EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

OBJECTIVE: To formulate EULAR recommendations for the management of early arthritis. METHODS: In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion. RESULTS: 15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research. CONCLUSIONS: 12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.

Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results.

OBJECTIVE: To assess methods to calculate achieving and sustaining remission in a double blind randomised trial in patients with RA who received etanercept, methotrexate, or an etanercept/methotrexate combination. METHODS: Remission was defined as DAS <1.6, DAS28 <2.6, and ACR70 response. Sustaining remission was analysed in three ways: (a) analysis of sustained DAS remission, DAS28 remission, or ACR70 response continuously for 6 months; (b) analysis of sustained remission appraised through a continuity rewarded scoring system, which is the weighted sum of all intervals in the study in which patients are in DAS or DAS28 remission; or (c) longitudinal modelling of remission odds using generalised estimating equations. RESULTS: Significantly more patients treated with the etanercept/methotrexate combination reached DAS remission (37%) than those treated with either methotrexate (14%) or etanercept (18%) alone (p<0.01). Results for DAS28 and for the ACR70 response were similar. Agreement between DAS remission and DAS28 remission was good, but agreement between either of these and the ACR70 response was less. Patients in DAS or DAS28 remission had a lower level of disease activity (fewer active joints, lower ESR) than those achieving ACR70 response; the converse was seen using pain VAS. The three methods were comparable for sustainability of remission and showed significant advantage for combination therapy, which increased the number and durability of remission periods. CONCLUSIONS: DAS and DAS28 remission results were similar for assessing achieving and sustaining remission in RA, frequently differing from patients classified as ACR70 responders. The three methods of examining duration of remission produced comparable results.

[The effects of long-term inhaled glucocorticoids on children's bones]. / Efectele glucocorticoizilor administrati de durata, pe cale inhalatorie, la copil, asupra osului.

The authors study, by calcanean ultrasonographic method, the effects of inhaled steroids, administered for long term, on the bone status, in children with persistent asthma. The study group consisted in 33 children with persistent asthma, treated for 12 months with low or moderate doses of either beclomethasone dipropionate or fluticasone propionate. In all of them there were measured the main ultrasonographic parameters, before and after treatment. The results were compared with those recorded in a control group. The control group consisted in 16 children with asthma that did not receive long term inhaled steroids. In the study group the were no statistically significant differences between ultrasonographic parameters measured before and after steroids inhaled treatment. There were no statistically significant differences between ultrasonographic parameters measured after steroid treatment in the study group and the same parameters recorded in the control group. The results of our study reveal that long term inhaled steroids therapy do not influence the bone density at the calcanean level.

[Fever of unknown origin in Romania. II. Diagnostic Procedures. Prospective multicenter study of 164 patients]. / Febra de origine necunoscuta: II. Mijloace diagnostice. Un studiu prospectiv multicentric pe 164 de pacienti.

BACKGROUND: The Diagnostic workup of patients with fever of unknown origin is a challenge, due to the great number of possible etiologies. After we studied the etiologic spectrum of fever of unknown origin in Romania, we tried to evaluate the diagnostic procedures used and their efficiency. METHODS: A multicenter cohort study of two years, with another two years of follow-up was carried out on 164 consecutive patients who met the classic, modified criteria of fever of unknown origin. We used a standardised diagnostic protocol. MAIN OUTCOME MEASURED: The role of every diagnostic procedure in establishing the final diagnosis. RESULTS: The diagnosis was made by microbiology and serology in 41 cases (25%), by histopathology in 22 cases (18%), with the help of imaging techniques in 30 cases (1.3%), based on the clinical evolution and response to treatment in 54 cases (33%) and by other methods in 12 cases (7.3%). The abdomino-pelvic ultrasonography had a sensitivity of 60%, a specificity of 70%, a positive likelihood ratio of 2.02 and a negative likelihood ratio of 0.57, while the scanner had a sensitivity of 81%, a specificity of 64%, a positive likelihood ratio of 2.23 and a negative likelihood ratio of 0.29. CONCLUSIONS: Of all the diagnostic procedures used, none had a good sensitivity/specificity. The clinical evolution and the treatment response had an important role in the diagnostic workup.

[Fever of unknown origin: 1. Etiology. A prospective multicenter study of 164 patients]. / Febra de origine necunoscuta. I. Etiologie. Studiu prospectiv multicentric pe 164 de pacienti.

BACKGROUND: The spectrum of fever of unknown origin seems to be determined by geographic and economic factors, and it appears to change in time. Excepting a small retrospective study, no other study on fever of unknown origin has been performed in Central or Eastern Europe. METHODS: A multicenter cohort study was carried out on 164 consecutive patients who met the classic, modified criteria of fever of unknown origin. The study lasted 2 years (1997-1998) and included a follow-up period of another 2 years. MAIN OUTCOME MEASURED: The final diagnosis at the end of follow-up. RESULTS: 74 (45%) patients had infections (tuberculosis: 27 patients, 16%), 41 patients (25%) had neoplasms, 30 (18%) had non-infectious inflammatory diseases, three (2%) drug fever, and four (2%) other causes. The etiology remained obscure for 12 patients (7%). CONCLUSIONS: Infections represent the most important etiology, among them predominating tuberculosis.

