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Physical and biological dosimetry were investigated in 45 rheumatoid arthritis patients treated by radiosynoviorthesis (RSO) with 186Re-sulphide (medium-sized joints) and 169Er-citrate (digital joints). Biological dosimetry involved scoring dicentrics in lymphocytes, cultured from blood samples withdrawn just before and 6 h, 24 h and 7 days after treatment. Physical methods included repeated blood sample counts and scintigraphy data. For erbium-169 (pure beta emitter), only bremsstrahlung could be measured and solely in the injection area. For rhenium-186 (both beta and gamma emitter), whole body scans and static images of joints and locoregional lymph nodes were performed. Dosimetry calculations were in accordance with the MIRDOSE 3 software and tables. For erbium-169 (21 patients), either metacarpophalangeal (30 MBq) or proximal interphalangeal (20 MBq) joints of the hands were treated (one joint per patient); 18 patients (out of 21) were interpretable for biological dosimetry, 10 (out of 11) for physical dosimetry and six (out of 10) for both. For rhenium-186, 23 wrists, nine elbows, three shoulders and two ankles were injected in 24 patients, with a maximum of three joints per patient (70 MBq per joint); 20 patients (out of 24) and 10 (out of 10) were interpretable for biological and physical dosimetry, respectively, and eight (out of 10) for both methods. Erbium-169 biological dosimetry was negative in all interpretable patients, and physical dosimetry gave a blood dose of 15 +/- 29 microGy and an effective dose lower than 1 mSv/30 MBq. For rhenium-186, biological results were negative in 16 patients (out of 20), but showed a blood irradiation around 200 mGy in the last four. A significant cumulative increase of dicentrics 7 days after injection (16/10,000 instead of 5/10,000 prior to treatment; p < 0.04) was also noted. Gamma counts gave a blood dose of 23.9 +/- 19.8 mGy/70 MBq and the effective dose was found to be 26.7 +/- 5.1 mGy/70 MBq, i.e. about 380 microGy.MBq-1. Erbium-169 RSO is very safe from both physical and biological dosimetry standpoints. Rhenium-186 leak is greater, as demonstrated by the higher blood activity and the measurable, although limited, dicentrics induction in blood lymphocytes. However, the effective dose remains moderate, i.e. 30 times lower than in 131I therapy in benign thyroid diseases.

Between 1970 and 1994, 116 chemical and 90 radioactive synovectomies were performed in 107 patients with severe haemophilia and two with type 3 von Willebrand's disease. The products used were osmic acid (OA) in 100 cases, 90-Yttrium in 35 cases, 186-Rhenium in 48, 169-Erbium in two, hexacetonide triamcinolone in 16 and radioactive gold in five cases. The use of radioactive colloids is not allowed in France in patients under 15 years of age. Twenty-nine patients had more than one synovectomy per joint. All patients were evaluated for 6 months post-synovectomy, using both a clinical and a radiological score. Six months after synovectomy, a good or excellent result was obtained for 81% of the joints treated with isotopes, compared with 44% of those treated with OA, P < 0.001. This superiority of isotopes over osmic acid was still observed after 6 months for the 89 joints that were re-evaluated, with follow-up ranging from 1 to 9 years. It was possible to calculate a radiological score in 84 cases. With OA the best results were from the joints with the lowest scores pre-synovectomy (

In a retrospective study of 206 patients with cystic fibrosis (CF), five cases of CF arthritis were recorded. This is a frequency of 2.5% and of 4.5% in patients aged over 10. Four patients had episodic arthritis, which was related to the course of pulmonary disease in two cases. In three patients, synovial fluid examination revealed minimal evidence of inflammation. In one of these three cases, synovial biopsy revealed a mild and non-specific synovitis. The fifth patient had chronic arthropathy and was positive for rheumatoid factor, but did not fulfil the criteria for rheumatoid arthritis. There were no radiographic abnormalities in any of these cases. CF arthritis is a rare syndrome of unknown pathogenesis.

T cell subpopulations were assessed by two colour flow cytometry with phycoerythrin conjugated anti-CD45RA and anti-CD29 and fluorescein conjugated anti-CD4 and anti-CD8 monoclonal antibodies, on peripheral blood lymphocytes from 12 patients with systemic sclerosis and from nine control subjects. The percentage of CD4+CD29+ cells was significantly higher in patients with systemic sclerosis than in controls (mean (SEM) 68.8 (3.1) v 47.9 (4.1) respectively). CD4+CD45RA+ cells were not significantly different in patients and controls. CD8+CD29+ and CD8+CD45RA+ subpopulations were significantly higher in patients with systemic sclerosis than in controls (83.0 (3.2) v 58.7 (6.8) and 80.2 (3.0) v 66.9 (3.2) respectively). The increase in the percentage of CD29+ cells suggests an activation of memory cells in patients with systemic sclerosis, which may play an important part in the pathogenesis of the disease.

