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ID PMID Title PublicationDate abstract
22376227 Summary of AHRQ's Comparative Effectiveness Review of Disease-Modifying Antirheumatic Drug 2012 Jan BACKGROUND: A systematic review on the comparative effectiveness of disease-modifying antirheumatic drugs (DMARDs) used to treat children with juvenile idiopathic arthritis (JIA) was published by the Agency for Health Care Research and Quality (AHRQ) in September 2011. Studies from 198 articles included in the review addressed the benefits and harms of DMARDs compared with conventional treatments and other DMARDs used to treat JIA. The review also incorporated studies comparing various clinical tools used for diagnosing JIA and measuring disease activity. Clinical outcome measures were analyzed to determine the most effective methods to measure disease state. The lack of current research for the treatment of JIA motivated AHRQ to contract with researchers to synthesize the available information with the intent of enabling health professionals to make evidence-based practice decisions for their patients. The review alsohighlights gaps in the research and areas that need to be addressed in the future. OBJECTIVES: To (a) educate health care practitioners on the findings from AHRQ's 2011 comparative effectiveness review on DMARDs used to treat children with JIA, (b) apply review findings to make diagnosis and treatment decisions in clinical practice, and (c) recognize limitations and gaps n the current research relating to the comparative benefits and harms of DMARDs for treatment of JIA. SUMMARY: JIA is a chronic inflammatory disease affecting approximately 300,000 children and adolescents in the United States.1 Initially manifesting with inflammation, swelling, pain, and stiffness of the joints, the disease as no apparent or known cause. JIA is a clinical diagnosis based on several actors including the number of affected joints and the involvement of other tissues (e.g., the skin and lymphoid tissues), and JIA has 7 categories: systemic-onset arthritis, oligoarthritis, rheumatoid-factor positive polyarthritis, rheumatoid-factor negative polyarthritis, enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis.2 Complete remission and resolution of disease activity are the ultimate treatment goals; however, there is no present cure. Inhibition of inflammation, prevention of joint damage, and promotion of a high level of functioning are the immediate goals of treatment. Even with treatment, patients with JIA continue to experience disease activity, joint destruction, suboptimal function, and impaired quality of life, all of which extend into adulthood.3 JIA can be severely debilitating and places a heavy physical and psychological burden on children and families affected by the disease. Methotrexate is a nonbiologic DMARD with an unknown mechanism of action. Methotrexate has been used for so long in the treatment of JIA that it is frequently considered a part of conventional treatment; the evidence shows that methotrexate is superior to conventional treatment with NSAIDsand/or intra-articular corticosteroids. The introduction of newer biologic DMARDs has spawned optimism that treatment will increasingly lead to improved outcomes for JIA, but the evidence is insufficient to support superiority over methotrexate. There is moderate evidence to support the claim that continued treatment from 4 months to 2 years with a biologic DMARD in children who have responded to a biologic DMARD decreases the risk of a flare. However, the safety of biologic DMARDs for long-term use has not been determined and may be associated with the developmentof cancer. The association between tumor necrosis factor (TNF) alpha inhibitors and potential increased risk of lymphoma caused the U.S. Food and Drug Administration (FDA) to place boxed warning labels on biologic DMARDs including etancercept, infliximab, and adalimumab. The effectiveness of the DMARDs appears to vary among categories of JIA and the treatment history of individual patients. Except for methotrexate, there is insufficient evidence to support selection of a specific drug or drug class over another in the treatment of JIA. The AHRQ review examines the scientific literature on DMARDs used in children with JIA in an effort to synthesize what is known about the subject, and the comprehensive review identifies important research gaps in the literature that need to be addressed. Only 8 studies (in 9 publications) were rated "good quality" by the AHRQ investigators.