The effect of methylprednisolone pulse therapy in polymyositis/dermatomyositis.

The study aim was to assess the effect of corticosteroid (CS) therapy on the clinical and biological features of dermatomyositis (DM) or polymyositis (PM).

Renal ostodystrophy during the developing stage of maintenance dialysis in Transylvania. Early development of periarticular calcifications and beta 2 microglobulin amyloidosis in spite of a relatively good prevention of secondary hyperparathyroidism.

BACKGROUND: Dialysis facilities have been introduced only recently in Transylvania with many limitations, in particular a standard high calcium dialysate, Al(OH)3 as phosphate binder and pharmacological doses of native vitamin D2, but neither CaCO3 nor 1 alpha hydroxylated vitamin D. Rheumatological complaints and metastatic calcifications were frequent, leading to suspect either overt hyperparathyroidism, adynamic bone disease or beta 2 microglobulin amyloidosis. AIMS OF THE STUDY: Evaluate the prevalence of radiological osteitis fibrosa, amyloid osteoarthropathy and periarticular calcification and their link with PTH secretion, phophocalcic disorders, acidosis, bone turn over, aluminum and beta 2 microglobulin accumulation in the dialysis population of Sibiu (Transylvania). METHODS: The clinical and radiological rheumatological data of the 49 uremic patients dialyzed in Sibiu since 1990 were reviewed as well as the monthly routine monitoring of their plasma phosphocalcic parameters. Furthermore in July 1994, 36 of them had an X rays of the hands for evaluation of subperiosteal resorption of the phalanges, periarticular calcifications and carpal cysts as well as a determination of plasma concentrations of intact PTH (normal range: 10-55; optimal range: 100-200 pg/ml), osteocalcin, bone alkaline phosphatase, aluminum and 25 OH vitamin D. RESULTS: The prevalence of subperiostal resorption of the phalanges was 8% and that of severe biological hyperparathyroidism (PTH > 400 pg/ml) 22%, whereas that of a relative hypoparathyroidism (PTH < 100 pg/ml) was 31%. Mean plasma concentrations of calcium was 2.07 +/- 0.15; of phosphate 2.50 +/- 0.35; of bicarbonate 15 +/- 2.0 mmol/l, of 25 OHD 30 +/- 20 ng/ml, of aluminum 1.1 +/- 0.5 mumol/l. Plasma PTH concentrations were negatively correlated to dialysis duration, and to plasma concentrations of aluminum, calcium and 25 OH vitamin D but not to those of phosphate and bicarbonate. Multivariate analysis showed however that only duration of dialysis and plasma aluminum concentration were independently and negatively correlated to plasma PTH concentrations. The prevalence of periarticular calcifications (26%) and of carpal cysts suggestive of beta 2 microglobulin amyloidosis (10%) were relatively high considering the young age of the population (42 years) and the short duration of dialysis (2.6 years). Patients with calcifications comparatively to those without calcifications were older, had longer duration on dialysis, higher prevalence of carpal cysts and higher plasma beta 2 microglobulin concentrations, lower plasma PTH (98 versus 313 pg/ml) and higher plasma aluminum concentration (1.3 versus 0.8 mumol/l). Patients with carpal cysts comparatively to those without cyst were older, had a longer duration on dialysis and a higher prevalence of periarticular calcifications. CONCLUSIONS: a) In spite of no use of 1 alpha hydroxylated vitamin D derivatives, and poor control of hyperphosphatemia and acidosis, hyperparathyroidism declined with duration of dialysis due to the use of a high dialysate calcium concentration, Al(OH)3 as sole phosphate binder and high supplement of native vitamin D. b) Considering the relative young age and short duration on dialysis, the prevalence of periarticular calcifications and carpal cysts were high. c) Calcifications were possibly favored by relative hypoparathyroidism and moderate aluminum overload. d) The association of periarticular calcifications and subchondrial cysts suggest a causal relationship.

von Willebrand factor in synovial fluid.

Von Willebrand factor (vWf), an endothelial product that arises in plasma in conditions associated with vascular damage and acute phase reaction, was evaluated in paired samples of plasma and synovial fluid obtained from 54 patients with inflammatory joint effusion, 19 patients with osteoarthritis, and from the plasma of 19 controls. Synovial fluid levels of vWf were detected in 36 of the patients. The mean value of vWf in the inflammatory joint effusion group was 18.27 +/- 3.03%, significantly higher than the mean value of 7.7 +/- 4.4% found in the osteoarthritis group (p less than 0.01). The significant difference between these groups was maintained when vWf was expressed as a ratio of albumin. vWf was correlated with synovial fluid levels of alpha-1-antitrypsin (r = 0.83, p less than 0.01) and with the white cell count (r = 0.74, p less than 0.01), but not with the levels of immunoglobulins or C3. vWf in the synovial fluid may reflect the local degree of inflammation.

