Psoriasis: Ritchlin CT

Pariser DM, Bagel J, Gelfand JM, Korman NJ, Ritchlin CT, Strober BE, Van Voorhees AS, Young M, Rittenberg S, Lebwohl MG, Horn EJ, Anonymous00184. · Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA, USA. · Arch Dermatol. · Pubmed #17310004 links to  free full text

Abstract: OBJECTIVES: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate the current severity criteria of mild, moderate, and severe psoriasis and to make recommendations concerning a 2-tiered categorization of severity based on current clinical practice and related to intent to treat. PARTICIPANTS: This volunteer task force, led by David M. Pariser, MD, included Jerry Bagel, MD, Joel M. Gelfand, MD, MSCE, Neil J. Korman, MD, PhD, Christopher T. Ritchlin, MD, Bruce E. Strober, MD, PhD, Abby S. Van Voorhees, MD, and Melodie Young, MSN, RN, ANP. Meetings were held by teleconference and were coordinated and funded by the National Psoriasis Foundation. EVIDENCE: This task force reviewed psoriasis severity criteria and other published psoriasis consensus statements. Current standards of care and expert opinion were used to inform the process. CONSENSUS PROCESS: Based on meetings of the task force and under the guidance of David M. Pariser, MD, a statement was drafted by Elizabeth J. Horn, PhD, presented to the task force, and reviewed and approved by the task force. This statement was then reviewed and approved by Robert E. Kalb, MD, Gerald G. Krueger, MD, and Alan Menter, MD. The National Psoriasis Foundation Medical Board reviewed and endorsed this statement by a majority vote on March 2, 2006, at the medical board meeting. CONCLUSIONS: This clinical consensus statement proposes a 2-tiered system for plaque psoriasis therapy that reflects more accurately than the current system how patients are treated in clinical practice. This statement, focused on plaque psoriasis, is intended to assist medical professionals and insurance payers in understanding these 2 categories of patients with psoriasis and choosing appropriate therapies for these patients.

Mensah KA, Schwarz EM, Ritchlin CT. · Department of Orthopaedics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA. · Curr Rheumatol Rep. · Pubmed #18662512 links to  free full text

Abstract: Bone is a highly dynamic organ that interacts with a wide array of cells and tissues. Recent studies have unveiled unanticipated connections between the immune and skeletal systems, and this relationship led to the development of a new field called osteoimmunology. This field will enable investigators to translate basic science findings in bone biology to clinical applications for inflammatory joint diseases such as psoriatic arthritis (PsA). This review examines the disruption of bone homeostasis in PsA and discusses the pivotal role of osteoclasts, osteoblasts, and signaling pathways in the altered remodeling observed in this inflammatory arthritis. It also discusses the effects of tumor necrosis factor inhibition on bone resorption and new bone formation in PsA.

Coates LC, Anderson RR, Fitzgerald O, Gottlieb AB, Kelly SG, Lubrano E, McGonagle DG, Olivieri I, Ritchlin CT, Tan AL, De Vlam K, Helliwell PS. · Academic Section of Musculoskeletal Disease, University of Leeds, United Kingdom. · J Rheumatol. · Pubmed #18609741 No free full text.

Abstract: This article summarizes a presentation on imaging of skin and joints in patients with psoriasis and psoriatic arthritis (PsA) from the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Plain radiography provides valuable insights into the pathogenesis of PsA but is limited because only calcified tissue can be imaged. Newer techniques such as magnetic resonance imaging (MRI) and ultrasound (US) provide additional clues to the pathogenesis of this peripheral, axial, and dermatologic disease. MRI and to a lesser extent US allow visualization of articular and periarticular structures, showing widespread juxtaarticular inflammation in PsA. Bone edema, a surrogate marker of inflammation, can occur throughout the digit in psoriatic dactylitis. Localization of inflammatory change at the juxtaarticular entheses suggests this as the primary site of inflammation. Recent imaging studies provide insights into the relationship between nail and articular disease, demonstrating extension of inflammation from entheseal structures at the distal interphalangeal joint to the nail bed, but the temporal or anatomical progression of these changes remains elusive. Imaging of the skin lags behind that of the articular structures, partly because the skin is readily available for biopsy; however, newer techniques such as laser Doppler imaging provide insights into angiogenesis at the advancing edge of psoriatic plaques. Future work will explore the relationship between immunohistology and imaging of skin and joints. Improvements in imaging articular soft tissues with ultra-short echo time MRI and skin with multiphoton fluorescence microscopy promise insights into anatomical and functional changes.

