John D. Reveille, Joann M. Moulds, Chul Ahn, Alan W. Friedman, Bruce Baethge, Jeffrey Roseman, Karin V. Straaton, and Graciela S. Alarcon, for the LUMINA Study Group 1161

Previous studies have suggested that socieconomic factors influence the activity of SLE, even at disease onset. The data obtained in the present study suggest that immunogenetic factors and other determinants associated with ethnicity, as well as socioeconomic factors, affect disease activity and major organ involvement at disease onset. Identification of these factors and determination of their effect on outcome will allow the design of targeted interventions that will minimize the impact of SLE.

Graciela S. Alarcon, Jeffrey Roseman, Alfred A. Bartolucci, Alan W. Friedman, Joann M. Moulds, Niti Goel, Karin V. Straaton, and John D. Reveille, for the LUMINA Study Group 1173

In this study, factors that influence disease activity early in the course of the disease in patients with SLE were assessed in 3 ethnic groups (Hispanics, African Americans, and Caucasians) in 2 geographic locations (Texas and Alabama). The study identified both genetic and nongenetic features related to disease activity in all 3 ethnic groups. Interventions to modify disease activity may need to be ethnic-specific to be successful.

Karin Manger, Roland Repp, Bernd M. Spriewald, Astrid Rascu, Anja Geiger, Ralf Wassmuth, Nomdo A. C. Westerdaal, Bernhard Wentz, Bernhard Manger, Joachim R. Kalden, and Jan G. J. van de Winkel 1181

The homozygous FcγRIIa-R/R131 genotype might be more frequent in SLE patients with nephritis. In this retrospective study of German SLE patients, the FcγRIIa polymorphism could be ruled out as a susceptibility factor for SLE, and a higher prevalence of R/R131 was not found in this cohort, although a higher and earlier morbidity was demonstrated. The FcγRIIa-H131 genotype was associated with a higher incidence of livedo only, possibly indicating a protective effect of this genotype on the development of SLE and/or lupus nephritis.

Mahmoud Abu-Shakra, Rita Toker, Daniel Flusser, Gideon Flusser, Michael Friger, Shaul Sukenik, and Dan Buskila 1190

This report compares the radiographs of 22 RA patients who were not given any second-line agents during the course of their disease with those of 22 RA patients who were treated with DMARDs and were matched for disease duration, sex, and number of actively inflamed joints. The results of this study indicate that untreated patients have more deformed and damaged joints, suggesting that second-line drugs have a role in slowing the rate of progression of joint damage in patients with RA.

B. Lanzillo, N. Pappone, C. Crisci, C. di Girolamo, R. Massini, and G. Caruso 1196

This study shows that patients with RA may have electrophysiologic and histologic findings of peripheral nerve damage in the absence of clinical evidence of such damage, and that the peripheral nerve damage is less severe in patients taking steroids. These findings may alert physicians to the need for the use of electrophysiologic methods to evaluate for peripheral nervous system involvement when there are minor symptoms of such involvement and may support the use of steroids to treat RA.

M. Sharif, C. Salisbury, D. J. Taylor, and J. R. Kirwan 1203

Concentrations of joint tissue metabolites were measured in the serum of RA patients with and without glucocorticoid treatment. Low-dose prednisolone had no significant effect on markers of cartilage turnover (GAG, 5D4) in early RA, suggesting that early erosions do not involve cartilage surfaces. However, treatment reduced the levels of markers of bone turnover (OC) and synovial tissue turnover (HA and PIINP), which supports the general view that prednisolone reduces synovitis and suppresses bone turnover.

S. Padeh and J. H. Passwell 1210

Intraarticular corticosteroid injection is now more commonly used in childhood arthritis. This report showed that in children with juvenile arthritis, injection of corticosteroids into the joints resulted in full remission of inflammation in 82.0% of the joints. The procedure was safe and resulted in long-term remissions. It may be the only therapy needed in patients with pauciarticular juvenile rheumatoid arthritis, obviating the need for prolonged oral medications. This treatment was also observed to be effective in correction of joint contractions and deformities.

Armin Schnabel, Michael Reuter, and Wolfgang L. Gross 1215

This observational study demonstrates that intravenous pulse cyclophosphamide can be an effective treatment for progressive interstitial lung disease due to collagen vascular diseases. High-resolution computed tomography and bronchoalveolar lavage data suggest that it primarily targets the inflammatory component of the disease.

Carlo Salvarani, Fabrizio Cantini, Pierluigi Macchioni, Ignazio Olivieri, Laura Niccoli, Angela Padula, and Luigi Boiardi 1221

In PMR, the marked and distinctive proximal aching and stiffness has tended to focus attention away from distal musculoskeletal manifestations, which also occur in this syndrome. This prospective followup study showed that articular and/or tenosynovial distal involvement occurred in 45% of PMR patients. The patients with peripheral arthritis and those with distal extremity swelling with pitting edema appeared to represent 2 subsets with, respectively, more severe and milder disease compared with patients with only the typical proximal symptoms. Awareness of these findings will help facilitate the proper diagnosis and institution of appropriate therapy for this disease.

Rosemarie Hirsch, Margaret Lethbridge-Cejku, Robert Hanson, William W. Scott, Jr., Ralph Reichle, Chris C. Plato, Jordan D. Tobin, and Marc C. Hochberg 1227

This study demonstrates sib-sib correlations for OA in a cohort of volunteers drawn from a community setting, after adjustment for the effects of age, sex, and body mass index. By demonstrating familial aggregation in a cohort ascertained without regard to OA status, these findings contribute to the evidence for heritability of OA.

