The Journal of Rheumatology (J RHEUMATOL)

Publications in this journal

• Article: C'mon, CAM.

  Richard S Panush
  The Journal of Rheumatology 05/2013; 40(5):544-6.
• Article: Can large simple trials help us understand when and how to use generic drugs for uncommon diseases?

  Jerry A Molitor, David L Demets
  The Journal of Rheumatology 05/2013; 40(5):539-41.
• Article: Decreased Pain Threshold in Juvenile Idiopathic Arthritis: A Cross-sectional Study.

  Anne Leegaard, Johanne Jeppesen Lomholt, Mikael Thastum, Troels Herlin
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  ABSTRACT: OBJECTIVE: To examine the pain threshold in children with juvenile idiopathic arthritis (JIA) compared with healthy children by using a digital pressure algometer. METHODS: Fifty-eight children with JIA born between 1995 and 2000 and 91 age-related healthy children participated in the study. We used a digital pressure algometer to measure the pain threshold on 17 symmetric, anatomically predefined joint-related or bone-related areas. All children were asked to rate their current pain on a Faces Pain Scale, and parents of children with JIA were asked to complete a parental revised version of the Child Health Assessment Questionnaire (CHAQ-R). Clinical data were registered on children with JIA. RESULTS: The pain threshold was significantly lower among children with JIA (total mean PT = 1.33 ± 0.69 kg/cm(2)) when compared with the healthy control group (total mean PT = 1.77 ± 0.67 kg/cm(2)). The same pattern was found in all areas measured, including negative control areas that are normally unaffected in JIA (p = 0.0001 to 0.005). Overall, the pain threshold was 34% lower in females than in males in both groups (p < 0.0001). We found no correlation between pain threshold and age, current pain experience, disease duration, or disease activity. CONCLUSION: Children with JIA had a substantially lower pain threshold even in areas usually unaffected by arthritis. Our findings suggest that JIA alters the pain perception and causes decreased pain threshold.
  The Journal of Rheumatology 05/2013;
• Article: Rapid Interaction Between CTLA4-Ig (Abatacept) and Synovial Macrophages from Patients with Rheumatoid Arthritis.

  Renata Brizzolara, Paola Montagna, Stefano Soldano, Maurizio Cutolo
  The Journal of Rheumatology 05/2013; 40(5):738-40.
• Article: Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry.

  Paula S Ramos, James C Oates, Diane L Kamen, Adrienne H Williams, Patrick M Gaffney, Jennifer A Kelly, Kenneth M Kaufman, Robert P Kimberly, Timothy B Niewold, Chaim O Jacob, [......], Barry I Freedman, R Hal Scofield, Anne M Stevens, Timothy J Vyse, Lindsey A Criswell, Kathy L Moser, Marta E Alarcón-Riquelme, Carl D Langefeld, John B Harley, Gary S Gilkeson
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  ABSTRACT: OBJECTIVE: Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate-related genes biological candidates for disease susceptibility. We analyzed variation in reactive intermediate genes for association with SLE in 2 populations with African ancestry. METHODS: A total of 244 single-nucleotide polymorphisms (SNP) from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls). Single-marker, haplotype, and 2-locus interaction tests were computed for these populations. RESULTS: The glutathione reductase gene GSR (rs2253409; p = 0.0014, OR 1.26, 95% CI 1.09-1.44) was the most significant single SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575; p = 0.0065, OR 2.10, 95% CI 1.23-3.59) and NO synthase gene NOS1 (rs561712; p = 0.0072, OR 0.62, 95% CI 0.44-0.88) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409; p = 0.00072, OR 1.26, 95% CI 1.10-1.44). Haplotype and 2-locus interaction analyses also uncovered different loci in each population. CONCLUSION: These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.
  The Journal of Rheumatology 05/2013;
• Article: Identifying Phenotypes of Knee Osteoarthritis by Separate Quantitative Radiographic Features May Improve Patient Selection for More Targeted Treatment.

