Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
15176161 Etanercept for the treatment of psoriasis: combination therapy with other modalities. 2004 May Etanercept is a self-administered medication that has FDA approval for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Etanercept is a human fusion protein of the tumor necrosis factor receptor (TNFR) and the Fc region of IgG1 that binds to and presumably inhibits the pro-inflammatory and pro-proliferative activity of the tumor necrosis factor (TNF). A recent multisite, randomized, double-blind, placebo-controlled study conclusively demonstrates that etanercept as monotherapy effectively treats patients with moderate-to-severe plaque psoriasis. This effect is dose-responsive, with the etanercept 50 mg twice-weekly dose significantly more effective than the 25 mg twice-weekly dose in reducing the Psoriasis Area and Severity Index (PASI) score over both 12 and 24 weeks of continuous therapy. Nevertheless, clinical trials do not instruct the dermatologist on how to practically integrate etanercept into a patient's pre-existing treatment regimen. Many psoriasis patients are already on other systemic therapies or have a medical history that necessitates a tailored approach to their therapy. Further, in some patients, etanercept at 25 mg twice weekly is ineffective in maximally clearing a patient of psoriasis. Below are cases that demonstrate how etanercept can be combined with other medications in order to both maximize clinical efficacy and minimize potential risk.
15457461 A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families provides 2004 Sep OBJECTIVE: Juvenile rheumatoid arthritis (JRA) represents a heterogeneous group of disorders with a complex genetic component. A genome scan was performed to detect linkage to JRA in 121 families containing 247 affected children in North America (the JRA Affected Sibpair [ASP] Registry). METHODS: Genotype data collected for HLA-DR and 386 microsatellite markers were subjected to multipoint nonparametric linkage analysis. Following analysis of the entire set of families, additional analyses were performed after a priori stratification by disease onset type, age at onset, disease course, and selected HLA-DRB1 alleles. RESULTS: Linkage of JRA to the HLA region was confirmed (logarithm of odds [LOD] score 2.26). Additional evidence supporting linkage of JRA was observed at 1p36 (D1S214; LOD 1.65), 19p13 (D19S216; LOD 1.72), and 20q13 (D20S100; LOD 1.75). For early-onset polyarticular disease, evidence of linkage was found at chromosome 7q11 (D7S502; LOD 3.47). For pauciarticular disease, evidence supporting linkage was observed on chromosome 19p13 (D19S216; LOD 2.98), the same marker that supported linkage to the "JRA" phenotype. Other regions supporting linkage with JRA disease subtype included 20q13, 4q24, 12q24, and Xp11. Stratification of families based on the presence of the HLA-DR8 allele in affected siblings resulted in significant linkage observed at 2p25 (D2S162/D2S305; LOD 6.0). CONCLUSION: These data support the hypothesis that multiple genes, including at least 1 in the HLA region, influence susceptibility to JRA. These findings for JRA are consistent with findings for other autoimmune diseases and support the notion that common genetic regions contribute to an autoimmune phenotype.
24387722 The pathology and evaluation of surgical treatment in a ruptured giant popliteal/crural cy 2004 Dec Abstract Popliteal cysts are often observed in patients with rheumatoid arthritis (RA), and giant cysts that extend from the popliteal to the crural region (popliteal/crural cysts) are occasionally encountered. We studied the background of popliteal/crural cysts and therapeutic results, and evaluated its etiologic factors and the effectiveness of surgical treatment. Nine knees of eight patients with popliteal/crural cyst secondary to RA, which was treated surgically because it resisted conservative treatment, and was followed up for 1 year or longer after surgery, were evaluated. The patients were five men and three women, with a mean age at surgery of 59.1 years and a mean duration of RA disease of 4.5 years. Only one male patient suffered pain in the bilateral joints. The mean level of erythrocyte sedimentation rate was 61.3 mm/h (range 3.9-100.2), the mean level of C-reactive protein was 3.6 (0.1-8.2) mg/dl, and the mean Lansbury index was 36.4 (12-61) at surgery. The cyst disappeared completely after surgery, and the postoperative course was uneventful in eight knees, but recurrence was observed in just one knee of the bilateral case. However, in this patient the cyst that recurred was not as large as the one before surgery, and it was eventually brought under control by subsequent outpatient medical management. Inflammatory reactions were suppressed, if temporarily, in all patients. The patients evaluated in this study showed the following characteristics: the male-female ratio of the patients was biased to males compared with that of RA patients in general; although knee joint damage was radiographically mild, marked symptoms of arthritis were observed in not only the knees but also other joints in all patients; and the disease could not be controlled effectively by medication. However, after surgical resection of the cysts, general as well as local signs of inflammation were mitigated, and surgery was considered to be very effective for the treatment of ruptured giant popliteal/crural cyst associated with RA.