Ritchlin CT. · Clinical Immunology Research Center, University of Rochester Medical Center, Rochester, New York 14642, USA. · J Rheumatol. · Pubmed #18609740 No free full text.

Abstract: In recent years, translational research has provided fresh insights into the mechanisms that underlie both skin and joint inflammation in psoriatic arthritis (PsA). Application of immunological and molecular techniques to the study of involved tissues, combined with magnetic resonance imaging and relevant preclinical models, has unveiled pivotal inflammatory cascades and cytokine networks that lead to sustained inflammation and altered tissue architecture. In this brief overview of a presentation from the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) the key pathophysiologic events associated with inflammation in psoriatic plaques, synovial membranes, and soft tissues (entheses, tendons), and with abnormal bone remodeling are discussed.

Mallbris L, Ritchlin CT, Ståhle M. · Department of Medicine, Dermatology Unit, Karolinska Institutet, 171 76 Stockholm, Sweden. · Curr Rheumatol Rep. · Pubmed #16973109 No free full text.

Abstract: Psoriasis is one of the common complex disorders in Western world, affecting 2% to 3% of the population. Recent studies indicate that psoriasis is associated with an increased risk of comorbidity and mortality compared to the general population. It appears that patients with psoriasis have a higher prevalence of metabolic disorders such as diabetes, hypertension, obesity, and hyperlipidemia, as well as a higher frequency of cigarette smoking. These concomitant diseases can complicate the treatment of psoriasis. Even though the etiology of these associations is elusive, physicians should be aware of them and take active steps to reduce the risk profiles of patients with psoriasis and psoriatic arthritis, in order to lessen mortality and comorbidity.

Kavanaugh AF, Ritchlin CT, Anonymous00134. · University of California at San Diego, San Diego, California, USA. · J Rheumatol. · Pubmed #16724373 No free full text.

Abstract: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disorder characterized by the association of arthritis and psoriasis. In addition to a heterogeneous and variable clinical course, PsA is complex and multifaceted and may include prominent involvement in the peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such as entheses. A central mission of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is to develop guidelines, based upon the best scientific evidence, for the optimal treatment of patients with PsA. We outline the specific methods and procedures used in this evidence-based, systematic review of treatments for PsA, which we hope will provide a basis for future treatment guidelines.

Ritchlin CT. · Clinical Immunology Research Unit, University of Rochester Medical Center, Rochester, New York 14642, USA. · J Rheumatol. · Pubmed #16724370 No free full text.

Abstract: Enthesitis is defined as inflammation at sites of tendon, ligament, joint capsule, or fascia insertion sites to bone, and is a hallmark feature of psoriatic arthritis. Several outcome measures have been developed to assess enthesitis, but none have been validated in psoriatic arthritis. In this evidence-based review, we assess the limited data on treatments for enthesitis and make recommendations for further studies in psoriatic enthesitis.

Ritchlin CT. · University of Rochester Medical Center, Rochester, New York 14642, USA. · Curr Opin Rheumatol. · Pubmed #15956836 No free full text.

