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Official Journal of the American College of Rheumatology

Special Articles

Conference Summary: Workshop on Chronic Pain, Pain Control, and Patient Outcomes in Rheumatoid Arthritis and Osteoarthritis

• Nicholas Bellamy and Laurence A. Bradley 357

Clinical Science

The Development and Initial Validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus

• Dafna Gladman, Ellen Ginzler, Charles Goldsmith, Paul Fortin, Matthew Liang, Murray Urowitz, Paul Bacon, Stefano Bombardieri, John Hanly, Elaine Hay, David Isenberg, John Jones, Kenneth Kalunian, Peter Maddison, Ola Nived, Michelle Petri, Martin Richter, Jorge Sanchez-Guerrero, Michael Snaith, Gunnar Sturfelt, Deborah Symmons, and Asad Zoma 363

• An instrument to assess accumulated damage in patients with SLE was developed, and its validity was demonstrated. This index will allow clinicians and researchers to assess accumulated damage in SLE patients, which will be helpful in clinical trials, studies of patient populations, and determination of prognosis in individual patients.

Laboratory Tests As Predictors of Disease Exacerbation in Systemic Lupus Erythematosus: Why Some Tests Fail

• John M. Esdaile, Michal Abrahamowicz, Lawrence Joseph, Todd MacKenzie, Yin Li, and Deborah Danoff 370

• This study demonstrates that changes in the results of commonly available laboratory tests are poor predictors of disease exacerbations in SLE patients who are seen in an academic setting. However, sustained abnormalities in selected test values have been observed in those patients who are destined to have different types of flares.

Disease Severity in Patients with Systemic Lupus Erythematosus Correlates with an Increased Ratio of Interleukin-10:Interferon-γ-Secreting Cells in the Peripheral Blood

• Eri Hagiwara, Mark F. Gourley, Susie Lee, and Dennis M. Klinman 379

• This study examines the production of immunoregulatory cytokines in patients with SLE. Disease severity correlated with increased numbers of cells secreting cytokines that augment humoral rather than cellular immune responses. Both T cells and monocytes were implicated in this process.

Interleukin-10 Functions as an Antiinflammatory Cytokine in Rheumatoid Synovium

• Pia Isomaki, Reijo Luukkainen, Riitta Saario, Paavo Toivanen, and Juha Punnonen 386

• The results of this study indicate that endogenously produced IL-10 functions as an immunoregulatory molecule in rheumatoid synovium. In addition, exogenous IL-10 has potent antiinflammatory effects on SFMC, suggesting that IL-10 may be useful in the treatment of patients with RA.

Increased Bone Mass with Pamidronate Treatment in Rheumatoid Arthritis: Results of a Three-Year Randomized, Double-Blind Trial

• Frank Eggelmeijer, Socrates E. Papapoulos, Henk C. van Paassen, Ben A. C. Dijkmans, Roelf Valkema, Marie Louise Westedt, Jan-Otto Landman, Ernest K. J. Pauwels, and Ferdinand C. Breedveld 396

• In this study, the use of pamidronate as a bone-sparing agent in RA was investigated. Long-term treatment of RA patients with oral pamidronate overcame bone loss and increased bone mass, compared with placebo. These findings indicate that oral bisphosphonate may be a useful bone-sparing agent for patients with RA.

Early Undifferentiated Connective Tissue Disease. IV. Musculoskeletal Manifestations in a Large Cohort of Patients with Undifferentiated Connective Tissue Diseases Compared with Cohorts of Patients with Well-Established Connective Tissue Diseases: Followup Analyses in Patients with Unexplained Polyarthritis and Patients with Rheumatoid Arthritis at Baseline

• Graciela S. Alarcon, Robert F. Willkens, John R. Ward, Daniel O. Clegg, John G. Morgan, Khe-Ni Ma, Joyce Z. Singer, Virginia D. Steen, Harold E. Paulus, Michael E. Luggen, Richard P. Polisson, Carol M. Ziminski, Cheryl Yarboro, and H. James Williams 403

• A cohort of patients with well-established connective tissue diseases (CTD) such as rheumatoid arthritis or with symptoms suggestive of CTD but not diagnostic of a specific disease, with a symptom duration of 1 year or less, were followed up for 5 years. Baseline predictors of the development of RA, the achievement of remission in RA, and other outcomes were assessed. The results have implications with regard to early treatment decisions.

The Effect of Progressive Resistance Training in Rheumatoid Arthritis: Increased Strength without Changes in Energy Balance or Body Composition

• Laura C. Rall, Simin Nikbin Meydani, Joseph J. Kehayias, Bess Dawson-Hughes, and Ronenn Roubenoff 415

• This study demonstrates that high-intensity strength training is both feasible and safe in reversing the weakness and functional impairment of RA, in patients with well-controlled disease. Strength training leads to significant improvements in strength, pain, and fatigue without exacerbating disease activity or joint damage. These findings provide an important additional treatment component for patients with RA.