15624748 The medical uses and side effects of etanercept with a focus on cutaneous disease. 2004 Nov Etanercept is a dimeric fusion protein that has been approved for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis and moderate to severe plaque psoriasis. It has been reported to be useful in other variants of psoriasis, Still's disease, recurrent aphthous ulcers, and a variety of rare cutaneous conditions. Its cutaneous side effects are rare and include injection site reactions, cutaneous lupus, and cutaneous vasculitis. Its systemic side effects are also rare and include induction or worsening of infections, lupus, multiple sclerosis, and congestive heart failure. Linkage to an increased risk of lymphoma is unclear. In short, etanercept is a promising medication with substantial benefits and use will probably increase in the future. This review surveys off-label uses and side effects of etanercept.
14979934 Novel approaches to gene expression analysis of active polyarticular juvenile rheumatoid a 2004 Juvenile rheumatoid arthritis (JRA) has a complex, poorly characterized pathophysiology. Modeling of transcriptosome behavior in pathologic specimens using microarrays allows molecular dissection of complex autoimmune diseases. However, conventional analyses rely on identifying statistically significant differences in gene expression distributions between patients and controls. Since the principal aspects of disease pathophysiology vary significantly among patients, these analyses are biased. Genes with highly variable expression, those most likely to regulate and affect pathologic processes, are excluded from selection, as their distribution among healthy and affected individuals may overlap significantly. Here we describe a novel method for analyzing microarray data that assesses statistically significant changes in gene behavior at the population level. This method was applied to expression profiles of peripheral blood leukocytes from a group of children with polyarticular JRA and healthy control subjects. Results from this method are compared with those from a conventional analysis of differential gene expression and shown to identify discrete subsets of functionally related genes relevant to disease pathophysiology. These results reveal the complex action of the innate and adaptive immune responses in patients and specifically underscore the role of IFN-gamma in disease pathophysiology. Discriminant function analysis of data from a cohort of patients treated with conventional therapy identified additional subsets of functionally related genes; the results may predict treatment outcomes. While data from only 9 patients and 12 healthy controls was used, this preliminary investigation of the inflammatory genomics of JRA illustrates the significant potential of utilizing complementary sets of bioinformatics tools to maximize the clinical relevance of microarray data from patients with autoimmune disease, even in small cohorts.
15176162 Off-label uses and side effects of infliximab. 2004 May Infliximab was first approved by the FDA in 1998 as a treatment of moderately-to-severely active Crohn's disease in patients who have an inadequate response to conventional therapies, and fistulizing Crohn's disease. In November 1999 the FDA approved it for use in rheumatoid arthritis with methotrexate, and further expanded this indication in December 2000. It appears to be a promising agent in the treatment of a variety of inflammatory diseases, psoriasis in particular. A MEDLINE search was performed for "infliximab" in February of 2004, and the 1,116 articles found were reviewed. Approximately 200 articles were identified that contained references to the treatment with infliximab of skin disease, off-label uses, systemic diseases with cutaneous manifestations, and systemic and cutaneous side effects. These articles were reviewed and their contents summarized. Infliximab has been proven in well-controlled trial trials to ameliorate inflammatory bowel disease, rheumatoid arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. Anecdotal reports report it useful in treating the cutaneous manifestations and associations of inflammatory bowel disease, Behçet's disease, graft versus host disease, Sjogren's syndrome, refractory sarcoidosis, and a variety of other conditions. Its notable side effects include an increased risk of the induction of infections (e.g., tuberculosis). Infliximab is a very promising medication in the treatment of inflammatory dermatological conditions and should be used in larger scale trials of more diseases.
12546141 Modulation of leukocyte recruitment and IL-8 expression by the membrane attack complex of 2002 Dec The complement system is thought to be a major physiological mediator of injury in a number of diseases including rheumatoid arthritis (RA). The membrane attack complex (MAC) of complement has been detected in RA tissue, suggesting that the MAC may be relevant to the pathogenesis of the disease. Deposition of sublytic concentrations of the MAC has been shown to promote the expression of proinflammatory mediators. In the present study, we utilized rabbits deficient in the complement protein C6 to elucidate the role of the MAC in mediating the pathogenesis of antigen-induced arthritis. Swelling, leukocyte accumulation, IL-8 expression, proteoglycan, and hydroxyproline content were assessed. Analysis of synovial tissue demonstrated a significant decrease in leukocyte influx and a parallel decrease in tissue associated IL-8 in joints of C6-deficient animals as compared to C6-sufficient animals. However, this did not correlate with the preservation of connective tissue. The results derived from this study provide evidence that the MAC has an important function in mediating leukocyte recruitment in antigen-induced arthritis but does not play a direct role in connective tissue breakdown.