[The treatment of severe psoriatic arthritis with methotrexate in a weekly "mini-pulse" dosage plan]. / Tratamentul artritei psoriazice severe cu metotrexat în schema posologica "mini-pulse" saptamînal.

The paper reports on the authors' own experience on the effect of therapy with methotrexate (MTX) in 18 patients with invalidant psoriatic arthritis (PA). The therapeutic scheme was of the weekly "mini-pulse" type (three doses of 2.5 mg administered at 12-hour interval, with a gradual increase to 15 mg/week). The results were very good in 12 cases (66.6%), good in 3 cases (16.6%) and absent in other two cases (11.1%). These results and the data in the literature lead to the conclusion that MTX is a valuable therapeutic alternative for severe P.A. under the conditions of a correct surveillance with the observance of the contraindications.

Levels of SC5b--9 complement complex in plasma and synovial fluid of patients with rheumatic disease.

Activation of the terminal complement pathway leads to formation of the C5b--9 complex. The main effects of C5b--9 generation are tissue injury by cell lysis or by stimulation of proinflammatory mediators. In a study carried out in 42 patients, using polyclonal antibodies against C5b--9 neoantigens and C9 in an ELISA assay, we found significantly higher levels of SC5b--9 complex in plasma from the 18 patients with active systemic lupus erythematosus than those found in 10 healthy controls (p less than 0.005). In the 18 patients presenting rheumatoid arthritis and the 6 with progressive systemic sclerosis the plasma levels of SC5b--9 complex did not differ significantly from those in controls. The SC5b--9 levels found in the synovial fluid samples from the 16 rheumatoid arthritis patients were higher than the corresponding plasma ones. The ratio between synovial fluid and plasma levels was 1.2. Immunoperoxidase staining for C5b--9 was intense in three rheumatoid synovial membranes and absent in two normal synovial membranes obtained during meniscectomy. Increased levels of plasma and synovial fluid SC5b--9 reflect pathologic systemic or local activation of the complement carcase in systemic lupus erythematosus and respectively rheumatoid arthritis. Synovial membrane deposits of C5b--9 are indicative for the lytic and proinflammatory effects of complement activation.

von Willebrand factor in the plasma of patients with rheumatic diseases.

von Willebrand factor (vWf), an endothelial cell product, was evaluated in 39 patients with rheumatoid arthritis, 19 patients with connective tissue diseases and vasculitis, 21 patients with nonrheumatoid inflammatory arthritides, 14 patients with osteoarthritis and 19 controls. High plasma vWf levels were found in rheumatoid arthritis patients: 196.35 +/- 85.8 (p less than 0.001 versus control) connective tissue diseases and vasculitides: 306.50 +/- 43.4 (p less than 0.001 versus control) and inflammatory nonrheumatoid arthritides: 193.35 +/- 90.6 (p less than 0.01 versus control). Highly increased vWf concentrations of more than 300%, were found in one patient presenting Wegener granulomatosis, 6 patients with vasculitis associated to connective tissue diseases, 7 patients with rheumatoid arthritis and 2 patients with active forms of inflammatory arthritides. vWf was correlated with fibrinogen in the subgroup of systemic lupus erythematosus patients. Elevated vWf levels may reflect vascular damage as well as the acute phase reaction. Highly elevated levels of vWf appear to indicate a poor prognosis.

Fibronectin in plasma and synovial fluid of patients with rheumatic diseases.

Fibronectin is a high molecular weight glycoprotein from plasma and other body fluids, connective tissue matrix and basement membranes. No significant differences in the mean values of plasma fibronectin were found in patients with rheumatic diseases compared to control subjects. The fibronectin in synovial fluids in these patients presented higher levels than in plasma. No other protein from the synovial fluid presented such a peculiar behaviour. The synovial fluid fibronectin/plasma fibronectin ratio is 2.49 in patients with rheumatoid arthritis, 1.56 in those with inflammatory nonrheumatoid arthritides and 1.60 in those with osteoarthritis. Statistically significant higher values of synovial fibronectin were found in patients with rheumatoid arthritis compared to those with osteoarthritis. No significant statistical correlations were found between the synovial fibronectin concentrations and the other clinical or biological parameters of the rheumatoid arthritis patients, but for synovial fluid C3. Immunohistochemical localization of fibronectin in the rheumatoid synovium showed more intense and extended specific deposits than in the control patients. These results suggest a local synthesis of fibronectin related to the chronic inflammatory process.