Work capacity of patients with inflammatory joint diseases. An eight-year follow-up study

In a prospective study of recent arthritis, 103 patients had rheumatoid arthritis (RA), 63 seronegative oligoarthritis (SO), 67 reactive arthritis (REA), 20 ankylosing spondylitis (AS), and 13 psoriatic arthritis (PA). At the 8-year check-up, 36% of patients with RA were at work, compared with 69% in PA (p less than 0.002), and 85-90% in AS, SO, and REA (p less than 0.001). Correspondingly 43% of the RA patients were disabled by arthritis, compared with 23% in PA (NS), 15% in AS (p less than 0.005), none in SO, and 4% in REA (p less than 0.001). No significant differences in work capacity were noted between patients with PA, AS, SO or REA. In RA, the educational backgrounds of patients unable to work (44 patients) and able to work (37 patients) did not differ from each other or from the overall population of Finland, but a significantly (p less than 0.01) smaller number of patients with arduous work were able to continue at work. The mean age of 49 years for RA patients unable to work differed highly significantly (p less than 0.001) from the 35 years of RA patients at work. However, the weightiest cause of limited work capacity was severity of disease.     

Elbow joint forces in patients with rheumatoid arthritis

Whilst developing an elbow endoprosthesis, the joint forces were estimated for patients with rheumatoid arthritis. Elbow flexion strength of rheumatoid patients was found to be 45% of normal. Muscle strengths and limb geometry data were found by a dissection technique, which allowed joint forces to be calculated during flexion, extension and abduction efforts. Forces up to 2.4 kN were predicted to act on the distal humerus, with similar forces acting in both radius and ulna. The skeletal structure is well adapted to carry the predicted forces, and onlay-type prostheses are recommended for elbow replacement.     

Incidence of yersinia enterocolitica antibodies in patients with inflammatory joint diseases

Summary Agglutinating antibodies against Yersinia enterocolitica serotypes 0:3, 0:8 and, to a minor extent, 0:6 were found in 18 out of 93 patients with inflammatory joint diseases. Patients with undifferentiated arthritis showed the highest prevalence of antibodies against Yersinia enterocolitica. The possibility that serotypes other than 0:3 may be involved in triggering arthritis is discussed.     

Assessment of mutilans-like hand deformities in chronic inflammatory joint diseases. A radiographic study of 52 patients

OBJECTIVES: To evaluate patients with mutilans-like hand deformities in chronic inflammatory joint diseases and to determine radiographic scoring systems for arthritis mutilans (AM). METHODS: A total of 52 patients with severe hand deformities were collected during 1997. A Larsen hand score of 0-110 was formed to describe destruction of the hand joints. Secondly, each ray of the hand was assessed individually by summing the Larsen grade of the wrist and the grades of the MCP and PIP joints. When the sum of these grades was > or = 13, the finger was considered to be mutilated. A mutilans hand score of 0-10 was formed according to the number of mutilans fingers. Surgical treatment and spontaneous fusions were recorded. RESULTS: The study consisted of 22 patients with juvenile rheumatoid arthritis (JRA), nine with rheumatoid factor (RF) positive and 13 with RF negative arthritis, 27 patients with RF positive RA, and three adult patients with other diagnoses. The mean age of patients with adult rheumatic diseases was 27 years at the onset of arthritis. The mean disease duration in all patients was 30 years. The mean Larsen hand score was 93. Four patients had no mutilans fingers and in 15 patients all 10 fingers were mutilated. The Larsen hand score of 0-110 and the mutilans hand score of 0-10 correlated well (rs = 0.90). Fourteen patients showed spontaneous fusions in the peripheral joints. A total of 457 operations were performed on 48 patients. CONCLUSION: Both the Larsen hand score of 0-110 and the mutilans hand score of 0-10 improve accuracy in evaluating mutilans-like hand deformities, but in unevenly distributed hand deformities the mutilans hand score is better in describing deformation of individual fingers.     

