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ID PMID Title PublicationDate abstract
15202729 ISAtx-247 (Isotechnika/Roche). 2004 May ISAtx-247 is a ciclosporin A analog under development by Isotechnika and Roche as an immunosuppressant for the potential prevention of organ rejection after transplantation, and for the potential treatment of autoimmune diseases such as rheumatoid arthritis, psoriasis and type 1 diabetes. A phase II renal transplantation study had been completed by June 2003.
14769518 Quantitative ultrasonography and magnetic resonance imaging of the parotid gland: can they 2004 Jan OBJECTIVE: To assess the diagnostic value of parotid gland quantitative assessment using ultrasound (US) as well as magnetic resonance imaging (MRI) in patients with Sjogren's syndrome (SS) and to evaluate the possibility of using such modalities as a predictor of the histopathologic score of salivary gland biopsy in this group of patients. METHODS: Sonographic and MRI studies were performed on the parotid glands of 47 patients diagnosed to have primary SS, 20 healthy control subjects of matched sex and age, and 20 subjects with sicca symptoms but without any evidence of SS. The patients and the control subjects were scored according to the structural changes seen in both radiologic modalities. In addition, sialography and labial gland biopsy were done for all patients as well as the control subjects and scored according to the degree of affection. RESULTS: Parenchymal inhomogenity (PIH) was seen in 93.6% of the patients studied by US, while nodular pattern was seen in 97.8% in the MRI study. The US and MRI results correlated significantly with the histopathologic score of the minor salivary glands (r = 0.82, 0.84, respectively) as well as sialography score (r = 0.69, 0.60, respectively). There was good agreement between US and MRI findings (r = 0.87) in both SS cases and control subjects. CONCLUSION: US and MRI are equally sensitive tools for the diagnosis of salivary involvement in patients with SS. Quantitative assessment of US and MRI images seem to represent an advance in the diagnosis of SS as they offer a good prediction of the pathology score of the salivary gland. MRI seems unnecessary as a routine diagnostic tool and should be considered as the second option in case of normal US.
15163114 Sinus histocytosis with massive lymphadenopathy (Rosai-Dorfman disease) in a patient with 2004 Sinus histocytosis with massive lymphadenopathy is a rare disease that has been described by Rosai and Dorfman. It is characterized by massive, cervical lymphadenopathy, with extranodal manifestations in about 40% of patients. It occurs as a distinct entity, never associated with other diseases, and in most cases the prognosis is good. Lymphadenopathy is also a frequent sign of patients with primary Sjogren's syndrome (SS), usually associated with disease activity or concurrent infection. However, excessive lymphadenopathy in SS patients is a sign of lymphoproliferative disorder development. In this report, we describe a patient with primary SS, and excessive lymphadenopathy and splenomegaly who developed Rosai-Dorfman disease, and we discuss the possible aetiopathophysiological mechanism linking these two entities.
11830822 Chronic synovitis caused by a date palm thorn: An unusual clinical picture. 2002 Feb Synovitis related to plant thorns is a rare pathology. As in this case, thorn prick injury, which is particularly caused by thin palm thorns, is frequently missed in clinical history. Clinical presentation of cases may simulate juvenile rheumatoid arthritis with monoarticular involvement and septic arthritis. Removal of all thorns with partial or total synovectomy is essential in definitive treatment. Arthroscopy is the most valuable method of meeting both diagnostic and therapeutic purposes as it provides the best visibility of the joint with lower morbidity.
15286090 Pharmacokinetics of meloxicam in patients with juvenile rheumatoid arthritis. 2004 Aug The pharmacokinetics of a meloxicam suspension were studied in 18 children with juvenile rheumatoid arthritis. Children received a single 0.25-mg/kg dose up to a maximum of 15 mg. Pharmacokinetic parameters after the first dose were calculated by noncompartmental methods. Geometric mean (percent coefficient of variation for geometric mean [gCV]) C(max), AUC(0- infinity ), apparent clearance, apparent volume of distribution, and elimination half-life values were 1.24 microg/mL (47% gCV), 25.6 microg x h/mL (81% gCV), 0.17 mL/min/kg (83% gCV), 0.19 L/kg (63% gCV), and 13.4 hours (54% gCV) in the younger group and 1.89 microg/mL (25% gCV), 35.8 microg x h/mL (21% gCV), 0.12 mL/min/kg (23% gCV), 0.13 L/kg (22% gCV), and 12.7 hours (21% gCV) for the older group, respectively. Area under the curve, volume of distribution, and clearance tended to be higher in the younger group, whereas elimination half-lives were similar. A post hoc comparison to pharmacokinetic data in adults revealed no relevant differences. Thus, a common body weight-normalized dose is considered appropriate for children older than 2 years.