Abstract: PURPOSE OF REVIEW: Heterogeneity in clinical presentation and disease course has hindered understanding of disease mechanisms in psoriatic arthritis, but recent studies have provided insights into pathogenesis. This review examines relevant animal models and genetic factors implicated in disease susceptibility. Also, recent reports on mechanisms related to synovial and entheseal inflammation are discussed. RECENT FINDINGS: Two transgenic mouse models (amphiregulin, STAT-3) were reported that have features of psoriatic arthritis and psoriasis respectively. Genetic studies did not find associations between psoriatic arthritis and several class I major histocompatibility complex alleles, the caspase-activating recruitment domain 15 domain, or the major histocompatibility complex class I chain-related gene A9 allele, in sharp contrast to previous reports. The striking association of psoriatic arthritis with mutations in the killer immunoglobulin receptors on natural killer cells is particularly exciting but needs further study. Psoriatic arthritis has histopathologic features that are more characteristic of other forms of spondyloarthritis than rheumatoid arthritis. Moreover, several of these features correlate with clinical disease activity. Matrix metalloproteinases are strongly expressed in psoriatic arthritis synovium, and serum matrix metalloproteinases-3 may be a reliable biomarker for monitoring disease response. Finally, the concept of an 'enthesis organ' may explain the magnetic resonance imaging findings and clinical signs of psoriatic enthesitis and dactylitis. SUMMARY: Recent findings highlight the importance of innate immune mechanisms in disease pathogenesis. Moreover, psoriatic arthritis and rheumatoid arthritis synovium have divergent histopathologic features that indicate distinct disease mechanisms. The generation of appropriate animal models coupled with reliable biomarkers will result in a deeper understanding of disease pathogenesis and will facilitate the identification of new therapeutic targets.

Anandarajah AP, Ritchlin CT. · Allergy, Immunology and Rheumatology Unit, University of Rochester Medical Center, Rochester, New York 14642, USA. · Curr Opin Rheumatol. · Pubmed #15201594 No free full text.

Abstract: PURPOSE OF REVIEW: Psoriatic arthritis is an inflammatory arthritis associated with psoriasis that is more common and severe than initially appreciated. The success of biologic agents in psoriatic arthritis has sparked great interest in this disorder, although the disease pathogenesis is poorly understood. This review focuses on recent advances in the genetic factors and immune pathways that have been implicated in susceptibility to disease. In addition, recent studies examining the mechanisms that underlie angiogenesis, enthesitis, and bone resorption in psoriatic arthritis are discussed. RECENT FINDINGS: Studies performed on several different populations indicate that the MHC class I allele Cw6 is associated with both early-onset psoriasis and psoriatic arthritis. Mutations in the caspase-activating recruitment domain 15 locus on chromosome 16 are also associated with psoriatic arthritis, providing support for a model involving innate immune mechanisms. Evidence for a CD8 antigen-driven acquired immune response in psoriatic synovium and blood was reported. The finding of elevated levels of vascular endothelial growth factor and angiopoietin 2 in psoriatic arthritis synovial vasculature may provide insights into events responsible for the tortuous vessel morphology, a histologic feature characteristic of psoriatic joints. Tumor necrosis factor (TNF)-alpha is a critical factor mediating inflammation in the synovium, enthesis, and bone. In particular, osteoclasts resorb bone via a receptor activator of nuclear factor kappaB-receptor activator of nuclear factor kappaB ligand signaling pathway that is potentiated by TNF-alpha. The lessening of bone marrow edema after anti-TNF therapy provides further support for the importance of this cytokine in disease pathogenesis. SUMMARY: Recent studies provide additional support for distinct pathogenetic mechanisms in psoriatic arthritis that arise from a complex interplay between genetic and environmental factors. Histopathologic data and results from clinical trials highlight the predominance of TNF-mediated inflammation in psoriatic joint tissues.

Anandarajah AP, Ritchlin CT. · Allergy, Immunology and Rheumatology Unit, University of Rochester Medical Center, Rochester, New York 14642, USA. · Expert Opin Biol Ther. · Pubmed #12718739 No free full text.