14609494 Clinical trials in pediatric uveitis. 2003 Dec Uveitis associated with juvenile rheumatoid arthritis is the most common form of ocular inflammation in children. Prevention of permanent visual damage by this silent disease requires heightened awareness from pediatric rheumatologists and ophthalmologists. Early prediction of severity and prognosis will aid in the identification of those patients requiring more aggressive management. Generally, reports using immunosuppressives in this population are small, uncontrolled, and retrospective. Large-scale collaborative studies have been proposed and are underway. Hopefully, collaborations between pediatricians, pediatric rheumatologists, and ophthalmologists will allow the development of straightforward treatment guidelines for children suffering from chronic uveitis and its related complications.
11846348 The role of personality in exposure and reactivity to interpersonal stress in relation to 2002 Jan The role of personality in the stress process was examined in older women with rheumatoid arthritis (RA) and osteoarthritis (OA) and in healthy controls (HCs). Reactivity was examined in relation to arthritis disease activity and negative affect. Interpersonal sensitivity and neuroticism were measured in questionnaires, and interpersonal stress, negative affect, and disease activity were assessed weekly for 12 weeks. Interpersonal sensitivity was defined as an excessive sensitivity to the behavior and feelings of others. Regarding exposure, neuroticism was related to interpersonal stress for all groups. Regarding reactivity, interpersonal sensitivity interacted with interpersonal stress to predicted elevations in negative affect in all groups and elevations in disease activity in the arthritis groups. There were no significant differences in the effects.
12563365 [Hepatitis C virus infection and arthritis. A clinico-serological investigation of arthrit 2002 Oct OBJECTIVE: To compare the clinico-serological features of arthritis from two HCV+ patient groups characterized by mixed cryoglobulinemia (MC) or chronic hepatitis (CH). METHODS: We retrospectively studied 157 MC patients (119 females, mean age 64.8 yrs, range 36-88) and 155 CH patients (103 females, mean age 58.8 yrs, range 30-81). Patients with HBV and/or HIV co-infections and a follow-up shorter than 1 year were excluded. MC was classified according to standard criteria, while CH classification was based on Desmet's criteria. RESULTS: No differences in epidemiology were demonstrated between the two series of patients. Although significantly prevalent in MC patients, extra-hepatic manifestations including nephropathy, neuropathy, pneumopathy, mixed cryoglobulins, RF positivity and hypocomplementemia were detected in both patient groups. Arthritis was present in 23 CH (15%) and 12 MC (8%) patients. A symmetrical polyarthritis was observed in 87% of 23 CH patients, while cryoglobulinemic arthritis was invariably asymmetrical and pauciarticular. Unlike MC patients, who had a constantly non-erosive arthritis, in 7/23 CH patients arthritis was erosive. Steroids and/or hydroxycloroquine or D-penicillamine were safe and useful in controlling the arthritis over the short-medium time, although clinical response was more evident in MC patients. Instead, in 5/23 CH and 3/12 MC patients, interferon-alpha treatment was able to trigger or exacerbate the arthritis despite a good control of liver function. CONCLUSIONS: HCV infection seems to be, possibly in genetically predisposed patients, responsible for arthritis at times similar to rheumatoid arthritis. In these patients a careful assessment of the interferon-alpha treatment is mandatory owing to the potential "arthritogenic effect" due to its immunoregulatory properties.
12141528 Interference by rheumatoid factor activity in the detection of antiavian antibodies in pig 2002 Jul The assessment of antiavian antibodies is relevant for the study of pigeon breeder's disease; nevertheless, different factors may hamper their accurate detection. The objective of this study was to determine whether an endogenous interfering effect in pigeon breeder's disease might explain the simultaneous presence of IgM, IgG, and IgA antiavian antibodies in high titers as assessed by ELISA. Fifty-nine patients with pigeon breeder's disease, 80 healthy controls, and 47 asymptomatic breeders were studied. To assess possible interfering effects by endogenous immunoglobulins, serum IgG was separated through protein A-Sepharose CL-4B chromatography. Antiavian antibodies were measured in whole and separated samples by ELISA. Since a decline of IgM antiavian antibodies following IgG removal was consistent with a false-positive effect, the causes were studied. High values of IgM, IgG, and IgA antiavian antibodies were found in 47.4% [corrected] of patients with pigeon breeder's disease. An IgM rheumatoid factor activity against IgG was found through ELISA in sera with false-positive IgM antiavian antibodies. Rheumatoid factor binding was confirmed by Western blot. Experimental addition of purified rheumatoid factor to sera with IgG antiavian antibodies replicated the interfering effect. A control group of rheumatoid arthritis with high rheumatoid factor values did not show positive antiavian antibodies tests. No IgG with anti-IgM or anti-IgA activity was found, and the detection of IgA against IgM and IgG was negative. In conclusion, the study of antiavian antibodies might be affected by different immunoassay conditions. An endogenous rheumatoid factor activity produced false-positive IgM results. Other similar interferences warrant a careful evaluation during the serological assessment of pigeon breeder's disease.