15002354 [Synovectomy of the knee joint]. 2003 PURPOSE OF THE STUDY: In this retrospective study, the results of arthroscopic and open synovectomy and radiosynovectomy with the use of Yttrium-90 colloid are evaluated. MATERIAL: In a group of 48 patients with different underlying diseases, 51 knee joints were treated by synovectomy in the years 1996 to 2001. Of these, 16 knees were treated by arthroscopic synovectomy (ASS group), nine by open synovectomy (OS group) and 26 by Yttrium 90 radiosynovectomy (YR). The average age was 67 years (range, 30 to 81) and average follow-up was 18 months. The patients' diagnoses involved grade I, II and III gonarthritis in three, 21 and 15 cases, respectively, Lyme disease in one patient, gouty arthropathy in one, rheumatoid arthritis in three and pyogenic arthritis in seven cases. METHODS: The evaluation was based on three aspects as follows: Subjective feelings of the patient: A, no complaints; B, intermittent complaints; C, no improvement. Joint function and range of motion on clinical examination: A, full function; B, slight motion restriction; C, severe restriction. Recurrence of synovitis: A, no recurrence; B, intermittent and short-term recurrence; C, no improvement. RESULTS: The ASS group showed a high recurrence rate, with no improvement in 44% of the patients. No recurrence was recorded in the OS group. In the patients treated for pyogenic arthritis, 40% had a slight and 40% a severe restriction of joint motion, which is an alarming outcome. In the YR group, radiosynovectomy was effective particularly in the patients with grade I and grade II gonarthritis. DISCUSSION: In our groups, only a low number of patients were diagnosed with rheumatoid arthritis, in contrast to the relevant studies mostly including patients with this disorder. However, the high recurrence rate in our ASS group is in agreement with the results of other authors. In comparison to open synovectomy, with no recurrence of synovitis, arthroscopic synovectomy is less radical and does not involve the fibrous capsule. Therefore, the remaining areas of the synovial membrane may give rise to recurrent synovitis. CONCLUSIONS: Arthroscopic synovectomy is a minimal invasive but demanding surgical procedure associated with a high recurrence of synovitis. Open synovectomy is a radical intervention with minimum recurrences but is associated with a risk of a restricted range of motion if healing is not complete. It is not suitable for treatment of pyogenic arthritis. Radiosynovectomy is a safe and economic method, with no need of subsequent rehabilitation, which is effective in patients with a milder form of synovitis.
12384930 The early pattern of joint involvement predicts disease progression in children with oligo 2002 Oct OBJECTIVE: To evaluate features during the first 6 months of disease that may be associated with a poor outcome as measured principally by extension to a polyarticular disease course in patients with oligoarticular-onset juvenile rheumatoid arthritis (oligo-JRA). METHODS: This study was a retrospective review of patients who fulfilled the American College of Rheumatology criteria for oligo-JRA, were followed up for at least 5 years, and did not have juvenile psoriatic arthritis, spondylarthropathy-like disease, or rheumatoid factor positivity. Data from the first 6 months of disease were collected. Continuous variables were dichotomized and then screened by univariate analysis for association with poor outcome at the last followup visit, as measured by extension of involvement (>4 accumulated involved joints) and by "clinically meaningful" extension (> or =10 accumulated joints). Variables significantly associated with this latter outcome, with the addition of disease duration as a confounding independent variable, were included in a multiple logistic regression analysis. The same variables were then examined in separate multiple logistic regression models to look at other measures of outcome, including use of disease-modifying antirheumatic drugs (DMARDs) at any time, erosive disease on radiographs, any remission of disease ever occurring, physician's global assessment of disease activity at the last visit, and disability as measured by the Childhood Health Assessment Questionnaire (C-HAQ)/HAQ. RESULTS: Of the 205 patients (160 of whom were female) studied for a median of 10.8 years (range 5-26.6 years), 39.5% developed extension to >4 joints and 17.6% developed arthritis in > or =10 joints. Using the logistic regression model, symmetric disease was predictive of all measures of poor outcome: extension to > or =10 joints (odds ratio [OR] 19.2), the need to use DMARDs (OR 11.5), radiographic demonstration of erosive disease (OR 4.73), inflammatory activity at last followup visit (OR 3.23), no remission of disease (OR 4.73), and disability as measured by a C-HAQ score >0.12 (OR 2.95). Ankle and/or wrist disease was predictive of extension (OR 6.61) and erosions (OR 3.59). Wrist disease alone was predictive of the need to use DMARDs (OR 5.87) and of inflammatory disease activity at the last followup visit (OR 4.01). An elevated erythrocyte sedimentation rate (ESR) was predictive of extension (OR 3.76), the need to use DMARDs (OR 6.47), and no remission of disease (OR 2.30). Disease duration was a confounding variable for extension (OR 1.18) and erosive disease (OR 1.19). CONCLUSION: The early presence of ankle and/or wrist disease, symmetric joint involvement, and an elevated ESR in a child with oligo-JRA indicates the likelihood of disease progression.