  Margot B Kinds, Anne C A Marijnissen, Max A Viergever, Pieter J Emans, Floris P J G Lafeber, Paco M J Welsing
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  ABSTRACT: OBJECTIVE: Expression of osteoarthritis (OA) varies significantly between individuals, and over time, suggesting the existence of different phenotypes, possibly with specific etiology and targets for treatment. Our objective was to identify phenotypes of progression of radiographic knee OA using separate quantitative features. METHODS: Separate radiographic features of OA were measured by Knee Images Digital Analysis (KIDA) in individuals with early knee OA (the CHECK cohort: Cohort Hip & Cohort Knee), at baseline and at 2-year and 5-year followup. Hierarchical clustering was performed to identify phenotypes of radiographic knee OA progression. The phenotypes identified were compared for changes in joint space width (JSW), varus angle, osteophyte area, eminence height, bone density, for Kellgren-Lawrence (K-L) grade, and for clinical characteristics. Logistic regression analysis evaluated whether baseline radiographic features and demographic/clinical characteristics were associated with each of the specific phenotypes. RESULTS: The 5 clusters identified were interpreted as "Severe" or "No," "Early" or "Late" progression of the radiographic features, or specific involvement of "Bone density." Medial JSW, varus angle, osteophyte area, eminence height, and bone density at baseline were associated with the Severe and Bone density phenotypes. Lesser eminence height and bone density were associated with Early and Late progression. Larger varus angle and smaller osteophyte area were associated with No progression. CONCLUSION: Five phenotypes of radiographic progression of early knee OA were identified using separate quantitative features, which were associated with baseline radiographic features. Such phenotypes might require specific treatment and represent relevant subgroups for clinical trials.
  The Journal of Rheumatology 05/2013;
• Article: Microvascular Angina: An Underappreciated Cause of SLE Chest Pain.

  Mariko L Ishimori, Lorraine Anderson, Michael H Weisman, Puja K Mehta, C Noel Bairey Merz, Daniel J Wallace
  The Journal of Rheumatology 05/2013; 40(5):746-7.
• Article: Serum Interleukin 6 Before and After Therapy with Tocilizumab Is a Principal Biomarker in Patients with Rheumatoid Arthritis.

  Keiko Shimamoto, Tomoki Ito, Yoshio Ozaki, Hideki Amuro, Akihiro Tanaka, Tohru Nishizawa, Yonsu Son, Muneo Inaba, Shosaku Nomura
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  ABSTRACT: OBJECTIVE: Biologic treatments including the humanized anti-interleukin 6 (anti-IL-6) receptor antibody tocilizumab (TCZ) provide therapeutic options for patients with rheumatoid arthritis (RA). We investigated useful biomarkers to predict the responsiveness to TCZ by measurement of serum proinflammatory cytokine concentrations. METHODS: Serum samples were collected from 61 patients with RA before biologic treatment and at 4 weeks after initial administration of either TCZ (n = 32) or infliximab (IFX; n = 29) and from 13 healthy serum donor controls. Disease Activity Score of 28 joints (DAS28) was determined at baseline and after treatment. RESULTS: Although IL-1β, IL-2, IL-6, IL-17A, IL-17F, interferon-α, and tumor necrosis factor-α (TNF-α) were all increased in sera from patients with RA compared with controls, only the IL-6 level was significantly correlated with DAS28 before treatment. The IL-6 level before treatment was positively correlated with DAS28 after TCZ treatment, and was significantly lower in TCZ-responsive patients (as judged by a post-treatment DAS28 < 3.2) than in TCZ-resistant patients (post-treatment DAS28 ≥ 3.2). DAS28 after TCZ was significantly lower than after administration of IFX in patients with low pretreatment IL-6 (< 51.5 pg/ml, the mean baseline value of IL-6 in all RA patients), but not in those with high pretreatment IL-6. These results indicate that low serum IL-6 is associated with a favorable response to TCZ. CONCLUSION: Although both TNF-α and IL-6 are major targets of therapeutic intervention in RA, baseline serum IL-6 but not baseline TNF-α level is a potential biomarker reflecting disease activity. Measurement of serum IL-6 in RA before treatment may be useful to estimate residual disease activity after TCZ treatment and to predict responsiveness to TCZ treatment.
  The Journal of Rheumatology 05/2013;
• Article: Higher-dose Anakinra Is Effective in a Case of Medically Refractory Macrophage Activation Syndrome.