22684572 Prediction of response of collagen-induced arthritis rats to methotrexate: an (1)H-NMR-bas 2012 Jun Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
21826093 Pharmacogenetics: implications for therapy in rheumatic diseases. 2011 Aug 9 DMARDs not only improve the joint pain and swelling associated with rheumatoid arthritis (RA), but also slow down the joint damage associated with the disease. The efficacy of biologic therapies, introduced in the past decade for the treatment of RA, has been unequivocally established. Similarly, in addition to traditional drugs such as hydroxychloroquine, new biologic agents such as rituximab have been introduced for systemic lupus erythematosus in recent years. However, considerable variability occurs in the responses of patients to these therapies. Pharmacogenetics, the study of variations in genes encoding drug transporters, drug-metabolizing enzymes and drug targets, and their translation to differential responses to drugs, is a rapidly progressing field in rheumatology. Pharmacogenetic applications, particularly to the old vanguard DMARD, methotrexate, and the newer, more expensive biologic agents, might make personalized therapy in rheumatic diseases possible. The pharmacogenetics of commonly used DMARDs and of biologic therapies are described in this Review.
22185278 Measurement of methotrexate polyglutamates in human erythrocytes by ion-pair UPLC-MS/MS. 2011 Dec BACKGROUND: Low-dose methotrexate is used for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis, but its effectiveness greatly varies between individuals. Therapeutic drug monitoring of intracellular methotrexate metabolites, the γ-polyglutamates (MTXGlu(n)), in human erythrocytes has shown promise in providing a basis for individualization of therapy. RESULTS: This work presents expedient methodology for the analysis of MTXGlu(1-7) in human erythrocytes by ion-pair UPLC with detection by tandem MS (UPLC-ESI-MS/MS). The use of N,N-dimethylheptylamine as an ion-pair agent was found to be favorable over others. Thermal extraction of erythrocyte lysates provides a simple one-step extraction procedure. The entire chromatographic run time is 6 min and the assay was validated within the therapeutic range of these metabolites CONCLUSION: The developed sample preparation procedure in combination with ion-pair UPLC-ESI-MS/MS analysis allowed for expedient quantitation of MTXGlu(1-7) in human erythrocytes. The rapid analysis time would enable therapeutic drug monitoring of MTXGlu(1-7) in the clinic.
21869709 Refractory adult-onset still disease successfully treated with abatacept. 2011 Sep Adult-onset Still disease (AOSD) is an inflammatory condition of unknown etiology that responds to glucocorticosteroids and disease-modifying antirheumatic drugs, particularly methotrexate. However, disease refractory to conventional treatment has led to the reported use of biologic therapy including tumor necrosis factor α inhibitors (infliximab, etanercept, and adalimumab), anakinra, rituximab, and tocilizumab. We report the successful use of abatacept in the treatment of a patient with AOSD manifested by polyarthritis, rash, fevers, elevated liver function tests, and ferritin levels refractory to treatment with methotrexate and hydroxychloroquine. Remission has been maintained for 35 months with the addition of abatacept administered once monthly. There is evidence that T-cell activity plays an important role in the autoimmune activity of AOSD, and modulation of CD28 costimulation of T cells by abatacept has specific immunosuppressive actions that make it an appealing alternative therapeutic option for refractory AOSD.
22334272 Successful use of interleukin 6 antagonist tocilizumab in a patient with refractory cutane 2012 Mar Tocilizumab (Actemra; Genentech, Inc) is the first biologic therapy targeting the cytokine interleukin 6 (IL-6). It is a humanized monoclonal immunoglobulin G1 antibody against the α-chain of the IL-6 receptor that prevents the binding of IL-6 to membrane-bound and -soluble IL-6 receptor. It was approved by the US Food and Drug Administration in January 2010 for rheumatoid arthritis refractory to other approved therapies and in April 2011 for systemic juvenile idiopathic arthritis. It has been used as an off-label treatment in many autoimmune diseases, where IL-6 plays a major role in pathogenesis. We report a case of refractory systemic lupus erythematosus in a 22-year-old woman with recurrent high-grade fever, polyarthritis, diffuse rash with urticarial vasculitis, and tumid lupus who did not respond to topical corticosteroids, photoprotection, antimalarials, methotrexate, anakinra, mycophenolate mofetil, etanercept, and intravenous immunoglobulin therapy. Symptoms recurred after corticosteroid tapers below 10 mg. She was noted to have an elevated IL-6 level, and tocilizumab was started. She responded favorably with remission of fever, arthritis, and skin manifestations and was able to taper corticosteroid therapy successfully.
