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ID PMID Title PublicationDate abstract
16454534 Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved tolerabili 2006 Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Traditional systemic treatments, including methotrexate, ciclosporin, psoralen plus UVA (PUVA), oral retinoids and fumaric acid esters, are widely used for severe disease and are effective in the short term. Severe psoriasis is a chronic disease and patients and physicians have expressed concerns about possible harm from organ toxicity, such as skin cancer (PUVA), hyperlipidaemia (retinoids), renal (ciclosporin) or hepatotoxicity (methotrexate). Long-term monitoring is required and may not detect early organ damage. The pathophysiology of psoriasis remains to be clarified, but advances toward the understanding of the immunological basis of psoriasis have uncovered the involvement of immunological pathways; for example, the role of tumour necrosis factor (TNF)-alpha, T cell proliferation and T cell activation, and migration to the epidermis. This advancement in knowledge combined with developments in recombinant technologies has led to the development of target-specific therapies. Biological agents are defined as proteins that can be extracted from animal tissue or produced via recombinant DNA technologies and possess pharmacological activity. Adalimumab, alefacept, infliximab, efalizumab and etanercept are examples of biological agents currently used for the treatment of psoriasis. Some of these are also therapy for other autoimmune conditions, such as rheumatoid arthritis and Crohn's disease. These biological agents are effective in psoriasis but raise new safety concerns. Information on the safety of biological agents in conditions such as rheumatoid arthritis and Crohn's disease can not be directly extrapolated to psoriasis. An increased incidence of lymphomas has been postulated to be associated with etanercept, infliximab and adalimumab; serious infections, such as tuberculosis, have also been reported with these three biologicals, all of which target TNF-alpha. Demyelinating disorders, such as multiple sclerosis, have been reported with some biologicals as has congestive heart failure. Alefacept, because of its mechanism of action of lowering the number of active T cells, is associated with low T cell counts. Efalizumab has been associated with thrombocytopenia and haemolytic anaemia. Data on the safety of >2.5 years' continuous treatment with efalizumab are reassuring and a valuable beginning to understanding the role and risk of harm of long-term therapy for a chronic disease. Longer follow-up studies and safety databases, for each of the biologicals used in psoriasis, are needed to ensure both prolonged efficacy and minimal risk of harm.
19019215 T-614, a novel immunomodulator, attenuates joint inflammation and articular damage in coll 2008 INTRODUCTION: T-614 is a novel oral antirheumatic agent for the treatment of rheumatoid arthritis. Whether it has immunomodulatory or disease-modifying properties and its mechanism of action are largely undetermined. METHODS: Rats with collagen-induced arthritis (CIA) were treated with T-614 (5 and 20 mg/kg) daily. Animals receiving methotrexate (1 mg/kg every 3 days) and the nonsteroidal anti-inflammatory agent nimesulide (10 mg/kg per day) were used as controls. A combination therapy group was treated with both T-614(10 mg/kg per day) and methotrexate (1 mg/kg every 3 days). Hind paw swelling was evaluated and radiographic scores calculated. Serum cytokine levels were assessed by Bio-plex analysis. Quantitative PCR was used to evaluate expression of mRNA for interferon-gamma, IL-4 and IL-17. Serum IL-17 and anti-type II collagen antibodies (total IgG, IgG1, IgG2a, IgG2b and IgM) were measured using ELISA. RESULTS: Oral T-614 inhibited paw swelling and offered significant protection against arthritis-induced cartilage and bone erosion, comparable to the effects of methotrexate. CIA rats treated with T-614 exhibited decreases in both mRNA expression of IL-17 in peripheral blood mononuclear cells and lymph node cells, and circulating IL-17 in a dose-dependent manner. T-614 also reduced serum levels of tumor necrosis factor-alpha, IL-1beta and IL-6. A synergistic effect was observed for the combination of methotrexate and T-614. In addition, T-614 (20 mg/kg per day) depressed production of anti-type II collagen antibodies and differentially affected levels of IgG2a subclasses in vivo, whereas IgM level was decreased without any change in the IgG1 level. Together, the findings presented here indicate that the novel agent T-614 has disease-modifying effects against experimental arthritis, as opposed to nimesulide. CONCLUSIONS: Our data suggested that T-614 is an effective disease-modifying agent that can prevent bone/cartilage destruction and inflammation in in CIA rats. Combination with methotrexate markedly enhances the therapeutic effect of T-614.
