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Volume 41, No. 11, November 1998

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Official Journal of the American College of Rheumatology

Special Articles

Current Comment: A New Hypothesis of Modular Glucocorticoid Actions: Steroid Treatment of Rheumatic Diseases Revisited

Frank Buttgereit, Martin Wehling, and Gerd-Rudiger Burmester 761

Review: Mixed Connective Tissue Disease: To Be Or Not To Be?

Josef S. Smolen and Gunter Steiner 768

Clinical Science

Estimates of the Prevalence of Arthritis and Selected Musculoskeletal Disorders in the United States

Reva C. Lawrence, Charles G. Helmick, Frank C. Arnett, Richard A. Deyo, David T. Felson, Edward H. Giannini, Stephen P. Heyse, Rosemarie Hirsch, Marc C. Hochberg, Gene G. Hunder, Matthew H. Liang, Stanley R. Pillemer, Virginia D. Steen, and Frederick Wolfe 778

This report provides prevalence estimates for arthritis overall as well as for selected musculoskeletal disorders in the US population, and gives caveats for the interpretation of these estimates. The estimates were ascertained by the National Arthritis Data Workgroup based on a review of data from various surveys. When necessary, estimates from the surveys were linked to 1990 US Bureau of the Census population data to determine figures for the entire country.

Arterial Disease and Thrombosis in the Antiphospholipid Syndrome: A Pathogenic Role for Endothelin 1

Tatsuya Atsumi, Munther A. Khamashta, Robert S. Haworth, Gavin Brooks, Olga Amengual, Kenji Ichikawa, Takao Koike, and Graham R. V. Hughes 800

The pathogenesis of arterial involvement, which differentiates APS from the majority of the other prothrombotic disorders, remains unknown. This study demonstrated increased plasma ET-1 levels in APS patients who had arterial disease, but not in APS patients who had venous thrombosis. This is the first demonstration of a specific risk factor for arterial thrombosis in patients with APS.

Sulfasalazine in the Treatment of Juvenile Chronic Arthritis: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

Marion A. J. van Rossum, Theo J. W. Fiselier, Marcel J. A. M. Franssen, Aeilko H. Zwinderman, Rebecca ten Cate, Lisette W. A. van Suijlekom-Smit, Wilma H. J. van Luijk, Renee M. van Soesbergen, Nico M. Wulffraat, Johanna C. M. Oostveen, Wietse Kuis, Piet F. Dijkstra, Clemens F. P. van Ede, and Ben A. C. Dijkmans, on behalf of the Dutch Juvenile Chronic Arthritis Study Group 808

This study is the first placebo-controlled study of sulfasalazine in the treatment of juvenile chronic arthritis. The results indicate significant efficacy of this treatment among patients with oligoarticular- and polyarticular-onset disease using, as outcome variables, joint scores for pain and tenderness, physician's, parents', and patient's overall assessments, and laboratory measures of inflammation.

The Influence of Sex on the Phenotype of Rheumatoid Arthritis

Cornelia M. Weyand, Dorle Schmidt, Ulf Wagner, and Jorg J. Goronzy 817

RA is a heterogeneous disease with variability in its clinical manifestations and course. It is believed that this heterogeneity is induced by multiple factors, including environmental and genetic elements. The current case-control study demonstrates an influence of sex on the disease phenotype.

Apoptosis of Lymphocytes Induced by Glucocorticoids and Relationship to Therapeutic Efficacy in Patients with Systemic Lupus Erythematosus

Manami Seki, Chifuyu Ushiyama, Noriyuki Seta, Kaori Abe, Toru Fukazawa, Junichi Asakawa, Yoshinari Takasaki, and Hiroshi Hashimoto 823

Findings of this study indicate that determination of the concentration of glucocorticoids that is lethal to 50% of the cells (the LC50) in patients with SLE seems to be a helpful predictor of the efficacy of glucocorticoid treatment in these patients. CD8 and Bcl-2 double-positive lymphocytes, which are insensitive to the apoptotic effect of glucocorticoids, may play a critical role in glucocorticoid resistancy in the clinical course of patients with SLE.