  Philip J Kahn, Randy Q Cron
  The Journal of Rheumatology 05/2013; 40(5):743-4.
• Article: High-density Lipoprotein Profiling Changes in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitors: A Cohort Study.

  Anna Jamnitski, Johannes H Levels, Inge A van den Oever, Michael T Nurmohamed
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  ABSTRACT: OBJECTIVE: We investigated changes in high-density lipoprotein (HDL) profiling in patients with rheumatoid arthritis who started treatment by taking tumor necrosis factor (TNF) inhibitors. The patients were stratified for European League Against Rheumatism (EULAR) response. METHODS: A group of 100 patients naive for TNF inhibitors at baseline were randomly selected from 204 adalimumab-treated and 203 etanercept-treated patients on the basis of their EULAR response. HDL profiling was measured using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. RESULTS: In EULAR good responders, mass charged markers representing serum amyloid A (SAA-1 and -2) decreased significantly after 4 months' therapy. There were no significant differences in HDL profiling in EULAR nonresponders. CONCLUSION: Effective suppression of inflammation with TNF inhibitors results in favorable changes in HDL composition.
  The Journal of Rheumatology 05/2013;
• Article: Severe vocal cord dysfunction: an unusual complication of juvenile dermatomyositis.

  Hosam O Althagafi, Kimberly Morishita, Ross E Petty
  The Journal of Rheumatology 05/2013; 40(5):744-5.
• Article: Quality guidelines for systemic lupus erythematosus: slow but steady progress.

  Daniel J Wallace
  The Journal of Rheumatology 05/2013; 40(5):542-3.
• Article: The Role of Complementary and Alternative Medicine (CAM) in Rheumatology -- It's Time for Integrative Medicine.

  Andreas Michalsen
  The Journal of Rheumatology 05/2013; 40(5):547-9.
• Article: Interaction of HLA-DRB1*09:01 and *04:05 with Smoking Suggests Distinctive Mechanisms of Rheumatoid Arthritis Susceptibility Beyond the Shared Epitope.

  So-Young Bang, Hye-Soon Lee, Kyung Wha Lee, Sang-Cheol Bae
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  ABSTRACT: OBJECTIVE: Although HLA-DRB1 shared epitope (SE) alleles and HLA-DRB1*09:01 have repeatedly been shown to be associated with susceptibility to rheumatoid arthritis (RA), the effect of each allele on levels of anticyclic citrullinated peptide autoantibodies (anti-CCP) and interaction with cigarette smoking in RA remains to be fully defined. We investigated whether HLA-DRB1 risk alleles influence anti-CCP levels and whether each allele interacts with smoking in anti-CCP-positive or-negative RA. METHODS: All patients with RA (n = 1924) and controls (n = 1119) were Korean. The HLA-DRB1 4-digit genotyping was performed by standard PCR-sequencing based typing method. OR and biologic interactions as departures from additivity or multiplicity were analyzed by logistic regression. RESULTS: SE alleles were significantly associated with increased anti-CCP levels. Conversely, HLA-DRB1*09:01 was associated with reduced levels, in both SE-positive and SE-negative patients. Each of SE alleles interacted significantly with smoking, whereas HLA-DRB1*09:01 did not. Interactions between the 2 most significant risk alleles, HLA-DRB1*04:05 and HLA-DRB1*09:01, (attributable proportion = 0.68, 95% CI 0.46-0.89, multiplicity p = 0.012) significantly increased RA susceptibility regardless of anti-CCP and smoking status. Smoking increased the risk for RA by significant interaction with the heterozygote HLA-DRB1*04:05/*09:01. CONCLUSION: HLA-DRB1*09:01 differs from SE alleles with regard to anti-CCP levels and interaction with smoking, suggesting a distinct mechanism of HLA-DRB1*09:01 in the pathogenesis of RA that may bypass anti-CCP formation. Also, a significant increase of the HLA-DRB1*04:05/*09:01 heterozygote in RA susceptibility may be attributable to the synergistic contribution of 2 different pathways in which 2 alleles participate independently.
  The Journal of Rheumatology 05/2013;
• Article: Soluble Biomarkers Associated with Response to Treatment with Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis.