Left ventricular dysfunction in systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance in coronary microcirculation. We evaluated the pharmacodynamic effect of the calcium channel blocker nicardipine on left ventricular function assessed by radionuclide ventriculography in 20 patients with systemic sclerosis. Resting gated, blood-pool images were obtained at baseline and 90 min after 40 mg of oral nicardipine. The mean (+/- SEM) left ventricular ejection fraction significantly increased from 65.4 +/- 2.3% at baseline to 71.3 +/- 2.3% after nicardipine (p less than 0.005). The mean global defect score significantly decreased from 2.90 +/- 0.73 without nicardipine to 1.50 +/- 0.52 with nicardipine (p less than 0.01). The mean number of left ventricular sectors with severe hypokinesis significantly decreased from 0.80 +/- 0.24 at baseline to 0.20 +/- 0.09 after nicardipine (p less than 0.05). No significant side effects were observed with nicardipine. These results demonstrate short-term improvement in left ventricular function with nicardipine in patients with systemic sclerosis.

Intra-articular injection of 169Erbium-citrate (169Er-citrate; radiosynoviorthesis or radiosynovectomy) is an effective local treatment of rheumatic joint diseases. However, its efficacy in corticosteroid-resistant rheumatoid arthritis-affected joints has not been clearly demonstrated.A double-blind, randomised, placebo-controlled, international multicentre study was conducted in patients with rheumatoid arthritis with recent (or = 24 months) ineffective corticosteroid injection(s) into their finger joint(s). Eighty-five finger joints of 44 patients were randomised to receive a single injection of placebo (NaCl 0.9%) or 169Er-citrate. Results of evaluation 6 months later were available for 82 joints (46 metacarpophalangeal and 36 proximal interphalangeal joints) of 42 patients: 39 169Er-citrate-injected joints and 43 placebo-injected joints. Efficacy was assessed using a rating scale for joint pain, swelling and mobility.Intent-to-treat analysis of the results of the 82 joints showed a significant effect of 169Er-citrate compared to placebo for the principal criteria decreased pain or swelling (95 vs 79%; p = 0.038) and decreased pain and swelling (79 vs 47%; p = 0.0024) and for the secondary criteria decreased pain (92 vs 72%; p = 0.017), decreased swelling (82 vs 53%; p = 0.0065) and increased mobility (64 vs 42%; p = 0.036). Per-protocol analysis, excluding 18 joints of patients who markedly changed their usual systemic treatment for arthritis, gave similar percentages of improvement but statistical significance was lower owing the reduced power of the statistical tests.These results confirm the clinical efficacy of 169Er-citrate synoviorthesis of rheumatoid arthritis-diseased finger joints after recent failure of intra-articular corticotherapy.

The aim of this international multicentric randomized phase 3 clinical trial was to compare prospectively radiosynoviorthesis (RSO) with rhenium-186-sulfide (186Re) to intra-articular corticotherapy in patients with clinically controlled rheumatoid arthritis (RA), but in whom one or a few medium-sized joints remained painful or swollen.One hundred and twenty-nine joints in 81 RA patients [stratified into 2 groups: wrists (group 1, n = 78) and all the other joints (group 2, n = 51, including 18 elbows, 21 shoulders and 12 ankles)] were randomized to receive intra-articular injections of either 186Re-sulfide (64 +/- 4 MBq), or cortivazol (Altim) 3.75 mg. Clinical assessment was performed before and then at 3, 6, 12, 18 and 24 months after local therapy, using a 4-step verbal rating scale (VRS) and a 100 mm visual analog scale for pain, a 4-step VRS for joint swelling and mobility and a 2-step VRS for the radiological stage. The Mantel-Haenszel test was used for qualitative variables, analysis of variance (ANOVA) for quantitative pain analysis and Kaplan-Meyer survival test for relapse analysis.186Re was observed to be statistically superior to cortivazol at 18 and 24 months while no statistical difference was seen for any criterion at 3, 6 and 12 months post injection. At 24 months, the difference in favor of 186Re was significant for pain (p = 0.024), joint swelling (p = 0.01), mobility (p = 0.05, non-wrists only), pain and swelling (p = 0.03) and pain or swelling (p = 0.02). "Survival" studies (Kaplan-Meyer) demonstrated a greater relative risk of relapse in corticoid treated joints, but only from the second year of follow-up. No serious side effect was observed in any patient, with only light and transient local pain and/or swelling occurring in 24% of cases, regardless of the treatment used.186Re-sulfide and cortivazol had similar efficacy up to 12 months post-injection, but 186Re became clearly more effective at 18 and 24 months, for all criteria monitored and for RA outcome. Therefore, 186Re RSO can be recommended for routine clinical use.

