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ID PMID Title PublicationDate abstract
20965550 Posterior interosseous nerve palsy: an unusual complication of rheumatoid arthritis: case 2011 Jun OBJECTIVES: Posterior interosseous nerve (PIN) palsy is a very rare complication of rheumatoid arthritis affecting the elbow joint. It results in weakness of extension of the fingers and may be confused with extensor tendon rupture and wrist drop due to radial nerve damage. METHODS: We present a case of PIN palsy secondary to rheumatoid synovitis and review the previously reported cases. RESULTS: Eighteen cases of PIN palsy due to rheumatoid arthritis have been reported so far in the literature. CONCLUSIONS: It is important to recognize this complication and early intervention is necessary to prevent permanent damage.
20051754 Cetuximab in the treatment of rheumatoid arthritis. 2010 Jan Members of the epidermal growth factor receptor (EGFR) family and their associated ligands are commonly expressed by synovial cells, and may be involved in the synovial hyperplasia seen in rheumatoid arthritis and its disease progression. This family of receptors is also expressed in cancer cells, and EGFR targeted therapy is now a mainstay of anticancer therapy. Cetuximab (Erbitux) is a monoclonal antibody directed against the EGFR extracellular receptor that has received Food and Drug Administration approval for the treatment of colorectal cancer as well as head and neck cancer. We report a case of a 61-year-old woman with an extensive history of rheumatoid arthritis requiring multiple therapies, who experienced a surprising remission of her disease and its symptoms while being treated with cetuximab for her head and neck cancer. The case as well as possible mechanisms of action are discussed. Further clinical investigations are clearly warranted.
20339893 Myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephrit 2010 Aug BACKGROUND: Several cases of rheumatoid arthritis (RA) with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated crescentic glomerulonephritis (CrGN) have been reported. However, its clinical characteristics are not clear. METHODS: We summarized 3 patients of concurrent RA and MPO-ANCA-associated CrGN, diagnosed in our hospital from 1992 to 2006, and compared their clinicopathological data with those of 10 MPO-ANCA-associated CrGN patients without RA in the same period. RESULTS: All three RA patients were middle-aged or young adult women with 7-14 years of RA history. The initial clinical symptom was microhematuria, and mean duration from hematuria onset to histological confirmation of CrGN was 17 months. At renal biopsy, serum creatinine concentration (sCr) was modestly elevated, with the mean value of 3.4 mg/dl. Crescents were detected in 30% of glomeruli, whereas advanced glomerular sclerosis, tubular atrophy, and interstitial fibrosis were also observed. In comparison with patients without RA, patients with RA were significantly younger and showed a longer duration from the onset to histological confirmation of CrGN. Serum creatinine concentration at referral was significantly lower; however, estimated glomerular filtration rate (eGFR) was comparable. The Birmingham Vasculitis Activity Score and the Disease Extent Index were significantly lower, and pathological examination showed less crescent formation and a tendency to advanced glomerular sclerosis in patients with RA. CONCLUSIONS: In patients with RA, MPO-ANCA-associated CrGN appeared to develop at younger ages and often showed a slowly progressive deterioration of the renal function with slight extrarenal manifestations. These smoldering clinical features may result in late referral from rheumatologists to nephrologists and therefore poor prognosis.
20090526 B cells in the pathogenesis and treatment of rheumatoid arthritis. 2010 May PURPOSE OF REVIEW: Our understanding of the multiple physiological and pathogenic functions of B cells in rheumatoid arthritis (RA) continues to expand. In turn, the availability of effective agents targeting the B cell compartment increases. In this review, we discuss novel insights into the roles of B cells in RA and recent evidence regarding the efficacy of B cell depletion and biomarkers of treatment response. RECENT FINDINGS: Recent data have further elucidated the requirements for the generation of ectopic lymphoid structures in the rheumatoid synovium, their frequency, and role in pathogenesis. Additional studies have described the phenotype of infiltrating B cells in the synovium and the unexpected role for B cells in bone homeostasis. In addition to pathogenic roles for B cells, there is also mounting evidence for regulatory B cell subsets that may play a protective role. New data on radiographic progression, efficacy in early disease, the role of retreatment, and biomarkers of treatment response continue to refine the role of B cell depletion in the treatment armamentarium. SUMMARY: The past few years have seen new advances in immunology applied to the study of RA with surprising observations and interesting new insights into cause and pathogenesis.