  Vinod Chandran, Hua Shen, Remy A Pollock, Fawnda J Pellett, Adele Carty, Richard J Cook, Dafna D Gladman
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  ABSTRACT: OBJECTIVE: To identify soluble biomarkers associated with response to therapy with tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA). METHODS: The study was conducted at a PsA clinic where patients are assessed every 6 months, and serum samples are collected and stored once a year at the time of clinical assessment. Forty patients with active PsA who gave serum samples prior to treatment with TNFi and after at least 3 months of therapy were identified. Patients were classified as TNFi responders if tender joint count was < 3, swollen joint count was 0, and Psoriasis Area and Severity Index score was < 4 at the time the second sample was collected. The following biomarkers were tested by ELISA: TNF superfamily 14, matrix metalloprotease-3 (MMP-3), receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, cartilage oligomeric matrix protein (COMP), CPII, C2C and C1-2C, CS-846, and highly sensitive C-reactive protein. Paired t tests and logistic regression was used for statistical analyses. RESULTS: After a mean treatment duration of 11 months with TNFi (etanercept 28 patients, adalimumab 6, golimumab 4, infliximab 2), 29 patients were classified as TNFi responders. Baseline level of MMP-3 was independently associated with responder status (OR 1.067 for each 1-unit increase, p = 0.045). A reduction in MMP-3 levels with therapy increased the odds of achieving response (OR 1.213 for each 1-unit change, p = 0.030), whereas a reduction in COMP decreased the odds (OR 0.587, for each 100-unit increase, p = 0.039). None of the other biomarkers was associated with response. CONCLUSION: Baseline as well as reduction in serum MMP-3 and increase in serum COMP are independently associated with response to TNFi therapy in patients with PsA.
  The Journal of Rheumatology 05/2013;
• Article: Use of Lipid-lowering Agents in Rheumatoid Arthritis: A Population-based Cohort Study.

  Bharath Manu Akkara Veetil, Elena Myasoedova, Eric L Matteson, Sherine E Gabriel, Cynthia S Crowson
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  ABSTRACT: OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality. Lipid-lowering therapy is reportedly underused in patients with RA. Longitudinal cohort studies comparing use of lipid-lowering medications in patients with RA versus the general population are lacking. METHODS: Cardiovascular risk factors, lipid measures, and use of lipid-lowering agents were assessed in a population-based inception cohort of patients with RA and a cohort of non-RA subjects followed from January 1, 1988, to December 31, 2008. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) guidelines were assessed at the time of each lipid measure throughout followup. Time from meeting guidelines to initiation of lipid-lowering agents was assessed using Kaplan-Meier methods. RESULTS: The study population included 412 RA and 438 non-RA patients with ≥ 1 lipid measure during followup and no prior use of lipid-lowering agents. Rates of lipid testing were lower among patients with RA compared to non-RA subjects. Among patients who met NCEP ATPIII criteria for lipid-lowering therapy (n = 106 RA; n = 120 non-RA), only 27% of RA and 26% of non-RA subjects initiated lipid-lowering agents within 2 years of meeting the guidelines for initiation. CONCLUSION: There was substantial undertreatment in both the RA and the non-RA cohorts who met NCEP ATPIII criteria for initiation of lipid-lowering agents. Patients with RA did not have as frequent lipid testing as individuals in the general population.
  The Journal of Rheumatology 05/2013;
• Article: Childhood-onset Eosinophilic Granulomatosis with Polyangiitis (formerly Churg-Strauss Syndrome): A Contemporary Single-center Cohort.