Nous avons interroge 157 patients atteints de polyarthrite rhumatoide consultants ou hospitalises dans un service de rhumatologie. Les patients ont ete questionnes sur leurs habitudes d’utilisation et leurs connaissances du maniement des antalgiques. Nous avons egalement consulte les patients prenant ou ayant pris des antalgiques sur leur appreciation de l’efficacite des antalgiques. Ainsi, il est apparu que pour la plupart des patients, la douleur est l’element principal a traiter, alors que les antalgiques sont consideres comme un element mineur du traitement. Les antalgiques centraux paraissent les plus efficaces, essentiellement sur les douleurs diurnes, a la dose de 2 comprimes par jour. La connaissance du maniement des antalgiques parait parcellaire et trop rarement precisee au patient. Si chez nos patients, les antalgiques sont souvent pris sur prescription medicale, ils sont le plus souvent pris insuffisamment, en fonction des poussees, a des horaires variables et sans connaissance des possibilites d’association entre antalgiques centraux et peripheriques ou aux anti-inflammatoires non steroidiens. Un effort d’education et de mise en place de regles de prescription des antalgiques dans la polyarthrite rhumatoide doit etre envisage.

We report here the second 2-yr extension of a clinical trial among postmenopausal women; 235 women continued blinded treatment with 5 or 10 mg alendronate daily, and 115 women who had been treated with alendronate for 5 yr were switched to blinded placebo. Continuous treatment with alendronate (10 mg daily) for 7 yr increased lumbar spine bone mineral density (BMD) by 11.4% compared to baseline. After the initial 18 months, each additional year of treatment through yr 7 increased spine BMD by 0.8% for the 10-mg dose and 0.6% for the 5-mg dose, with significant increases during yr 6-7. Previously reported increases in BMD at other skeletal sites and decreases in biochemical markers of bone turnover remained stable during yr 6-7. Among women previously taking alendronate for 5 yr who were switched to placebo, there was no significant decline in BMD at the spine or hip, whereas small, but significant, decreases in BMD at the forearm and total body and small increases in biochemical markers were observed. The safety and tolerability profiles were similar to those of placebo. This is the largest published long-term study of antiresorptive therapy. Our findings indicate that long-term alendronate treatment is well tolerated and effective for 7 yr. Increases in spinal BMD continue for at least 7 yr, and other skeletal benefits are maintained. Discontinuation does not lead to accelerated bone loss, but continuous treatment yields better skeletal benefits than shorter treatment.

To investigate the expression of inducible nitric oxide synthase (iNOS) in subpopulations of peripheral blood and synovial fluid (SF) leukocytes in patients with rheumatoid arthritis (RA).iNOS was detected in peripheral blood and SF samples after cell permeabilization, by 2 color immunofluorescence flow cytometry. Samples from 14 patients with RA and 8 with osteoarthritis (OA) were studied. Nitrite concentration was determined by Griess reaction, interleukin 1beta and tumor necrosis factor alpha by an immunoenzymatic assay, and C-reactive protein (CRP) by an immunonephelometric method.In SF, iNOS was detected in 11 of 14 patients with RA and 2 of 8 with OA. In blood cells, iNOS was detected in 8 of 14 patients with RA and none of the OA group. iNOS was consistently detected in monocytes and was not detected in granular cells. In RA, there was no correlation between the number of iNOS positive mononuclear cells and cytokine concentrations. CRP concentration was correlated with the number of iNOS positive mononuclear cells in RA SF samples.SF mononuclear cells from patients with RA express iNOS and are involved in NO production in the joint. The number of positive cells is correlated with CRP concentration, suggesting the implication of NO production in the inflammatory process.

Nitric oxide (NOo) is an inorganic radical produced after the activation of a NO synthase involved in inflammatory and immune reactions. It can react with protein thiols to form nitrosothiols, a bioactive molecule or can generate in nitrite or nitrate. High concentrations of these metabolites have been found in sera and synovial fluids from patients with osteoarthritis, the higher synovial concentrations suggesting NOo intra-articular production. The aim of this study was to evaluate the capacity of osteoarthritic chondrocytes to produce bioactive NOo metabolites and to study the inhibitory effect of rhein, the active form of diacerhein. Chondrocytes were stimulated by interleukin-1 beta (1 ng/ml) during 24 hours in presence or absence of rhein (1.3 x 10-5, 6.5 x 10-6, 1.3 x 10-6 M) or diclofenac (10-5, 10-6 M). After 24 hours, nitrite and nitrosothiols were measured in the supernatants and nitrosothiols were also determined in cell lysats. After interleukin-1 beta stimulation chondrocytes produced great quantities of nitrosothiols and nitrite. This effect was inhibited in a dose dependent manner by rhein but not by diclofenac. In conclusion, chondrocytes produce high quantities of nitrosothiols after IL-1 beta stimulation and this effect is inhibited by rhein. This drug could be beneficial to prevent the destruction of osteoarthritic cartilage.