21044429 Measuring methotrexate polyglutamates. 2010 Sep Methotrexate is the most commonly used drug in the treatment of rheumatoid arthritis, although 30-40% of patients fail to adequately respond. An accurate method for measuring methotrexate polyglutamates, the stable active metabolite of methotrexate, has recently been described. The objective of this review article is to determine if clinical use of this measurement would improve methotrexate efficacy, or decrease adverse reactions. Additionally the pharmacologic rationale for this test is discussed. Although methotrexate response improves at higher methotrexate polyglutamate levels, there is no absolute correlation of level with effect. Moreover, overlapping methotrexate polyglutamate levels between clinical responders and nonresponders limits the clinical utility of this measurement.
19995857 Maintenance of physical activity after Internet-based physical activity interventions in p 2010 Jan OBJECTIVES: To investigate the maintenance of physical activity 12 months after two 1-year Internet-based physical activity interventions in patients with RA. METHODS: This follow-up study was a randomized comparison of an Internet-based individualized training (IT) and a general training (GT) programme in sedentary RA patients. Outcome measures included physical activity (meeting public health recommendations for moderate physical activity, i.e. 30 min for at least 5 days/week; or vigorous physical activity, i.e. 20 min for at least 3 days/week), functional ability and quality of life (QoL). RESULTS: Of the 152 RA patients who completed the initial study, 110 (72%) were available at follow-up. At 24 months, the proportions of patients meeting public health recommendations for moderate intensity physical activity were significantly higher compared with baseline in both the IT and GT groups (19 and 24%, respectively, P < 0.05), whereas the proportions of patients meeting the recommendation for vigorous activity was only significantly higher compared with baseline in the IT group (P < 0.05) but not in the GT group. There were no differences between the IT and GT groups concerning proportions of patients meeting moderate or vigorous physical activity recommendations at 24 months. Apart from a significantly higher RAQoL score in the IT group at 24 months compared with baseline, there were no significant differences within or between the programmes regarding functional ability or QoL. CONCLUSION: In RA patients, the effectiveness of both an individualized and a general 1-year Internet-based physical activity programme is sustained with respect to moderate intensity physical activity up to 12 months after the interventions.
19481003 Latent infection and tuberculosis disease in rheumatoid arthritis patients. 2009 Feb New drug classes, biologics, have been developed over the past 10 years based on human or chimeric antibodies against cytokines or receptors with pivotal roles in the inflammatory pathways of immune-mediated inflammatory disease. Anti-tumor necrosis factor agents carry the largest infection risk of all the biologics, predisposing patients to mycobacterial infections. Patients receiving biologics are at higher risk for developing tuberculosis. New cases of tuberculosis or reactivation of latent tuberculosis infections may occur during the course of treatment, so a high level of vigilance is highly recommended.
20461787 Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrull 2010 May OBJECTIVE: To compare the clinical utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) testing in predicting both functional outcome and response to treatment in early inflammatory polyarthritis (IP) patients. METHODS: A total of 916 IP subjects from a primary care incidence registry (1990-1994) had anti-CCP antibody and RF status determined at baseline. Mean change in Health Assessment Questionnaire (HAQ) score between baseline and 5 years was compared by antibody status. The effect of treatment with disease-modifying antirheumatic drugs and/or steroids over 5 years, early (<6 months of symptom onset) versus late initiation, and duration of treatment were also compared by anti-CCP antibody status. The analysis was adjusted for treatment decisions and censoring over the followup, using marginal structural models. RESULTS: Anti-CCP antibody-positive patients (n = 268) had more severe disease both at presentation and 5 years of followup, and this was independent of RF. On adjustment, anti-CCP antibody-negative patients treated early experienced a significant improvement in functional disability compared with anti-CCP antibody-negative patients who were never treated (-0.31; 95% confidence interval [95% CI] -0.53, -0.08), and experienced additional benefit for each additional month of early treatment. Anti-CCP antibody-positive patients treated early did not have a significant improvement in HAQ score compared with those not treated (-0.14; 95% CI -0.52, 0.24). CONCLUSION: In this first observational study to examine the influence of anti-CCP antibody status on treatment response, anti-CCP antibody-positive IP patients showed less benefit from treatment, particularly early treatment, than anti-CCP antibody-negative patients. This provides support for the inclusion of anti-CCP antibodies as well as RF in the classification criteria for rheumatoid arthritis and for stratification by anti-CCP antibody status in clinical trials.