22735757 Bucillamine inhibits CD40-mediated Akt activation and antibody production in mouse B-cell 2012 Sep The improvement of rheumatoid factor titers in patients with rheumatoid arthritis is one of the significant clinical effects of bucillamine (Buc). In this study, we investigated the effects of SA981, an active metabolite of Buc, and methotrexate (MTX) on CD40-mediated antibody production using mouse B-cell lymphoma, BCL1. SA981 significantly attenuated CD40-mediated antibody production in a concentration-dependent manner, but weakly affected cell proliferation. In contrast, MTX did not attenuate CD40-mediated antibody production until it had strongly inhibited cell proliferation at a concentration of 100 nM. CD40 signaling induced protein phosphorylation, including Akt phosphorylation, p38 mitogen-activated protein kinase (p38MAPK), and IκBα. SA981 at a concentration of 30 μM attenuated CD40-mediated Akt phosphorylation, but not p38MAPK or IκBα phosphorylation. MTX at a concentration of 100 nM did not affect CD40-mediated Akt, p38MAPK, or IκBα phosphorylation. Commercially available Akt inhibitor VIII significantly attenuated CD40-mediated IgM production at a concentration of 100 nM without significant inhibition of cell proliferation. These results suggest that SA981 inhibits CD40-mediated antibody production in mouse B-cell lymphoma, at least in part, by attenuation of Akt phosphorylation.
21637066 FDG PET/CT in a patient with spontaneous remission of methotrexate-associated lymphoprolif 2011 Jul We report a case that fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) depicted systemically multiple lesions of methotrexate (MTX)-associated lymphoproliferative disorders. A 70-year-old man receiving MTX for rheumatoid arthritis complained of neck swelling. FDG PET/CT revealed multiple FDG-avid lesions in lymph nodes, lungs, bones, and muscles. Lesions in bones and muscles were not detected on X-CT. Final diagnosis of cervical node was confirmed as MTX-associated lymphoproliferative disorders. FDG PET/CT performed 148 days after discontinuing MTX demonstrated complete remission.
21618461 Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis. 2011 Sep OBJECTIVE: To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 [G5]) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and to investigate the activity of an FA- and methotrexate (MTX)-conjugated dendrimer (G5-FA-MTX) as a therapeutic for the inflammatory disease of arthritis. METHODS: In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescence-tagged G5-FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen-induced arthritis to evaluate the therapeutic potential of G5-FA-MTX. RESULTS: Folate-targeted dendrimer bound and internalized in a receptor-specific manner into both folate receptor β-expressing macrophage cell lines and primary mouse macrophages. The conjugate G5-FA-MTX acted as a potent antiinflammatory agent and reduced arthritis-induced parameters of inflammation such as ankle swelling, paw volume, cartilage damage, bone resorption, and body weight decrease. CONCLUSION: The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.
23363021 Possible antistenotic effect of tranilast in a patient with small bowel tuberculosis to pr 2013 May Small intestinal tuberculosis is a rare disorder of the small intestine. We report the development of deep small bowel tuberculosis in a rheumatoid arthritis patient who was taking methotrexate. The diagnosis of small bowel tuberculosis was ascertained by typical endoscopic findings and production of interferon gamma in the peripheral blood. The patient was successfully treated with antituberculous chemotherapy combined with an antifibrotic agent, tranilast, to suppress the progression of intestinal stenosis toward symptomatic stricture.