Gender, Paid Work, and Symptoms of Emotional Distress in Rheumatoid Arthritis Patients

• Judith Fifield, Susan Reisine, T. Joseph Sheehan, and Julia McQuillan 427

• Emotional distress is a major problem for patients with RA. This report offers data as to the social and disease-based factors that contribute to the gender gap in depressive symptoms among RA patients in the paid workforce.

Psychiatric Diagnoses in Patients with Fibromyalgia Are Related to Health Care-Seeking Behavior Rather than to Illness

• Leslie A. Aaron, Laurence A. Bradley, Graciela S. Alarcon, Ronald W. Alexander, Mireya Triana-Alexander, Michelle Y. Martin, and Kristin R. Alberts 436

• Psychiatric diagnoses and psychological distress were assessed among patients with fibromyalgia syndrome (FMS), community residents with FMS who had not seen a physician for their symptoms (``FMS nonpatients''), and healthy controls, to determine the relationship between psychiatric morbidity and FMS. Patients with FMS exhibited significantly higher rates of lifetime psychiatric diagnoses than FMS nonpatients and controls. Nonpatients did not differ from controls in number of diagnoses, suggesting that psychiatric morbidity is more strongly rerlated to health care-seeking behavior than to FMS itself.

Basic Science

High Frequencies of Identical T Cell Clonotypes in Synovial Tissues of Rheumatoid Arthritis Patients Suggest the Occurrence of Common Antigen-Driven Immune Responses

• Yoko Ikeda, Kayo Masuko, Yuta Nakai, Tomohiro Kato, Tomoko Hasanuma, Shin-Ichi Yoshino, Yutaka Mizushima, Kusuki Nishioka, and Kazuhiko Yamamoto 446

• This study demonstrates for the first time that large numbers of identical T cell clones are present in different areas of RA synovial tissues. This suggests that the immune responses in RA lesions are not random and points to the existence of a strong T cell response against common antigens.

Limited Heterogeneity of Rearranged T Cell Receptor Vα and Vβ Trancss in Synovial Fluid T Cells in Early Stages of Rheumatoid Arthritis

• Dagmar-Christiane Fischer, Bertram Opalka, Axel Hoffmann, Wolfgang Mayr, and Hans-Dieter Haubeck 454

• Evidence shows that T cells play a critical role in the etiology and pathogenesis of RA. To identify these T cells, it is essential to analyze the TCR repertoire in the early stages of the disease. The present study uses RT-PCR to amplify TCR Vα and Vβ trancss of synovial T cells in the early stages of RA. The results show a limited heterogeneity of V[ga] and Vβ TCRs in synovial fluid T cells, and a preferential usage of TCR Vα17 in the early stages of RA, which suggests a pathogenetic role for Vα17 T cells.

High Seroprevalence of Anti-HTLV-I Antibody in Rheumatoid Arthritis

• Katsumi Eguchi, Tomoki Origuchi, Hiroyuki Takashima, Kokichi Iwata, Shigeru Katamine, and Shigenobu Nagataki 463

• In this study, the age-adjusted summary odds ratio of HTLV-I infection among female RA patients in an HTLV-I-endemic area, as compared with a general population of blood donors, was 2.8 (95% CI 1.8- 4.6). The etiologic fraction, i.e., the proportion of RA in the study population that is attributable to HTLV-I infection, was estimated to be 13.2% (95% CI 5.1-21.2). These results support the notion that HTLV-I infection is a risk factor for RA.

Regulation of Adhesion Molecule Expression by Human Synovial Microvascular Endothelial Cells In Vitro

• Shing S. T. To, Peter M. Newman, Valentine J. Hyland, Bruce G. Robinson, and Leslie Schrieber 467

• Adhesion molecules play important roles in inflammation. This study demonstrates that the expression of these molecules by synovial microvascular endothelium differs from their expression by neonatal foreskin and human umbilical vein endothelium. Understanding the regulation of adhesion molecules on synovial microvascular endothelium may provide insights into the pathogenesis of rheumatoid arthritis.

The Superficial Layer of Human Articular Cartilage Is More Susceptible to Interleukin-1-Induced Damage than the Deeper Layers

• H. J. Hauselmann, J. Flechtenmacher, L. Michal, E. J.-M.A. Thonar, M. Shinmei, K. E. Kuettner, and M. B. Aydelotte 478

• Development of successful therapy for patients with various forms of arthritis will depend to a large extent on a better understanding of the metabolism of normal human articular cartilage and of how the metabolic processes in diseased joints might be modulated by biochemical and biomechanical factors. The stratified nature of articular cartilage, resulting from variations in chondrocyte metabolism, is critical for the normal properties and load-bearing functions of the tissue. This study demonstrates that cells in the superficial layer of articular cartilage are significantly more responsive to damage induced by IL-1 and are less readily protected by the naturally occurring IL-1 receptor antagonist protein than are cells that lie deeper in the tissue. Since IL-1 may play a role in cartilage damage in the arthritides, these findings of important metabolic differences between chondrocytes from different zones of normal human articular cartilage shed new light on possible disease mechanisms.