12223982 Attained adult height in juvenile rheumatoid arthritis with or without corticosteroid trea 2002 Sep Growth impairment has been described in patients with juvenile rheumatoid arthritis (JRA). Both the direct action of underlying disease and prolonged corticosteroid usage for disease management may contribute to growth impairment. The purpose of this retrospective study was to evaluate the effect of systemic corticosteroid treatment on attained adult height in patients with JRA. We reviewed patients who first visited our hospital from 1973 to 1995 with a diagnosis of JRA. Adult height (AH) and the reported parental heights of these patients were recorded. Target height (TH) is estimated according to midparental height. Patients who never had or had only transient (less than 1 week) systemic corticosteroid therapy were classified as group 1. Group 2 included patients who had corticosteroid therapy for more than 1 week but never continuously for more than 12 months, and group 3 included patients on long-term steroid treatment (continuously for more than 1 year). Height data were analysed using adult height and the difference between adult height and target height (AH minus TH). Thirty-three patients fulfilling the diagnostic criteria for JRA were reviewed. Fourteen belonged to group 1, 13 to group 2 and six to group 3. The difference between adult height and target height in group 1 was 2.96 +/- 4.54 cm, in group 2 0.71 +/- 6.08 cm (group 1 vs. group 2, P = 0.28), and in group 3 -11.65 +/- 10.71 cm (group 1 vs. group 3, P<0.05). In 15 patients who never received corticosteroid therapy continuously for more than 1 year, AH-TH was statistically correlated neither with the cumulative corticosteroid exposure dose nor with cumulative corticosteroid exposure period by linear regression ( P = 0.408, P = 0.278, respectively). We concluded that continuous systemic corticosteroid usage for less than 1 year does not affect attained adult height in JRA patients; however, prolonged corticosteroid treatment for more than 1 year can lead to irreversible growth impairment.
15378386 Ocular manifestations of juvenile rheumatoid arthritis in Olmsted County, Minnesota: a pop 2005 Mar BACKGROUND: Juvenile rheumatoid arthritis (JRA) is the most common systemic cause of uveitis in Europe and North America. The cumulative incidence of uveitis in JRA has been reported at between 8.5% and 25% in series from referral centers in the USA. There have been no population-based studies of the cumulative incidence of uveitis in JRA in the USA. METHODS: We performed a population-based, retrospective cohort study of patients residing in Olmsted County, Minnesota between 1 January 1960 and 31 December 2000 who met American College of Rheumatology diagnostic criteria for JRA. The patients were identified using the Rochester Epidemiology Project (REP), a surveillance and medical records-linkage system which provides access to medical records of residents of Olmsted County. Patient histories were reviewed and information regarding rheumatic and ocular disease was extracted and analyzed. The main outcome measures were: cumulative incidence of uveitis, of complications of uveitis, of keratoconjunctivitis sicca (KCS) and of adverse visual outcome. RESULTS: Of the 88 patients identified, three patients developed uncomplicated uveitis [3.4%; 95% confidence intervals [CI] 0.7-9.6%), all with pauciarticular onset JRA. Two patients developed KCS (2.3%; 95% CI 0.3-8.0%). The visual acuity of these five patients at last follow-up (mean length of follow-up 22.6 years, range 8-36 years) was 20/20. There were no patients with visual loss attributable to JRA. CONCLUSIONS: In a population-based study of JRA in the United States, uveitis occurred at a lower frequency than expected. In the limited number of cases in this cohort with JRA-associated ophthalmologic complications there was no resulting loss of visual acuity.