21232092 Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene exp 2011 Jan 13 BACKGROUND: Methotrexate (MTX) is the most commonly prescribed disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis. ATP-binding cassette transporter-A1 (ABCA1) and 27-Hydroxylase (HY27) are known antiatherogenic proteins that promote cellular cholesterol efflux. In THP-1 macrophages, MTX can promote the reversal of cholesterol transport, limit foam cell formation and also reverse COX-2 inhibitor-mediated downregulation of ABCA1. Despite its antiatherogenic potential in vitro, the impact of clinical use of low-dose MTX on cholesterol metabolism in humans is unknown. Objective of the study was to examine whether clinical MTX use is associated with altered blood lipids and/or ABCA1/HY27 expressions. METHODS: In all, 100 rheumatoid arthritis subjects were recruited from a medical center in central Taiwan. Plasma lipid profiles and peripheral blood mononuclear cell HY27 and ABCA1 expressions were compared between subjects taking MTX (MTX+) and other disease-modifying antirheumatic drugs (DMARDs) (MTX-). Dietary intake was assessed by a registered dietician. RESULTS: Though no difference observed in the blood lipids between MTX+ and MTX- subjects, the expressions of ABCA1 and HY27 were significantly elevated in MTX+ subjects (n = 67) compared to MTX- subjects (n = 32, p < 0.05). ABCA expression correlated with MTX doses (r = 0.205, p = 0.042), and MTX+ subjects are more likely to have increased HY27 compared to MTX- subjects (OR = 2.5, p = 0.038). Prevalence of dyslipidemia and overweight, and dietary fat/cholesterol intake were lower than that of the age-matched population. Although no differences were observed in the blood lipids, the potential impacts of MTX on cholesterol metabolism should not be overlooked and the atheroprotective effects from MTX induced HY27 and ABCA1 expressions may still be present in those persons with pre-existing dyslipidemia. CONCLUSIONS: We demonstrated novel findings on the increased gene expressions of atheroprotective protein HY27 and ABCA1 in human peripheral blood mononuclear cells (PBMCs) with clinical use of low-dose MTX. Whether MTX induced HY27 and ABCA1 expressions can protect against cardiovascular disease in patients with chronic inflammation through the facilitation of cholesterol export remains to be established. Further studies on the impacts of low-dose MTX on hypercholesterolemic patients are underway.
22157270 Inflammatory and noninflammatory arthropathy in patients with 18q deletion syndrome. 2012 Jan A 7-year-old girl with 18q deletion syndrome developed chronic progressive polyarticular inflammatory arthropathy. Atypical features of her arthritis included lack of morning stiffness, absence of pain and discomfort, normal acute-phase reactants, and the presence of clinodactyly, low-set thumbs, metatarsus adductus of her feet, and overriding nontender swollen toes. She had a positive antinuclear antibody test, negative rheumatoid factor and anti-cyclic citrullinated peptide, and undetectable immunoglobulin A level. Magnetic resonance imaging of the right knee and the result of the synovial biopsy were consistent with synovitis. She was treated with naproxen, short course of prednisone, and methotrexate with good clinical response that plateaued over time. We analyzed the scarce reports of inflammatory arthropathy in 18q deletion syndrome and proposed an outline for investigating arthropathies in patients with chromosomal aberrations.
22021991 Evaluation of the role of erythropoietin and methotrexate in multiple sclerosis. 2011 Sep BACKGROUND: Erythropoietin, originally recognized for its role in erythropoiesis, has been shown to improve neurological outcome after stroke. Low-dose methotrexate is effective against certain inflammatory diseases, such as severe psoriasis and rheumatoid arthritis as well as Crohn's disease. Immunosuppressive effect of methotrexate also reduces the proportion of patients with chronic progressive multiple sclerosis with modest clinical benefits. Combination of erythropoietin and methotrexate can target neuroinflammation along with immunosupression. OBJECTIVE: To evaluate the role of erythropoietin and methotrexate in experimental autoimmune encephalomyelitis, a commonly used animal model of several degenerative human diseases like multiple sclerosis. MATERIALS AND METHODS: In the present study, C57BL/J6 mice were immunized with 200 μg of myelin basic protein (MBP) emulsified in complete Freund's adjuvant (CFA) supplemented with 1 mg/ml of killed mycobacterium tuberculosis (MBP: CFA in 1:1 ratio). These animals were given a combination of methotrexate and erythropoietin. Neurological function tests were scored daily by grading of clinical signs. Cerebral histopathology was performed to detect inflammatory infiltrates and demyelination. RESULTS: Treatment with erythropoietin and methotrexate significantly improved the neurological function recovery, reduced inflammatory infiltrates, and demyelination as compared to controls possibly by stimulating oligodendrogenesis and down-regulating proinflammatory infiltrates. CONCLUSION: The findings suggest an adjunctive use of methotrexate in demyelinating disease.