We describe the case of a 44-yr-old woman, suffering from rheumatoid arthritis for 15 yr, who developed porphyria cutanea tarda while being treated with methotrexate. The cutaneous lesions healed and the metabolic anomalies improved after a few months, despite continuing the treatment.

Meningeal metastatic disease usually occurs as a complication of a brain tumor and is exceptionally isolated in patients with solid tumors. We report the case of a 74-year-old woman admitted for mechanical S1 sciatica refractory to drug therapy. She had been treated for breast cancer three years earlier. Physical findings were pain upon hyperextension of the lumbar spine and absence of the ankle jerks. Analysis of cerebrospinal fluid sampled during an intrathecal glucocorticoid injection showed 1 g/L of protein and 11 normal cells per mm3. Grade 3 L5-S1 spondylolisthesis was seen on plain radiographs, computed tomography scans, and magnetic resonance imaging scans. At that point, the patient developed sphincter dysfunction and motor loss in the left lower limb in the distribution of several nerve roots. Findings were normal from a myelogram and a magnetic resonance imaging study of the brain. A repeat cerebrospinal fluid analysis showed 1.1 g/L of protein and 5 cells/mm3. Because of the discrepancy between the clinical and imaging study findings, the patient was transferred to a neurology department. A third cerebrospinal fluid study showed numerous adenocarcinoma cells, and a repeat magnetic resonance imaging demonstrated a mass in the dural sac opposite L2. A program of monthly intrathecal methotrexate injections was started. A fatal meningeal relapse occurred eight months later.This case shows that a leptomeningeal metastasis can cause isolated nerve root pain, and demonstrates the diagnostic value of magnetic resonance imaging and cerebrospinal fluid cytology in patients with atypical symptoms, particularly when there is a history of malignant disease.

To evaluate the efficacy and tolerance of a platelet activating factor-acether (PAF) antagonist, BN 50730, in patients with rheumatoid arthritis (RA).A total of 56 patients with active RA were enrolled in a multicenter, double blind, placebo controlled study of BN 50730. Patients received either BN 50730 (40 mg orally bid) or placebo for 84 days.Treatment with BN 50730 resulted in no improvement and was no more effective than placebo in improving clinical and biological indices of RA activity. Adverse events were observed in the 2 treatment groups, and BN 50730 was generally well tolerated.PAF antagonist BN 50730 at a daily dose of 80 mg was ineffective in the treatment of RA.

We describe a 50-year-old woman with seropositive rheumatoid arthritis and Sjögren's syndrome who underwent autologous blood stem cell transplantation after relapse of associated non-Hodgkin's lymphoma. This resulted in complete remission not only of the lymphoma, but also the arthritis.

Glucocorticoids are powerful antiinflammatory agents widely used for the treatment of rheumatoid arthritis (RA). Synthesis and/or secretion of annexin I (A-I) is induced by these steroids. Annexins V and VI are also found extracellularly but are not induced by glucocorticoids. Annexins may be potent antagonists of phospholipase A2 (PLA2). Since autoantibodies to A-I have been reported in patients with RA, we studied the reactivity of sera from patients with RA to A-V and A-VI.Sera from 26 patients with RA were assessed for anti-A-V and anti-A-VI antibodies and compared with sera from 26 sex/age matched healthy subjects. IgG and IgM antibodies were analyzed in an ELISA: A correlation study with disease activity and corticosteroid treatment schedule was performed.Sera from patients with RA contained significantly higher levels of IgG [anti-A-V and anti-A-VI] autoantibodies than control sera, both being correlated. This rise in antiannexin antibody titers was correlated with the RA activity score, and negatively correlated with the daily dose of corticosteroids.High levels of IgG (anti-A-V and anti-A-VI) antibodies were found in sera from patients with RA. We suggest that antiannexin autoantibodies may play a role in the clinical course of RA by impairing the anti-PLA2 effect of annexins.

Symphysitis of the pubis due to Streptococcus occurred after endoscopic resection of the prostate in a 69-year-old man. Despite a well conducted antibiotic regimen, signs persisted one year later and required arthrography that showed a prostato-symphysis fistula. This procedure might be used to find an explanation of certain persistent cases of symphysitis. Fistulization between the prostate and the pubic symphysis would be a new pathogenic hypothesis for symphysitis of the pubis.

