[Sodium gold thiosulfate therapy: an open, viewed, multicenter trial in rheumatoid arthritis patients followed for two years]. / Terapia con tiosolfato di sodio e oro: studio osservazionale, aperto, multicentrico in pazienti con artrite reumatoide seguiti per due anni.

OBJECTIVE: To evaluate if parenteral gold-therapy with Sodium gold thiosulfate is effective and safe for the treatment of rheumatoid arthritis we began an open, multicenter trial. METHODS: 126 rheumatoid arthritis patients were treated with Sodium gold thiosulfate for two years. Efficacy, quality of life, progression of joint damage, inflammatory parameters and side effects were evaluated. RESULTS: Gold salts reduced joint inflammation and improved subjective and objective symptoms, quality of life and activity of illness within 6 months. Side effects appeared in 13,8% of all cases and regressed, promptly, when gold therapy stopped. The poor efficacy caused the interruption and the change from the gold therapy to others disease-modifying anti-rheumatic drugs (DMRDs) in 17,8 % of the patients. CONCLUSIONS: The follow-up showed Sodium gold thiosulfate was effective in Rheumatoid Arthritis and the survival in therapy was of 77,8% to one year and of 68,4% to two years.

Impaired glutathione reductase activity and levels of collagenase and elastase in synovial fluid in rheumatoid arthritis.

OBJECTIVE: To test the activity of elastase, collagenase and glutathione reductase in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and in patients with osteoarthritis (OA); to correlate the elastase and collagenase activity with the glutathione reductase activity, which is important for the inactivation of oxygen free radicals. METHODS: 24 patients affected by osteoarthrosis and 24 patients affected by rheumatoid arthritis took part in the study. We measured elastase activity towards the substrate metoxysuccinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide (MeOSuc-ala-ala-proval-p-NA) which is highly specific for elastase, and insensitive to the other serine proteases, such as cathepsin G; collagenase activity was measured using [14C]-acetylated collagen as the substrate. Glutathione reductase activity was measured following the oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the presence of oxidized glutathione (GSSG). RESULTS: The concentrations of elastase, collagenase and glutathione reductase were statistically higher in patients with RA than in patients with OA. Moreover, in the SF of patients with RA we found positive correlation between enzyme activity levels. CONCLUSION: These results confirm a high activity of collagenase and elastase in the SF of patients with RA, which is about 30 times higher than that found in the SF of patients with OA. These data underline the synergic action of these enzymes in the pathogenesis of joint damage. RA patients also exhibit higher levels of glutathione reductase, which is important for the detoxification pathway of oxygen free radicals. However, compared with findings for collagenase and elastase, the increase in glutathione reductase is only three times higher than level found in the SF of OA patients. The limited increase in glutathione reductase activity during the inflammatory process might lead to an insufficient protective effect at the joint level in rheumatoid arthritis.

Lymph-node-based malignant lymphoma and reactive lymphadenopathy in eosinophilic fasciitis.

BACKGROUND: Lymph node enlargement in patients with eosinophilic fasciitis is a rare occurrence and its clinical significance is unknown. METHODS: The literature and authors' registries were searched for eosinophilic fasciitis associated with lymphadenopathy. Clinical data, time sequence of appearance of either disorder, and pathological diagnoses were analyzed. RESULTS: Six patients presenting with eosinophilic fasciitis had a lymph-node-based lymphoma and 4 patients had a reactive lymphadenopathy. The patients with lymphoma were elderly and the subcutaneous induration preceded the lymphadenopathy by 2 to 36 months. The patients with eosinophilic fasciitis and reactive lymphadenopathy were young and the onset of subcutaneous induration and lymph node enlargement coincided with one another. Favorable response of the eosinophilic fasciitis to prednisone therapy was attained in 3 of 3 patients with reactive lymphadenopathy and in 4 of the 6 cases with lymphoma. CONCLUSIONS: Eosinophilic fasciitis is rarely associated with clinically significant lymph node enlargement. Subcutaneous induration preceding the lymphadenopathy by 6 months or more, especially in elderly patients, suggests an underlying lymphoma. A favorable response of the subcutaneous induration to prednisone treatment does not exclude the diagnosis of lymphoma; therefore, it does not supersede the need of a pathological evaluation. A lymph node biopsy is mandatory in all cases.

Bladder involvement in systemic sclerosis: urodynamic and histological evaluation in 23 patients.