11882030 Extra-articular cartilage affected in collagen-induced, but not pristane-induced, arthriti 2002 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily affecting cartilaginous joints but also extra-articular tissues such as the nose and upper respiratory tract. We have investigated extra-articular cartilage involvement in two commonly used animal models for RA, collagen-induced and pristane-induced arthritis, by immunizing rats with different susceptibility to disease (LEW.1 A, LEW.1F and DA rats). We found that nasal and tracheolaryngeal cartilage is affected in LEW.1 A and DA rats to varying degrees in collagen-induced arthritis but not in any strain in the pristane-induced model. Antibodies to matrilin-1, a cartilage-specific protein expressed mainly in tracheolaryngeal and nasal cartilage but not in joints, were positively associated with the presence of inflammation in nasal cartilage. In contrast, no antibody response to matrilin-1 could be detected in pristane-induced arthritis. In addition, nasal vaccination with collagen type II prior to immunization in DA rats significantly decreased the antibody response to matrilin-1 at day 56, but not at earlier time points, indicating a late protective effect on extra-articular cartilage. We conclude that pristane-induced arthritis is a joint-specific model whereas collagen-induced arthritis affect joints as well as extra-articular cartilage. Furthermore, collagen immunization induces an antibody response to matrilin-1.
11806162 Rheumatology, a clinical overview. 2002 Jan Abnormalities in the foot and ankle can often be initial manifestations of several rheumatic diseases including rheumatoid arthritis, the spondylo-arthropathies, and crystal deposition disease. An accurate history is essential for early diagnosis of systemic rheumatic diseases presenting with foot and ankle symptoms. Also, certain subsets of patients are more at risk for distinct rheumatic diseases that can involve the foot and ankle. Laboratory tests such as rheumatoid factor, antinuclear antibodies, erythrocyte sedimentation rate and C-reactive protein can be helpful in diagnosis provided their limitations are recognized.
16285183 [Interstitial granulomatous dermatitis without arthritis: successful therapy with hydroxyc 2003 Feb Interstitial granulomatous dermatitis is a rare entity characterized by cutaneous linear strands (the "rope sign") and rheumatoid arthritis. In the past years, 12 other cases have been described with variable cutaneous symptoms. All showed similar histological features, resembling those of granuloma annulare or 'palisaded neutrophilic and granulomatous dermatitis', suggesting a wide spectrum for a single entity. A 60-year-old patient presented with erythematous patches with an indurated, violaceous border resembling the "rope sign" on both flanks. The histological investigation revealed dense diffuse interstitial inflammatory infiltrates composed of eosinophils, neutrophils, lymphocytes, macrophages and multinucleated giant cells in the superficial and deep dermis. In the deep dermis, prominent eosinophilic degenerated collagen fibres with surrounding macrophages ('floating sign') occurred. In contrast to most previously described patients, our patient did not have arthralgias. The skin findings cleared following therapy with hydroxychloroquine.
17041325 Another look at synovial fluid leukocytosis and infection. 2002 Apr Synovial fluid white blood cell counts are considered to be useful in diagnosing infectious arthritis, however, considerable overlap exists between infectious and noninfectious types of inflammatory arthritis. We undertook this review of synovial fluid studies at our institution to better define this degree of overlap and characterize the features of infectious arthritis in relationship to synovial fluid white cell counts. The records of 202 consecutive patients with synovial fluid white blood cell counts >2000/mm were reviewed. Infectious arthritis was diagnosed in 77% (10/13) of patients with counts >100,000, 47% (8/17) in the 50,000-100,000 range, and 5% (9/172) with counts <50,000. Crystal-induced arthritis and rheumatoid arthritis made up 81% of patients in the 15,000-50,000 range. Overall, 10 of 27 (37%) cases of infectious arthritis had white cell counts >100,000, and 18 of 27 (67%) had counts >50,000. A majority of these infections (14/18) were related to Staphylococcus aureus, while 5 of 7 infections associated with counts <20,000 were associated with atypical organisms. This study confirms that a majority of patients with very high synovial fluid white blood cell counts have infectious arthritis, and that the likelihood of infection is markedly reduced, but certainly not excluded, below this level. The presence of atypical infections in a small percentage of patients with low counts emphasizes the importance of clinical judgment in evaluating all patients with inflammatory arthritis, regardless of synovial fluid white cell counts.
