Return to Arthritis & Rheumatism Table of Contents Page

Official Journal of the American College of Rheumatology

Special Articles

ACR Presidential Address: The American College of Rheumatology as a ``Professional'' Society: An Oxymoron?

• Shaun Ruddy 887

A Remembrance of Fred, The Lowland Gorilla

• John P. Atkinson 891

Review: Nephritogenic Autoantibodies in Lupus: Current Concepts and Continuing Controversies

• James B. Lefkowith and Gary S. Gilkeson 894

Basic Science

Oligoclonal T Cell Proliferation in Patients with Rheumatoid Arthritis and Their Unaffected Siblings

• Inge Waase, Corinna Kayser, Paula J. Carlson, Jorg J. Goronzy, and Cornelia M. Weyand 904
  
• This study reveals that patients with rheumatoid arthritis have a defect in maintaining T cell homeostasis, as demonstrated by oligoclonal expansions of CD4+ T cells in the peripheral blood compartment. Family studies have suggested that there may be a genetic basis for this abnormality.

Expression and Functional Expansion of Fibroblast Growth Factor Receptor T Cells in Rheumatoid Synovium and Peripheral Blood of Patients with Rheumatoid Arthritis

• Victor Byrd, Xiao-Ming Zhao, Wallace L. McKeehan, Geraldine G. Miller, and James W. Thomas 914
  
• Vascular (angiogenic) growth factors such as fibroblast growth factor-1 may be critical determinants of synovial inflammation in rheumatoid arthritis by enhancing mesenchymal proliferation and new blood vessel formation. This study identifies a connection between nonhematopoietic growth factors and T cell activation that suggests growth factor-immune networks may contribute to the pathogenic mechanisms of RA.

Inhibition of Synoviocyte Collagenase Gene Expression by Adenosine Receptor Stimulation

• David L. Boyle, Fereydoun G. Sajjadi, and Gary S. Firestein 923
  
• In this study, adenosine receptor stimulation significantly decreased collagenase gene expression by cultured synoviocytes, with little or no effect on stromelysin or on its natural inhibitor, TIMP-1. This raises the possibility that novel adenosine-based therapies have potential both as antiinflammatory and as chondroprotective agents.

Synergy Between T Cell Receptor β Gene Polymorphism and HLA-DR4 in Susceptibility to Rheumatoid Arthritis

• Hua Mu, Patrick Charmley, Mary-Claire King, and Lindsey A. Criswell 931
  
• Polymorphisms in T cell receptor β (TCRB) genes may play an important role in the formation of the TCR repertoire and in the development of autoimmune disease. Previous studies have shown that a nucleotide sequence shared by allelic variants of HLA-DR4 and DR1 is associated with RA. The findings of this study suggest that TCRB gene polymorphism may contribute to RA susceptibility through an interaction with HLA-DR4.

Clinical Correlations with HLA Type in Japanese Patients with Connective Tissue Disease and Anti-U1 Small Nuclear RNP Antibodies

• Masataka Kuwana, Yutaka Okano, Junichi Kaburaki, and Hidetoshi Inoko 938
  
• HLA-clinical associations were examined in Japanese patients with connective tissue disease and serum anti-U1 RNP antibody. Significant associations included DQB1*0303 with lupus-related symptoms, DR2 with pleuritis, DR4 with swollen hands, and DRB1*0405 with arthritis. These results suggest that HLA genes influence clinical expression in patients with anti-U1 RNP antibody.

A Comparative Study of HLA Genes in HLA-B27 Positive Ankylosing Spondylitis and HLA-B27 Positive Peripheral Reactive Arthritis

• Pia Westman, Marjatta Leirisalo-Repo, Jukka Partanen, and Saija Koskimies 943
  
• Ankylosing spondylitis and reactive arthritis are heterogeneous diseases that have a high association with the genetic marker HLA-B27. Because these diseases clearly differ in their clinical picture, and also in their long-term prognosis, a molecular study of other HLA markers in well-characterized groups of HLA-B27 positive patients was conducted, focusing on certain amino acid residues that are speculated to be functionally relevant and are shared by different HLA specificities. The differences observed support the idea of genetic heterogeneity between HLA-B27 positive patients with ankylosing spondylitis and reactive arthritis.