To define the clinical, pathological and molecular genetic characteristics of a family with mild spondyloepiphyseal dysplasia (SED) and precocious osteoarthritis.The proband was a 46-year-old man with precocious generalized OA, tall stature, mild chondrodysplasia and moderate deafness. His daughter, aged 21, showed similar clinical features. Electron microscopic (EM) analysis of collagen from an affected joint of the proband was performed. DNA was extracted from whole blood on the proband, his affected daughter, unaffected wife and second daughter, to look for a mutation in exons 31 or 11, sites where point mutations have been previously described in mild forms of SED. After finding no mutation in exon 31, exon 11 of COL2A1 was further analyzed. Exon 11 was amplified using polymerase chain reaction (PCR), and screening for the mutation was undertaken using a restriction enzyme digestion, the recognition sequence of which is altered by this point mutation. Sequence analysis was then performed.Electron microscopic (EM) analysis of cartilage from the proband showed thin appearing collagen fibrils organized into parallel lamellar structures. DNA studies revealed a single base change in one allele of exon 11 which produced an arginine to cysteine mutation at position 75 of the triple helix of type II collagen in the proband and his affected daughter.This is the 2nd example of an Arginine75-Cysteine mutation associated with SED; in our case, however, contrasting clinical features were present. Recurrent mutations at a few specific sites of COL2A1 suggest the possibility of susceptibility "hot spots" for mutational events.

The authors used data from a study conducted under the auspices of the Société Française de Rhumatologie to evaluate the sensitivity and specificity of the individual items of two sets of criteria for spondylarthropathy. The study included 124 patients with spondylarthropathy and 1,964 controls. They found that the spondylarthropathy criteria with the highest sensitivities and specificities were useful not only for classifying patients but also for assisting in the diagnosis of spondylarthropathy.

In order to address the issue of the role of mast cells (MC) and nitric oxide (NO) in rheumatic synovial-fluid diseases, synovial fluid (SF) collected from the knee of patients with osteoarthritis (OA), articular chondrocalcinosis (ACC) or rheumatoid arthritis (RA) was examined for the levels of mast cells (MC), histamine, tryptase, phospholipase A2 and nitrite. MC counts were found to be elevated in the SF of OA patients as compared with RA patients. Histamine content in SF parallelled the number of MC. Tryptase levels were elevated in OA in comparison to RA and ACC, but the difference was not statistically significant. Identical PLA2 levels were recorded among the 3 groups. Nitrite concentrations were also higher in SF from OA patients as compared to RA patients. These results suggest that mast cells (MC), in association with various inflammatory cells, may contribute to inflammation and cartilage breakdown in osteoarthritis (OA).

Extracorporeal photochemotherapy (ECP) consists of collection of mononuclear cells, their irradiation with UV-A light in the presence of a photoactivable molecule--8-methoxy-psoralen (8-MOP) being the most widely used--and their reinjection into a patient. Two technical approaches have been developed. The photopheresis procedure involves four steps: (i) 8-MOP is given to the patient orally, 2 h before collection of white blood cells; (ii) a discontinuous flow cell separator (UVAR, Therakos, West Chester, PA, U.S.A.) is used for cell collection. The final product (740 mL) has a hematocrit of 4.5 +/- 1.7%); (iii) irradiation, performed with the same UVAR apparatus, begins before all the cells are collected, and lasts for 180 min after collection; and (iv) after irradiation, the buffy-coat is reinjected into the patient. We developed a technique summarized as follows: (i) mononuclear cell collection is performed using the Spectra (Cobe, Denver, CO, U.S.A.) cell separator, which provides a highly enriched mononuclear cell concentrate (always > 90% purity), in a small volume < 150 mL, subsequently adjusted to 300 mL for irradiation. Hematocrit of the final product is always < 2%. (ii) Soluble 8-MOP is added to the mononuclear cell concentrate at a final concentration of 200 ng/mL. (iii) Mononuclear cell concentrate is transferred in an EVA plastic bag (Macopharma, Tourcoing, France) to ensure an efficient irradiation with a UV irradiator (Vilber Lourmat, Marne-la-Vallee, France). (iv) After irradiation at 2 J/cm2 (time < 20 min), the cells are reinfused into the patient. Experimental and clinical data suggest that ECP has potential applications in the treatment of connective tissue disorders, such as systemic sclerosis and rheumatoid arthritis. Although encouraging data have been obtained, further clinical trials are warranted to establish the role of this therapy in these indications.

Intraarticular treatment has been considered for osteoarthritis since the first attempts at local injection of steroid derivatives. To assess the effectiveness of intraarticular drugs, in view of the variability of the disease and the remarkable placebo response, a control group of patients is necessary. The main outcome measures are pain and joint effusion when using symptomatic slow acting drugs. If a chondroprotective effect is to be demonstrated the main criterion is measurement on standardized radiography of the knee medial femorotibial joint space.

New compounds appear to improve symptoms of osteoarthritis (OA), and others are putative chondroprotective agents. We suggest experimental designs for studying the effects of these agents in subjects with hip and knee OA. The course of the articular cartilage lesion is the primary outcome measure to be assessed in putative chondroprotective agent trials. Serial radiographic studies suggest that the annual rate of joint space narrowing in patients with hip or knee OA is about 0.25 mm. Other approaches to quantitation of cartilage loss, e.g., radiographic measurement of the area of joint space, ultrasonography, magnetic resonance imaging and fiberoptic arthroscopy (for knee OA) are under investigation.