19033291 Multinational evidence-based recommendations for the use of methotrexate in rheumatic diso 2009 Jul OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
16777581 Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy. 2006 Jun The main objectives of medical therapy in ankylosing spondylitis (AS) are to relieve pain, stiffness and fatigue and to prevent structural damage. The Assessment in Ankylosing Spondylitis Working Group has proposed different domains with specific instruments to assess the efficacy of therapeutic agents classified as symptom-modifying and disease-controlling antirheumatic drugs. Non-steroidal antiinflammatory drugs (NSAIDs) are still the first-line treatment in the management of AS, and they are effective in controlling symptoms such as pain and stiffness and maintaining mobility in many patients. A recent randomized trial suggested that the progression of radiological damage occurs less on continuous use of celecoxib compared with on-demand use. If such findings were confirmed by other studies, the therapeutic value of NSAIDs in AS may extend beyond symptom control. However, for each individual patient, the expected advantages of treatment with NSAIDs should be weighted against any possible gastrointestinal and cardiovascular disadvantages. Disease-modifying antirheumatic drugs (DMARDs) are widely used for second-line therapy in AS, but the evidence for their efficacy is poor. The term 'DMARD' has been borrowed from rheumatoid arthritis, and none of the DMARDs have been shown to prevent or significantly decrease the rate of progression of structural damage which is required to be qualified as a disease-controlling antirheumatic drug for AS. Sulphasalazine is the most extensively studied DMARD and studies suggest some degree of clinical benefit confined to peripheral joint involvement, but no evidence of benefit in axial disease. Methotrexate, which is the gold standard DMARD in rheumatoid arthritis, does not seem to have a substantial therapeutic effect in AS on axial or peripheral joint involvement. Leflunomide appears to exert little beneficial effect, if any, even on peripheral joint involvement. There is also good evidence that local therapy with corticosteroids is effective and may be used in selected patients. Oral corticosteroids may be somewhat effective in relieving the symptoms of AS, but this has not been formally studied. Small studies have reported favourable results with intravenous methylprednisolone pulse therapy, but the effect is temporary. Pamidronate and thalidomide have been used in some preliminary trials but need further studies to assess their potential role in treating AS patients resistant or intolerant to other forms of treatment. Treatment with tumour necrosis factor blockers is not discussed in this review.
16406545 Retrospective case review of pediatric patients with uveitis treated with infliximab. 2006 Feb PURPOSE: To assess the response and adverse events associated with infliximab treatment for refractory, noninfectious pediatric uveitis. DESIGN: Retrospective noncomparative case series of pediatric patients with refractory uveitis treated with infliximab. PARTICIPANTS: Six patients were identified. Diagnoses of the participants included idiopathic uveitis (n = 1), juvenile rheumatoid arthritis with uveitis (n = 3), idiopathic retinal vasculitis with uveitis (n = 1), and bilateral pars planitis, with vitreitis and papillitis of the left eye (n = 1). Uveitis developed in the patients (5 female, 1 male) at a mean age of 9.0 years (+/-5.0 years; range, 0.9-14.8 years). All patients had bilateral eye involvement. These patients were refractory to or dependent on topical steroids (n = 4), oral prednisone (n = 3), or both, and were also refractory to the following therapies: methotrexate (n = 6), cyclosporine (n = 3), mycophenolate mofetil (n = 3), etanercept (n = 3), and daclizumab (n = 1). INTERVENTION: All patients initially received infliximab at doses between 5 and 10 mg/kg at 2- to 4-week intervals, and then were maintained at 4- to 8-week intervals at doses of 5 to 18 mg/kg. Mean follow-up time on treatment has been 48.1 weeks (+/-14.9 weeks; range, 32-74 weeks). MAIN OUTCOME MEASURES: Primary outcome measures included the quantitative measurement of the amount of ocular inflammation in different locations within the eye. Patients were monitored for infusion reactions as well as other potential side effects. The children's clinical status, complete blood counts, and liver function panels were monitored by pediatric rheumatologists every 6 weeks. RESULTS: All 6 patients showed reduction in their intraocular inflammation after infliximab therapy was initiated. Furthermore, control of ocular inflammation was achieved while receiving infliximab therapy. Topical and systemic corticosteroids were able to be discontinued in all patients except for 1 patient, who is currently weaning off prednisone. The only adverse reactions seen were the development of vitreous hemorrhage in 1 patient and a case of transient upper respiratory infusion reaction. No patient has had to discontinue treatment. CONCLUSIONS: Infliximab seems to be an effective agent for the treatment of refractory pediatric uveitis without apparent serious toxicity in this series of patients.