Risk Factors for Ovarian Failure in Patients with Systemic Lupus Erythematosus Receiving Cyclophosphamide Therapy

Chi Chiu Mok, Chak Sing Lau, and Raymond Woon Sing Wong 831

CYC is a common cytotoxic agent used in the treatment of serious manifestations of SLE. Ovarian toxicity is a major concern because premature ovarian failure induced by CYC predisposes SLE patients to accelerated osteoporosis and cardiovascular disease. This study analyzed the scope of this complication of CYC treatment and identified the risk factors for it in a local SLE population. The high incidence of CYC-induced ovarian failure among patients over the age of 40 should alert clinicians to prescribe a lower dosage and shorter course of CYC for the treatment of SLE, as far as possible.

Decreased Production of Interleukin-12 and Other Th1-Type Cytokines in Patients with Recent-Onset Systemic Lupus Erythematosus

David A. Horwitz, J. Dixon Gray, Steven C. Behrendsen, Marek Kubin, Manthrasalam Rengaraju, Kazuo Ohtsuka, and Giorgio Trinchieri 838

Cytokine networks play a critical role in the development of lymphocyte regulatory and effector functions. This study provides new information concerning the cytokine profile in patients with early SLE, a disease involving disordered immune regulation.

Lack of Correlation Between the Detection of Chlamydia trachomatis DNA in Synovial Fluid from Patients with a Range of Rheumatic Diseases and the Presence of an Antichlamydial Immune Response

Nicola Z. Wilkinson, Gabrielle H. Kingsley, Joachim Sieper, Jurgen Braun, and Michael E. Ward 845

Both Chlamydia trachomatis and Chlamydia pneumoniae have been proposed to play a triggering role in reactive arthritis (ReA) and undifferentiated oligoarthritis. This study presents further evidence that C trachomatis DNA can be detected in the synovial fluid of a substantial number of patients with ReA and undifferentiated oligoarthritis, supporting a role for this organism in their pathogenesis. Interestingly, there was little correlation between the presence of this microbe and an antibacterial immune response to it, which casts doubt on the use of serology and T cell responses to establish the diagnosis of ReA and undifferentiated oligoarthritis. Despite the previous case reports implicating C pneumoniae in ReA, this study revealed no evidence of DNA from the organism in the synovial fluid, which suggests that it is not an important cause of ReA or undifferentiated oligoarthritis.

Persistence of Yersinia Antigens in Peripheral Blood Cells from Patients With Yersinia enterocolitica O:3 Infection With or Without Reactive Arthritis

Kaisa Granfors, Riitta Merilahti-Palo, Reijo Luukkainen, Timo Mottonen, Riitta Lahesmaa, Peter Probst, Elisabeth Marker-Hermann, and Paavo Toivanen 855

This report addresses the important issue of persistence of bacteria and/or bacterial antigens in patients with reactive arthritis. It shows directly and for the first time that bacterial antigens are still present in the peripheral blood cells of most patients with reactive arthritis at 4 years after the onset of infection. These findings also suggest that live bacteria probably persist somewhere in these patients, and that the bacteria and their antigens contribute to the disease pathogenesis.

Prevalence of the Diffuse Infiltrative Lymphocytosis Syndrome Among Human Immunodeficiency Virus Type 1-Positive Outpatients

Francis M. Williams, Philip R. Cohen, Junaid Jumshyd, and John D. Reveille 863

The diffuse infiltrative lymphocytosis syndrome (DILS) is a disorder clinically resembling Sjogren's syndrome that occurs in HIV-infected individuals. It is characterized by sicca symptoms, often massive parotid gland enlargement, and a circulating CD8 lymphocytosis. In the present study, the prevalence of DILS was ascertained to be 3-4% in a large, ethnically mixed HIV-positive outpatient population. Patients with DILS were found to be more likely to have dryness of the eyes, facial swelling, and elevated CD8 lymphocyte counts. These data suggest that DILS occurs not infrequently in the outpatients with HIV, and that rheumatologists evaluating patients for parotid gland enlargement accompanied by sicca symptoms should consider HIV testing.

