[Fibromyalgia]. / La fibromyalgie.

PURPOSE: We review the current knowledge about fibromyalgia, adding to the clinical aspects, the nosology, epidemiology and pathogenesis. The therapeutic and social management of these suffering patients are discussed. KEY POINTS: The limitations of the American College of Rheumatology classification criteria used as diagnostic criteria are discussed. Fibromyalgia is not a simple psychiatric disorder, even if psychiatric symptoms are constantly found. Based on functional brain imaging, there is some evidence pointing to an abnormal function of the supra-spinal centres for pain regulation. CONCLUSION: Fibromyalgia is a clinical autonomous entity. Physiopathology knowledge is improving, but must be confirmed by new research. Patients will take profit of multimodal individualized treatment programs, including explanations about the diagnosis. In most cases, fibromyalgia is compatible with the maintenance of a professional activity, possibly adapted to the patient. Recognized disability requiring compensation is infrequent.

Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group.

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.

The effect of captopril on thallium 201 myocardial perfusion in systemic sclerosis.

In systemic sclerosis, abnormalities of myocardial perfusion are common and may be caused by a disturbance of the coronary microcirculation. We evaluated the long-term effect of captopril (75 to 150 mg per day) on thallium 201 myocardial perfusion in 12 normotensive patients with systemic sclerosis. Captopril significantly decreased the mean (+/- SD) number of segments with thallium 201 myocardial perfusion defects (6.5 +/- 1.9 at baseline and 4.4 +/- 2.7 after 1 year of treatment with captopril; p less than 0.02) and increased the mean global thallium score (9.6 +/- 1.7 at baseline and 11.4 +/- 2.1 after captopril; p less than 0.05). In a control group of eight normotensive patients with systemic sclerosis who did not receive captopril, no significant modification in thallium results occurred. Side effects with captopril included hypotension (six patients), taste disturbances (one patient), and skin rash (one patient). These side effects subsided when the dosage was reduced. These findings demonstrate that captopril improves thallium 201 myocardial perfusion in patients with systemic sclerosis and may therefore have a beneficial effect on scleroderma myocardial disease.

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Recombinant interferon-gamma in the treatment of systemic sclerosis.

PURPOSE: Recombinant interferon-gamma (IFN-gamma) is a potent and selective inhibitor of collagen production by dermal fibroblasts in vitro and has numerous immunoregulatory activities. We assessed the effects of recombinant IFN-gamma in the treatment of patients with systemic sclerosis. PATIENTS AND METHODS: Ten patients entered the study and nine completed the six-month study period. Recombinant IFN-gamma was administered once daily for seven days per week by intramuscular injections: 10 micrograms/day for 10 days, 25 micrograms/day for 10 days, 50 micrograms/day for 10 days, and 100 micrograms/day for the next five months. RESULTS: After the six-month treatment period, a significant improvement, as compared with base-line values, was observed in total skin score, maximal oral opening, range of motion of wrists and elbows, grip strength, functional index, dysphagia, and creatinine clearance. No serious side effects were observed; however, a significant decrease in white blood cell counts and in peripheral blood lymphocytes was noted. CONCLUSION: These results suggest that recombinant IFN-gamma may be beneficial in the treatment of patients with systemic sclerosis.

HLA class I and class II are both associated with the genetic predisposition to primary Sjögren syndrome.

Primary Sjögren syndrome (pSS) is an autoimmune disease characterized by progressive destruction of the exocrine glands leading to mucosal and conjunctival dryness. It is marked by lymphocytic infiltration of the glands and the accumulation of several types of autoantibodies such as rheumatoid factor (RF), antinuclear, anti-SS-A (anti-Ro) and anti-SS-B (anti-LA) autoantibodies. The susceptibility to pSS and/or the presence of SS-A/SS-B autoantibodies in pSS patients is associated with DRB1*03-DQB1*02 and DRB1*02-DQB1*06 haplotypes, whereas no associations have been described with any HLA class I allele. To define the impact of HLA class I alleles in predisposition to pSS, 46 patients responding to the European criteria and 222 healthy unrelated Caucasians were analyzed for their HLA class I and class II haplotypes. Our results confirm the association of the DRB1*03-DQB1*02 haplotype with SS-A/SS-B autoantibodies positive pSS and demonstrate a significant association of the HLA-A24 with the disease. Moreover, HLA-A24 is more often associated with DRB1*11-DQB1*0301 and/or DRB1*0301-DQB1*02 in pSS patients than in the controls. The novel association of HLA class I alleles with susceptibility to pSS provides new insights to the genetic predisposition to this disease and subsequently to its physiopathology.