18062353 The therapy of Sjogren's syndrome: a review. 2007 Sep The Sjogren's syndrome (SS) is an chronic inflammatory autoimmune disease of the exocrine glands as well as of internal apparatus. The therapy of exocrinopathy is represented by parasympathomimetic drugs such as pilocarpine and cevimeline. The therapy of systemic manifestations, actually is represented by the inhibitors of TNF alfa, as well as leflunomide, methotrexate and cyclosporine-A, but the results are quite insufficient and disappointed. In order to the involvement of B-cell function in the pathogenesis of SS, one of the most important option in the future should be specific inhibitors of that cells.
18601859 [Effects of Tongbi Mixture 2 on expressions of CD28 and CD152 and content of tumor necrosi 2008 Jul OBJECTIVE: To study the effects of Tongbi Mixture 2, a compound traditional Chinese herbal medicine for treating rheumatoid arthritis (RA), on immunoregulation of T lymphocytes in rats with collagen-induced arthritis (CIA). METHODS: Forty Wistar rats were randomly divided into normal control group, untreated group, Tongbi Mixture 2-treated group, methotrexate (MTX)-treated group and Tripterygium wilfordii polyglycoside (TWP)-treated group. Except for the rats of the normal control group (injection with normal saline), rats of the other four groups were subcutaneouly multipoint-injected with collagen protein II to induce CIA. The rats were treated with normal saline, Tongbi Mixture 2, MTX tablets and TWP tablets respectively for 36 days. The expressions of CD28 and CD152 were detected by flow cytometry, while the content of tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme-linked immunosorbent assay. RESULTS: The expression of CD28 among the three drug treated groups had no statistical difference (P>0.05), while significantly higher than that of the normal control group (P<0.01) and lower than that of the untreated group (P<0.01). The expression of CD152 in the Tongbi Mixture 2 treated-group was lower than those of the MTX- and TWP-treated groups (P<0.05, P<0.01), but had no statistical difference as compared with the normal control group (P>0.05). There were no statistical differences in content of TNF-alpha between the drug treated groups and the normal control group (P>0.05), but the content of TNF-alpha of the drug treated groups was lower than that of the untreated group (P<0.05 or P<0.01). CONCLUSION: Tongbi Mixture 2 can inhibit T lymphocytes through down-regulating the expressions of CD28 and CD152 and the content of TNF-alpha, which may be the major mechanisms in treating RA.
17006270 Epstein-Barr virus associated Hodgkin lymphoma in a 9-year-old girl receiving long-term me 2006 Sep We describe a case of Hodgkin lymphoma developing in a 9-year-old girl with polyarticular, rheumatoid factor-positive juvenile idiopathic arthritis treated with methotrexate (MTX), prednisone, and naproxen for 5 years. Pathologic and molecular analyses revealed that the Hodgkin cells contained Epstein-Barr virus and the viral DNA was monoclonal. She achieved complete remission after MTX withdrawal, chemotherapy, and radiation. To the best of my knowledge, this is the sixth report of Hodgkin lymphoma in patients with juvenile idiopathic arthritis receiving low dose MTX therapy.