The Effect of Methotrexate on Mouse Bone Cells in Culture

• Kimberly P. May, Don Mercill, Michael T. McDermott, and Sterling G. West 489

• This study demonstrates that diminished osteoblastic cell function occurs in mouse bone cells after administration of low mean doses of methotrexate. This finding suggests that methotrexate therapy may contribute to osteoporosis in patients receiving this therapy for rheumatoid arthritis or other inflammatory diseases.

Interleukin-10 Inhibition of the Progression of Established Collagen-Induced Arthritis

• Marita Walmsley, Peter D. Katsikis, Erika Abney, Sarah Parry, Richard O. Williams, Ravinder N. Maini, and Marc Feldmann 495

• This study demonstrates that IL-10, injected after the onset of arthritis in mice with collagen-induced arthritis, induces a dose-dependent amelioration of both joint inflammation and destruction, as assessed histologically. This supports the possibility that IL-10 is a candidate therapeutic agent. Its efficacy needs to be assessed by clinical trial.

Disease-Modifying Activity of SK&F 106615 in Rat Adjuvant-Induced Arthritis: Multiparameter Analysis of Disease Including Magnetic Resonance Imaging and Bone Mineral Density Measurements

• Jeremy N. Bradbeer, Rasesh D. Kapadia, Susanta K. Sarkar, Hugh Zhao, George B. Stroup, Barbara A. Swift, David J. Rieman, and Alison M. Badger 504

• SK&F 106615 is a member of a class of compounds known as the azaspiranes and is currently in phase I clinical trials for rheumatoid arthritis. These compounds demonstrate therapeutic activity in animal models of autoimmune disease and transplantation. Their protective effects on joint integrity in rats with adjuvant-induced arthritis, as demonstrated in the present study, indicate that they may be disease-modifying agents.

The Effect of Leukotriene Synthesis Inhibitors in Models of Acute and Chronic Inflammation

• Cheryl L. Nickerson-Nutter and Eugene D. Medvedeff 515

• This study demonstrates the efficacy of 2 leukotriene synthesis inhibitors, Bay y 1015 and Bay x 1005, in combination with naproxen in the collagen-induced arthritis model in mice. The results indicate that combination therapy with leukotriene synthesis inhibitors and nonsteroidal antiinflammatory drugs may be a more effective treatment, with fewer side effects, than treatment with either class of drugs administered alone.

Some Autoantibodies to Ro/SS-A and La/SS-B are Antiidiotypes to Anti-Double-Stranded DNA

• Wei Zhang and Morris Reichlin 522

• In many systemic lupus erythematosus patients who produce anti-Ro/SS-A and anti-La/SS-B, anti-dsDNA antibodies are rarely seen, even after long followup. Correspondingly, the prevalence of nephritis in these patients is low. This study shows that in such patients, subpopulations of anti-Ro/SS-A and anti-La/SS-B are antiidiotypes to anti-dsDNA and probably down-regulate the production of anti-dsDNA.

Concise Communication

Systemic Pseudovasculitis from Scurvy in Anorexia Nervosa

• Cindy L. Mehta, Derek Cripps, and Alan J. Bridges 532

Letters

Low Shed L-Selectin Levels in Kawasaki Disease with Coronary Artery Lesions: Comment on the Article by Furukawa et al

• Shoko Kanekura, Isao Kitajima, Junichiro Nishi, Masao Yoshinaga, Koichiro Miyata, and Ikuro Maruyama 534

Human T Cell Leukemia/Lymphoma Virus Type I DNA and Polymyositis/Dermatomyositis: Comment on the Article by Sherman et al

• Louis-Jean Couderc, Maria-Pia Flammang, Isabelle Caubarrere, and Jean-Claude Vernant 535

American College of Rheumatology Preliminary Definition of Improvement in Rheumatoid Arthritis: Comment on the Article by Felson et al

• Anke van Gestel and Piet van Riel 535

Reply

• David T. Felson 536

Monoclonal Antiphospholipid Antibodies and Germline VH Genes: Comment on the Article by Harmer et al

• Anisur Rahman, David A. Isenberg, and David S. Latchman 537

Reply

• Ian J. Harmer, Sozos Loizou, Alex K. L. So, Mark J. Walport, Charles Mackworth-Young, and Keith M. Thompson 538

ACR Announcements 9A