Lower tract involvement of systemic sclerosis is an uncommon manifestation. In this study we have evaluated the functional and morphologic vesical changes in 23 female patients with systemic sclerosis to investigate if bladder dysfunction was correlated with an extended skin sclerosis and/or a more serious organ involvement. Urodynamic alterations were observed in only 3 cases. Urinary symptoms and urodynamic features were correlated neither with severity of vesical fibrosis nor with visceral involvement. Autonomic dysfunction was detected in 13 patients.

Cryoglobulinemic peripheral neuropathy: neurophysiologic evaluation in twenty-two patients.

The aim of this study was to evaluate the frequency and degree of peripheral neuropathy in 22 consecutive patients with mixed cryoglobulinemia, whether symptom-free or with subjective neurological symptoms. Electrophysiological investigations were carried out and a biopsy of the sural nerve was performed in six patients. Peripheral neuropathy of the lower limbs was demonstrated, which was mostly sensory and light or moderate in 86% of cases (19 patients). F-Wave and H-reflex recordings were found to be the most reliable methods; in 77% of cases, they were abnormal (17 patients). Using somatosensory evoked potentials, we were able to exclude simultaneous central nervous system involvement in 10 patients.

A placebo-controlled study on urokinase therapy in systemic sclerosis.

A 4-month randomized placebo controlled trial on urokinase therapy in 36 consecutive systemic sclerosis patients randomly treated with urokinase or placebo was conducted. While patients on placebo did not show any significant improvement, in those following urokinase therapy there was a noticeable improvement in skin sclerosis observed via hand-print and ultrasonography of the skin. Vascular involvement improved: this was demonstrated by capillaroscopy results, showing an improvement in pattern and signs of revascularization and the resolution of skin ulcers. Vascular damage is a typical occurrence in systemic sclerosis cases and various vasoactive drugs are used symptoms for some such as Raynaud's syndrome or skin ulcers. At the moment these drugs seem to constitute the most effective therapy, and have few side effects. We have found only one previous study utilizing urokinase therapy for acute digital ischemia in systemic sclerosis. Our study is the first in which urokinase therapy has been used for the treatment of systemic sclerosis in a large number of patients.

Densitometric and biochemical alterations in bony tissue induced by ureterosigmoidostomy.

The mineral content of bone was measured in 134 male patients who underwent ureterosigmoidostomy within the past 18 years. Moreover, the principal humoral indices of bone metabolism, together with hematic pH and alkaline reserve (BE) values were evaluated. This study showed that after approximately 6 years from a ureterosigmoidostomy there was significant bone demineralization. These data, supported by a parallel increase of serum osteocalcin, show that ureterosigmoidostomy represents a risk factor for osteoporosis especially in those patients who already have below normal values of bone mineral density prior to surgery.

D-penicillamine and gold salt treatments were complicated by myasthenia and pemphigus, respectively, in the same patient with rheumatoid arthritis.

A 53-year-old woman with rheumatoid arthritis developed myasthenia gravis after 6 months of therapy with D-penicillamine. Nineteen months after D-penicillamine was discontinued and 12 months after the beginning of gold therapy, she developed pemphigus vulgaris. This is the first reported case of gold-induced pemphigus in rheumatoid arthritis. This study further underlines the complex interactions between the effects of treatment with sulfhydryl-disulfide exchange drugs and the altered immunological system of patients affected by rheumatoid arthritis.

Polymyositis-like syndrome in hypothyroidism: report of two cases.

An increase of muscle enzymes in hypothyroidism has sometimes been correlated with a polymyositis-like syndrome and hypothyroid patients have been misdiagnosed and mismanaged as suffering from polymyositis. Actually, muscle symptoms, such as aches and pain, stiffness, weakness and cramps or, more rarely, hypertrophy, are observed in hypothyroidism and increased serum muscle enzyme values, particularly the level of creatine phosphokinase (CPK), indeed seem to suggest polymyositis. The muscular groups most commonly affected by the above mentioned symptomatology are those of the shoulder and pelvic girdles. In this report two hypothyroid patients complaining of muscle symptoms, whose serum muscle enzymes were particularly elevated, are described. In the first case the patient had been suffering from pain and weakness of the thenar eminence for about 4 months. The clinical features suggested a diagnosis of Carpal Tunnel Syndrome, but thyroid function tests revealed primary hypothyroidism. In the second case the patient had been afflicted with muscular weakness of the shoulder girdle for 2 months and was unable to keep his arms raised over his head. A study of thyroid function demonstrated a picture of hypothyroidism. Both patients were treated with L-thyroxine and in a relatively short time biochemical parameters improved remarkably, and the symptoms disappeared. The hypothesis that a muscular effort of long duration by hypothyroid patients may have been responsible for the muscular damage and the symptoms may explain why only a few hypothyroid patients develop a clinical picture similar to polymyositis.