Abstract: Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis, can lead to disability from progressive joint destruction and bony fusion. To date, conventional disease modifying antirheumatic drugs (DMARDS) have not convincingly lessened joint pain and inflammation in PsA and there is very little data on the limitation of radiographic progression with these agents. The biological agent etanercept (Enbrel, Amgen, Inc, Thousand Oaks, California, USA) is a soluble TNF receptor fusion protein with proven efficacy in the treatment of rheumatoid arthritis (RA). In a Phase II and Phase III trial, conducted in moderate-to-severe PsA, etanercept significantly reduced joint pain and swelling and lowered the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. A significant decline in structural damage was observed as early as 6 months after starting the drug. Etanercept also improved quality of life measures (Health Assesment Questionnaire [HAQ] and global assessment scores). Up to a third of patients experienced transient injection-site reactions. Rare cases of opportunistic infection, demyelinating disorders and aplastic anaemia have been reported, but a causal link has not been established. In summary, etanercept is a safe and effective agent for the treatment of PsA and represents a major advance in the therapy of this potentially crippling disease.

Anandarajah AP, Schwarz EM, Totterman S, Monu J, Feng CY, Shao T, Haas-Smith SA, Ritchlin CT. · Department of Allergy, Immunology and Rheumatology, University of Rochester, New York, USA. · Ann Rheum Dis. · Pubmed #17967829 No free full text.

Abstract: OBJECTIVE: The frequency of osteoclast precursors (OCPF) and the presence of bone marrow oedema (BMO) are potential response biomarkers in psoriatic arthritis (PsA). Previous studies suggest a central role for tumour necrosis factor (TNF) in the formation of osteoclast precursors. To better understand this association, the effect of etanercept on OCPF and BMO was analysed in PsA patients with erosive arthritis. METHODS: A total of 20 PsA patients with active erosive PsA were enrolled. Etanercept was administered twice weekly for 24 weeks. OCPF was measured and clinical assessments were performed at baseline, 2, 12 and 24 weeks. Gadolinium enhanced MR images were obtained at baseline and 24 weeks. RESULTS: Significant improvements in joint score (p<0.001), HAQ scores (p<0.001) and SF-36 parameters were observed after 6 months of therapy with etanercept compared to baseline. The median OCPF decreased from 24.5 to 9 (p = 0.04) and to 7 (p = 0.006) after 3 months and 6 months of treatment, respectively. MR images were available for 13 patients. The BMO volume decreased in 47 and increased in 31 sites at 6 months. No correlation was noted between OCPF, BMO and clinical parameters. CONCLUSION: The rapid decline in OCPF and overall improvement in BMO after anti-TNFalpha therapy provides one mechanism to explain the anti-erosive effects of TNF blockade in PsA. Persistence of BMO after etanercept treatment, despite a marked clinical response, was unexpected, and suggests ongoing subchondral inflammation or altered remodelling in PsA bone.

Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, Sharp JT, Ory PA, Perdok RJ, Weinberg MA, Anonymous00459. · Seattle Rheumatology Associates, Swedish Medical Center, Seattle, Washington 98104, USA. · Arthritis Rheum. · Pubmed #16200601 links to  free full text

Abstract: OBJECTIVE: Adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA). METHODS: Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area. RESULTS: At week 12, 58% of the adalimumab-treated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and well-tolerated. CONCLUSION: Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.

Mease PJ, Ritchlin CT, Martin RW, Gottlieb AB, Baumgartner SW, Burge DJ, Whitmore JB. · Seattle Rheumatology Associates, 1101 Madison,. Suite 230, Seattle, WA 98104, USA. · J Rheumatol. · Pubmed #15229957 No free full text.