Articular chondrocalcinosis is identified by radiological opacity of articular cartilage and fibrocartilage with calcium intensity. This disease is often asymptomatic. The most significant clinical pattern is an acute arthritis, caused by microcrystals of calcium pyrophosphate dihydrate, the so-called pseudo-gout syndrome. Chronic pyrophosphate arthropathy can blend mechanical illness and inflammatory flares. When the X-rays are normal or display ordinary osteoarthritis, arthrocentesis makes the diagnosis thanks to the identification of calcium pyrophosphate crystals by polarizing microscope. Large joints are usually involved but the disease can impair the spine, small joints, tendon sheaths or synovial bursae. Though unpredictable the evolution can be worse than that of common osteoarthritis and strike joints that are usually spared by primary arthrosis. One can even see articular destruction. Thus certain patients may resemble rheumatoid arthritis, others a Charcot joint. The disease does not exist in children. Its outcome before the age of fifty implies the search for familial occurrence or a secondary form (hyperparathyroidism, hypophosphatasia, hemochromatosis, hypomagnesemia). The sporadic, primary chondrocalcinosis is very frequent in old age.

To determine the etiology of acute arthritis observed in adults and to define its relationship with human immunodeficiency virus 1 (HIV-1) infection in Kigali, capital city of Rwanda.From September 1, 1989 until March 31, 1990 we conducted a study of all new patients admitted with acute arthritis to the outpatient and inpatient services of the Department of Internal Medicine at the Centre Hospitalier de Kigali, in Kigali, Rwanda, a city highly endemic for HIV infection.Thirty-six patients (27 men 9 women; mean age: 31 years, range 18-65) were included in the study. Twenty-six (72%) were HIV seropositive. Two main diagnostic categories emerged, both strongly associated with HIV infection: (1) aseptic arthritis: 16 (44.5%) patients including 12 (33.5%) patients with spondyloarthropathy of whom 10 (83%) were HIV seropositive, and 4 (11%) patients with HIV related arthritis, (2) septic arthritis: 11 (30%) patients of whom 9 (82%) were HIV seropositive, including 4 with gonococcal, 2 with staphylococcal, 1 with Salmonella B and 2 with tuberculous arthritis.In an area highly endemic for HIV, acute arthritis should be considered a possible manifestation of HIV infection and should prompt HIV testing.HIV infection is highly endemic in Kigali, Rwanda. The authors report findings from a study conducted from September 1, 1989 to March 31, 1990, to determine the etiology of acute arthritis observed in adults and its relationship with HIV-1 infection in the city. Careful medical histories and full clinical evaluations were conducted upon each new patient admitted with acute arthritis to the outpatient and inpatient services of the Department of Internal Medicine at the Centre Hospitalier de Kigali over the period. 27 men and 9 women of mean age 31 years in a range of 18-65 years presented, of whom 72% were HIV seropositive. Aseptic arthritis was diagnosed in 16 patients of whom 14 were HIV seropositive. 12 patients fulfilled the criteria of spondylarthropathy of whom 10 were HIV seropositive. There were 4 cases of HIV-related polyarthritis, while septic arthritis was identified in 11 patients of whom 9 were HIV seropositive, including 4 with gonococcal, 2 with staphylococcal, 1 with Salmonella B, and 2 with tuberculosis arthritis. The authors stress on the basis of these findings the need in an area highly endemic for HIV to consider acute arthritis a possible manifestation of HIV infection which necessitates the testing for HIV.

A 16-month prospective study of adult patients who had been suffering from arthritis for less than one year was conducted in the Internal Medicine department of the hospital of Kigali, Rwanda. Seventy-six patients were included in the study. Out of 72 patients whose sera were tested for human immunodeficiency virus (HIV), 52 were positive, this being 72.2 percent compared with the 20.7 percent figure observed in the urban population of adults in Rwanda. Two main groups arthropathies were individualized: septic arthritis (24 patients including 19 seropositive subjects) and inflammatory rheumatism with criteria of spondyloarthropathies in some of them (34 patients, 32 tested, 28 serum positive). Thus, the finding of acute arthritis in a region with high HIV infection prevalence should suggest a possible HIV infection, especially when the arthritis itself is suggestive of this diagnosis.

Whipple's disease is a worrying disease because of its protean manifestations. It may sometimes take on the appearance of sarcoidosis with polyvisceral granulomatous dissemination. We describe 2 cases of sarcoid-like Whipple's disease including one with synovial granulomatous involvement. It therefore appears to be essential, in view of the therapeutic possibilities, to perform periodic acid Schiff stain on all granulomas and duodenal fibroscopy with biopsies, even in the absence of any gastrointestinal symptoms, before concluding that the diagnosis is sarcoidosis.