16700080 Changes in use of disease-modifying anti-rheumatic drugs in Australia over the period 1992 2006 Jul PURPOSE: Evidence is growing that early use of disease-modifying anti-rheumatic drugs (DMARDs) and combinations of these drugs provide optimal care for people with rheumatoid arthirits. The aim of this study was to describe objectively the pattern of consumption of DMARDs in the Australian community (community-based prescribing, specialist and general practitioner) 1992-2004, and to compare this with prescribing patterns reported in other countries. METHOD: Dispensing statistics from the Pharmaceutical Benefit Scheme (PBS-Australia's universal prescription subsidy scheme) were analysed and temporal trends evaluated. Drug consumption was calculated as the number of dispensed defined daily doses (DDD)/1000 inhabitants/day (WHO ATC/DDD classification 2005). RESULTS: The consumption of DMARDs in the Australian community increased steadily from 2.6 DDD/1000 inhabitants/day in 1992 to 5.5 DDD/1000 inhabitants/day. Over the period 1992-2004, methotrexate (MTX) was the most commonly used DMARD (from 0.6 to 3.0 DDD/1000 inhabitants/day). Consumption of gold (parenteral and oral) and penicillamine declined during this time. The inclusion of leflunomide on the PBS in 2000 contributed to the increase in DMARD usage. CONCLUSION: Use of DMARDs within the Australian community has increased in recent years, coinciding with the change in guidelines for therapy for rheumatoid arthritis (RA) to earlier use of DMARDs and the more common use of combinations. This study used DDD methodology to quantify trends for DMARD consumption and these trends are broadly consistent with international prescribing patterns assessed using different methodologies.
16646003 A comparison of response criteria to evaluate therapeutic response in patients with juveni 2006 May OBJECTIVE: There are no validated criteria to evaluate clinical response in juvenile idiopathic arthritis (JIA). The purpose of this study was to compare 4 sets of criteria (2 from the American College of Rheumatology [ACR] and 2 from the European League Against Rheumatism [EULAR]) for clinical response evaluation in JIA patients treated with methotrexate and/or anti-tumor necrosis factor alpha drugs. METHODS: Seventy-five patients with JIA were evaluated at baseline and after 6 months of therapy with second-line drugs. Mean age at study onset was 12.8 years (range 2-32.9 years). Diagnoses were systemic JIA (n = 16), rheumatoid factor-positive JIA (n = 5), rheumatoid factor-negative JIA (n = 9), persistent oligoarticular JIA (n = 10), extended oligoarticular JIA (n = 33), and psoriatic arthritis (n = 2). Clinical response was evaluated with the ACR Pediatric 30 criteria and the ACR 20% response criteria (ACR20), and with the EULAR Disease Activity Score (DAS) and 28-joint DAS (DAS28). Patients with EULAR criteria responses of "good" or "moderate" were classified as responders. Responders and nonresponders according to the different criteria were then compared. RESULTS: For patients younger than 16 years, Cohen's kappa varied between 0.51 and 0.72, with a good-to-excellent reproducibility index for all comparisons, except for the DAS28/ACR20 comparison. The best agreement was obtained by comparing the DAS and the ACR Pediatric 30. For patients older than 16 years, the reproducibility index was good or excellent in only 2 cases, i.e., comparing the DAS and the ACR Pediatric 30 and comparing the DAS and the DAS28 (as expected). CONCLUSION: Our study shows a good agreement overall for the different criteria tested. The highest concordance was observed between the DAS and the ACR Pediatric 30, the lowest between the DAS28 and the ACR20. Our data suggest that the ACR Pediatric 30 criteria can be used also in adult patients affected by JIA, and that the original DAS can be an alternative to the ACR Pediatric 30 in both children and young adults with JIA.
