Archive for November, 2007

Synovial fluid fibroblasts and lymphocytes support the osteoclastogenesis in human psoriatic arthritis.

Thursday, November 29th, 2007

Related ArticlesSynovial fluid fibroblasts and lymphocytes support the osteoclastogenesis in human psoriatic arthritis.

Ann N Y Acad Sci. 2007 Nov;1117:159-64

Authors: Mori G, Cantatore FP, Brunetti G, Oranger A, Colaianni G, Quarta L, Corrado A, Colucci S, Grano M

Aggressive bone resorption is well recognized in psoriatic arthritis (PsA). By using in vitro osteoclastogenesis models, consisting of unstimulated mononuclear cells from peripheral blood (PBMCs) and synovial fluid (SFMCs) of PsA patients, we demonstrated the spontaneous OC formation in both culture systems. In PBMCs the osteoclastogenesis was T cell-dependent while it was T cell- and fibroblast-dependent in SFMCs. T cells isolated from PBMCs and SFMCs of PsA patients overexpressed RANKL and TNF-alpha, and fibroblasts from SFMCs overexpressed RANKL. Thus, T cells and fibroblasts from synovial fluid through the production of osteoclastogenic cytokines could support the OC formation in PsA patients.

PMID: 17646267 [PubMed - in process]

]]>

Psoriasis and psoriatic arthritis: separate or one and the same?

Thursday, November 29th, 2007

Related ArticlesPsoriasis and psoriatic arthritis: separate or one and the same?

Br J Dermatol. 2007 Nov;157(5):850-60

Authors: Ciocon DH, Kimball AB

The presence and severity of skin and joint symptoms in patients with psoriasis and psoriatic arthritis frequently do not correspond, a discrepancy that has raised the question of whether they represent two related but different disease processes. The fact that some agents seem to work preferentially in one state over the other reinforces this idea. However, there are also several agents with combined efficacy against cutaneous and articular inflammation that appear to support the existence of a common aetiology. Here we review the clinical, epidemiological and genetic evidence for and against a common pathogenesis for the two diseases. We then discuss the cellular and molecular targets of their selected therapies and how they potentially implicate effector pathways as a common immunopathogenic mechanism. Finally, we examine a recently proposed model of psoriasis pathogenesis involving type 1 interferon-producing plasmacytoid dendritic cells and how it may provide further clues to the aetiological links between psoriasis and psoriatic arthritis.

PMID: 17725671 [PubMed - in process]

]]>

Sensitivity and specificity of plain radiographic features of peripheral enthesopathy at major sites in psoriatic arthritis.

Thursday, November 29th, 2007

Related ArticlesSensitivity and specificity of plain radiographic features of peripheral enthesopathy at major sites in psoriatic arthritis.

Skeletal Radiol. 2007 Nov;36(11):1061-6

Authors: Helliwell PS, Porter G,

BACKGROUND: It has been proposed that the defining difference between rheumatoid arthritis and spondyloarthropathy (including psoriatic arthritis) is the initial pathological lesion where the emphasis in psoriatic arthritis is on the enthesis and in rheumatoid arthritis on the synovium. Classical radiological descriptions of seronegative spondyloarthropathy include enthesopathy at major entheseal insertions characterised by erosions and exuberant new bone formation. In this study, the plain radiographic features of spondyloarthropathy are compared between psoriatic arthritis, other spondyloarthropathies and rheumatoid arthritis. METHODS: The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician diagnosed psoriatic arthritis and 525 controls with other inflammatory arthritis, 70% of which had rheumatoid arthritis. Plain radiographs of the pelvis and heels were part of the study protocol, although radiographs of other potential entheseal sites such as the knee, elbow and shoulder, were interpreted if available. All radiographs were read blind by two observers working in tandem. RESULTS: Significant differences in entheseal erosion and entheseal new bone formation were found between psoriatic arthritis, ankylosing spondylitis, undifferentiated spondyloarthropathy, rheumatoid arthritis and other diagnoses (entheseal erosion, chi-squared 20.8, p=0.008; entheseal new bone formation, chi-squared 24.5, p=0.001). These differences were mainly due to a higher proportion of these features in ankylosing spondylitis. No differences in the plain radiographic features of enthesopathy were found between psoriatic arthritis and rheumatoid arthritis except in the case of entheseal new bone formation at sites of attachment of inguinal ligament, sartorius and rectus femoris muscles to the ilium (OR 3.01, 95% CI 1.13-8.02). Very few subjects with symptomatic heel involvement had radiographic changes and minimal differences were found between those with and without symptoms in terms of new bone formation and erosion at either calcaneal site. CONCLUSIONS: New bone formation and erosion at major entheseal sites is most commonly seen in ankylosing spondylitis. Plain radiographic features of major enthesopathy are poor discriminators between psoriatic arthritis and rheumatoid arthritis.

PMID: 17849113 [PubMed - in process]

]]>

Value of contrast-enhanced ultrasound in rheumatoid arthritis.