21490773 Methotrexate in atherogenesis and cholesterol metabolism. 2011 Methotrexate is a disease-modifying antirheumatic drug commonly used to treat inflammatory conditions such as rheumatoid arthritis which itself is linked to increased cardiovascular risk. Treatments that target inflammation may also impact the cardiovascular system. While methotrexate improves cardiovascular risk, inhibition of the cyclooxygenase (COX)-2 enzyme promotes atherosclerosis. These opposing cardiovascular influences may arise from differing effects on the expression of proteins involved in cholesterol homeostasis. These proteins, ATP-binding cassette transporter (ABC) A1 and cholesterol 27-hydroxylase, facilitate cellular cholesterol efflux and defend against cholesterol overload. Methotrexate upregulates expression of cholesterol 27-hydroxylase and ABCA1 via adenosine release, while COX-2 inhibition downregulates these proteins. Adenosine, acting through the A(2A) and A(3) receptors, may upregulate proteins involved in reverse cholesterol transport by cAMP-PKA-CREB activation and STAT inhibition, respectively. Elucidating underlying cardiovascular mechanisms of these drugs provides a framework for developing novel cardioprotective anti-inflammatory medications, such as selective A(2A) receptor agonists.
22018177 History of the development of corticosteroid therapy. 2011 Sep The first clinical evidence that an extract of animal adrenocortical tissue could counteract human adrenal failure was demonstrated in 1930. As chemical analyses of cortical extracts proceeded, mainly in the laboratories of Kendall at the Mayo Clinic and Reichstein in Zurich, it became evident that there is not one cortical hormone, but that all are steroids. By 1940 it was understood that there are two categories: those that cause sodium and fluid retention and those that counteract shock and inflammation. Structurally the presence or lack of oxygenation at C11 on the steroid skeleton was critical. In 1948 the first patient with rheumatoid arthritis was treated with cortisone and soon thereafter other rheumatologic patients received cortisone or, to stimulate native cortisone production, ACTH. Oral and intra-articular administration of cortisone and hydrocortisone began in 1950-51. Several lines of research to produce cortisone semi-synthetically showed some success by 1952. Between 1954 and 1958 six synthetic steroids were introduced for systemic anti-imflammatory therapy. By 1960 all of the toxic effects of chronic corticosteroid administration had been described, as well as protocols to withdraw such drugs while minimising symptoms of cortical insufficiency. To enable use of lower corticosteroid dosages, companion use of non-steroidal anti-inflammatory drugs began in the late 1950s, with phenylbutazone the first. In the 1970s the introduction of methotrexate and other anti-metabolites further circumscribed the dosages and indications for corticosteroids in the rheumatic diseases.
21990059 [Generalized osteoarthritis in a young adult with type II collagenopathy]. 2011 Oct HISTORY AND ADMISSION FINDINGS: In the 20-year-old patient increasing arthralgia since the age of seven years had caused functional impairment. As seronegative osteodestructive rheumatoid arthritis had been suspected, he was treated with methotrexate and steorid for ovemore than one year, without success.r INVESTIGATIONS: The clinical examination revealed a compromised function of the knee and hip joints. Conventional radiographs showed severe degenerative changes in these regions. The radiographs of the lumbar and the thoracic spine were suggestive of osteoporotic fractures. DIAGNOSIS, TREATMENT AND COURSE: The clinical and radiological findings led to the suspicion of a hereditary collagenous disease. Genetic analyses revealed a COL2A1 mutation. The treatment included analgesics, non-steroidal antirheumatic drugs, opiates and regular physiotherapy to build up and maintain muscle strength. CONCLUSION: In young adult patients with osteoarthritis mutations in the COL2A1 gene should considered. This mutation with the substitution pArg75Cys should be in focus because of the phenotypes in clinical manifestations.