17875071 Pulmonary lymphoma developed during long-term methotrexate therapy for psoriasis. 2007 Sep Low dose weekly administration of methotrexate has been thought to be effective for both rheumatoid arthritis (RA) and psoriasis. However, there is a possibility that methotrexate therapy may be oncogenic. This report presents a case of pulmonary lymphoma developed during long-term methotrexate therapy for psoriasis. Physicians should be aware that Epstein-Barr virus-associated lymphoproliferative disorders that occur during treatment with methotrexate are not specific to patients with RA.
17101059 Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 ad 2006 Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A3 adenosine receptor (A3AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A3AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A3AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A3AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A3AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A3AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A2AAR and A3AR over-expression in paw cells from treated animals. Moreover, increased A3AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A3AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A3AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA.
18494155 [The liver and methotrexate]. 2008 Feb Methotrexate is proposed for the treatment of inflammatory disorders such as rheumatoid arthritis, psoriasis and Crohn's disease. The liver toxicity of methotrexate has been investigated and prolonged treatment can induce liver fibrosis. Moreover, alcohol consumption, diabetes and obesity are associated with liver fibrosis in patients treated with this drug. Therefore, liver fibrosis associated with methotrexate could be due to associated factors instead of methotrexate itself. Recommendations to monitor and diagnose methotrexate induced liver damage vary depending on the disease. Frequent evaluation of liver fibrosis with liver biopsy is recommended during therapy, especially in patients treated for psoriasis. Noninvasive methods, such as the FibroScan, could be useful for the assessment of liver fibrosis associated with methotrexate and hence, need further evaluation.
17538801 Folic acid in general medicine and dermatology. 2007 Folic acid is a vitamin B essential for the integrity and function of DNA. Relative deficiency of folic acid may occur in conditions such as pregnancy and hyperproliferative or chronic inflammatory disorders. Folic acid supplementation has been proven to be beneficial in the prevention of neural tube defects and in limiting methotrexate side effects, and may reduce the risk of colorectal cancer. Folate is a critical vitamin in determining plasma homocysteine levels, which in turn is a major risk factor for cardiovascular diseases. The results of large clinical trials with dietary supplementation of folic acid, vitamin B12 and vitamin B6 have shown that this homocysteine-lowering therapy is effective in the secondary prevention of non-fatal strokes, but had no effect in the prevention of fatal cardiovascular diseases. Hyperhomocysteinemia has also been reported in age-related neurological conditions with cognitive impairment (e.g. dementia), and psychiatric disorders such as depression. Elevated homocysteine levels are frequent in patients with chronic immune-mediated disorders including rheumatoid arthritis, systemic lupus erythematosus, chronic plaque psoriasis and psoriatic arthritis, which have in common a tendency to an accelerated atherosclerosis leading to increased deaths from cardiovascular events. Folic acid supplementation appears as a reasonable therapeutic option in patients affected by chronic inflammatory skin diseases, such as moderate to severe psoriasis; in particular, those with concomitant hyperhomocysteinemia, low plasma folate and additional cardiovascular risk factors.
18516314 Update on the treatment of ankylosing spondylitis. 2007 Dec Non-steroidal anti-inflammatory agents (NSAIDs) remain the mainstay of treatment for ankylosing spondylitis (AS) though one recent trial suggests that continuous as opposed to on-demand use may be superior in preventing progression of structural damage. One particular NSAID, which is a highly selective cyclo-oxygenase 2 inhibitor, etoricoxib, may be superior to standard NSAIDs for AS. Second-line agents typically used for rheumatoid arthritis appear to lack efficacy. Salazopyrin is only moderately effective in the subgroup of AS patients with concomitant peripheral arthritis and not in those with purely axial disease. A recent trial showed that there is no greater efficacy in patients presenting early in their disease course. Three anti-tumor necrosis factor alpha agents, infliximab, etanercept, and adalimumab, are now available for the treatment of AS, the latest being adalimumab. All possess similar clinical efficacy in phase III trials with response rates of about 60%. Imaging studies using magnetic resonance show substantial amelioration of inflammatory lesions in the spine and sacroiliac joints. There is as yet no evidence that any of these agents prevent progression of structural damage. One study that evaluated etanercept demonstrated no impact on damage progression. Increasing evidence points to the superiority of the two monoclonal antibodies, infliximab and adalimumab, over etanercept for the treatment of extra-articular manifestations typically seen in AS such as acute anterior uveitis and inflammatory bowel disease. All three agents can be used as monotherapy and concomitant methotrexate appears to offer no advantages although insufficient doses have been used to date. Future studies should target patients earlier in their disease course as well as those with adverse prognostic factors such as elevated serum metalloproteinase 3 levels and radiographic evidence of spinal ankylosis.