Elevated serum concentrations of acute-phase proteins (APPs) are a characteristic finding of rheumatic diseases, including RA. CRP is the most useful measure of disease activity and is frequently assessed in clinical trials to determine systemic improvement. The effects of different therapies for RA on CRP have been assessed in many studies. The DMARDs such as gold salts, D-penicillamine, sulphasalazine and azathioprine have been shown to reduce serum CRP concentrations significantly in patients with RA. CRP serum concentration is also reduced by the corticosteroids such as prednisone, but addition of pulse therapy with i.v. methylprednisolone had no additive effect compared with DMARDs alone. Many studies have shown that serum CRP concentrations are not reduced by NSAIDs; however, one recent study has demonstrated that CRP concentration was reduced by the NSAIDs flurbiprofen and sustained-release ibuprofen in a subgroup of patients.

Experimental results suggest that substance P (SP) may play an important role in pain and inflammation in rheumatic diseases. Measurements of SP-like immunoreactivity (SPLI) were performed in synovial fluid (SF) and synovial tissue from 40 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). High levels of SPLI were found in the SF of patients with RA compared with OA. Conversely, SPLI content in synovial tissue was higher in OA than in RA, suggesting that there is an active secretory process of SPLI into the SF in RA, thus depleting SPLI stores in the synovium. Our data support the involvement of SP in the perpetuation and exacerbation of inflammation in RA, and may also explain some clinical features of this disease.

The results of an open retrospective study of 49 patients treated with salazosulfapyridine (SASP) (sulphasalazine) for rheumatoid arthritis (RA) are reported. The patients, 7 men and 42 women, had a mean age of 53 years, and their mean duration of evolution of RA was 13.3 years. Sixty percent of them had undergone more than 3 previous disease-modifying drugs. The mean length of SASP treatment was 15.3 months. The initial response was favorable in 34 patients (69%). Treatment was ineffective and stopped in 12 cases (24.5%); the inefficacy was primary in 6 and tachyphylactic in the other 6. Twenty patients (41%) experienced at least one side effect. SASP was stopped in 11 patients (20.4%) due to undesirable side effects; 9 of the 11 times were during the first 2 months of treatment. Digestive system intolerance was the most common but led to drug withdrawal in less than half the patients. In all cases, mucocutaneous, neurosensory, hematological and hepatic side effects regressed during the month following SASP withdrawal. The therapeutic maintenance level was 67% at 1 year, 60% at 18 months, 52% at 2 years and 45% at 3 years. SASP has a role in the treatment of relatively slightly evolved forms of RA, before prescribing methotrexate. The possibility of delayed intolerance reactions, notably hematological and hepatic, justify prolonged biological monitoring of these patients.

A 49 year old white woman with systemic lupus erythematosus and bronchiolitis obliterans was treated with prednisone (1 mg/kg daily), which led to a transitory improvement in pulmonary status. Cyclophosphamide was then added--4 mg/kg daily intravenously for five days, then 2 mg/kg daily orally--and this was followed by a dramatic and prolonged improvement.

We describe an unusual intestinal bypass arthritis in a 37-year-old man. The intestinal bypass was unusual because the intestinal blind loop was entirely composed of colon. The arthritis was first a typical bypass arthritis but later resembled rheumatoid arthritis. In spite of this resemblance, all rheumatic symptoms disappeared after jejunocaecal reanastomosis.

Chronic hepatitis is infrequently reported in the course of RA (1.9%). We report 6 cases with such an association. The six patients were all female (mean age: 59.5 years) with typical RA (ACR criteria), and sicca syndrome in 5 cases. Chronic hepatitis always developed after the onset of RA (delay: 1 to 47 years). Laboratory findings revealed a mild increase of transaminases. Alkaline phosphatase were increased in 3 cases. Liver insufficiency was present in 4 cases and polyclonal hypergammaglobulinemia in 6 cases. Rheumatoid factors were detected in 5 cases; antinuclear antibodies and anti-smooth muscle antibodies were also detected in 5 cases. Histological examination of liver biopsy disclosed active chronic hepatitis in 5 cases (with cirrhosis in 3 cases) and persistent chronic hepatitis in 1 case. Steroid therapy was administered in 4 cases of active chronic hepatitis with clinical and biological improvement (18 months to 6 years follow-up). One patient died of gastric bleeding.

1. Cisapride is a novel prokinetic drug which facilitates or restores motility throughout the gastrointestinal tract. Its mechanism of action is thought to involve enhancement of acetylcholine release in the myenteric plexus of the gut. 2. The effect of intravenous cisapride 10 mg on gastro-oesophageal dysfunction was investigated in 20 patients with systemic sclerosis, using a double-blind, randomised, cross-over, placebo-controlled manometric study design. 3. The increase in lower oesophageal sphincter pressure was significantly higher after cisapride (mean +/- s.e. mean, 8.3 +/- 2.1 cm H2O) than after placebo (mean +/- s.e. mean. 0.1 +/- 0.3 cm H2O) (P less than 0.001). The increase in the number of fundic gastric contractions during the 30 min study period was significantly higher after cisapride (mean +/- s.e. mean, 7.7 +/- 2.3) than after placebo (mean +/- s.e. mean, 0.9 +/- 0.6) (P less than 0.01). 4. No serious clinical adverse effects were observed. 5. The study demonstrates that intravenous cisapride induces a significant increase in lower oesophageal sphincter pressure and in the number of fundic gastric contractions, which may be beneficial in the treatment of scleroderma gastro-oesophageal dysfunction. Further long-term studies of the effect of oral cisapride in patients with systemic sclerosis are warranted.