Thursday, November 29th, 2007

Related ArticlesValue of contrast-enhanced ultrasound in rheumatoid arthritis.

Eur J Radiol. 2007 Nov;64(2):222-30

Authors: De Zordo T, Mlekusch SP, Feuchtner GM, Mur E, Schirmer M, Klauser AS

The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter’s syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity.

PMID: 17768022 [PubMed - in process]

]]>

Male osteoporosis with vertebral fractures? Look for ankylosing spondylitis! A report of 10 cases.

Thursday, November 29th, 2007

Related ArticlesMale osteoporosis with vertebral fractures? Look for ankylosing spondylitis! A report of 10 cases.

J Rheumatol. 2007 Nov;34(11):2271-2

Authors: Laroche M, Lassoued S, Billey T, Bernard J, Mazi B

OBJECTIVE: Several authors have described the association of ankylosing spondylitis (AS) and osteoporosis. Usually vertebral fractures complicate severe AS. METHODS: We report a series of 10 men in whom benign spondyloarthropathy was discovered during etiological investigation for osteoporosis. Eight patients had B27+ AS and 2 had psoriatic arthritis with axial involvement. The mean number of vertebral fractures was 1.5. No patient had an appendicular fracture. RESULTS: Phosphorus and calcium levels and measurements of 25OHD3, parathyroid hormone, osteocalcin, and serum CTX were in the normal range. The decrease in bone mineral density was greater in the spine (mean T-score at L2-L4 -2.95, mean total hip T-score -1.67). CONCLUSION: Osteoporosis with fractures may reveal benign spondyloarthropathy whose clinical expression is sometimes incomplete. Our findings demonstrate that osteoporosis is not always correlated with the severity of AS.

PMID: 17918785 [PubMed - in process]

]]>

A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment.

Thursday, November 29th, 2007

Related ArticlesA pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment.

J Eur Acad Dermatol Venereol. 2007 Nov 19;

Authors: Hroch M, Chladek J, Simkova M, Vaneckova J, Grim J, Martinkova J

Background Clinical studies of low-dose oral methotrexate (MTX) in the treatment of psoriasis and rheumatoid arthritis document a large interpatient variability in the pharmacokinetics of MTX, including its polyglutamates (MTXPGs) in erythrocytes (RBC). This can be a factor contributing to the variability of therapeutic and toxic effects. Aim This pilot trial aimed to investigate the MTXPG concentrations in RBC as well as their relation to therapeutic and adverse effects during the initial 4 months of pharmacokinetically guided therapy with a divided-dose schedule (three doses of MTX separated by 12-h intervals once a week). Subjects and methods Sixteen psoriatic patients (4 men and 12 women; mean age, 53 years; range, 28-69 years) with moderate-to-severe chronic plaque psoriasis [mean Psoriasis Area and Severity Index (PASI) = 24; range, 9-42] were enrolled in the study. Concentrations of plasma MTX and that of MTXPGs in RBC were assayed using liquid chromatography methods. The area under the concentration-time curve of plasma MTX in the interval 0-8 h post-dose (AUC(0-8 h)) was measured after a test bolus dose of 10 mg, and the starting weekly dose was individualized in order to achieve the target AUC(0-8 h) of 1800 nmol.h/L. The PASI, biochemistry, and haematology tests and MTXPGs levels in RBC were evaluated at baseline and at 4-week intervals. Results The AUC(0-8 h )achieved 1360 +/- 425 nmol.h/L (mean +/- SD: range, 778-2400 nmol.h/L). The mean (range) of individualized doses was 14.5 mg/week (7.5-22.5 mg). The mean (SD) steady-state concentration of total MTXPGs observed between days 85 to 110 reached 113 (34.6) nmol/L (range, 66.1-174 nmol/L). The PASI decreased from 24.0 +/- 8.0 (mean +/- SD) at baseline to 8.0 +/- 6.1 at day 110 (P

PMID: 18031504 [PubMed - as supplied by publisher]

]]>

The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: results of a pilot randomised 6-month trial with methotrexate.

Thursday, November 29th, 2007

Related ArticlesThe effectiveness of a traditional therapeutical approach in early psoriatic arthritis: results of a pilot randomised 6-month trial with methotrexate.

Clin Rheumatol. 2007 Nov 21;

Authors: Scarpa R, Peluso R, Atteno M, Manguso F, Spanò A, Iervolino S, Di Minno MN, Costa L, Del Puente A

Thirty-five patients with Early Psoriatic Arthritis (EPA) (17 female and 18 male; mean age 25.6 years) entered this randomised 6-month study. At the enrolment, all patients were on non-steroidal anti-inflammatory drug (NSAID) therapy on demand and were divided in two matched groups (A and B). Group A continued NSAID therapy at full dosage in the following 3 months and then added methotrexate (MTX) for another 3 months. Group B was under the combination of NSAID and MTX for the entire 6-month period. Clinical and laboratory assessment included the count of tender joints and/or entheses (TJC), the count of swollen joints and/or entheses (SJC), patient’s global assessment (PGA), physician’s global assessment (PhGA), patient’s assessment of pain (VAS), erythrocyte sedimentation rate (ESR) and serum concentration of C-reactive protein (CRP). All variables were done at baseline (T0), at 3 (T3) and at 6 months (T6). In both group A and in group B, there was a significant improvement of all variables at T3 and T6. However, in comparison to the patients of group A, patients included in group B showed a more rapid and marked improvement of TJC and SJC, which was statistically significant at T3 (p

PMID: 18030515 [PubMed - as supplied by publisher]

]]>

Tumor necrosis factor as a therapeutic target of rheumatologic disease.