14719217 Angiotensin converting enzyme gene insertion-deletion polymorphism is associated with juve 2003 Dec OBJECTIVE: To investigate the incidence of angiotensin converting enzyme (ACE) gene insertion-deletion (I/D) polymorphism genotypes in children with juvenile rheumatoid arthritis (JRA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism influences the plasma and tissue levels of ACE and has an involvement in inflammatory mechanisms. METHODS: The incidence of ACE gene I/D polymorphism genotypes was determined in 82 children with JRA from Kuwait and compared to that in 48 ethnically matched healthy controls using polymerase chain reaction. RESULTS: A considerably higher incidence of II genotype was observed in the JRA patients compared to controls (p < 0.003). In contrast, no statistically significant difference was detected in the incidence of DD and ID genotypes in JRA patients and controls (p = 0.276 and 0.460, respectively). The incidence of ACE gene polymorphism genotypes was also studied in clinical subclasses of JRA patients and controls. There was no significant difference in the incidence of DD and ID genotypes in either of the 3 JRA subclasses (oligoarticular, polyarticular, and systemic) when compared to controls. However, the incidence of II genotype was found to be significantly higher in all the 3 JRA subclasses compared to controls. The strongest association between II genotype and JRA subclasses was detected in systemic JRA, followed by oligoarticular and polyarticular JRA. This was also reflected in a higher prevalence of I-allele in the systemic JRA cases (13/26, 50%) compared to the D-allele (11/26, 42%). In contrast, D-allele of the ACE gene was more prevalent in oligoarticular and polyarticular JRA cases, than the I-allele (61% and 58%, respectively). CONCLUSION: Our data suggest a significant association of the I-allele of the ACE gene I/D polymorphism with the 3 clinical subclasses of JRA in children, and the highest association was observed in systemic JRA cases.
15201598 Recent advances in the management of psoriatic arthritis. 2004 Jul PURPOSE OF REVIEW: The incidence of psoriatic arthritis is currently estimated at 7 to 42% of the population with active psoriasis, considered to affect 2 to 3% of the general population. Unmanaged psoriatic arthritis may result in progressive radiologic erosion, severe physical limitations, and disability. Newer trials in psoriatic arthritis therapy demonstrate ongoing ability to control disease symptoms and signs and the progression of the disease significantly. RECENT FINDINGS: Recognition of the immunopathogenesis of psoriatic arthritis, as with rheumatoid arthritis and psoriasis, prompts ongoing examination of the efficacy of several disease-modifying antirheumatic drugs. A new crop of biologics and pharmaceuticals with increased molecular specificity compared with traditional immunosuppressant disease-modifying antirheumatic drugs have been shown to be highly effective in inhibiting the symptoms and progression of psoriatic arthritis with less severe side effects. SUMMARY: Therapies either recently approved or pending approval by the Food and Drug Administration for psoriatic arthritis management are safe and effective in the treatment of symptoms, significantly improve quality of life, and prevent long-term progression of the disease.
11920410 Long-term risk of mortality and lymphoproliferative disease and predictive classification 2002 Mar OBJECTIVE: Primary Sjögren's syndrome (SS) may lead to lymphoproliferative disease (LPD) and death in certain patients. We sought to determine the incidence and predictors of adverse long-term outcomes to achieve a rational predictive classification of the syndrome. METHODS: Predictive modeling was performed in a cohort of 723 consecutive patients with primary SS (587 newly diagnosed [incident] cases and 136 prevalent cases). RESULTS: During 4,384 person-years of followup, we recorded 39 deaths (7 due to lymphoma) and 38 diagnoses of LPD. The standardized mortality ratio was 1.15 (95% confidence interval [95% CI] 0.86-1.73) compared with the general population of Greece. In incident cases, the probability of LPD was 2.6% at 5 years and 3.9% at 10 years. Mortality rates were significantly higher in patients with low C4 levels at the first study visit (hazard ratio [HR] 4.39, 95% CI 2.18-8.83). LPD was independently predicted by the presence of parotid enlargement (HR 5.21, 95% CI 1.76-15.4), palpable purpura (HR 4.16, 95% CI 1.65-10.5), and low C4 levels (HR 2.40, 95% CI 0.99-5.83) at the first study visit. All patients who eventually developed lymphoma resulting in death during the followup period had either low C4 levels or palpable purpura at the first study visit. Training-validation split-cohort modeling confirmed the predictive importance of low C4 levels and palpable purpura, both of which were present in 20.9% of patients at their first visit. CONCLUSIONS: In patients with primary SS, 1 in 5 deaths is attributable to lymphoma. The presence of palpable purpura and low C4 levels at the first visit adequately distinguishes high-risk patients (type I primary SS) from patients with an uncomplicated disease course (type II [low-risk] primary SS).