16678646 Treatment of psoriatic arthritis with etanercept, methotrexate, and cyclosporin A. 2006 Feb BACKGROUND: Psoriatic arthritis (PsA) is seen in approximately 5% to 42% of individuals with psoriasis. CASE SUMMARY: A 37-year-old white male weighing 90 kg presented with erythrodermic psoriasis and PsA. The overall duration of PsA was 3 years. Serum levels of glucose, electrolytes, and tumor markers were normal, as were the results of tests of hepatic and renal function and urinalysis. The findings of posteroanterior radiographic examination of the chest were also normal. However, radiographic examination showed porosis and degeneration in the lumbar vertebrae; narrowing of the L2-L3, L3-L4, and L5-S1 spaces; degenerative changes and narrowing of the proximal interphalangeal and distal interphalangeal (DIP) joints; and osseous ankylosis of the DIP joints of the hands. The cutaneous eruption improved with cyclosporin A (CsA) 3.5 mg/kg p.o., but the severity of PsA did not change. Therefore, parenteral methotrexate (MTX) 15 mg/wk and an indomethacin suppository 100 mg/d were added to the regimen. CsA and MTX were continued for 3 months, during which the patient's PsA symptoms did not abate, based on tender and swollen joint counts, hand-to-floor distance, erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), antistreptolysin O, and rheumatoid factor. Therefore, etanercept 25 mg s.c. twice weekly was added to the regimen. Three weeks after the initiation of this combination, the patient's arthritis had improved. The visual analog scale score decreased from 9 to 4. Tender and swollen joint counts decreased from 28 and 24 to 15 and 10, respectively. The hand-to-floor distance decreased from 20 to 10 cm. The erythrocyte sedimentation rate and levels of CRP, antistreptolysin O, and rheumatoid factor decreased from 72 mm/h, 162 mg/L, 250 IU/mL, and 304 IU/mL at baseline to 23 mm/h, 64 mg/L, 48 IU/mL, and 56.1 IU/mL, respectively. No change was observed in radiographs of the patient's back, hands, and feet. Based on the American College of Rheumatology scoring system, the patient showed 50% improvement in disease severity. Etanercept was discontinued at the end of 4 weeks, and maintenance therapy was continued with MTX alone. No adverse events were reported during or after the completion of etanercept therapy. CONCLUSION: In this patient with PsA that was refractory to CsA and MTX, either alone or in combination, the severity of PsA was reduced after 4 weeks of the combined use of etanercept, CsA, and MTX.
17113808 Polymyalgia rheumatica: diagnosis and treatment. 2006 Dec Polymyalgia rheumatica (PMR) typically manifests as inflammatory pain in the shoulder and/or pelvic girdles in a patient over 50 years of age. This condition was long underrecognized and therefore underdiagnosed. Today, however, overdiagnosis may occur. Physicians must be aware that many conditions may simulate PMR, including diseases that carry a grim prognosis or require urgent treatment. PMR may be the first manifestation of giant cell arteritis, and a painstaking search for other signs is mandatory. PMR may inaugurate other rheumatologic diseases such as rheumatoid arthritis, RS3PE syndrome, spondyloarthropathy, systemic lupus erythematosus (SLE), myopathy, vasculitis, and chondrocalcinosis. Finally, PMR may be the first manifestation of an endocrine disorder, a malignancy, or an infection. Failure to respond to glucocorticoid therapy should suggest giant cell arteritis, malignant disease, or infection. Ultrasonography may assist in the diagnosis by showing bilateral subdeltoid bursitis. Glucocorticoids are the mainstay of the treatment of PMR. Although the optimal starting dosage and tapering schedule are not agreed on, a low starting dosage and slow tapering may decrease the relapse rate. Methotrexate is probably useful when glucocorticoid dependency develops. In contrast, TNF-alpha antagonists are probably ineffective.