Evaluation of the effectiveness and safety of etodolac in prolonged treatment of active osteoarthritis.

Patients affected by osteoarthritis totalling 358 (142 males and 216 females) were recruited in an open study which lasted up to three months. All patients started treatment with etodolac 600 mg/die per os. 74 patients were treated and followed for 15 days, 94 for one month, 54 for two months, and 132 for three months. Clinical evaluations, performed at baseline and after 15, 30, 60, and 90 days of treatment were made on the following parameters: intensity of pain, index of sleep disturbance caused by symptoms related to osteoarthritis, investigator's evaluation of the global patient's condition, patient's self-evaluation about his own condition, presence and duration of morning stiffness, presence and duration of stiffness at rest, and finally the investigator's integrated evaluation about the effectiveness tolerance of etodolac during the study. All the parameters showed a noticeable and significant improvement in all groups of patients, stratified by sex, age, and duration of the disease. The younger patients and those patients with osteoarthritis of a less prolonged duration achieved the best results. Only slight differences were registered by examining the baseline values of the various parameters or the extent of the different improvements achieved, on the basis of sex, and duration of osteoarthritis and the non-steroidal anti-inflammatory drugs previously used. Among the 27 patients who withdrew, eight dropped out for clinical inefficacy and 15 for intolerance. In all these latter cases a prompt and complete resolution of the adverse reaction was achieved and maintained after the interruption of therapy. In the 49 patients who presented side-effects, these were almost always related to the gastrointestinal tract and of slight intensity. A complete resolution was promptly achieved in 25 cases, while in 17 other patients the side-effect persisted during the course of the study, but it was considered not worthy of the patient dropping out. The profile of routine laboratory parameters, measured both at inception and at the end of the study, did not show relevant changes after treatment with etodolac. In conclusion this study demonstrated that etodolac is effective and well tolerated in the prolonged treatment of patients with active osteoarthritis.

Activation of murine autoreactive b cells by interleukin 1-like factors released from synovial inflammatory cells of rheumatoid arthritis patients.

The effect of interleukin 1 (IL-1)-like factor(s), produced by cells isolated from the synovial fluids of rheumatoid arthritis (RA) patients, on an in vitro murine model of spontaneous autoimmunity, i.e., the development of plaque-forming cells (PFC) to bromelain-treated mouse red blood cells (Br-MRBC) in mouse peritoneal cell (PC) cultures, has been investigated. It has been found that IL-1-containing culture supernatants from cells isolated from joint fluids of RA patients, as well as recombinant IL-1, determine a marked increase in anti-Br-MRBC PFC development. Moreover, factor(s) of 10-20 KD molecular weight, with IL-1-like biological activity, capable of increasing the anti-Br-MRBC PFC development in mouse PC cultures, have been demonstrated in joint fluids from RA patients. The finding that synovial inflammatory cells produce factors that activate autoreactive B cells further supports the role of autoimmunity in the pathogenesis of rheumatoid arthritis, as self-perpetuing disorder.

Polyclonal B cell activation in ankylosing spondylitis.

The peripheral blood lymphocyte response of patients with ankylosing spondylitis (AS) to several polyclonal B cell activators was investigated. No differences were found in the reactivity to pokeweed mitogen and protein A between patients and controls; in contrast, the peripheral blood lymphocyte response to Staphylococcus aureus strain Cowan I (SAC) was significantly higher in patients with AS than in controls. This responsiveness was not influenced either by the presence of the HLA-B27 antigen or by environmental factors or associated diseases, and it was higher in patients with active AS than in those with inactive disease. The percentage of circulating B cells was normal. The responses to T cell mitogens and the percentages of T cell subpopulations were similar in patients and in controls. The peripheral blood lymphocyte hyperactivity of patients with AS to SAC was associated with an increased in vitro production of immunoglobulins.

Effectiveness and safety of etodolac in treatment of rheumatoid arthritis: a multicentre two-months' open study.