Clinical Image

Cutaneous Ulceration in Type II Cryoglobulinemia

Jeffrey J. Wisnieski and Barbara S. Breen 868

Basic Science

Inhibition of Activator Protein 1 Activity by Paclitaxel Suppresses Interleukin-1-Induced Collagenase and Stromelysin Expression by Bovine Chondrocytes

A. Hui, W. X. Min, J. Tang, and T. F. Cruz 869

It is thought that increased levels of matrix metalloproteinases, such as collagenase 1 (MMP-1) and stromelysin 1 (MMP-3), are the major cause of irreparable cartilage degradation in osteoarthritis and rheumatoid arthritis. The expression of these enzymes is dependent on AP-1 activation by cytokines such as IL-1. This study demonstrates that paclitaxel inhibition of AP-1 activity results in the suppression of IL-1-induced MMP-1 and MMP-3 expression by chondrocytes. At similar concentrations, paclitaxel did not alter proteoglycan and collagen expression or induce chondrocyte toxicity. These results provide evidence that inhibitors of AP-1 activity may have therapeutic potential for the treatment of arthritis.

Collagenase 1 and Collagenase 3 Expression in a Guinea Pig Model of Osteoarthritis

Janet L. Huebner, Ivan G. Otterness, Edward M. Freund, Bruce Caterson, and Virginia B. Kraus 877

Collagenase 1 (MMP-1) and collagenase 3 (MMP-13) cleave collagen and have been implicated in the pathogenesis of OA. Spontaneously occurring OA of the knees in the Hartley strain guinea pig makes it a useful animal model for understanding the pathogenesis of OA in humans. This study characterized the regulation of these collagenases using the guinea pig model of naturally occurring OA.

Osteoblast-Like Cells from Human Subchondral Osteoarthritic Bone Demonstrate an Altered Phenotype In Vitro: Possible Role in Subchondral Bone Sclerosis

George Hilal, Johanne Martel-Pelletier, Jean-Pierre Pelletier, Pierre Ranger, and Daniel Lajeunesse 891

Findings in the present study indicate that subchondral osteoblasts from patients with osteoarthritis have an abnormal phenotype. This suggests that osteoblasts may play an important role in the etiopathogenesis of osteoarthritis.

The Murine Homolog of the Interleukin-8 Receptor CXCR-2 is Essential for the Occurrence of Neutrophilic Inflammation in the Air Pouch Model of Acute Urate Crystal-Induced Gouty Synovitis

Robert Terkeltaub, Stephen Baird, Peter Sears, Robert Santiago, and William Boisvert 900

The migration of neutrophils into the joint is essential for both initiation and perpetuation of acute crystal-induced arthritis. Prevention and rapid control rely on the use of a variety of nonselective antiinflammatory agents that are frequently, but not uniformly, effective. This study demonstrates that IL-8 receptor-binding chemokines are critical for the occurrence of acute neutrophilic inflammation in response to free urate crystals, suggesting the means for more selective approaches to prophylaxis and therapy of refractory crystal-induced articular inflammation.

Involvement of Macrophage Migration Inhibitory Factor in the Evolution of Rat Adjuvant Arthritis

Michelle Leech, Christine Metz, Leilani Santos, Tina Peng, Stephen R. Holdsworth, Richard Bucala, and Eric F. Morand 910

Macrophage migration inhibitory factor (MIF) is a recently cloned cytokine whose profile of proinflammatory activity suggests its likely involvement in human rheumatoid arthritis and experimental arthritis in animals. In this study of MIF in rat adjuvant arthritis, the presence of MIF was demonstrated in synovial macrophages from diseased joints. Moreover, antagonism of MIF by monoclonal antibody treatment led to profound inhibition of disease. These results suggest an important role for MIF in adjuvant arthritis, and therefore investigation of its role in human disease is warranted.