Molecular Detection of Bacterial DNA in Venereal-Associated Arthritis

• Feng Li, Rula Bulbul, H. Ralph Schumacher, Jr., Thomas Kieber-Emmons, Peter E. Callegari, Joan M. Von Feldt, Daniel Norden, Bruce Freundlich, Bin Wang, Victor Imonitie, Chen Pei Chang, Irving Nachamkin, David B. Weiner, and William V. Williams 950
  
• Venereal-associated arthritis comprises a group of common rheumatologic conditions, the diagnosis of which currently relies on clinical critieria because of a lack of reliable diagnostic tests. This study evaluates patients with venereal-associated arthritis (Neisseria, Chlamydia, and Ureaplasma infections) for evidence of bacterial DNA in their synovial fluid, which would suggest that an infectious process is responsible for the joint lesions. The study is relevant to the pathogenesis of the arthritis as well as to the techniques that may be useful in the diagnosis of venereal-associated arthritis (i.e., PCR or other methods of detecting bacterial DNA).

In Situ Hybridization Analysis of Synovial and Systemic Cytokine Messenger RNA Expression in Superantigen-Mediated Staphylococcus aureus Arthritis

• Yi-Xue Zhao, Ake Ljungdahl, Tomas Olsson, and Andrej Tarkowski 959
  
• The pathogenic mechanisms that operate in infectious arthritides, and which lead to rapid cartilage and subchondral bone destruction despite an adequate antibiotic treatment, are largely unknown. This experimental study reveals synovial cytokine responses as a consequence of joint infection with Staphylococcus aureus. The pattern of cytokine messenger RNA expression observed locally in the joint strongly suggests that not only antibacterial, but also immunomodulatory, treatment should be considered to diminish the risk of sequelae.

Normal Expression of Type 1 Insulin-Like Growth Factor Receptor by Human Osteoarthritic Chondrocytes with Increased Expression and Synthesis of Insulin-Like Growth Factor Binding Proteins

• Ginette Tardif, Pascal Reboul, Jean-Pierre Pelletier, Changshan Geng, Jean-Marie Cloutier, and Johanne Martel-Pelletier 968
  
• This study provides new and valuable information on the mechanism underlying human OA chondrocyte resistance to stimulation by insulin-like growth factor 1. The findings point to a normal expression of type 1 IGF receptor in OA chondrocytes, but an enhancement in the expression and synthesis of 3 of the known IGF binding proteins (IGFBPs 2, 3, and 4).

Clinical Science

Why Health Care Costs More in the US: Comparing Health Care Expenditures Between Systemic Lupus Erythematosus Patients in Stanford and Montreal

• Gail Gironimi, Ann E. Clarke, Vivian H. Hamilton, Deborah S. Danoff, Daniel A. Bloch, James F. Fries, and John M. Esdaile 979
• In this first study comparing health care costs incurred by patients with SLE in the US (Stanford) and Canada (Montreal), the annual direct costs (representing health services utilized) of the American SLE patients exceeded those of their Canadian counterparts by 2-fold ($10,530 versus $5,271). These higher costs are explained by the higher price of health services in the US and the greater disease severity in the patient mix. Canadian SLE patients utilize at least as many, and in some health resource categories, more, services than their American counterparts.

Risk of Osteoarthritis Associated with Long-Term Weight-Bearing Sports: A Radiologic Survey of the Hips and Knees in Female Ex-Athletes and Population Controls

• Tim D. Spector, Pat A. Harris, Deborah J. Hart, Flavia M. Cicuttini, Dalbir Nandra, John Etherington, Roger L. Wolman, and David V. Doyle 988
• In a retrospective cohort study from London, it was found that long-term weight-bearing sports activity in women is associated with a 2-3-fold increased risk of radiologic OA (particularly the presence of osteophytes) of the knees and hip. The risk was similar in ex-elite athletes and in a subgroup from the general population who reported long-term sports activity, suggesting that duration rather than frequency of training is important. Long-term participation in sports at any level increases the risk of OA.

