Vitamin D level: is it related to disease activity in inflammatory joint disease?

The objectives of this study are to assess the vitamin D status in patients (pts) with inflammatory joint diseases (IJD), and its correlation with disease activity. 121 consecutive pts (85 rheumatoid arthritis (RA), 22 psoriatic arthritis (PSA), 14 ankylosing spondylitis (AS)) underwent clinical and laboratory evaluation which included kidney and liver function tests, serum calcium and phosphor levels, 25(OH)D and parathyroid hormone (PTH). Disease activity was assessed by DAS 28 in RA and PSA pts and by BASDAI in AS pts, sedimentation rate (ESR) and CRP. According to activity indexes, pts were divided into subgroups with low (DAS28 < 3.2 and BASDAI < 4), and moderate-to-high disease activity (DAS28 > 3.2 and BASDAI > 4). Associations between serum levels of 25(OH)D and age, gender, ethnicity, type and disease duration, treatment, (anti-tumor necrosis factorα (TNFα) agents or DMARDs), seasonal variations, and disease activity were assessed. Vitamin D deficiency was found in 51 pts (42.1%). The incidence was higher among Arab pts (76.7%) compared to Jews (23%). The difference of 25(OH)D levels between Arabs (mean 9.4 ± 4.2 ng/ml) and Jews (mean 17.8 ± 8.4 ng/ml) was statistically significant (p < 0.0001). We did not find correlation between vitamin D levels and the other evaluated factors. A surprisingly high incidence of vitamin D deficiency was found in IJD patients in a sunny Mediterranean country. This finding justifies the inclusion of vitamin D in the routine lab work-up of pts with IJD. The only statistical significant correlation was found between vitamin D level and ethnic origin. Further studies are needed to look for genetic polymorphism of vitamin D receptors.

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 degrees 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.

Comparison of capsule endoscopy with ileocolonoscopy for detecting small-bowel lesions in patients with seronegative spondyloarthropathies.

BACKGROUND AND STUDY AIMS: Patients with spondyloarthropathies are often found to have signs of small-bowel inflammation when examined by ileocolonoscopy. Because capsule endoscopy has been found to be superior to other endoscopic and radiological modalities in the detection of small-bowel inflammation, we aimed to compare the diagnostic yield of capsule endoscopy with that of ileocolonoscopy in the detection of small-bowel lesions in patients with spondyloarthropathies. PATIENTS AND METHODS: Twenty patients with documented seronegative peripheral arthritis, ankylosing spondylitis, or sacroiliitis, who had not taken nonsteroidal anti-inflammatory drugs (NSAIDs) in the preceding 2 months, participated in the study. The patients underwent capsule endoscopy, followed by ileocolonoscopy within 7 days, with blinded assessment of both examinations. Biopsies were taken when indicated and adverse events were monitored. Patients completed a questionnaire on their satisfaction with the two procedures. RESULTS: A total of 20 patients (11 men, 9 women; mean age 41+/-13 years) with seronegative inflammatory spondyloarthropathies but without abdominal complaints completed the study. No adverse effects were reported and all the capsules were excreted. Of these 20 patients, 11 (55%) had a normal small bowel on both examinations. Significant small-bowel findings (erythema, mucosal breaks, aphthous or linear ulcers, erosions) were detected by capsule endoscopy in six patients (30%) and by ileocolonoscopy in only one patient. In addition, capsule endoscopy detected significant upper gastrointestinal pathology in 40% of patients. The patients preferred capsule endoscopy to ileocolonoscopy. CONCLUSIONS: Capsule endoscopy detected more small-bowel lesions than ileocolonoscopy, and provided additional potentially relevant information on upper gastrointestinal pathology in patients with spondyloarthropathies.

Silica-related rheumatoid arthritis without lung involvement.

We report a young male with recent onset of rheumatoid arthritis (RA) in whom the remarkable severity of the disease led to additional investigations. The only significant finding was mediastinal lymphadenopathy, without lung involvement. Biopsy of the mediastinal lymph node revealed pathological findings typical of silicosis. To our knowledge, this is the first report of silicosis apparent solely in the mediastinal lymph node of an RA patient. This suggests that lung involvement is not crucial for the development of silica-related arthritis.

[Chemical synovectomy in arthritis by intra-articular injection of osmic acid].

18 patients suffering from persistent synovitis despite medical therapy were treated with an intra-articular injection of osmic acid. After 1 year of follow-up, 68% had good results and there were no complications nor detectable radiographic evidence of disease progression. Because osmic acid is almost as effective as surgical synovectomy and is cheap and easy to administer, it can be recommended as the first choice for treatment of corticosteroid-resistant arthritis in the early stages of the disease.

Intravenous immunoglobulin treatment of experimental T cell-mediated autoimmune disease. Upregulation of T cell proliferation and downregulation of tumor necrosis factor alpha secretion.