Nonpharmacological approaches to pain in osteoarthritis. Available options.

Many treatments or techniques have been developed to combat pain in osteoarthritis. These can reduce drug consumption and toxicity, or even delay the need for joint replacement surgery. Pain management in osteoarthritis should start with education, psychological support and environmental measures, reassuring patients that such pain is a reversible state, not associated with aging and irreversible loss of ability. Physiotherapy and exercises are very important for maintaining muscle strength, joint stability and mobility, but should be closely monitored for optimal efficacy. Splints and weight reduction in the obese are useful, depending on the joints involved. Preventive surgery such as cruciate ligament repair or osteotomy should be considered for cases with moderate osteoarthritis. Intraarticular lavage is effective in the short term, and the effectiveness is increased with the use of an arthroscope when meniscus tears or cartilage fragments are associated with osteoarthritis. Nonconventional therapies such as homeopathy, acupuncture and transcutaneous electrical nerve stimulation can be tried at all stages; even if not really efficient, most of these techniques are usually innocuous. Doctors should be aware of these neglected techniques for a better, well tolerated and cost-effective management of pain associated with osteoarthritis.

Nerve growth factor (NGF) autoantibodies and NGF in the synovial fluid: implications in spondylarthropathies.

We investigated the presence of nerve growth factor (NGF) autoantibodies and NGF in the synovial fluid (SF) of patients with different forms of chronic arthritis such as spondylarthropathy (SpA), rheumatoid arthritis (RA), calcium pyrophosphate dihydrate crystal deposition disease (CPPD) and osteoarthritis (OA) and compared them to their levels in serum. NGF autoantibodies were detected by ELISA and by their capacity to immunoprecipitate NGF and to inhibit its biological activity. NGF was measured with a two-site enzyme-linked immunosorbent assay. Significantly high NGF autoantibody levels (p < 10(-4)) and high frequency of detectable NGF (p < 0.01) were observed in the SF of SpA patients and to a lesser degree in RA patients as compared to CPPD and OA patients. In the serum high frequency of detectable NGF was observed only in RA patients. These results suggest a role of NGF autoantibodies and NGF in joint inflammation especially in spondylarthropathies.

Action of anti-inflammatory drugs on interleukin-1 beta-mediated glucose uptake by synoviocytes.

Synovial cell cultures prepared from samples taken from osteoarthritic and rheumatoid patients were treated with different anti-inflammatory agents (cortisol, indomethacin, ibuprofen and piroxicam) to determine their 'anti-interleukin-1 beta' action, using inhibition of interleukin-1 beta-mediated glucose uptake stimulation as a biological test. Confluent cells were treated for 24 h with different concentrations of these drugs (10(-5), 10(-6) and 10(-7) mol/l) to study their effect on the inflammation process. 6 h before glucose uptake studies, interleukin-1 beta (1 ng/ml) was added. Whereas non-steroid anti-inflammatory agents were inefficient, cortisol inhibited the action of interleukin-1 beta on glucose uptake. In osteoarthritic cells, cortisol, 10(-5) mol/l, reduced interleukin-1 beta-mediated glucose uptake by 27% after a 24-h incubation. In rheumatoid cells, stimulated 2-deoxy-D-glucose uptake was reduced by 40.6%. Results were similar when interleukin-1 beta and cortisol were added simultaneously, 6 h before glucose uptake was measured. This rapid effect of cortisol was protein synthesis-dependent (inhibited by cycloheximide). Cortisol decreased glucose uptake by synoviocytes by acting on basal and interleukin-1 beta-mediated glucose uptake. This effect was more pronounced in rheumatoid synovial cells. The inhibition of interleukin-1 beta-mediated glucose uptake could be proposed as a new model for studying the anti-interleukin-1 beta effects of anti-rheumatic drugs.