Abstract: OBJECTIVE: Therapeutics used to treat inflammatory diseases, including psoriatic arthritis (PsA), may potentially interfere with normal immune system function. Immune system function can be assessed by evaluating response to vaccination. We assessed the ability of patients with PsA treated with etanercept to produce antibodies in response to pneumococcal antigen challenge. METHODS: Patients with PsA (n = 205) were stratified by methotrexate (MTX) use and randomly assigned to receive either placebo or etanercept 25 mg twice weekly by subcutaneous injection. After 4 weeks of treatment with study drug, a 23-valent pneumococcal vaccination was administered. Antibody levels to 5 antigens (9V, 14, 18C, 19F, and 23F) were measured by ELISA before and 4 weeks after vaccination in 184 patients. The proportion (%) of patients with 2- and 4-fold increases in antibody titers was analyzed. RESULTS: Patients treated with etanercept or placebo had similar responses to the vaccine. A 2-fold increase in titer to at least 2 antigens was achieved by 67% of patients, and a 4-fold increase to at least 2 antigens was achieved by 47% of patients. Approximately 20% of patients in each group failed to show a 2-fold response to any antigens. Logistic regression analysis showed MTX use and age were predictors of a poor response. CONCLUSIONS: Patients with PsA treated with etanercept were able to produce antibodies in response to pneumococcal vaccination. Patients receiving MTX had lower mean antibody levels in response to the vaccine. There was no increased risk of poor response with etanercept treatment given alone or with MTX.

Mease PJ, Ory P, Sharp JT, Ritchlin CT, Van den Bosch F, Wellborne F, Birbara C, Thomson GT, Perdok RJ, Medich J, Wong RL, Gladman DD. · Swedish Medical Center and University of Washington, Seattle, Washington, USA. · Ann Rheum Dis. · Pubmed #18684743 links to  free full text

Abstract: OBJECTIVE: To evaluate the long-term effectiveness and tolerability of adalimumab in the treatment of psoriatic arthritis (PsA). METHODS: Patients with PsA who completed a 24-week, double-blind study of adalimumab versus placebo were eligible to enroll in an open-label extension study and receive adalimumab 40 mg subcutaneously every other week for up to an additional 120 weeks. At the time of this analysis, available efficacy evaluations throughout 2 years of treatment (n = 245) included American College of Rheumatology (ACR) 20%, 50% and 70% improvement scores, measures of joint disease and skin disease, disability and quality of life; modified total Sharp scores (mTSS) were available for 2.75 years of treatment for patients who received adalimumab in the 24-week study. RESULTS: After 24 weeks of double-blind treatment, the mean change in mTSS was -0.2 for the adalimumab group (N = 144) and 1.0 for the placebo group (N = 152; p<0.001), and outcomes for all individual ACR component variables were significantly improved in adalimumab compared with placebo-treated patients. Compared with 24-week responses, inhibition of radiographic progression and improvements in joint disease were maintained in most patients during long-term, open-label adalimumab treatment. Also, improvements in skin disease were maintained, with >20% of patients achieving the strict criterion of psoriasis area and severity index 100. The nature and frequency of adverse events during long-term adalimumab treatment were consistent with the safety profile during short-term treatment. CONCLUSIONS: The clinical and radiographic efficacy of adalimumab demonstrated during short-term treatment was sustained during long-term treatment. Adalimumab has a favourable risk-benefit profile in patients with PsA. Trial registration number: NCT00195689.

Gladman DD, Mease PJ, Strand V, Healy P, Helliwell PS, Fitzgerald O, Gottlieb AB, Krueger GG, Nash P, Ritchlin CT, Taylor W, Adebajo A, Braun J, Cauli A, Carneiro S, Choy E, Dijkmans B, Espinoza L, van der Heijde D, Husni E, Lubrano E, McGonagle D, Qureshi A, Soriano ER, Zochling J. · No affiliation provided · J Rheumatol. · Pubmed #17477480 No free full text.