Zinc is an Essential Cofactor for Recognition of the DNA Binding Domain of Poly(ADP-Ribose) Polymerase by Antibodies in Autoimmune Rheumatic and Bowel Diseases

Patrice Decker, Jean-Paul Briand, Gilbert de Murcia, Ron W. Pero, David A. Isenberg, and Sylviane Muller 918

An autoimmune response to poly(ADP-ribose) polymerase is potentially important because this enzyme is involved in DNA repair and is rapidly cleaved during the ``execution phase'' of apoptosis. The high prevalence in certain autoimmune rheumatic and bowel diseases of antibodies to the two fingers F1 and F2 of this enzyme, which are directly involved in the repair process, is further evidence implicating the DNA repair system in chronic inflammatory diseases.

Polymorphisms of HLA Class II Genes and Autoimmune Responses to Ro/SS-A-La/SS-B Among Japanese Subjects

Sachiko Miyagawa, Koji Shinohara, Mitsuru Nakajima, Kin-Ichi Kidoguchi, Tomio Fujita, Takaya Fukumoto, Akira Yoshioka, Kazuhiro Dohi, and Toshihiko Shirai 927

Based on the PCR-RFLP results in 41 anti-Ro/SS-A positive Japanese women, it was found that HLA class II allele distributions differed among anti-Ro/SS-A positive subjects according to the presence or absence of coexisting anti-La/SS-B antibodies, but not according to disease expression. There were significant associations between autoimmune response to Ro/SS-A and La/SS-B, but not to anti-Ro/SS-A alone, and the HLA class II haplotype DRB1*08032/DQA1*0103/DQB1*0601 and DRB1*08032 allele. These data differ from the accepted association of the same autoantibody responses with HLA-DR3 (DRB1*0301/DQA1*0501/DQB1*0201) in other ethnic groups.

Case Report

Segmental Mediolytic Arteriopathy of the Splenic and Hepatic Arteries Mimicking Systemic Necrotizing Vasculitis

Roland J. Chan, Thomas A. Goodman, Thomas H. Aretz, and J. T. Lie 935

Erratum 938

Concise Communications

Pseudogout Following Intraarticular Injection of Sodium Hyaluronate

Michael J. Luzar and Badi Altawil 939

The Polymorphic CYP17 Allele is Not Found with Increased Frequency in Systemic Lupus Erythematosus

Kathleen E. Sullivan, Tarah Mannery, and Michelle A. Petri 940


The Original ``DAS'' and the ``DAS28'' are Not Interchangeable: Comment on the Articles by Prevoo et al

Desiree M. F. M. van der Heijde and Johannes W. G. Jacobs 942


Piet L. C. M. van Riel and Anke M. van Gestel 943

Long-Term Outcome of Total Lymphoid Irradiation in Rheumatoid Arthritis: Comment on the Article by Westhovens et al

R. Blanco, S. Sanchez-Andrada, V. Mart|finez-Taboada, J. L. Pena Sagredo, and V. Rodr|figuez-Valverde 945


R. Westhovens, J. Verwilghen, and J. Dequeker 946

HLA-DMA and DMB Genes in Rheumatoid Arthritis: Comment on the Article by Pinet et al

Dharam P. Singal and Ming Ye 946


Valerie Pinet and Jean-Francois Eliaou 947/p>

Collagen Crosslinks in Fibromyalgia: Comment on the Article by Sprott et al

Pete Malleson 948


Haiko Sprott, Andreas Muller, and Hartmut Heine 948

HLA-B27 and the Spondylarthropathies in Lebanon: Comment on the Article by Awada et al

Alexander Abdelnoor 949


H. Awada and R. Tamouza 949

Does Knuckle Cracking Lead to Arthritis of the Fingers?

Donald L. Unger 949


Robert L. Swezey 950

ACR Announcements 18A