Analysis of intraarticular fibrinolytic pathways in patients with inflammatory and noninflammatory joint diseases

Objective. Intraarticular activation of the fibrinolytic system has been suspected to occur in patients with arthritis. We undertook the present study to investigate the relation of this activation to clinical symptoms, and the molecular pathways involved. Methods. We quantitatively assessed levels of plasmin–α₂-antiplasmin (PAP) complexes in synovial fluid (SF) from 25 patients with rheumatoid arthritis (RA), 7 with seronegative spondylarthropathy (SSA), and 10 with osteoarthritis (OA), and conducted an analysis to determine the plasminogen-activating pathway via which these complexes were generated. In addition, we studied the relationship of intraarticular fibrinolysis to clinical and biochemical parameters. Results. All patients studied had increased SF levels of PAP complexes. Levels in patients with RA and SSA were slightly higher than those in patients with OA. These complexes were probably formed by activation of urokinase-type plasminogen activator (u-PA), and not tissue-type plasminogen activator (t-PA), since SF levels of both u-PA antigen and u-PA–plasminogen activator inhibitor (PAI) complexes were increased in 27 of the 42 patients. Conversely, SF levels of t-PA were below normal in all but 1 patient. In some patients, activation of factor XII presumably also contributed to plasminogen activation in SF, since levels of factor XIIa–C1 inhibitor in SF were increased in 8 of the 42 patients and correlated, as did u-PA–PAI levels, with levels of PAP complexes. Several of the parameters of fibrinolysis in SF, particularly u-PA antigen and u-PA-PAI–1 complexes, were found to correlate with clinical and biochemical parameters. Conclusion. Our results suggest that plasminogen is frequently activated in the joints of patients with inflammatory or noninflammatory arthropathy and that this activation mainly occurs via a u-PA–, and in some cases also via a factor XII–, dependent pathway. The possible relation of this activation process to stimulation of synovial cells by cytokines is discussed.     

Cr1, CD35 IN synovial fluid from patients with inflammatory joint diseases

Objective. To investigate synovial fluid (SF) for the presence of CR1 and to study its relationship to SF leukocytes and to serum levels of soluble CR1 (sCR1) in patients with rheumatic diseases. Methods. Synovial fluids were collected from 35 patients with rheumatoid arthritis (RA) and 26 patients with other inflammatory joint diseases. Total CR1 in the SF and serum were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) that recognized both soluble and transmembrane forms of CR1. The characteristics of CR1 in SF were analyzed by ultracen-trifugation and by a second ELISA specific for trans-membrane CR1. Results. CR1 was found in all SF samples tested (range 5-281 ng/ml). SF CR1 was higher in patients with RA (mean ± SD 81 ± 66 ng/ml) than in those with other inflammatory joint diseases (31.8 ± 23.8 ng/ml) (P < 0.001). Serum sCR1 was not significantly increased in the patients compared with the normal subjects. There was no correlation between serum sCR1 and SF CR1. In 44% of the patients, the SF CR1 level was higher than the serum sCR1 level. A fraction (30–80%) of SF CR1 was pelleted by ultracentrifugation and, unlike serum sCR1, it reacted in an ELISA specific for transmembrane CR1. Thus, SF contained 2 forms of CR1: a membrane-associated and a soluble form, which was confirmed by sucrose density-gradient ultracentrifugation. SF CR1 levels correlated directly with the number of SF total leukocytes and polymorphonuclear leukocytes (PMN). These 2 forms of CR1 were also found in the supernatant of in vitro—activated PMN from normal subjects. SF CR1 exhibited the capacity to act as a cofactor for the factor I degradation of C3b. Conclusion. CR1 is found in the SF of patients with joint inflammation. The data suggest that SF CR1 originates from the infiltrating leukocytes, which shed both a soluble and a membrane-associated form. Whether SF CR1 participates in the local regulation of complement activation remains to be examined.     

Analysis of intraarticular fibrinolytic pathways in patients with inflammatory and noninflammatory joint diseases.