Outcome in Patients with Early Rheumatoid Arthritis Treated According to the ``Sawtooth'' Strategy

• Timo Mottonen, Leena Paimela, Jari Ahonen, Tapani Helve, Pekka Hannonen, and Marjatta Leirisalo-Repo 996
• Since long-term outcome in RA is often poor, it is generally agreed that there is a need for a change in antirheumatic treatment strategy, and more aggressive use of antirheumatic drugs has been proposed. The present study showed that the "sawtooth" strategy approach to antirheumatic drug treatment improved the average 6.2-year outcome in 142 patients with early RA, compared with that in historical controls. This strategy, which entails early, aggressive treatment with antirheumatic drugs, is thus recommended.

Slow Progression of Joint Damage in Early Rheumatoid Arthritis Treated with Cyclosporin A

• Giampiero Pasero, Francesco Priolo, Ettore Marubini, Flavio Fantini, Gianfranco Ferraccioli, Mario Magaro, Roberto Marcolongo, Pasquale Oriente, Vincenzo Pipitone, Italo Portioli, Giuseppe Tirri, Francesco Trotta, and Ornella Della Casa-Alberighi 1006
• Despite numerous trials, there are no definitive data regarding how disease-modifying antirheumatic drugs work in rheumatoid inflammation or whether they are effective in terms of controlling disease progression. This study investigated the impact that low-dose cyclosporin A may have on both the treatment and course of RA, by randomly allocating homogeneous patients with early active RA to CsA or traditional DMARD treatment groups. The 12-month results show that CsA delays and even prevents RA progression, and efficaciously controls symptoms with an acceptable tolerability profile.

Acute Febrile Toxic Reaction in Patients with Refractory Rheumatoid Arthritis Who Are Receiving Combined Therapy with Methotrexate and Azathioprine

• Ricardo Blanco, Victor M. Martinez-Taboada, Miguel A. Gonzalez-Gay, Jose Armona, Jose L. Fernandez-Sueiro, M. Carmen Gonzalez-Vela, and Vicente Rodriguez-Valverde 1016
• This report describes 4 RA patients who developed acute febrile toxic reaction while undergoing treatment with MTX and AZA. The knowledge of this side effect is particularly important since it mimics severe infectious complication related to immunosuppressive therapy. It is suggested that, when AZA is prescribed simultaneously with MTX, the patient should be closely monitored during the first few months.

N-[4-Hydroxyphenyl] Retinamide in Rheumatoid Arthritis: A Pilot Study

• Ellen M. Gravallese, Malcolm L. Handel, Jonathan Coblyn, Ronald J. Anderson, Richard I. Sperling, Elizabeth W. Karlson, Agnes Maier, Eric M. Ruderman, Franca Formelli, and Michael E. Weinblatt 1021
• An uncontrolled, open study was undertaken to determine the efficacy and tolerability of N-[4 hydroxyphenyl] retinamide (4-HPR), a synthetic retinoid, in the treatment of RA. No clinical improvement was observed, and there was no beneficial effect on the laboratory parameters studied, except for a modest decrease in C-reactive protein. Other retinoids may be more efficacious in the treatment of RA.

Failure of Low-Dose Intravenous Immunoglobulin Therapy to Suppress Disease Activity in Patients with Treatment-Refractory Rheumatoid Arthritis

• Keith S. Kanik, Cheryl H. Yarboro, Yaakov Naparstek, Paul H. Plotz, and Ronald L. Wilder 1027
• High doses of intravenous immunoglobulins have shown some efficacy in the treatment of RA, but are very expensive. Low doses of intravenous immunoglobulins are less expensive, but have shown efficacy only in the rat model. The results of this trial suggest that low-dose immunoglobulins do not have benefit in the treatment of RA that has been refractory to standard medications.

Renal Vascular Damage in Systemic Sclerosis Patients Without Clinical Evidence of Nephropathy

• Roberto Rivolta, Barbara Mascagni, Vittorio Berruti, Filippo Quarto Di Palo, Attilio Elli, Raffaella Scorza, and Daniela Castagnone 1030
• In this study, color-flow-Doppler ultrasonography was found to be a very sensitive technique for studying renal vascular damage in patients with SSc. Abnormalities of blood flow were detected even in the presence of normal renal clearance. The use of this technique in the evaluation of SSc patients may allow earlier diagnosis and better monitoring of the renal vascular impairment associated with the disease.