17110316 Malignancies and soluble tumor antigens in rheumatic diseases. 2006 Nov Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplastic syndromes is important, as it may lead to an early diagnosis of cancer. There is some evidence that systemic inflammatory diseases, such as rheumatoid arthritis (RA), lupus, scleroderma or dermatomyositis may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. However, reports are somewhat controversial. Immunosuppressive and cytotoxic drugs used in antirheumatic therapy, such as methotrexate, cyclophosphamide, azathioprine or anti-TNF biologicals may also lead to the development of such tumors. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in RA and other autoimmune diseases.
16540551 Reactive haemophagocytic syndrome in adult-onset Still's disease: a report of six patients 2006 Dec OBJECTIVE: To examine the prevalence and characteristics of patients with reactive haemophagocytic syndrome (RHS) complicating adult-onset Still's disease (AOSD). METHODS: Of 50 patients with AOSD fulfilling Yamaguchi and Fautrel criteria followed in our department, clinical and laboratory data, course and treatment of six patients with histologically proven RHS and without any obvious cause other than AOSD were retrospectively recorded. RESULTS: RHS led to AOSD in two cases, whereas it appeared after a mean duration of 3.5 years from onset of AOSD in the other cases. The main symptoms were fever (n = 6), polyarthralgias or myalgias (n = 4), lymphadenopathy or splenomegaly (n = 3), pharyngitis (n = 3), rash (n = 3), pleuritis (n = 3), hepatomegaly (n = 1), normal or low leucocyte count (n = 4), anaemia (n = 6), lymphocytopenia (n = 6), thrombocytopenia (n = 4), hyperbasophilic lymphocytes (n = 2), abnormal liver function tests (n = 6) and increased serum triglyceride level (n = 6). Serum ferritin concentration was constantly increased (>10,000 microg/l in five cases, with <5-35% in glycosylated form). Two patients presented with coagulopathy. Treatment comprised corticosteroids (n = 4) and intravenous immunoglobulins (n = 3), whereas prednisone was unchanged in one case. One death due to pneumonia occurred 15 days after RHS. With a follow-up ranging from 2 to 7.5 years, the other patients were in remission with prednisone plus etanercept (n = 1), prednisone plus methotrexate (n = 1), low-dose prednisone (n = 2) or without treatment (n = 1). CONCLUSION: RHS is not uncommon in AOSD. It should be evoked in a patient with AOSD in the absence of hyperleucocytosis, thrombocytopenia, lymphopenia and coagulopathy, or in the presence of high serum ferritin and triglyceride levels.
18349863 A paraneoplastic case of palmar fasciitis and polyarthritis syndrome. 2008 May BACKGROUND: A 58-year-old woman presented with arthritis of the small joints of her hands and rapidly progressive joint contractures. She was wheelchair bound within 2 months of the onset of her symptoms. Physical examination revealed synovitis of the small joints of her hands and palmar fasciitis. The patient had been diagnosed with pancreatic carcinoma approximately 1 year before the presentation of her rheumatic symptoms, and had undergone radical pancreatico-duodenectomy. INVESTIGATIONS: Physical examination; routine laboratory work, including full blood count and measurement of erythrocyte sedimentation rate and C-reactive protein; serological tests for rheumatoid factor, antinuclear antibodies and extractable nuclear antibodies; measurement of serum tumor markers; radiological investigations, including X-rays of her hands and feet, whole-body CT-scans and radioisotope bone scan. DIAGNOSIS: The patient's rheumatic presentation was diagnosed as a paraneoplastic syndrome associated with pancreatic carcinoma. MANAGEMENT: The patient's condition was managed with corticosteroids and methotrexate. No residual tumor or evidence of metastatic disease have been detected in the 1.5 years since the initial presentation of her rheumatic symptoms.