Abstract: A psoriatic arthritis (PsA) module was convened at OMERACT 8 in order to achieve consensus on the core domains that should be included in randomized controlled trials and longitudinal observational cohorts of subjects with PsA. Following a plenary session at which current status of measures used to assess PsA were reviewed, and discussion at breakout groups, the group achieved consensus on 6 core domains: peripheral joint activity, skin activity, pain, patient global assessment, physical function, and health-related quality of life. In addition the following domains were considered important but not mandatory: spinal disease, dactylitis, enthesitis, fatigue, nail disease, radiography, physician global assessment, and acute-phase reactants. A research agenda was proposed to include development and validation of instruments for the domains where none existed, and in particular further research was recommended for the following areas: magnetic resonance imaging and ultrasound of joints, enthesitis, skin and synovial tissue analysis, and "participation."

Gladman DD, Mease PJ, Ritchlin CT, Choy EH, Sharp JT, Ory PA, Perdok RJ, Sasso EH. · University of Toronto, and Toronto Western Hospital, Toronto, Ontario, Canada. · Arthritis Rheum. · Pubmed #17265483 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of treatment with adalimumab, a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, over 48 weeks in patients with moderate to severe psoriatic arthritis (PsA). METHODS: Patients who completed the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), a 24-week, double-blind study of adalimumab versus placebo in PsA, could elect to receive open-label adalimumab, 40 mg subcutaneously every other week after week 24. Radiographs were obtained at week 48 and were read with radiographs obtained previously. Clinical and radiographic efficacy data were analyzed overall and in patient subsets. Safety data were collected over 48 weeks. RESULTS: At week 48, patients from the adalimumab arm of ADEPT (n = 151) had achieved American College of Rheumatology 20% improvement (ACR20), ACR50, and ACR70 response rates of 56%, 44%, and 30%, respectively. Among those evaluated with the Psoriasis Area and Severity Index (PASI) (n = 69), PASI50, PASI75, PASI90, and PASI100 response rates (> or =50%, > or =75%, > or =90%, and 100% reduction in PASI scores, respectively) were 67%, 58%, 46%, and 33%, respectively (ACR and PASI response rates were analyzed using nonresponder imputation). Improvements in disability, as measured by the Disability Index of the Health Assessment Questionnaire (mean change in score -0.4) were sustained from week 24 to week 48. At week 24 and week 48, the mean changes from baseline in the modified total Sharp score were -0.1 and 0.1, respectively, for patients who received adalimumab for 48 weeks (n = 133), and 0.9 and 1.0, respectively, for patients who received placebo for 24 weeks followed by adalimumab for 24 weeks (n = 141). Adalimumab demonstrated clinical and radiographic efficacy regardless of whether patients were receiving methotrexate (MTX) at baseline. Adalimumab was generally safe and well tolerated through week 48. CONCLUSION: Adalimumab improved joint and skin manifestations, reduced disability, and inhibited radiographic progression over 48 weeks in patients with PsA who were participants in ADEPT. MTX use at baseline was not required for clinical or radiographic efficacy. Adalimumab had a good safety profile through week 48.

Batliwalla FM, Li W, Ritchlin CT, Xiao X, Brenner M, Laragione T, Shao T, Durham R, Kemshetti S, Schwarz E, Coe R, Kern M, Baechler EC, Behrens TW, Gregersen PK, Gulko PS. · Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, NY 11030, USA. · Mol Med. · Pubmed #16622521 links to  free full text