OBJECTIVE. Intraarticular activation of the fibrinolytic system has been suspected to occur in patients with arthritis. We undertook the present study to investigate the relation of this activation to clinical symptoms, and the molecular pathways involved. METHODS. We quantitatively assessed levels of plasmin-alpha 2-antiplasmin (PAP) complexes in synovial fluid (SF) from 25 patients with rheumatoid arthritis (RA), 7 with seronegative spondylarthropathy (SSA), and 10 with osteoarthritis (OA), and conducted an analysis to determine the plasminogen-activating pathway via which these complexes were generated. In addition, we studied the relationship of intraarticular fibrinolysis to clinical and biochemical parameters. RESULTS. All patients studied had increased SF levels of PAP complexes. Levels in patients with RA and SSA were slightly higher than those in patients with OA. These complexes were probably formed by activation of urokinase-type plasminogen activator (u-PA), and not tissue-type plasminogen activator (t-PA), since SF levels of both u-PA antigen and u-PA-plasminogen activator inhibitor (PAI) complexes were increased in 27 of the 42 patients. Conversely, SF levels of t-PA were below normal in all but 1 patient. In some patients, activation of factor XII presumably also contributed to plasminogen activation in SF, since levels of factor XIIa-C1 inhibitor in SF were increased in 8 of the 42 patients and correlated, as did u-PA-PAI levels, with levels of PAP complexes. Several of the parameters of fibrinolysis in SF, particularly u-PA antigen and u-PA-PAI-1 complexes, were found to correlate with clinical and biochemical parameters. CONCLUSION. Our results suggest that plasminogen is frequently activated in the joints of patients with inflammatory or noninflammatory arthropathy and that this activation mainly occurs via a u-PA-, and in some cases also via a factor XII-, dependent pathway. The possible relation of this activation process to stimulation of synovial cells by cytokines is discussed.     

Yersinia antibodies in inflammatory joint diseases

The occurrence of IgM, IgG and IgA class Yersinia antibodies was studied at the beginning of an inflammatory joint disease and one year later in 354 adult patients using an ELISA technique. The control groups consisted of age and sex matched healthy persons living in the same geographical area as the patients, and of 64 patients with chronic rheumatoid arthritis. Yersinia antibodies of any Ig class were found in 9.0% of all the patients at the beginning of the disease, in 4.0% of the healthy controls and in 1.6% of the patients with chronic rheumatoid arthritis. Patients with ankylosing spondylitis, Reiter's disease or other reactive arthritis showed the highest prevalence (19.4%) of Yersinia antibodies, but in the whole material one half of the patients with Yersinia antibodies were clinically classified as rheumatoid or nonspecific arthritis. The elevated prevalence of Yersinia antibodies in patients with probable rheumatoid or nonspecific arthritis may indicate a reactive etiopathogenesis of arthritis also in some cases without previous evidence of gastrointestinal infection. Quantitation of IgG and IgA antibodies to Yersinia is important in the diagnosis of Yersinia arthritis. These antibodies may not be detected by the generally used agglutination test.     

Nitric oxide and inflammatory joint diseases

Nitric oxide (NO) is synthesized from L-arginine by the NO synthases. At present, mainly three NO synthase isoenzyme groups are differentiated: two constitutive NO synthases, responsible for homeostatic cardiovascular and neuronal functions of NO, and an inducible NO synthase. After induction by certain cytokines or endotoxin, this latter isoform produces large quantities of NO with cyto- and bacteriotoxic effects. High amounts of NO, synthesized systemically and intra-articularly, play an important role in inflammatory joint diseases, as shown in animal models of arthritis and in patients with rheumatoid arthritis or spondyloarthropathies. In experimental arthritis, administration of NO synthase inhibitors profoundly reduced disease activity. In humans, beneficial effects of NO synthesis inhibition are inferred from indirect evidence: glucocorticoids, inhibiting induction of the inducible NO synthase, reduce enhanced NO synthesis and disease activity. Thus, selective inhibition of the pathologically enhanced NO synthesis emerges as a new experimental therapeutic approach in the treatment of inflammatory joint diseases.      

Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis

OBJECTIVE: To investigate sensitive ultrasonographic imaging methods for detection of synovial thickness and vascularity to discriminate between patients with early rheumatoid arthritis (RA) receiving infliximab + methotrexate (MTX) versus placebo + MTX over 18 weeks, and to compare the relationship between synovial thickening and vascularity at baseline and radiologic damage to joints of the hands and feet at 54 weeks. METHODS: Patients with early RA (duration <3 years) receiving stable dosages of MTX were randomly assigned to receive blinded infusions of 5 mg/kg infliximab (n = 12) or placebo (n = 12) at weeks 0, 2, 6, and then every 8 weeks until week 46. At baseline and week 18, clinical assessments were performed, and metacarpophalangeal joints were assessed by high-frequency ultrasonography and power Doppler ultrasonography measurements. Radiographs of the hands and feet taken at baseline and at 54 weeks were evaluated using the van der Heijde modification of the Sharp method (vdH-Sharp score). RESULTS: Using changes in the total vdH-Sharp score over 54 weeks and changes in synovial thickening and joint vascularity at 18 weeks, we were able to distinguish those patients receiving infusions of infliximab + MTX from those receiving placebo + MTX. Sonographic measurements of synovial thickening and vascularity at baseline in the placebo + MTX group demonstrated clear relationships with the magnitude of radiologic joint damage at week 54. Infliximab + MTX treatment abolished these relationships. CONCLUSION: The delay or reversal of inflammatory and joint-destructive mechanisms in patients with early RA was already apparent following 18 weeks of treatment with infliximab + MTX and was reflected in radiologic changes at 54 weeks.     

Prognosis of inflammatory joint diseases. A three-year follow-up study

The prognosis 3 years after the onset of the disease was studied in 107 patients with definite rheumatoid arthritis, 161 with probable RA or non-specific arthritis, 84 with either ankylosing spondylitis, Reiter's disease or reactive arthritis, 14 with psoriatic arthritis and 10 with a systemic connective tissue disease. Prognosis was measured by clinical involvement of joints, radiological erosions in joints, deterioration in joint function, ESR, and working ability. A total of 44% of all patients were symptomless after 3 years. The prognosis was best in patients with an "HLA B 27-associated" disease and non-specific arthritis, and worst in RA. Two patients died during the follow-up of systemic connective tissue disease and one committed suicide with an overdose of hydroxychloroquine. Two HLA B27-positive patients developed systemic amyloidosis.     

Evaluation of knee joint cartilages and menisci in patients with chronic inflammatory joint diseases. A prospective arthroscopic study before, six and twelve months after open synovectomy

Destruction of joint cartilage is an important feature in chronic inflammatory joint diseases. This article considers the areas of the cartilages of the knee joint prone to destructive changes, pannus growth and marginal erosions, and the changes of pattern after open synovectomy. Twenty-eight patients with chronic inflammatory joint disease which gave indication for synovectomy of the knee joint had arthroscopy immediately before, 6 and 12 months after open synovectomy. A method of grading the changes of the cartilage, pannus growth, menisci and marginal erosions is described. There was an increase in cartilage pathology 12 months after synovectomy (p less than 0.001), particularly on the weight bearing areas of the femur and on the tibial condyles. No significant deterioration in areas with pathology at the time of synovectomy was found in the follow up. Pannus growth was particularly located to areas 2 and 4 on the femoral condyles. We conclude that cartilage destruction after synovectomy is more likely to be a result of osteoarthrosis than arthritic changes.     

Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases

Patients with inflammatory bowel disease (IBD) are more likely to have concurrent immune-mediated inflammatory diseases (IMIDs) than those without IBD. IMIDs have been observed to alter the phenotype and outcomes of IBD in recent studies. Several studies have found that IBD patients with concurrent IMIDs may have more extensive or severe disease phenotypes, and are considered to be at increased risk of requiring biologics and IBD-related surgeries, suggesting that having multiple IMIDs is a poor prognostic factor for IBD. Furthermore, IBD patients with primary sclerosing cholangitis and Takayasu arteritis are reported to have unique endoscopic phenotypes, suggesting concurrent IMIDs can influence IBD phenotype with specific intestinal inflammatory distributions. In this review, we discuss the pathogenesis, disease phenotypes, and clinical outcomes in IBD patients with concomitant IMIDs.     