15194165 A role of FcgammaRIIB in the development of collagen-induced arthritis. 2004 Jun Immune inhibitory receptors play an important role in the maintenance of adequate activation threshold of various cells in our immune system. The inhibitory Fc receptor, type IIB Fc receptor for IgG (FcgammaRIIB), is one of the critical molecules for the regulation of immune responses through antibodies. Analysis of murine models indicates that FcgammaRIIB plays an essential role in the suppression of various autoimmune disorders. Recent studies reveal the novel regulatory role of FcgammaR in the development of collagen-induced arthritis (CIA), an animal model relevant to human rheumatoid arthritis (RA). This review provides an overview of FcgammaRIIB-mediated immune regulation, highlighting the implication of FcgammaRIIB in the selection of peripheral B cell development during the CIA course.
11982303 Lyme arthritis. 2002 Mar Infection with B. burgdorferi can cause a large joint inflammatory arthritis in patients who have not been treated for early Lyme disease; the knee is the most common joint affected. The diagnosis depends on a history of known exposure to the spirochete, characteristic clinical features, and serologic studies (ELISA and Western blot) confirming exposure to the spirochete. In most patients, antibiotic therapy is curative, but in a smaller percentage of patients, the presence of the HLA-DR beta 1*0401 haplotype can trigger treatment-resistant arthritis, in which antibiotic therapy is ineffective; in these instances, remittive agents, such as hydroxychloroquine and methotrexate, are indicated. Arthroscopic synovectomy may be considered when antibiotic therapy is not curative. Fibromyalgia can follow infection with B. burgdorferi but is unresponsive to antibiotic therapy; it is treated with tricyclic antidepressants and an exercise program. Lyme arthritis is the only chronic inflammatory arthritis in which the specific cause is known and can be cured. As such, it serves as an excellent model with which to study the pathogenesis of more common inflammatory arthritides, such as rheumatoid arthritis.
15251085 Magnetic resonance imaging of psoriatic arthritis: insight from traditional and three-dime 2004 Aug The magnetic resonance imaging (MRI) findings in psoriatic arthritis (PsA) are the same and at the same time different from those seen in other inflammatory arthritides. Synovial hypertrophy is seen on MRI in all arthritides. However, the location and extent of bone marrow edema in PsA is different from those seen in rheumatoid arthritis (RA) and osteoarthritis. Progression studies in PsA are hard to justify. However, treatment monitoring studies have given insight into the pattern of progression of the MRI findings and information regarding the mechanism of the effect of the drugs used for treatment. Three-dimensional image analysis tools provide volumetric information and information regarding the spatial and temporal relationship between different MRI findings. The three-dimensional perfusion image analysis tool, which is used to evaluate the effect of antiangiogenic drugs in cancer treatment, can provide information regarding the disease mechanism when used in disease monitoring studies.
15494535 Targeting IL-15 receptor-bearing cells with an antagonist mutant IL-15/Fc protein prevents 2004 Nov 1 It has been suggested that the inflammatory cytokine IL-15 plays an important role in the development of several autoimmune diseases, including rheumatoid arthritis. We have generated a unique lytic and antagonistic IL-15 mutant/Fcgamma2a fusion protein (CRB-15) that targets the IL-15R. In the present study we examined the effects of targeting the IL-15R on the prevention and treatment of collagen-induced arthritis (CIA) in mice and probed the possible mechanisms of action of this IL-15 mutant/Fcgamma2a protein. Upon immunization with type II collagen, DBA/1 mice develop severe articular inflammation and destruction. Treatment of DBA/1 mice with a brief course of CRB-15 at the time of type II collagen challenge markedly inhibited the incidence and severity of arthritis. Moreover, in animals with ongoing established arthritis, treatment with CRB-15 effectively blocked disease progression compared with that in control-treated animals. The therapeutic effect of CRB-15 on either disease development or disease progression is remarkably stable, because withdrawal of treatment did not lead to disease relapse. A detailed analysis revealed that treatment with CRB-15 decreased synovitis in the joints; reduced bone erosion and cartilage destruction; reduced in situ production of the proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and IL-17; and decreased the responder frequency of autoreactive T cells. Our study suggests that the effective targeting of IL-15R-triggered events with CRB-15 can be of therapeutic importance in the treatment of rheumatoid arthritis.