Abstract: Psoriatic arthritis (PsA) is a chronic and erosive form of arthritis of unknown cause. We aimed to characterize the PsA phenotype using gene expression profiling and comparing it with healthy control subjects and patients rheumatoid arthritis (RA). Peripheral blood cells (PBCs) of 19 patients with active PsA and 19 age- and sex-matched control subjects were used in the analyses of PsA, with blood samples collected in PaxGene tubes. A significant alteration in the pattern of expression of 313 genes was noted in the PBCs of PsA patients on Affymetrix U133A arrays: 257 genes were expressed at reduced levels in PsA, and 56 genes were expressed at increased levels, compared with controls. Downregulated genes tended to cluster to certain chromosomal regions, including those containing the psoriasis susceptibility loci PSORS1 and PSORS2. Among the genes with the most significantly reduced expression were those involved in downregulation or suppression of innate and acquired immune responses, such as SIGIRR, STAT3, SHP1, IKBKB, IL-11RA, and TCF7, suggesting inappropriate control that favors proin-flammatory responses. Several members of the MAPK signaling pathway and tumor suppressor genes showed reduced expression. Three proinflammatory genes--S100A8, S100A12, and thioredoxin--showed increased expression. Logistic regression and recursive partitioning analysis determined that one gene, nucleoporin 62 kDa, could correctly classify all controls and 94.7% of the PsA patients. Using a dataset of 48 RA samples for comparison, the combination of two genes, MAP3K3 followed by CACNA1S, was enough to correctly classify all RA and PsA patients. Thus, PBC gene expression profiling identified a gene expression signature that differentiated PsA from RA, and PsA from controls. Several novel genes were differentially expressed in PsA and may prove to be diagnostic biomarkers or serve as new targets for the development of therapies.

Gladman DD, Mease PJ, Krueger G, van der Heidje DM, Antoni C, Helliwell PS, Kavanaugh AF, Nash P, Ritchlin CT, Strand CV, Taylor W. · University of Toronto, Psoriatic Arthritis Program, University Health Network, Toronto, Canada. · J Rheumatol. · Pubmed #16265714 No free full text.

Abstract: Recent advances in biologic therapies have provided hope for patients with psoriatic arthritis (PsA). However, studies have been hampered by the lack of acceptable and validated outcome measures. This article reviews outcome measures used in the assessment of both skin and joints in PsA, and provides a summary of the Psoriatic Arthritis Workshop during OMERACT 7. A set of domains to be included in the assessment of patients with PsA was derived, and a research agenda was developed.

Ritchlin CT. · No affiliation provided · Curr Rheumatol Rep. · Pubmed #15251080 No free full text.

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Ritchlin CT. · No affiliation provided · Curr Rheumatol Rep. · Pubmed #15251079 No free full text.

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Ritchlin CT. · No affiliation provided · Curr Rheumatol Rep. · Pubmed #15251078 No free full text.

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Ritchlin CT. · No affiliation provided · Curr Rheumatol Rep. · Pubmed #15251077 No free full text.

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Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM. · Allergy, Immunology and Rheumatology Unit, University of Rochester Medical Center, Rochester, New York 14642, USA. · J Clin Invest. · Pubmed #12639988 links to  free full text

Abstract: Psoriatic arthritis (PsA) is an inflammatory joint disease characterized by extensive bone resorption. The mechanisms underlying this matrix loss have not been elucidated. We report here that blood samples from PsA patients, particularly those with bone erosions visible on plain radiographs, exhibit a marked increase in osteoclast precursors (OCPs) compared with those from healthy controls. Moreover, PsA PBMCs readily formed osteoclasts in vitro without exogenous receptor activator of NF-kappaB ligand (RANKL) or MCSF. Both osteoprotegerin (OPG) and anti-TNF antibodies inhibited osteoclast formation. Additionally, cultured PsA PBMCs spontaneously secreted higher levels of TNF-alpha than did healthy controls. In vivo, OCP frequency declined substantially in PsA patients following treatment with anti-TNF agents. Immunohistochemical analysis of subchondral bone and synovium revealed RANK-positive perivascular mononuclear cells and osteoclasts in PsA specimens. RANKL expression was dramatically upregulated in the synovial lining layer, while OPG immunostaining was restricted to the endothelium. These results suggest a model for understanding the pathogenesis of aggressive bone erosions in PsA. OCPs arise from TNF-alpha-activated PBMCs that migrate to the inflamed synovium and subchondral bone, where they are exposed to unopposed RANKL and TNF-alpha. This leads to osteoclastogenesis at the erosion front and in subchondral bone, resulting in a bidirectional assault on psoriatic bone.