20025584 Etiological and biological aspects of cigarette smoking in rheumatoid arthritis. 2009 Dec Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by the chronic inflammation of the synovium, which develops to joint destruction. Quite interestingly RA has not been present in the old world until 17 century. Tobacco has come from the new world, and epidemiological studies revealed cigarette smoking as a major risk factor for the disease. However, the mechanism how cigarette smoking contributes to RA has been largely unknown. It has been demonstrated that polycyclic aromatic hydrocarbons, constituents of cigarette smoke, and cigarette smoke extracts are able to induce proinflammatory cytokines from RA patient-derived fibroblast-like synoviocytes. Recent studies also suggest an important role of Th17 in RA and contribution of aryl hydrocarbon receptor to the induction and development of Th17 and RA. These new findings lead to uncovering the basis for the etiological role of cigarette smoking in the disease.
19577564 Deacetylase inhibition increases regulatory T cell function and decreases incidence and se 2009 Oct Collagen-induced arthritis (CIA) is an established mouse model of disease with hallmarks of clinical rheumatoid arthritis. Histone/protein deacetylase inhibitors (HDACi) are known to inhibit the pathogenesis of CIA and other models of autoimmune disease, although the mechanisms responsible are unclear. Regulatory T cell (Treg) function is defective in rheumatoid arthritis. FOXP3 proteins in Tregs are present in a dynamic protein complex containing histone acetyltransferase and HDAC enzymes, and FOXP3 itself is acetylated on lysine residues. We therefore investigated the effects of HDACi therapy on regulatory T cell function in the CIA model. Administration of an HDACi, valproic acid (VPA), significantly decreased disease incidence (p<0.005) and severity (p<0.03) in CIA. In addition, VPA treatment increased both the suppressive function of CD4(+)CD25(+) Tregs (p<0.04) and the numbers of CD25(+)FOXP3(+) Tregs in vivo. Hence, clinically approved HDACi such as VPA may limit autoimmune disease in vivo through effects on the production and function of FOXP3(+) Treg cells.
19431078 The IL-12/IL-23 axis and its role in Th17 cell development, pathology and plasticity in ar 2009 May Rheumatoid arthritis (RA) was originally thought to be a T-helper (Th)1-, not a Th2-, associated disorder; however, it currently is unclear whether RA is a Th1- and/or Th17-mediated disease, and what the contributions of these T-cell subsets are in the pathogenesis of RA. Results from studies using different arthritis models have demonstrated that IL-17-producing T-cells are the dominant cell type in the development of arthritis. In addition, a critical role of the IL-23/IL-17 axis in the progression to chronic destructive arthritis has been demonstrated. Interestingly, Th1 and Th17 cells both may have unique pathogenic potential, and the recent insights into T-cell plasticity may change the understanding of the role of T-cell subsets in chronic autoimmune diseases.
20634116 Unexpected death of a patient with rheumatoid arthritis complicated by a cervical deformit 2010 Sep An elderly female with a 43-year history of rheumatoid arthritis died 2weeks after the onset of chest discomfort, electrolyte disturbance, and interstitial pneumonia. She had frequent premature ventricular contractions, fluctuating heart rate, and hypotension. Ischemic heart disease and interstitial pneumonia were excluded as the cause of death based on clinical course and autopsy findings. A severe cervical deformity with myelopathy likely contributed to circulatory instability, possibly through injury to the intra-spinal sympathetic nervous system, which can induce cardiovascular instability and suppress respiratory function. This likely led to death.
19833745 Early life factors and adult-onset rheumatoid arthritis. 2010 Jan OBJECTIVE: Early life factors have been associated with risk of developing autoimmune disease in adulthood. We investigated the association of preterm birth and being breastfed with the incidence of rheumatoid arthritis (RA) in 2 large prospective cohorts. METHODS: We studied participants from the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII) who provided information on perinatal factors. The NHS (n = 121,701) and NHSII (n = 116,608) are large prospective cohorts of women followed since 1976 and 1989, respectively. Incident RA was confirmed using the American College of Rheumatology criteria and a medical record review. Cox models were used to estimate the hazard ratio of RA associated with being born preterm and being breastfed and its duration, adjusting for potential confounders. Random effects metaanalytic methods were used to compute combined estimates from the 2 cohorts. RESULTS: We found no statistically significant association between preterm birth and incident RA [relative risk (RR) = 1.1, 95% CI 0.8, 1.5]. Being breastfed was not associated with increased incidence of RA (RR = 1.0, 95% CI 0.7, 1.4), regardless of the duration of breastfeeding. CONCLUSION: In these cohorts of women, neither being preterm birth nor being breastfed was associated with the onset of RA.