12370365 Amelioration of collagen-induced arthritis by blockade of inducible costimulator-B7 homolo 2002 Oct 15 B7 homologous protein (B7h)/B7-related protein 1 (B7RP-1) is a new member of the B7 family of costimulatory molecules that specifically interacts with inducible costimulator (ICOS) expressed on activated T cells. Collagen type II (CII)-induced arthritis (CIA) is an experimental model of arthritis that has been used to dissect the pathogenesis of human rheumatoid arthritis. In this study, we have investigated the effect of neutralizing anti-B7h mAb on the development and disease progression of CIA. Administration of anti-B7h mAb significantly ameliorated the disease as assessed by clinical arthritis score and histology in the joints, and a beneficial effect was also obtained by a delayed treatment after the onset of disease. Expression of ICOS and B7h was observed in the inflamed synovial tissue as well as in the draining lymph nodes (LNs) and expansion of ICOS(+) T cells in the LN was reduced by the anti-B7h mAb treatment. Expression of mRNA for proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 in the joints was inhibited by the treatment. Proliferative responses and production of IFN-gamma and IL-10 upon restimulation with CII in vitro were significantly inhibited in LN cells from the anti-B7h mAb-treated mice. Serum anti-CII IgG1, IgG2a, and IgG2b levels were also reduced. Our present results showed a beneficial effect of the B7h blockade on CIA through anti-inflammatory actions and inhibition of both Th1- and Th2-mediated immune responses, suggesting that the ICOS-B7h interaction plays an important role in the pathogenesis of CIA and thus the blockade of this pathway may be beneficial for the treatment of human rheumatoid arthritis.
12093872 Critical roles for interleukin 1 and tumor necrosis factor alpha in antibody-induced arthr 2002 Jul 1 In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also required, although seemingly less critically than IL-1, because a proportion of TNF-alpha-deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFalpha for bone destruction. The variability in the requirement for TNF-alpha, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.
12635500 Advances in the management of septic arthritis. 2003 Feb Bacterial arthritis still is a common and serious problem at mayor urban medical centers and is one of the most rapidly destructive forms of acute arthritis. The yearly incidence of bacterial arthritis varies from 2 to 10 per 100,000 in the general population to 30 to 70 per 100,000 in patients with rheumatoid arthritis and in patients with joint prostheses. Irreversible loss of joint function may develop in up to 50% of the patients. Despite better antimicrobial agents and improved hospital care, the fatality rate for this medical problem has not changed substantially during the past 25 years. An understanding of the risk factors and the pathogenesis of nongonoccocal bacterial arthritis and other forms of infectious arthritis, primarily in the context of a differential diagnosis and treatment, are important in order to avoid the delay in making a correct diagnosis and to improve the prognosis.
14975191 Gene therapy of collagen-induced arthritis by electrotransfer of human tumor necrosis fact 2004 Feb Electrotransfer is a simple and efficient strategy of nonviral gene delivery. We have used this method to deliver plasmids encoding three human tumor necrosis factor-alpha soluble receptor I variants (hTNFR-Is) a monomeric hTNFR-Is, a chimeric hTNFR-Is/mIgG1, and a dimeric (hTNFR-Is)(2) form. Electrotransfer parameters were studied and because anti-TNF strategies have proven efficient for the treatment of rheumatoid arthritis in clinics, we used a collagen-induced arthritis (CIA) mouse model to assess the efficacy of our constructs in the treatment of the disease. All proteins were proven bioactive, both in vitro and ex vivo. Plasmid intramuscular electrotransfer in mice resulted in a local expression of the three variants for at least 6 months; systemic expression lasted also more than 6 months for the hTNFR-Is/mIgG1 form, while it was shorter for the two other forms. This expression was plasmid dose-dependent. Electrotransfer of 50 microg of hTNFR-Is/mIgG1 at the onset of a CIA induced a clear-cut decrease in both clinical and histologic signs of the disease; the dimeric form also showed some efficacy. Moreover, the long-lasting protective effect was observed for more than 5 weeks. Comparison of this electrotransfer approach with repeated recombinant protein (etanercept) injections highlighted the potential practical interest of gene therapy approach for CIA, which leads to sustained therapeutic effect after single treatment. These results show that electrotransfer may be a useful method to deliver cytokine or anticytokine therapy in rheumatoid arthritis and also illustrate the potentiality of plasmid intramuscular electrotransfer for the rapid screening and assessment of different variant forms of secreted proteins.