One hundred and seventeen outpatients (87 females and 30 males; mean age 53.5 +/- 13.2 years) encompassing the 1987 American Rheumatism Association criteria for rheumatoid arthritis were admitted into a multicentre open study. All patients were evaluated at baseline and after two months of therapy with etodolac (400 or 600 mg/die per os). Clinical evaluation was performed by using the following indicators: viso-analogic scale of global pain; index of pain on active movements; index for sleep disturbances, and duration of morning stiffness. The erythrocyte sedimentation rate was chosen for the laboratory evaluation of the activity of the disease. One hundred patients received 400 mg/die, while only 17 patients received 600 mg/die; 115 patients undertook the evaluation after treatment, whereas two patients were considered "lost to follow-up". One hundred and five patients completed the study while ten patients withdrew (seven because of inefficacy and three because of intolerance of the gastrointestinal tract). Only nine patients presented side-effects, among these: five were judged etodolac-related, whereas four were not. A complete resolution of all these side-effects was achieved in all cases. Significant improvements were registered for all the four clinical variables. At the end of the study 56.5% of patients expressed a preference for etodolac, 16.5% for one of the non-steroidal anti-inflammatory drugs previously taken and 27% did not answer or were not able to express any definite preference. Strict concordance was found between the degree of clinical improvement achieved and the preferences expressed. The laboratory parameters did not reveal any variation at the end of the study in comparison with baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavior of prealbumin in the acute phase of polymyalgia rheumatica treated with 6-methylprednisolone.

Serum levels of prealbumin, fibronectin, fibrinogen, alpha 1-acid glycoprotein, C-reactive protein, immunoglobulins, and white blood cell count were prospectively studied in 33 patients affected by polymyalgia rheumatica during the first 45 days of treatment with 6-methylprednisolone. Almost all parameters considered, except for fibronectin and IgM, settled within the normal range fairly quickly, while prealbumin showed a specular course compared with the other reactants. This behavior reflected the improvement of clinical symptoms registered in all patients after steroid treatment. Finally, the genesis of the low baseline prealbumin levels found in polymyalgia rheumatica/giant cell arteritis and their behavior during treatment are discussed.

Etodolac versus diclofenac: double-blind cross-over study in rheumatoid arthritis.

A 14-day double-blind clinical study was conducted on 16 patients with clinically active rheumatoid arthritis to compare the effects of etodolac (600 mg daily) and diclofenac (150 mg daily). Admission criteria were: functional impairment between Steinbrocker's classes I to III, Ritchie's index greater than 10 and erythrocyte sedimentation rate greater than 25 mm/h, and finally active involvement of the small joints of the hands. Following a wash-out period of at least two days from their previous non-steroidal anti-inflammatory drugs, trial patients received etodolac or diclofenac for five consecutive days by random allocation; after that, and after another two day wash-out period, all patients were crossed-over to the alternate drug for another five consecutive days. One day before intake and on the last day of each treatment lap, each patient was examined in regard to the circadian grip strength (of the more severely affected hand), Ritchie's index and acute phase reactants; at the end of the second treatment period, subjective drug preference was explored. Grip strength was assessed by the patients themselves with a dynamometer at 08h00 and every two hours thereafter until 20h00. The overall daily value was calculated by measuring the area under curve (AUC) depicting the grip strength profile. Both groups of patients showed significant improvement of the Ritchie's index (p less than 0.01) and grip strength AUC (p less than 0.05), while taking medication, whereas no significant variations were noted in regard to the values of the acute phase parameters both between the two treatment groups, and within each treatment group. At termination, four patients expressed preference for etodolac, eight were in favour of diclofenac, and four gave an indifferent judgement. No statistically significant differences were detected between the two treatment groups; also no adverse events were seen in this short-term study. The results confirm the effectiveness and tolerability of etodolac in the acute stage of rheumatoid arthritis.

HLA antigens in palindromic rheumatism. An Italian study.

Forty-four patients with typical palindromic rheumatism were typed for HLA-A,B,C and DR antigens. The mean duration of follow-up of our patients was 4.0 yrs. (range 1-12 yrs.). During this time 27% of patients showed a seropositivity; 22% of patients developed polyarthritis, 1 patient revealed a Sjögren syndrome and 3 patients showed a spontaneous improvement. The HLA-B16 antigen was increased in patients compared with controls, but the difference was not statistically significant. A, C and other B antigens were found with normal frequencies. The HLA-DR antigens did not reveal any differences between patients' and controls' values, either 40% of patients who developed RA carried the HLA DR4 antigen.