19408036 Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis 2009 Aug Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti-inflammatory effects, attributed to the main constituent andrographolide proposed as alternative in the treatment of autoimmune disease. A prospective, randomized, double blind, and placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks, after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale (VAPS). In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs placebo group at the end of treatment, although these differences were not statistically significant. A significant diminishing for week in tender joint -0.13 95% confidence interval (CI; -0.22 to 0.06; p = 0.001), number of swollen joints -0.15 95%CI (-0.29 to -0.02; p = 0.02), total grade of swollen joint -0.27 95%CI (-0.48 to -0.07; p = 0.010), number of tender joints -0.25 95%CI (-0.48 to -0.02; p = 0.033), total grade of swollen joints -0.27 95%CI (-0.48 to -0.07; p = 0.01), total grade of tender joints -0.47 95%CI (-0.77 to -0.17; p = 0.002) and HAQ -0.52 95%CI (-0.82 to -0.21; p < 0.001) and SF36 0.02 95%CI (0.01 to 0.02; p < 0.001) health questionnaires was observed within the group with the active drug. Moreover, it was associated to a reduction of rheumatoid factor, IgA, and C4. These findings suggest that A. paniculata could be a useful "natural complement" in the treatment of AR; however, a larger trial and a more extended period of treatment is necessary in order to corroborate these results.
18662929 Hyperlipidaemia, statin use and the risk of developing rheumatoid arthritis. 2009 Apr OBJECTIVE: To evaluate whether statins are associated with a protective effect on the development of rheumatoid arthritis (RA). METHODS: A nested case-control study was conducted using data from the General Practice Research Database. A study population consisting of three groups of subjects aged 40-89 years was identified: (1) patients exposed to a statin or other lipid-lowering agent (LLA); (2) patients with a diagnosis of hyperlipidaemia in the absence of lipid-lowering drug treatment and (3) a random sample of 25 000 individuals with no diagnosis of hyperlipidaemia nor a prescription for a LLA. From this population incident cases of RA and up to four controls for each case were identified, matched on age, sex, general practice, number of years of recorded history in the database and index date. The independent effects of hyperlipidaemia and statins on the development of RA were evaluated using conditional logistic regression. RESULTS: 313 cases of RA and 1252 matched controls were identified. Compared with patients with untreated hyperlipidaemia, or hyperlipidaemia treated with LLA other than statins, the adjusted odds ratio for patients with no hyperlipidaemia was 0.68 (95% CI 0.50 to 0.91). When those with hyperlipidaemia who received statins were compared with those with hyperlipidaemia who did not use statins (ie, untreated hyperlipidaemia patients or those treated with non-statin LLA) the OR was 0.59 (95% CI 0.37 to 0.96). CONCLUSION: These data provide evidence to support the hypothesis that statins may be protective against the development of RA in patients with hyperlipidaemia.
19842941 Identification of candidate genes for rituximab response in rheumatoid arthritis patients 2009 Oct AIMS: Transient CD20+ B-cell depletion with rituximab is an effective treatment for rheumatoid arthritis (RA). However, there is a subgroup of patients that do not show significant clinical response to rituximab and for these patients, other modes of treatment are preferred. Finding biomarkers for drug response in RA has immense potential for improving treatment and lowering healthcare costs for treating RA patients by facilitating the optimization of their pharmacotherapy. In the present study, we report on gene expression profiles of three different blood cell types in rituximab responders and nonresponder RA patients identifying new candidate genes associated with rituximab response. MATERIALS & METHODS: Transcriptional profiles of whole-blood, CD4+ T cells and B cells were analyzed from nine female patients (mean age 53 +/- 11 years) with active RA disease (DAS28 > 5.1), starting rituximab therapy using Illumina (CA, USA) gene-expression microarrays. Whole-blood RNA was extracted using the PAXgene system (PreAnalytix, Hombrechtikon, Switzerland) whilst the lymphocyte RNA was obtained following cell isolation using negative selection. Flow cytometry analysis was performed to determine whole blood subpopulations, as well as the lymphocyte isolation purity. A whole-genome expression profiling was performed on the RNA samples prepared from the three blood cell populations using the Illumina Human 6 Beadchip array system version 1 (Illumina). From the group of statistically significant genes showing differential expression in rituximab responders compared with nonresponder RA patients, we selected a group of candidate genes that were subsequently validated in the same RNA samples using TaqMan real-time PCR assays. RESULTS: Several genes were identified whose level of expression is associated significantly with the response to rituximab in all three blood cell types evaluated (multiple-test corrected p-value < 0.05). Real-time PCR-validated genes include ARG1 (1.6-fold downregulated in responders) and TRAF1 (1.4-fold upregulated in responders) genes in whole blood and TLR4 (1.3-fold upregulated in responders) in CD4+ T cells. CONCLUSIONS: The present study is the first gene expression microarray analysis reporting on biomarkers of the clinical response to rituximab in RA in blood cells. Following validation in larger cohorts, the identified genes may serve as biomarkers for treatment choice in RA.