Methotrexate (MTX) is used as sequential treatment of rheumatoid arthritis in doses ranging from 5 to 20 mg per week, but its effectiveness is impaired by undesirable and sometimes severe side-effects, notably on the lungs. We report three cases of lung disease in patients with rheumatoid arthritis under MTX therapy. Two patients had a lung infection caused by Escherichia coli and Pneumocystis carinii respectively and the third patient was a case of fatal pneumonia imputed to MTX. The signs and symptoms of these acute infectious or iatrogenic lung diseases are not specific. Bronchial endoscopy with bronchoalveolar lavage usually leads to a diagnostic of opportunistic infection, but it may also show an isolated excess, in both number and percentage, of alveolar leucocytes, pointing to a drug-induced pneumopathy. Acute respiratory failure due to MTX-induced pneumonia is not uncommon. It rapidly regresses either spontaneously or under corticosteroid therapy, but a number of deaths, as in our last patient, have been reported. The occurrence of these lung diseases is unrelated to the total dose of MTX. Reintroducing MTX does not mean that the condition will necessarily recur, but this can only be done in the absence of any other possible treatment.

Two sets of criteria have been proposed to discriminate spondylarthropathies (SA) from other rheumatic diseases. To evaluate their performance, we conducted a cross-sectional study in the patients observed during one week in 28 French Departments of Rheumatology by 91 staff-teaching physicians. The physicians had to apply these criteria to all their patients and had to classify them as definite SA, definite other rheumatic disease or possible SA. The analysis performed on the 2,088 patients with a definite diagnosis (124 SA and 1,964 controls) showed the following results: (table; see text) Of the 140 patients with possible SA, 37 fulfilled both sets of criteria, 22 the ESSG criteria alone and 12 the Amor criteria alone. These data suggest that a) the overall performance of these two sets of criteria is similar; b) this performance is better in the group of patients with a definite diagnosis; c) the patients without a definite diagnosis require a longer follow-up to assess the clinical relevance of these two sets of criteria.

Disappearing bone disease is a rare syndrome, characterized by an idiopathic and spontaneous progressive resorption of bone, for which different etiologies must be considered. The classification of this disease is difficult; acro-osteolysis involves the phalanges or the carpus and tarsus. Massive osteolysis corresponds to diffuse multicentric cystic hemangiomatosis and Gorham and Stout's disease. We describe two cases of acro-osteolysis and one of Gorham and Stout's disease. The mechanism of disappearing bone disease remains unknown and no treatment has yet been found to stop its evolution.

The authors retrospectively evaluated the results of methylprednisolone pulse in 15 children with chronic arthritis (JRA - 13 cases, spondyloarthropathy - 2 cases). Methylprednisolone succinate was administered at a dosage of 700 mg/m2 by an I.V. infusion pump on 3 consecutive days. A dramatic clinical improvement was obtained in 12/15 cases at day 4. In 7 cases, multiple pulses (between 2 and 8 courses) were administered to obtain better control of the disease and a decrease in the daily dosage of corticosteroids. Only mild and transient side effects were observed; moreover, previous corticosteroid side effects (especially growth retardation) decreased. The duration of clinical benefit was between 2 weeks and 10 months. Disease modifying agents should always be associated with MP pulse therapy to obtain a prolonged response.

Intra-articular injections of triamcinolone hexacetonide (THA) are a useful therapy in JRA and HLA B 27 related arthritis (B 27 RA). Published data have indicated good results and few side effects. We evaluate here the frequency of occurrence of local side effects in 35 children with JRA (115 joints treated) and 13 children with B 27 RA (29 joints treated). With a mean follow up of 25 months in JRA and 18 months in B 27 RA, we observed 12 cases (8.3%) of subcutaneous tissue atrophy with local depigmentation (knees 5 cases, wrists 2 cases, ankles 3 cases, metatarsophalangeal joints 2 cases) and 7 cases (4.9%) of intra-articular calcifications all in the JRA group (wrists 3 cases, knees 2 cases, ankles 2 cases). Youth and joint size are possible predisposing factors for subcutaneous tissue atrophy and intra-articular calcification. Spontaneous improvement previously reported for these local side effects was not observed in our study. These results underline the necessity of discussing on a case by case basis whether intra-articular, non long-acting corticosteroid or THA are indicated. THA must be injected with a rigorous technique and with a dosage adapted to the articular volume.