Administration of methylprednisolone pulse in chronic arthritis in children.

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.

Complications of intra-articular injections of triamcinolone hexacetonide in chronic arthritis in children.

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.

Chronic hepatitis during rheumatoid arthritis.

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.

Chronic erosive arthritis associated with an unusual intestinal bypass.

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.

Increased nitric oxide in exhaled air in patients with systemic sclerosis.

OBJECTIVE: To assess the lung production of nitric oxide (NO) in patients with systemic sclerosis. METHODS: The NO concentration and its rate of production by the lungs were measured in the exhaled air in 14 patients with systemic sclerosis and in 12 healthy control subjects using the chemiluminescent method. RESULTS: The NO concentration and its rate of production were significantly increased in scleroderma patients (mean +/- SEM, 18.7 +/- 1.7 ppb and 5.8 +/- 0.5 nmol/min, respectively), as compared with control subjects (11.2 +/- 0.8 ppb and 4.3 +/- 0.4 nmol/min, p < 0.01 and p < 0.05, respectively). CONCLUSION: The pulmonary production of NO is increased in scleroderma patients, which might reflect and contribute to the inflammatory processes of the lungs in systemic sclerosis.

Better results with rhenium-186 radiosynoviorthesis than with cortivazol in rheumatoid arthritis (RA): a two-year follow-up randomized controlled multicentre study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

169Erbium-citrate synoviorthesis after failure of local corticosteroid injections to treat rheumatoid arthritis-affected finger joints.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These results confirm the clinical efficacy of 169Er-citrate synoviorthesis of rheumatoid arthritis-diseased finger joints after recent failure of intra-articular corticotherapy.

Lyme arthritis.

Evanescent arthralgias and myalgias are common early symptoms of Lyme disease. Transient, intermittent episodes of monoarticular, oligoarticular, or sometimes migratory polyarticular arthritis, lasting weeks to months, with disease-free intervals, are frequently observed in untreated patients with erythema chronicum migrans. A minority of patients develop chronic joint involvement, most commonly affecting the knee. Antibiotic therapy given during erythema chronicum migrans is often protective with regard to late joint manifestations. In chronic Lyme arthritis, however, the response to antibiotics is variable.

Pyogenic infection of the sacro-iliac joint. Report of thirteen cases.

Thirteen cases of infectious sacro-iliitis caused by pyogenic organisms are reported and compared with thirty-four cases in the literature. Staphylococcus was the commonest infecting organism (six cases). Two clinical patterns were noted, acute (nine cases) and subacute (four cases). Treatment was by antibiotics and bed rest in all patients. Surgery was indicated for diagnosis in three patients and for abscess in three patients. All of our patients had very good functional recovery.

Physical and biological dosimetry in patients undergoing radiosynoviorthesis with erbium-169 and rhenium-186.

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.

Upper cervical spine surgery in rheumatoid arthritis: retrospective study of 30 patients followed for two years or more after Cotrel-Dubousset instrumentation.

PURPOSE: To evaluate the efficacy of upper cervical spine surgery in symptomatic atlantoaxial instability due to rheumatoid arthritis (RA). MATERIAL AND METHODS: Thirty RA patients (29 women and one man) with a mean age of 56 years were studied retrospectively. Symptomatic forward slippage of the atlas on the axis with a synovial pannus surrounding the odontoid and magnetic resonance imaging evidence of spinal cord compression was present in all 30 patients; 18 patients had vertical translocation of the odontoid and 14 had basilar invagination. Surgery, performed between 1991 and 1997, consisted of occipitocervical fusion in 18 patients and atlantoaxial fusion in 12. Cotrel-Dubousset instrumentation was performed in all 30 patients. RESULTS: Mean follow-up was four and a half years. All patients were satisfied with the procedure and exhibited marked functional gains and objective neurological improvement (by one class in the Ranawat scheme). Stable fusion was documented in all 30 patients. CONCLUSION: Cervical instrumentation and bone grafting seems to provide functional and neurological gains in carefully selected RA patients with atlantoaxial instability and spinal cord compression. Long term follow-up suggests that the benefits are sustained and that morbidity is low.