Leena Sharma, Debra E. Hurwitz, Eugene J-M. A. Thonar, Jeffrey A. Sum, Mary Ellen Lenz, Dorothy D. Dunlop, Thomas J. Schnitzer, Gretchen Kirwan-Mellis, and Thomas P. Andriacchi 1233

In this study, the adduction moment, a major determinant of medial-to-lateral load distribution at the knee, strongly correlated with disease severity in OA, adding support to the notion that the adduction moment may play a pathogenetic role in medial compartment tibiofemoral OA. If consistent results are obtained in longitudinal studies, interventions to reduce the adduction moment, including gait retraining, should be developed and tested; such interventions may have a disease-modifying effect in knee OA. The adduction moment and the serum hyaluronan level, a measure of one aspect of joint metabolic activity shown to have prognostic value in knee OA, represent both of the major pathogenetic categories in OA. The findings reported herein raise the possibility that concurrent examination of these factors in patients with medial tibiofemoral OA may allow identification of those destined to have rapid disease progression.

Martin Herrmann, Reinhard E. Voll, Otmar M. Zoller, Manuela Hagenhofer, Botond B. Ponner, and Joachim R. Kalden 1241

This study suggests a contribution of defective apoptotic cell removal in the etiology of SLE. Further characterization of this phagocyte defect may provide a basis for the hitherto missing therapy directed at the cause of SLE.

Kiyoshi Sakai, Hiroaki Matsuno, Isaya Morita, Takeshi Nezuka, Haruo Tsuji, Toshikazu Shirai, Shin Yonehara, Tomoko Hasunuma, and Kusuki Nishioka 1251

This study sought to clarify the histologic effect of Fas-mediated apoptosis in rheumatoid synovia using a novel RA model, by grafting human rheumatoid synovia in SCID mice. The present effectiveness of anti-Fas monoclonal antibody in diminishing rheumatoid synovium in vivo suggests the possibility of a new strategy for RA therapy.

Ewa M. Paleolog, Sylvia Young, Alison C. Stark, Richard V. McCloskey, Marc Feldmann, and Ravinder N. Maini 1258

The invasive pannus in RA is highly vascularized, suggesting that targeting blood vessels in RA may be an effective future therapeutic strategy. This study demonstrates that serum levels of VEGF, which is a very potent stimulus for blood vessel formation, are elevated in patients with active RA. Serum VEGF concentrations in RA patients were markedly reduced following treatment with anti-TNFα monoclonal antibody, which has been previously shown to exert a marked beneficial effect in RA. These data suggest that anti-TNFα may decrease the supply of nutrients to the developing pannus, and thereby reduce the inflammatory processes in RA.

Sanshiro Hashimoto, Kenji Takahashi, David Amiel, Richard D. Coutts, and Martin Lotz 1266

During the early phases of experimentally induced OA in rabbits, chondrocyte apoptosis occurred in the superficial and middle zones of cartilage and at the pannus-cartilage junction. The prevalence of apoptotic cells was significantly correlated with the levels of nitric oxide production and OA grade. Therefore, inhibitors of nitric oxide synthesis and of chrondrocyte apoptosis may be of therapeutic value in the management of cartilage injury or OA.

Jean-Pierre Pelletier, Dragan Jovanovic, Julio C. Fernandes, Pamela Manning, Jane R. Connor, Mark G. Currie, John A. Di Battista, and Johanne Martel-Pelletier 1275

An increased production of nitric oxide by OA tissues is believed to play an important role in the pathophysiology of this disease. This study demonstrates that, in the experimental OA dog model, the cartilage produces an increased amount of NO, which is related to an increased level of the inducible form of nitric oxide synthase, and that in vivo, a selective inhibitor of iNOS can reduce the progression of OA structural changes. These data support the implication of NO in the OA process.

Iiro Eerola, Heli Salminen, Pirkko Lammi, Mikko Lammi, Klaus von der Mark, Eero Vuorio, and Anna-Marja Saamanen 1287

Controversial views exist concerning whether the presence of type X collagen in articular cartilage is specific for OA. The present study demonstrates that type X collagen is a natural component of articular cartilage, both in normal mice and in a genetically engineered mouse model of OA.

Georg Kienzle and Johannes von Kempis 1296

Cartilage is the major target of destructive mechanisms in inflammatory joint diseases such as RA. Chondrocytes in damaged cartilage may interact with synovial fluid cells through mechanisms mediated by cell-cell contact. This study provides evidence that T cell attachment to chondrocytes via the adhesion molecules VCAM-1 and ICAM-1 is regulated by cytokines that are present at high levels in the synovial fluid of inflamed joints.

Karl-Heinz Frank, Monika Fussel, Karsten Conrad, Hans-Peter Rihs, Rainer Koch, Berno Gebhardt, and Jurgen Mehlhorn 1306

The results of this retrospective immunogenetic study of SSc patients exposed to quartz/metal dust (qSSc; mainly uranium miners) and patients with idiopathic SSc (iSSc) show that a neutral or protective haplotype in iSSc anti-topo I responders is a susceptibility haplotype in qSSc. From the data, it is assumed that the capacity of silica to induce the production of TNFα and reactive oxygen species by macrophages, the unique metal-catalyzed susceptibility of topo I to cleavage at specific regions by reactive oxygen species, as well as sex homone differences could favor the use of HLA/TNF haplotypes in qSSc patients with higher TNFα-producing capacities. This report adds to the knowledge of the interplay of genetic and environmental factors such as silica and/or metals in the development of SSc, and emphasizes the need for more attention to environmental factors in case history and epidemiologic studies.