Thursday, November 29th, 2007

Related ArticlesTumor necrosis factor as a therapeutic target of rheumatologic disease.

Expert Opin Ther Targets. 2007 Nov;11(11):1369-84

Authors: Ackermann C, Kavanaugh A

TNF-alpha is a crucial pro-inflammatory and immunoregulatory cytokine that is central to the pathogenesis of various inflammatory and autoimmune conditions. A number of controlled trials have shown effectiveness for TNF-alpha inhibitors in several diseases, in particular rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn’s disease. These agents may also be useful in additional autoimmune conditions. The introduction of TNF-alpha inhibitors has revolutionized the therapeutic approach and treatment paradigms especially for patients with rheumatoid arthritis. Despite extensive investigation, the full profile of their mechanisms of action remain incompletely understood. Optimal use of these agents requires consideration of their possible adverse effects. In addition to the presently available TNF-alpha blockers, other agents targeting this key mediator are under study. Recent advances and future directions in anti-TNF-alpha therapy are discussed in this paper.

PMID: 18028004 [PubMed - indexed for MEDLINE]

]]>

Clinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate-to-severe plaque psoriasis in Taiwan: results of an open-label, single-arm pilot study.

Thursday, November 29th, 2007

Related ArticlesClinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate-to-severe plaque psoriasis in Taiwan: results of an open-label, single-arm pilot study.

J Eur Acad Dermatol Venereol. 2007 Nov 14;

Authors: Tsai TF, Liu MT, Liao YH, Licu D

Background No clinical trial of efalizumab has been conducted in Asia. Objective To determine the efficacy and safety of efalizumab in Taiwanese patients with psoriasis. Methods This is an open-label, single-arm pilot study conducted at two centres. Patients were given 1 mg/kg efalizumab subcutaneously once a week for 12 weeks and were then followed up for a further 12 weeks. Results A total of 49 patients participated in the study. The median improvement in Psoriasis Area and Severity Index (PASI) during the treatment period was 19.6%, and a >/= 50% improvement in PASI was seen in 20.4%. Rebound was seen in 17.8% of patients, and anti-efalizumab antibodies were detected in 41% of patients. The most frequent adverse events were headache (34.7%), arthralgia/arthritis (28.6%), psoriasis events (new form/exacerbation; 26.5%) and pruritus (22.4%). Conclusions This small pilot study indicated that efalizumab was effective in improving psoriasis symptoms in Taiwanese patients, with no new safety issues identified.

PMID: 18005021 [PubMed - as supplied by publisher]

]]>

Multiplex Cytokine Analysis in Human Serum: An Evaluation of Technologies for the Simultaneous Detection of Eight Analytes.

Thursday, November 29th, 2007

Related ArticlesMultiplex Cytokine Analysis in Human Serum: An Evaluation of Technologies for the Simultaneous Detection of Eight Analytes.

Clin Vaccine Immunol. 2007 Nov 14;

Authors: Toedter G, Hayden K, Wagner C, Brodmerkel C

The accurate detection and quantitation of cytokines in serum is important in the study of disease mechanisms, pathogenesis, and treatment. Serum cytokines can reflect processes that are occurring at the cellular or tissue level, and thus provide a means of indirectly monitoring these processes. Multiplex detection of cytokines allows the simultaneous measurement of multiple cytokines in a sample, increasing the efficiency of measuring the cytokines while reducing the serum sample volumes required for the testing. Two commercially available multiplex platforms were evaluated (Pierce Searchlight and Mesoscale Discovery (MSD), using multiplexes capable of simultaneously detecting eight cytokines. The cytokines analyzed in this study were IFNgamma, VEGF, TNFalpha, IL-6, MIP-1beta, MCP-1, IL-12p40, and IL-4. The range of quantitation of the platforms, the recovery of spiked cytokines, and the detection of the cytokines in serum samples from subjects with ulcerative colitis, Crohn’s Disease, rheumatoid arthritis, and psoriasis were examined. The findings showed that the detection of the cytokines was highly dependent upon the platform, with the consistency of the detection of cytokines across platforms being dependent upon the cytokine being analyzed. A careful examination of platform assay performance must be made prior to utilizing multiplex platforms in a study. While some cytokines will give similar patterns of results across platforms, others will be highly variable. The use of the same platform within a study or across studies where data will be compared is advised.

PMID: 18003817 [PubMed - as supplied by publisher]

]]>