Depressive Symptoms Associated with Scleroderma

• Robert P. Roca, Fredrick M. Wigley, and Barbara White 1035
• The present study was undertaken to assess the prevalence and correlates of comorbid depression in scleroderma. Depressive symptoms among the study cohort were more strongly related to personality, self-rated disability, and adequacy of emotional support than to objective medical indices of illness severity. These findings have important implications for prognosis, management, and future research in scleroderma.

Childhood-Onset Scleroderma: Is it Different from Adult-Onset Disease?

• Rama Vancheeswaran, Carol M. Black, Joel David, Nathan Hasson, John Harper, David Atherton, Premila Trivedi, and Patricia Woo 1041
• This study demonstrates that in childhood-onset scleroderma, the antibody profile, as well as the endothelial activation markers, are different from what one sees in adult-onset scleroderma. The suppression of collagen synthesis is novel and highly relevant in growing children with this disease, and therefore early intervention of the inflammatory phase or progression of fibrosis is imperative to prevent gross deformity.

Malignancy in Systemic Lupus Erythematosus

• Mahmoud Abu-Shakra, Dafna D. Gladman, and Murray B. Urowitz 1050
• The risk of cancer was estimated in a group of 724 patients with SLE and compared with that of the general population of Ontario, as well as with patients with RA and SSc. The overall standardized risk of cancer in the SLE population was not increased compared with the Ontario population. However, the risk for hematologic malignancies was increased 4-fold, mainly due to an increased risk for non-Hodgkin's lymphoma. Risk for cancer was significantly lower in SLE than in RA and SSc.

Utility of Anti-Sm, Anti-RNP, Anti-Ro/SS-A, and Anti-La/SS-B (Extractable Nuclear Antigens) Detected by Enzyme-Linked Immunosorbent Assay for the Diagnosis of Systemic Lupus Erythematosus

• Jorge Sanchez-Guerrero, Robert A. Lew, Anne H. Fossel, and Peter H. Schur 1055
• This study utilized an enzyme-linked immunosorbent assay to test for anti-ENA antibodies among patients with positive antinuclear antibody results. The findings suggest that the presence of anti-ENA antibodies, especially anti-Ro, helps to confirm the diagnosis of SLE among ANA+ patients who lack anti-dsDNA antibodies.

Case Reports

Pyoderma Gangrenosum in Association with Undifferentiated Seronegative Spondylarthropathy

• Ignazio Olivieri, Angela Maria Costa, Fabrizio Cantini, Laura Niccoli, Raffaela Marini, and Silvio Ferri 1062

Monoclonal Cryo-Antifibrinogenemia

• Hans H. Euler, Rainald A. Zeuner, Rosemarie Beress, Hans J. Gutschmidt, Enno Christophers, and Johann O. Schroeder 1066

Clinical Images

Influence of Ballet Season on Radiology Reports

• Peter H. Schur 1069

Concise Communication

Treatment of Systemic Sclerosis with Topical Tretinoin: Report of Two Cases

• Joel M. Kremer 1070

Letters

More on Vasodilatation, Joint Swelling, and Nitric Oxide

• Johan Ahlqvist 1071

Fibroblast Adhesion to Articular Cartilage

• Hugo E. Jasin 1072

Reply

• Warren D. Blackburn, Jr., and W. Winn Chatham 1072

Giant Cell Arteritis and Amyloidosis: Comment on the Article by Salvarani et al

• Miguel A. Gonzalez-Gay, Carmen Gonzalez-Vela, Ricardo Blanco, Maria J. Cereijo, and Fernando Bal 1073

Reply

• Carlo Salvarani, Sherine Gabriel, and Gene G. Hunder 1073

Polymyositis, Lung Fibrosis, and Cranial Neuropathy in a Patient with Hepatitis C Virus Infection

• Clodoveo Ferri, Luca La Civita, Piera Fazzi, Giampiero Pasero, and Anna Linda Zignego 1074

Reply

• Robert W. McMurray 1075

Lack of Radiographic Evidence of Tracheostenosis: Comment on the Clinical Image from Kraus and Valencia

• E.A. McFadden 1075

Erratum 1076

ACR Announcements 15A