12022031 Free fascia temporalis interpositioning as a treatment for wrist ankylosis. 2002 May The fascia temporalis is a thin and well-vascularized tissue and, for this reason, its use in reconstructive surgery is versatile. It can be used as an island flap in defects of the head and neck or as a free flap in reconstructions of different anatomic regions. As a "living" spacer in the treatment of wrist ankylosis, its use has not yet been described. The authors present the transfer of the free fascia temporalis into the wrist as a treatment of wrist ankylosis in patients affected by severe rheumatoid arthritis. Four flaps in three patients were performed. Preoperative flexion/extension in the wrist was absent or almost absent and painful, resulting in severely impaired daily activities. After resection of the distal ulna, distal radius, and the proximal surfaces of the proximal row of the carpal bones was performed, the free fascia was used to replace the wrist joint. Postoperative wrist flexion/extension was 45 to 50 degrees on average. In all patients, this procedure allowed painless motion of the wrist, and in all patients, daily activities were improved. A 2-year follow up showed no recurrence of wrist problems and a maintained articular space. In the treatment of wrist ankylosis, the use of the free fascia temporalis offers a good alternative to arthrodesis, maintaining sufficient function for daily activities.
15484858 [Prognostic significance of juvenile chronic arthritis onset types]. 2004 Juvenile chronic arthritis (JCA) is a disease or a group of diseases with chronic nonsuportive connective tissue inflammation. Depending of the onset of the disease and its course in the first six months there are three major types: systemic, poliyarticular and pauciarticular disease. Indicators of bad prognosis were: systemic form with signs of inflammation in the first six months, poliarticular onset and course, RF positivity, positive ANA and eye involvement. In the period from 1996 to 2002 at the Cardiology-Rheumatology Department in Sarajevo Pediatric Clinic 63 patients were addmited. Out of this 49 (78%) were new cases JCA was more frequent among school age girls 35 (57%). Systemic--onset JCA 9 patients (14%), polyarticular onset 19 patients (30%), pauciarticular onset 35 (55%). 15 (23.8%) was RF (rheumatoid factor) negative, 4 (6.3%) RF positive. Pauciarticular forms type 1 were 20 (31.7%), type II were 15 (23.8%). In 11 (17.5%) patients laboratory tests and clinical signs indicated poor prognosis. All patients with indicators of poor prognosis needed more aggressive therapy. Although JCA is the most frequent rheumatic disease and the leading cause of invalidity, and one of the most frequent chronic disease in children, we still do not know enough. The optimal treatment is still a challenge especially onset of JCA with poor prognosis.
15775286 [Therapeutic effect of hyaluronic acid injection for knee and shoulder joint]. 2002 Jan It is known that hyaluronic acid can protect against damage to articular cartilage and helps to lessen friction between joint surfaces. Furthermore, it is reported that hyaluronic acid is effective for pain relief and for the risk of adhesion, and contractures of joints. The injection of hyaluronic acid is useful for the treatment of frozen shoulder, osteoarthritis, and rheumatoid arthritis. The risk of infection is a rare, though important, possibility, however this method is relatively safe.
15775142 [Pathophysiology, diagnosis and treatment of osteoporosis]. 2003 Jun Patients with rheumatoid arthritis (RA) develop both generalized and periarticular osteoporosis. Osteoporosis in RA causes by increase of bone resorption, however the decrease of bone formation has been concerned in development of osteoporosis. Drug therapy have to bigin as early as osteopenia, and a potent inhibitor of bone resorption will be effective to suppress the increse of bone resorption in RA patients. RA-associated osteoporosis including grucocorticoid induced osteoporosis decreases bone formation, vitamin D and parathyroid hormon would become the useful drug for promoting the bone formation by examination of new agents, method and dosage of treatment for osteoporosis in RA patients.
15570736 Understanding valvular heart disease in patients with systemic autoimmune diseases. 2004 Nov Specific systemic autoimmune diseases are associated with distict valvular heart disorders. We discuss the valvular disorders associated with rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid antibody syndrome, the seronegative spondyloarthropathies, the systemic vasculitides, and scleroderma.