic size BCP (70-250 Å) detection is particularly difficult. Objectives The aim of the study was to identify CC in SF of OA patients through compensated polarized light microscopy (CPML) and alizarin red S staining (AS), and by ultrasensitive analysis with scanning electronic microscopy (SEM), to detect whatever concordance exists between them. Methods We analyzed the SF74 patients with knee osteothritis (KOA) (48 F, mean age 64.85±9.33, range 50-89 yrs) by CPML, AS and by SEM. The concordance between CPML and SEM was evaluated by Cohen’s kappa coefficient Results CPP crystals were found in 28.4% by CPML and in 32.4% by SEM. BCP crystals were suspected in 32.4% of the samples that were positive according to AS, while they we found by SEM in 10.8% of SF. By according to kappa coefficient, the concordance between CPML and SEM was 0.78% for CPP and 0.69% for BCP. CPP and BCP were simultaneously positive in 26% of the samples by SEM. Conclusions CPML and AS are tecniques routinely used to detect CC in SF of OA patients. However use of a highly sensitive method such as SEM, ensures accurate detection of CC and this could help to clarify the its potential role in pathogenetic mechanisms and in progression of OA. References AK Rosenthal. Crystls, inflammation, and osteothritis 2011;Curr Opin Rheumatol 23:170-3 S Nalbant, JAM Martinez, T Kitumnuaypong, G Clayburnet, M Sieck and HR Jr. Synovial fluid features and their relations to osteothritis severity: new findings from sequential atudies. Osteoarthritis and Cartilage 2003;11:54-4 GM McCarthy, HS Cheung. Point: Hydroxyapatite crystal deposition is intimately involved in the pathogenesis and progression of human osteoarthritis. Curr Rheumatol Rep. 2009;11:141-7. YZ Liu, AP Jackson and SD Cosgrove. Contribution of calcium-containing crystals to cartilage degradation and synovial inflammation in osteothritis. Osteoarthritis and Cartilage 2009;17:1333-40 Disclosure of Interest None Declared
Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects the axial skeleton and evolves in stiffnes followed by ankylosis and disability. However, it may be difficult to exactly establish the natural history of the disease and the influence of risk factors of progression, since most patients are treated with various pharmacologic or non-pharmacologic agents, which may potentially influence the natural progression of the disease. In this context, we report here a very interesting case of a 40 year old man, presented to our outpatient clinic, 28 years after the onset of AS. Previously for personal reasons, did not choose not to undergo any treatment. This case allows us to evaluate the natural radiological progression of the disease and the influence of predictive risk factors.
The atherosclerotic process is accelerated in several autoimmune rheumatic diseases. Effector cells of innate and adaptive immunity along with pro-inflammatory cytokines and other immune mediators are found in atherosclerotic lesions, where they play an important role in induction, progression and rupture of plaques. Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterized by arthritis, enthesitis, dactilytis, osteitis, and axial involvement, along with skin manifestations. PsA is frequently associated with obesity, diabetes, dyslipidemia, hypertension, accelerated atherosclerosis and with increased cardiovascular morbidity and mortality. Disease-specific and traditional risk factors seem to account for the atherosclerotic burden in PsA patients. Some immunological factors which are involved in PsA can also contribute to atherosclerosis including C reactive protein (CRP), TNF-α, IFN-γ, IL-1, Il 6, IL23, and Th17.
Increased cardiovascular mortality have been observed in several immune mediated rheumatic diseases, including psoriatic arthritis (PsA). We evaluated subclinical atherosclerosis in PsA patients according with hypertensive status by studying non invasively structural and functional properties of arteries. We studied 41 consecutive patients with PsA (of whom, 48% hypertensives) attending hospital outpatient clinics. 40 normotensives healthy subjects (NC) and 18 hypertensives (HT-C) served as controls. We evaluated by B-mode ultrasound the carotid intima media thickness (IMT) expressed as mean-IMT (cumulative mean of mean IMT measured in each carotid segment, common, bulb, and internal carotid artery, bilaterally) and as M-MAX (cumulative mean of maximum IMT). Endothelial function was evaluated by post-occlusion flow mediated dilation (FMD) of the brachial artery using ultrasonography. NO-independent vasodilation was evaluated by the response to sublingual glyceril trinitrate (GTN). PsA had a higher mean-IMT compared to NC. Hypertensive PsA displayed higher M-MAX versus both HT-C (p=0.007) and normotensive PsA (p=0.026). FMD was lower in PsA than in NC, whereas there was no difference between hypertensive PsA, normotensive PsA, and HT-C. GTN response was similar in all groups. In conclusion, our data show that subclinical atherosclerosis is enhanced in PsA compared to NC. In PsA, the hypertensive status proved to exert an additional effect on M-MAX, a parameter of advanced pro-atherogenic remodeling. FMD was reduced in PsA irrespective of hypertensives status. Thus, PsA per se implies a pro-atherogenic remodeling which is enhanced by the hypertensive status.
Objective: The aim of this study was to evaluate the prevalence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA), correlated with some traditional risk factors of atherosclerosis and with PsA-related disease factors.Methods: Forty-one patients and 41 healthy subjects were evaluated for intima-media thickness (IMT) and flow-mediated dilation (FMD), using carotid duplex scanning. IMT values were expressed like IMT mean (cumulative mean of all the IMT mean) and M-MAX (cumulative mean of all the higher IMT). Subclinical atherosclerosis markers were correlated with age, body mass index (BMI) and blood pressure in both groups, with duration of arthritis, duration of psoriasis, tender and swollen joints, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients.Results: IMT mean and M-MAX were both higher in PsA patients compared with controls (0.7 +/- 0.15 vs 0.62 +/- 0.09 mm; p<0.01 and 0.86 +/- 0.21 vs. 0.74 +/- 0.13 mm; p<0.01 respectively). FMD was smaller in patients than in controls (5.9 +/- 2 vs 7.5 +/- 2.8%; p< 0.01). Univariate analysis showed a correlation between IMT mean and SBP (r=0.217; p=0.05) and a correlation between M-MAX and age (r=0.392; p<0.001), BMI (r=0.252; p<0.05), SBP (r=0.446; p<0.001) in both groups. In PsA patients M-MAX resulted correlated with ESR (r=0.338; p<0.05) and BASDAI (r=0.322; p<0.05).Conclusions: PsA patients exhibited endothelial dysfunctions which is an early marker of subclinical atherosclerosis, as well as an higher IMT. An interesting correlation between M-MAX and PsA activity index (ESR and BASDAI) was found.
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.