20686298 Organizing pneumonia with a positive result for anti-CCP antibodies as the first clinical 2010 We report an 86-year-old woman who presented with organizing pneumonia (OP) with a positive anti-cyclic citrullinated peptide (anti-CCP) antibodies as the first manifestation of rheumatoid arthritis (RA). She experienced dyspnea, chest X-ray showed diffuse alveolar exudates indicated OP histologically. Although she did not present with articular symptoms initially, anti-CCP antibodies measured for differentiation of RA were positive. Eight months later, she showed representative manifestations of RA. Even though OP following joint involvement is frequent in RA, in rare cases it could be the first manifestation. This is the first case showing OP with a positive result for anti-CCP antibodies as the first manifestation of RA.
20149320 Induction of psoriatic skin lesions in a patient with rheumatoid arthritis treated with ri 2009 Nov Rituximab is a chimeric monoclonal therapeutic antibody which causes depletion of CD20-positive B cells. Apart from its apparent efficacy in the treatment of non-Hodgkin lymphoma and of several rheumatic diseases, it is associated with adverse events including the induction of autoimmune phenomena. We describe here the development of psoriatic skin lesions in a patient with rheumatoid arthritis after the second course of treatment with rituximab. This report supports the hypothesis that autoimmune phenomena may occur by biologic agents and there is a link between B-cell depletion and the induction of psoriatic skin lesions, which were confirmed histologically. However, further studies are needed in order to identify the underlying mechanism, as well as the risk factors associated with rituximab-induced psoriatic skin lesions.
20112396 Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 2010 Feb OBJECTIVE: Smoking is associated with rheumatoid arthritis (RA) in individuals with the HLA-DRB1 shared epitope (SE). SE alleles have been shown to be predominantly associated with anti-cyclic citrullinated peptide (anti-CCP)-positive RA. These risk factors have not been identified for anti-CCP-negative RA. The aim of this study was to investigate whether SE-containing HLA-DRB1 alleles, smoking, or the combination of these factors contributes to the development of RA, depending on the presence or absence of serologic markers, in a Korean population. METHODS: All of the patients with RA (n =1,482) and all of the control subjects (n = 1,119) were Korean. Four-digit HLA-DRB1 typing was performed by a conventional polymerase chain reaction-sequence-based typing method. Information about smoking history was obtained through a questionnaire. The patients with RA were tested for anti-CCP antibodies and rheumatoid factor (RF). RESULTS: The SE alleles had significant effects on anti-CCP antibody and RF formation. The DRB1*0901 allele was associated with the presence of anti-CCP antibodies (odds ratio [OR] 2.49) and RF (OR 2.09). SE alleles and smoking were associated with both anti-CCP-positive and anti-CCP-negative RA. The combination of smoking and double copies of the SE allele increased the risk of anti-CCP-positive RA 36.11-fold and increased the risk of anti-CCP-negative RA 12.29-fold, compared with the risk among nonsmokers not carrying SE alleles. Interactions between SE alleles and smoking were observed for both anti-CCP-positive and RF-positive RA, although the associations of RF-positive RA could be consequences of the underlying anti-CCP antibody status. CONCLUSION: We demonstrated that the combination of SE alleles and smoking is associated with RA susceptibility regardless of anti-CCP antibody or RF status, but that the combination shows stronger effects in anti-CCP-positive/RF-positive patients with RA than in anti-CCP-negative/RF-negative patients with RA. The SE-smoking interactions were present in anti-CCP-positive and RF-positive RA.
20485848 Oxazole-modified glycopeptides that target arthritis-associated class II MHC A(q) and DR4 2010 Jun 28 The glycopeptide CII259-273, a fragment from type II collagen (CII), can induce tolerance in mice susceptible to collagen-induced arthritis (CIA), which is a validated disease model for rheumatoid arthritis (RA). Here, we describe the design and synthesis of a small series of modified CII259-273 glycopeptides with oxazole heterocycles replacing three potentially labile peptide bonds. These glycopeptidomimetics were evaluated for binding to murine CIA-associated A(q) and human RA-associated DR4 class II major histocompatibility complex (MHC) proteins. The oxazole modifications drastically reduced or completely abolished binding to A(q). Two of the glycopeptidomimetics were, however, well tolerated in binding to DR4 and they also induced strong responses by one or two DR4-restricted T-cell hybridomas. This work contributes to the development of an altered glycopeptide for inducing immunological tolerance in CIA, with the long-term goal of developing a therapeutic vaccine for treatment of RA.