  Samantha Gendelman, Andrew Zeft, Steven J Spalding
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  ABSTRACT: OBJECTIVE: To date only 38 cases of childhood-onset eosinophilic granulomatosis with polyangiitis (cEGPA; formerly Churg-Strauss syndrome) have been reported. Additional patients with cEGPA could enhance the understanding of this rare and life-threatening condition. Our objectives were (1) to determine the frequency of specific organ system involvement; (2) to examine initial therapeutic regimen; and (3) to document disease and therapy-related morbidity in a contemporary cohort of patients with cEGPA. METHODS: Retrospective review of patients evaluated at the Cleveland Clinic between 2003 and 2011 who met either American College of Rheumatology or Lanham criteria for EGPA and whose age was < 18 years at symptom onset. RESULTS: Nine patients (8 female; 7 white) were identified. Median age at onset of rhinitis/asthma symptom was 13 years and median age at diagnosis of cEGPA was 15 years. All patients demonstrated eosinophilia, upper airway disease (allergic rhinitis, chronic sinusitis, and/or nasal polyps), and pulmonary involvement. Other frequently involved organ systems included musculoskeletal (67%), gastrointestinal (67%), cutaneous (67%), neurologic (56%), and cardiac (44%). Antineutrophil cytoplasmic antibody (ANCA) serologies were negative in all patients. The medications used most frequently for initial therapy included oral (44%) or intravenous corticosteroids (56%) and azathioprine (67%). Disease or therapeutic complications occurred in half of the cohort and included heart failure, stroke, and sequela from longterm, high-dose steroids. CONCLUSION: Eosinophilia, in combination with upper airway, pulmonary, musculoskeletal, neurologic, and cardiac manifestations, is frequently observed in cEGPA. ANCA titers are often negative. Steroids are the mainstay of initial therapy but steroid-related side effects occur regularly.
  The Journal of Rheumatology 05/2013;
• Article: Clinical Course, Prognosis, and Causes of Death in Mixed Connective Tissue Disease.

  Agota Hajas, Peter Szodoray, Britt Nakken, Janos Gaal, Eva Zöld, Renata Laczik, Nora Demeter, Gabor Nagy, Zoltan Szekanecz, Margit Zeher, Gyula Szegedi, Edit Bodolay
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  ABSTRACT: OBJECTIVE: To study the survival rate and prognostic indicators of mixed connective tissue disease (MCTD) in a Hungarian population. METHODS: Two hundred eighty patients with MCTD diagnosed between 1979 and 2011 were followed prospectively. Clinical features, autoantibodies, and mortality data were assessed. Prognostic factors for survival were investigated and survival was calculated from the time of the diagnosis by Kaplan-Meier method. RESULTS: A total of 22 of 280 patients died: the causes of death were pulmonary arterial hypertension (PAH) in 9 patients, thrombotic thrombocytopenic purpura in 3, infections in 3, and cardiovascular events in 7. The 5, 10, and 15-year survival rates after the diagnosis was established were 98%, 96%, and 88%, respectively. The deceased patients were younger at the diagnosis of MCTD compared to patients who survived (35.5 ± 10.4 vs 41.8 ± 10.7 yrs; p < 0.03), while there was no difference in the duration of the disease (p = 0.835). Our cohort study showed that the presence of cardiovascular events (p < 0.0001), esophageal hypomotility (p = 0.04), serositis (p < 0.001), secondary antiphospholipid syndrome (p = 0.039), and malignancy (p < 0.001) was significantly higher in the deceased patients with MCTD. The presence of anticardiolipin (p = 0.019), anti-β2-glycoprotein I (p = 0.002), and antiendothelial cell antibodies (p = 0.002) increased the risk of mortality. CONCLUSION: Overall, PAH remained the leading cause of death in patients with MCTD. The prevalence of cardiovascular morbidity and mortality, malignancy, and thrombotic events increased during the disease course of MCTD. The presence of antiphospholipid antibodies raised the risk of mortality.
  The Journal of Rheumatology 05/2013;