20737185 Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with 2011 Feb A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.
22008049 Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic 2011 Oct Methotrexate (MTX) is the first-line treatment for rheumatoid arthritis and is frequently used in the management of other forms of inflammatory arthritis. It is currently challenging to predict which patients will achieve adequate disease control and which patients will develop adverse effects while taking MTX. As an analog of dihydrofolic acid, MTX enters cells through the reduced folate carrier-1 protein, and is polyglutamated. MTX polyglutamates inhibit key enzymes in the folate pathway to produce an anti-inflammatory effect. It has been suggested that genetic polymorphisms in the folate pathway may influence intracellular folate and MTX polyglutamates pools, and thus MTX response. However, studies to identify genetic predictors have yielded inconclusive results. Nonreplication across studies has been attributed to insufficient statistical power as well as pharmacological and clinical confounders. Prospective studies, standardizing the definitions of response and toxicity, and application of genome-wide approaches may advance the search for genetic predictors of MTX response.
20658239 Assessment of cardiac and pulmonary function in children with juvenile idiopathic arthriti 2012 Jan Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time (IRT) compared to control. Regarding pulmonary function tests, children with JIA showed significant decrease in FVC, PEF, Pimax, Pemax and DLCO compared to normal controls. This decrease was not related to age, height or weight of these patients. There was significant inverse correlation between lung function parameters and the rheumatoid factor titer, erythrosedimentation rate, disease duration and the duration of methotrexate use (P < 0.01). Despite of an asymptomatic cardiopulmonary status, significant systolic and diastolic functional abnormalities exist in children with JIA. Also, both restrictive and obstructive lung impairments were found.
21636626 Chronic polyarthritis as the first manifestation of juvenile systemic lupus erythematosus 2011 Aug OBJECTIVE: To evaluate the prevalence of chronic polyarthritis in juvenile systemic lupus erythematosus (JSLE) and to describe the manifestations, treatments, and outcomes in these patients. METHODS: From January 1983 to July 2010, 5419 patients were followed up at the Pediatric Rheumatology Unit of the University Hospital and 271 (5%) of them had JSLE (American College of Rheumatology [ACR] criteria). 'Rhupus' was classified as the overlap of juvenile idiopathic arthritis (International League of Associations for Rheumatology [ILAR] criteria) and JSLE. We evaluated demographic data, polyarthritis and other clinical manifestations, disease activity and damage, laboratory exams, radiographic findings, treatments, and outcomes. RESULTS: The prevalence of chronic polyarthritis in this JSLE population was 2.6% (7/271). This articular involvement was the initial manifestation in all seven JSLE patients. The median duration of chronic polyarthritis was 11 months (range 2-15 months). Interestingly, rhupus with chronic polyarthritis and limitation of movement, presence of rheumatoid factor, autoantibodies, and/or radiographic abnormalities (juxtaarticular osteopenia, joint-space narrowing, or erosions) was evidenced in three patients. No patient had deformities of hands and feet associated with Jaccoud's arthropathy or osteonecrosis. All patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs, naproxen 10-15 mg/kg/day) when polyarthritis diagnosis was established. Prednisone and antimalarials were administered at JSLE diagnosis. The three non-responsive rhupus patients were treated in conjunction with immunosuppressive drugs (methotrexate, azathioprine, and/or cyclosporine). CONCLUSIONS: Chronic polyarthritis was a rare lupus manifestation in active pediatric patients. The interesting overlap between chronic arthritis and lupus, called rhupus suggests a new entity with a different clinical profile and a poor response to treatment with NSAIDs alone. In addition, the occurrence of this association in JSLE patients could be classified as a clinical sub-group of JSLE with possible specific genetic determinants.