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.     

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.     

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.     

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.     

细胞间粘附分子-1和P-选择素的检测在炎性腹水和非炎性腹水鉴别诊断中的价值

目的　通过检测肿瘤性腹水、结核性腹水和肝硬化腹水患者的细胞间粘附分子 1(I CAM 1)和P$C选择素 (P selection)水平 ,探讨其鉴别炎性和非炎性腹水的意义。方法　采用酶联免疫吸附法 (ELISA)检测 2 9例肿瘤性腹水、2 0例结核性腹膜炎腹水和 13例肝硬化性腹水患者腹水的ICAM 1和P 选择素水平。结果　肿瘤性腹水ICAM 1水平为 (63 .5 4± 3 7.68)ng/L ,结核性腹水水平为 (12 3 .85± 41.85 )ng/L ,肝硬化腹水水平为 (3 5 .95± 11.5 0 )ng/L ,肿瘤性腹水P 选择素水平为 (3 .0 3± 1.2 6)ng/L ,结核性腹水水平为 (4 .2 6± 1.63 )ng/L ,肝硬化腹水水平为 (2 .72±1.49)ng/L。结核性腹水患者ICAM 1和P 选择素水平明显高于肿瘤性腹水 (P <0 .0 5 )和肝硬化性腹水 ,两者水平在肿瘤性腹水和肝硬化腹水之间的差异无显著性 (P >0 .0 5 )。结论　ICAM 1和P 选择素的表达与机体炎症反应被激活有关 ,结核性腹膜炎患者腹水中ICAM 1和P 选择素水平明显增高 ,检测腹水中ICAM 1和P 选择素的水平对鉴别炎性和非炎性腹水有帮助     

Elbow clinical,ultrasonographic and radiographic study in patients with inflammatory joint diseases

The main objective of this cross-sectional observational study was to investigate the relationship between clinical, ultrasonographic (US) and radiographic elbow features in patients with inflammatory joint diseases (IJD). The secondary objective was to evaluate the association between regional clinical elbow diagnoses and imaging findings. Consecutive patients with IJD attending follow-up visits were assessed for elbow pain and standardized elbow examination. Seven regional clinical  diagnoses were defined. Digital elbow radiographs were read for 9 abnormalities. A standardized elbow grayscale (GS) and power Doppler (PD) scan recorded 13 defined abnormalities. Analysis encompassed 361 clinical, 361 US and 340 radiographic elbow assessments from 181 patients. US and clinical assessments showed an overall higher agreement than radiographic and clinical assessments (68.8 vs 59.1 %, p = 0.001). When structural US abnormalities were compared with radiographic findings, agreement was slightly higher than when comparing all US abnormalities with radiographic findings (77.3 %, k 0.533 and 73.5 %, k 0.492). Enthesophytes, the most common abnormalities, were not associated with clinical findings. Subclinical US-synovitis and US-enthesopathy were found, respectively, in 17.3 and 14.1 % of the clinically normal elbows. Clinical elbow arthritis prevalence and bias-adjusted kappa (PABAK) agreement was good for radiographic fat pad sign, PD-synovitis and GS-synovitis. Clinical elbow enthesopathy PABAK agreement was moderate for GS-enthesopathy and radiographic calcifications. US showed acceptable agreement with clinical and radiographic assessments for detecting elbow inflammatory and structural abnormalities in patients with IJD. Because US detected more abnormalities than radiography and has the capability to detect more subclinical abnormalities, US may be potentially used as a first-line elbow diagnostic tool in this clinical setting.     

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.      

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.     

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.     

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.     

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.     

Pathophysiologic aspects of inflammatory and degenerative joint diseases

Authors describe the physiological particularities of components of articular system (cartilage, synovialis, synovia, subchondral bone, ligamentous and neuromuscular apparatus). The essential resultant pathophysiological pattern in rheumatoid arthritis and osteoarthritis are demonstrated. Differences between temporary attendant synovitis in osteoarthritis and rheumatoid arthritis are pointed out.     

Anterior sonography of glenohumeral joint in patients with inflammatory joint disease

Ultrasonography (US) was shown as an effective imaging modality in evaluating the shoulder. The shoulder joint is probably the most accessible joint for sonography in adults. However, inflammatory changes of the shoulder have received too little attention in US studies. Anterior access for US assessment of glenohumeral joint (GHJ) has not been investigated. Another problem of patients with acute synovitis of glenohumeral joint is the difficulty to perform a 90° abduction for the axillary US because of severe pain and active and passive limitation. We offer the anterior access for assessment of glenohumeral joint synovitis (GHS). Sonographic evaluation (Sonosite-Titan) was carried out in 25 patients with acute GHS and 15 healthy controls. The diagnosis of GHS was made after the patients underwent physical examination and the laboratory evidence was obtained. We used the anterior position of transducer applied laterally to coracoid processus along the anterior joint cavity. The problem of anterior joint cavity investigation in neutral position is a poor presentation of the joint and the application of the biceps tendon. The problem is simply resolved after supination of the hand and external rotation of the shoulder. We measured and compared upper, middle, and lower width of the anterior GHJ cavity. Echogenicity of joint cavity was assessed by comparison with adjacent tissues. Homogeneity and regularity of GHJ cavity was designated in both groups as well. We measured labrum-infraspinatus distance on posterior view for assessment of GHJ synovitis. All cases of GHJ synovitis were confirmed by a US Doppler study. US investigation of healthy controls enabled to find normal values of the width of the anterior GHJ cavity that was less than 7.4 mm. The synovitis group showed GHJ cavity expansion: 8.3±2.4 (p=0.001) and 10.5±3.1 (p<0.001) for the middle and the lower anterior part of the GHJ respectively. The upper part width was not different in synovitis and control groups. Anterior joint cavity extension to 7.4 mm and upper in its lower part was high sensitive (96%) and specific (86%) US sign of synovitis with the test power above 0.9. The posterior labrum-infraspinatus extension had high specificity for synovitis (100%), but only seven of 25 patients (28%) had increased (>2 mm) the value of the labrum-infraspinatus dimension, which was previously proposed as the US sign of synovitis. Echogenicity of the anterior joint cavity in healthy controls was moderately high (far more echogenic than deltoid muscle). Echogenicity of synovitis declined, and mild effusions were found to be common. Those were not to be seen on US of GHJ in neutral position and were revealed only in supination and external rotation of the shoulder. Intra-articular tissue of healthy controls was relatively echo-homogenic compared with nonhomogenic one of the synovitis group. Bone irregularity was found in patients with long-standing GHJ synovitis reflecting erosive process. A certain position of the shoulder and good knowledge of the normal anterior joint cavity parameters enabled us to diagnose synovitis by anterior shoulder sonography, with the patients experiencing minimal pain during movements.