It has been reported previously that intravenous administration of normal human immunoglobulins (IVIg) to human patients can suppress the clinical signs of certain autoimmune diseases. However, the mechanism(s) by which normal Ig interferes with the various disorders and the scheduling of treatment have been poorly delineated. To study these questions, we examined IVIg treatment of two experimentally induced T cell autoimmune diseases in rats: experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA). We now report that IVIg treatment (0.4 g/kg) inhibited the active induction of both EAE and AA, and that this treatment did not affect the acquisition of resistance to reinduction of EAE. The importance of the site of administration and schedule of treatment were studied in the AA model. Ig was effective when given intravenously, but not when administrated subcutaneously or intraperitoneally. IVIg treatment was effective when given daily from immunization to outbreak of disease; but it was also effective when given once at the time of immunization or once 2 wk after induction of AA, just at the clinical outbreak of disease. Administration of IVIg between immunization and outbreak of AA was less effective. Prevention of disease by IVIg occurred despite the presence of T cell reactivity to the specific antigens in the disease. In fact, IVIg administrated to naive rats activated T cell reactivity to some self-antigens. Nevertheless, IVIg treatment led to decreased production of the inflammatory cytokine TNF alpha. Thus, IVIg treatment may exert its therapeutic power not by inhibiting T cell recognition of self-antigens, but by inhibiting the biological consequences of T cell recognition.

Autoimmune thyroiditis (EAT) in genetically resistant mice mediated by a T cell line.

Experimental autoimmune thyroiditis (EAT) can be induced in genetically susceptible strains of mice by immunization to mouse thyroglobulin (Tg). EAT also can be produced by administration of anti-mouse Tg T cell lines and clones. Previously we were able to raise virulent anti-Tg T cell lines from mice genetically susceptible to EAT. These virulent lines, upon attenuation, were able to vaccinate the susceptible mice against EAT. We now report the isolation of a virulent T cell line from C57BL/6 mice genetically resistant to EAT. The T cell line and its clones recognize a Tg epitope cross-reactive between mouse and bovine Tg. Unexpectedly, the virulent anti-Tg line attenuated in various ways failed to vaccinate C57BL/6 mice against EAT mediated by the line itself. These results shed some light on the regulation of autoimmunity.

Juvenile rheumatoid arthritis patients manifest immune reactivity to the mycobacterial 65-kDa heat shock protein, to its 180-188 peptide, and to a partially homologous peptide of the proteoglycan link protein.

Immune reactivity to the 65-kDa mycobacterial heat shock protein (hsp65) has been associated with arthritis in rats and humans. In this report we evaluated patients with juvenile rheumatoid arthritis for such immunity. A high proportion of affected children showed both antibody and T lymphocyte responses to hsp65 and to two related peptides: the nonapeptide 180-188 sequence of hsp65 and a partially homologous peptide of the cartilage proteoglycan link protein. The titer of circulating antibodies was generally higher in patients with clinically active disease. In contrast to the juvenile rheumatoid arthritis patients, patients with adult rheumatoid arthritis tended to have lower responses of their peripheral blood T lymphocytes to the whole hsp65 molecule. Moreover, the adult rheumatoid arthritis patients did not respond to the peptides. Thus, there appear to be immunological differences between juvenile and adult forms of rheumatoid arthritis related to hsp65 reactivity.

Induction and therapy of autoimmune diabetes in the non-obese diabetic (NOD/Lt) mouse by a 65-kDa heat shock protein.

Insulin-dependent diabetes mellitus is caused by autoimmune destruction of the insulin-producing beta cells of the pancreas. The results described here indicate that a beta-cell target antigen in non-obese diabetic (NOD/Lt) mice is a molecule cross-reactive with the 65-kDa heat shock protein (hsp65) of Mycobacterium tuberculosis. The onset of beta-cell destruction is associated with the spontaneous development of anti-hsp65 T lymphocytes. Subsequently hsp65 cross-reactive antigen becomes detectable in the sera of the prediabetic mice and some weeks later anti-hsp65 antibodies, anti-insulin antibodies, and anti-idiotypic antibodies to insulin antibodies become detectable. The hsp65-cross-reactive antigen, the autoantibodies, and the T-cell reactivity then decline with the development of overt insulin-dependent diabetes. The importance of hsp65 in the pathogenesis of insulin-dependent diabetes was confirmed by the ability of clones of anti-hsp65 T cells to cause insulitis and hyperglycemia in young NOD/Lt mice. Moreover, hsp65 antigen could be used either to induce diabetes or to vaccinate against diabetes, depending on the form of its administration to prediabetic NOD/Lt mice. Other antigens such as the 70-kDa heat shock protein (hsp70) had no effect on the development of diabetes.