Contact thermography in assessing inflammatory joint diseases

Cutaneous hyperthermia represents a symptom of inflammatory joint diseases and "activated" arthroses. Arthritis and arthrosis may be differentiated by the different distribution and extent of hyperthermia. In an equal number of different joint diseases the symptoms and signs and the course of the diseases were investigated with the aid of contact thermography. The results indicate different exact localisations of temperature changes in the affected joints which together with the clinical findings may make it possible to establish differential diagnostic definitions between arthrosis and rheumatoid arthritis. In the authors' opinion contact thermography is, however, not suited for observations of the course of the diseases.     

Magnetic resonance imaging of the wrist and finger joints in patients with inflammatory joint diseases.

OBJECTIVE: To study magnetic resonance imaging (MRI) features in the wrist and metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints in 4 patient groups: early rheumatoid arthritis (RA) (< 3 yrs); established RA (> 3 yrs); other arthritis; arthralgia. METHODS: MRI was obtained before and after contrast (gadodiamide) injection of the wrist and finger joints in 103 patients and 7 controls. The study included: (1) 28 patients with disease duration < 3 yrs who fulfilled the American College of Rheumatology (ACR) criteria for RA; (2) 25 patients with RA disease duration > 3 yrs who fulfilled the ACR criteria. (3) 25 patients with reactive arthritis, psoriatic arthritis, or mixed connective tissue disease; and (4) 25 patients with arthralgia. The following MRI variables were assessed: number of joints with enhancement after contrast injection, number of joints with joint fluid, and number of bones with edema in the wrist and fingers. The volume of the enhancing synovial membrane after contrast injection in the MCP, PIP, and DIP joints was manually outlined. MR images were scored independently under blinded conditions. RESULTS: Bone marrow edema was found in 68% of the patients with established RA, and the number of bones with edema was significantly higher in patients with established RA compared to patients with early RA, other arthritis, and arthralgia (Mann-Whitney p < 0.04). Bone edema was not found in patients with arthralgia. There was marked overlap within and between the patient groups. No differences in MRI features were found between patients with early RA and patients with other arthritis. The volumes of the synovial membrane in the MCP, PIP, and DIP joints were significantly higher in patients with arthritis compared to patients with arthralgia. CONCLUSION: Although there was marked overlap between the arthritis patient groups, MRI determined bone marrow edema and synovial membrane volumes provided additional information about disease activity and may be used as a marker of it. Bone marrow edema appeared with the highest percentage in patients with long duration of RA (> 3 yrs) and is probably secondary to changes in inflammatory activity.     

Microbiologic aspects of inflammatory joint diseases

Regarding of microbiological aspects of arthritis three forms of joint diseases are under investigation: the septic arthritis, the reactive arthritis and the Rheumatoid Arthritis. In 95% of patients with septic arthritis microorganisms as causative agents responsible for the disease are described: Staphylococci, Streptococci, some gram-negative bacteria. By an haematogenic route of infection predominantly patients with immunosuppressive therapy are altered. In newborns and children septic arthritis is to observe more rarely. A reactive arthritis is a postinfectious sterile process in dependence on an infection occurred at an earlier time. As etiologic agents Yersinia, Enterobacteriaceae and Campylobacter have been discovered. 80% of the patients suffering such a reactive arthritis are carrier of the HLA-B27 system. The etiology of the Rheumatoid Arthritis is an open, unanswered problem. Of importance are: immunogenetic conditions, autoimmune phenomena, endocrinologic, dietetic and psychologic factors as well as bacteria and viruses as causative agents: cocci, bacilli, Diphteroids, endoparasitic bacteria (Listeria, L-forms, Mycoplasma, Chlamydiae), viruses (Adeno-, Mumps-, Measles-, ECHO-, Coxsackie-A- and B-, Hepatitis-, Cytomegalo-, Para-influenza-, Retro-, Parvo- and Rubella viruses). In the last years the EBV is of interest covering the question of a distinct virus persistence in tissues and the adequate limiting factors. Perhaps a defect of the hu-IFN-gamma-system might be of immunopathological and clinical significance.     

Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease

INTRODUCTION: We sought to examine the relationship between C-reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). METHODS: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow-through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohn's disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. RESULTS: One-hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate-severe clinical activity (OR, 4.5; 95% CI, 1.1-18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4-8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1-104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. CONCLUSIONS: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity.