Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry.

OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.

Identification of patients with gout: elaboration of a questionnaire for epidemiological studies.

OBJECTIVES: In France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians and assessed its performance. METHODS: We designed a 62-item questionnaire covering comorbidities, clinical features and treatment of gout. In a case-control study, we enrolled patients with a history of arthritis who had undergone arthrocentesis for synovial fluid analysis and crystal detection. Cases were patients with crystal-proven gout and controls were patients who had arthritis and effusion with no monosodium urate crystals in synovial fluid. The questionnaire was administered by phone to cases and controls by non-physicians who were unaware of the patient diagnosis. Logistic regression analysis and classification and regression trees were used to select items discriminating cases and controls. RESULTS: We interviewed 246 patients (102 cases and 142 controls). Two logistic regression models (sensitivity 88.0% and 87.5%; specificity 93.0% and 89.8%, respectively) and one classification and regression tree model (sensitivity 81.4%, specificity 93.7%) revealed 11 informative items that allowed for classifying 90.0%, 88.8% and 88.5% of patients, respectively. CONCLUSIONS: We developed a questionnaire to detect gout containing 11 items that is fast and suitable for use in a telephone survey by non-physicians. The questionnaire demonstrated good properties for discriminating patients with and without gout. It will be administered in a large sample of the general population to estimate the prevalence of gout in France.

Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the 'Orencia and Rheumatoid Arthritis' registry.

OBJECTIVES: Very limited data are available regarding the efficacy of abatacept (ABA) in real life. The aims of this study were to determine the efficacy of ABA in rheumatoid arthritis and predicting factors of efficacy in common practice. METHODS: The Orencia and Rheumatoid Arthritis" (ORA) prospective registry, promoted by the French Society of Rheumatology, has included 1003 patients with RA. RESULTS: 773 patients had already fulfilled the 6-month follow-up visit. Only 21.3% of patients would have fulfilled inclusion criteria used in pivotal controlled trials. The European League Against Rheumatism (EULAR) response, was observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%, moderate response: 38.7%) and was similar in patients who did and in patients who did not fulfill inclusion criteria of controlled trials. Among EULAR responders, initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0-6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs 66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In multivariate analysis adjusted on initial 28-joint disease activity score and CRP, anti-CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to 2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti-CCP positivity was also significantly associated with a higher ABA retention rate at 6 months. CONCLUSIONS: Real life efficacy of ABA in the ORA registry was similar as that reported in clinical trials. Anti-CCP positivity was associated with a better response to ABA, independently from disease activity.

Predictive factors of change in BMD at 1 and 2 years in women with anorexia nervosa: a study of 146 cases.

UNLABELLED: Bone mineral density (BMD; measured by DXA) changes were observed at all sites at 1 year in 146 patients with anorexia nervosa. Four independent factors accounted for the variation in BMD at the spine: duration of anorexia, bone-specific alkaline phosphatase (BAP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and triiodothyronine (T3). No change in BMD was observed from 1 to 2 years during follow-up. INTRODUCTION: The purpose of this study was to assess changes in BMD at 1 and 2 years in anorexia nervosa patients, and to explore the relationships between change in BMD and various clinical and biological parameters measured at the first visit. METHODS: BMD was measured in anorexia nervosa patients at inclusion, at 1-year follow-up (n = 146) and at 2-year follow-up (n = 89). RESULTS: Bone loss was observed at all sites at 1 year. When multivariate analyses were performed, four independent factors accounted for the variation in BMD at the spine: duration of anorexia nervosa, BAP, ICTP, and T3. At the total hip site, leptin level was the main factor accounting for the variation in BMD. Strong correlations were also observed between weight at 1 year and change in BMD at 2 years. At the 2-year follow-up, no significant change in BMD was observed at the spine or femoral neck. In patients who were no longer amenorrheic at 1 year, a significant improvement in BMD at 2 years was observed at the total hip (+1.2%, p = 0.02) and femoral neck (+3.7%, p = 0.02). Similarly, in patients with a body mass index >17 kg/m(2) at 1 year, an improvement in BMD at the total hip at 2 years was observed (+3%, p = 0.02) CONCLUSION: Bone loss in anorexia nervosa patients occurs at an early stage, and the factors influencing such are different at the spine and hip.

Comparison of patient satisfaction with two different etanercept delivery systems. A randomised controlled study in patients with rheumatoid arthritis.

The objective of this study was to investigate patients' perceptions of the acceptability of two devices delivering etanercept for rheumatoid arthritis (RA) treatment and to explore whether specific patients' attributes are associated with device preferences. Two similar multicenter, open-label, randomised, parallel-design studies were conducted in a total of 13 European countries. A total of 640 adult patients with RA were randomised to receive etanercept 50 mg once-weekly subcutaneously for 12 weeks in either a pre-filled syringe (PFS) or a pre-filled pen (PFP). Patient satisfaction at week 12 was measured on a 0- to 10-point Likert scale (primary endpoint). The study was powered to demonstrate non-inferiority of a PFP over PFS for the primary endpoint. At week 12, mean patient satisfaction was 8.3 (± 2.4) points in the pen group and 7.2 (± 2.6) points in the syringe group. Non-inferiority and even superiority of the pen over the syringe was demonstrated. In conclusion, this study showed higher patient satisfaction in the group of patients injecting etanercept with a PFP compared with the group of patients using a PFS.

Predictors of radiographic progression in the ESPOIR cohort: the season of first symptoms may influence the short-term outcome in early arthritis.

OBJECTIVES: To determine predictors of short-term radiographic progression in an inception cohort of patients with early arthritis. METHODS: Patients presenting with synovitis of at least two joints for 6 weeks to 6 months were included in the Etude et Suivi des POlyarthrites Indifferenciées Récentes (ESPOIR) cohort. Univariate analysis was used to determine the relationship between baseline variables and radiographic outcome (assessed by the modified total Sharp score (mTSS)) after 6 and 12 months. Stepwise multiple logistic regression was used to select independent predictive factors. The sensitivity and specificity of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) at baseline in discriminating between erosive and non-erosive disease were determined by receiver operating characteristic (ROC) curves. RESULTS: From data available for 736 patients, radiographic progression at 6 months was independently predicted by baseline ACPA, human leucocyte antigen (HLA)-DRB1*01 and/or 04 genes, erythrocyte sedimentation rate and mTSS. Interestingly, the season of onset of the first symptoms was associated with the severity of early arthritis (OR 1.66, 95% CI 1.07 to 2.59, in winter and spring vs summer and autumn). Univariate analysis revealed similar results for season at 12 months (OR 1.68, 95% CI 1.20 to 2.37). The peak of the ROC curves for radiographic outcome occurred with ACPA and RF values similar to the cut-offs provided by manufacturers. CONCLUSION: The authors found the onset of arthritis symptoms during winter or spring associated with greater radiographic progression at 6 months for patients with early arthritis. These data could reinforce the role of environmental factors in the development and outcome of rheumatoid arthritis.

Risk factors for severe infections in patients with rheumatoid arthritis treated with rituximab in the autoimmunity and rituximab registry.

OBJECTIVE: The risk of severe infection is a crucial factor in the assessment of the short-term risk:benefit ratio of biologic drugs in rheumatoid arthritis (RA). There is no increase in severe infections in RA patients treated with rituximab (RTX) in controlled trials, but this has not yet been assessed in daily practice. We undertook this study to investigate the occurrence of and risk factors for severe infections in off-trial patients using data from the AutoImmunity and Rituximab (AIR) registry. METHODS: The AIR registry was set up by the French Society of Rheumatology. The charts of patients with severe infections were reviewed. RESULTS: Of the enrolled patients, 1,303 had at least 1 followup visit at 3 months or later, with a mean ± SD followup period of 1.2 ± 0.8 years (1,629 patient-years). Eighty-two severe infections occurred in 78 patients (5.0 severe infections per 100 patient-years), half of them in the 3 months following the last RTX infusion. Multivariate analysis showed that chronic lung disease and/or cardiac insufficiency (odds ratio 3.0 [95% confidence interval 1.3-7.3], P = 0.01), extraarticular involvement (odds ratio 2.9 [95% confidence interval 1.3-6.7], P = 0.009), and low IgG level (<6 gm/liter) before initiation of RTX treatment (odds ratio 4.9 [95% confidence interval 1.6-15.2], P = 0.005) were significantly associated with increased risk of a severe infection. CONCLUSION: The rate of severe infections in current practice is similar to that reported in clinical trials. The risk factors for severe infections include chronic lung and/or cardiac disease, extraarticular involvement, and low IgG before RTX treatment. This suggests that serum IgG should be checked and the risk:benefit ratio of RTX discussed for patients found to have low levels of IgG.

Systematic review of the management of canine osteoarthritis.

This review assesses the evidence for the efficacy of therapies used in the management of osteoarthritis in dogs on the basis of papers published in peer-reviewed journals in English between 1985 and July 2007. Sixty-eight papers were identified and evaluated. They considered four alternative therapies, one use of functional food, two intra-articular agents, six nutraceutical agents, 21 pharmacological agents, two physical therapies, three surgical techniques and two combinations of weight control. There was a high level of comfort (strong evidence) for the efficacy of carprofen, firocoxib and meloxicam, and a moderate level of comfort for the efficacy of etodolac in modifying the signs of osteoarthritis. There was a moderate level of comfort for the efficacy of glycosaminoglycan polysulphate, licofelone, elk velvet antler and a functional food containing green-lipped mussel for the modification of the structures involved in the disease. There was weak or no evidence in support of the use of doxycycline, electrostimulated acupuncture, extracorporeal shockwave therapy, gold wire acupuncture, hyaluronan, pentosan polysulphate, P54FP (extract of turmeric), tiaprofenic acid or tibial plateau levelling osteotomy.

Eligibility of rheumatoid arthritis patients for anti-TNF-alpha therapy according to the 2005 recommendations of the French and British Societies for Rheumatology.

OBJECTIVES: Several anti-TNF-alpha prescription guidelines in RA have been published, among which those issued by the British (BSR) and French (SFR) Societies for Rheumatology in 2005 are the most comprehensive. Objectives of the PRISME II survey were to assess and compare eligibility for anti-TNF-alpha therapy of RA patients consulting their usual rheumatologist according to (i) the SFR and BSR guidelines and (ii) the rheumatologist's opinion. METHODS: PRISME II was a postal, cross-sectional, observational survey proposed to all office-based rheumatologists practising in France in 2005. Rheumatologists were to include three consecutive consulting anti-TNF-alpha-naïve RA patients. Disease activity was assessed using the disease activity score 28 (DAS28). Structural damage progression was estimated based on the reading by the usual rheumatologist. The factors determining eligibility in the rheumatologists' opinion were identified by a logistic regression analysis. RESULTS: Four hundred and thirty-four rheumatologists included 1132 patients. Ongoing RA structural progression was reported for 41% of the patients. According to the SFR and BSR criteria, 64 patients (7.0%) and 10 patients (0.9%), respectively, were eligible for anti-TNF-alpha therapy, while 10% were deemed eligible according to the rheumatologists' opinion. Determinants of eligibility according to the rheumatologists were: high disease activity (DAS28 >5.1), ongoing structural progression and elevated daily corticosteroid intake. These three determinants feature in the SFR guideline. CONCLUSIONS: The proportion of RA patients eligible for anti-TNF-alpha therapy varies greatly according to the BSR or SFR guidelines. In France, there is a remarkable convergence between rheumatologists' opinion and SFR guideline regarding the main factors to consider for initiation of an anti-TNF-alpha therapy.

Long-term follow-up of patients with tuberculosis as a complication of tumour necrosis factor (TNF)-alpha antagonist therapy: safe re-initiation of TNF-alpha blockers after appropriate anti-tuberculous treatment.

This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-alpha blocker therapy. All TB cases (n = 21) complicating TNF-alpha blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-alpha antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-alpha antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.

[Cutaneous manifestations during treatment with TNF-alpha blockers: 11 cases]. / Manifestations cutanées observées au cours d'un traitement par anti-TNF alpha: 11 observations.

BACKGROUND: TNFalpha blockers have recently extended the therapeutic arsenal available in dermatology. However, dermatologists must be informed of their potential adverse dermatological effects. While the chief adverse effect of TNFalpha blockers is risk of infection, cutaneous adverse effects have not yet been clearly elucidated and publications on this topic are few and far between. The aim of our study is to report various dermatological problems noted during treatment with TNFalpha blockers. PATIENTS AND METHODS: This was a retrospective study of patient files. The study population comprised patients receiving TNFalpha blockers and presenting cutaneous reaction, and seen in the dermatology department between August 2001 and December 2004. RESULTS: Eleven patients were included. The following cutaneous reactions were seen: delayed skin rash (1 case), lupus syndrome (1 case), cutaneous vasculitis (2 cases), palmoplantar pustulosis (2 cases), psoriasis vulgaris (1 case), atopic dermatitis (1 case), lichenoid rash (1 case), purpuric capillaritis (1 case) and melanoma (1 case). DISCUSSION: The cutaneous manifestations seen represented a wide range of different clinical pictures. Dermatologists must be aware of these potential adverse effects. Future improvement of knowledge of the physiopathological mechanisms as well as the institution of prospective cohort studies should provide clearer guidance on the management of such symptoms.

[Dropped head syndrome: report of two cases]. / Le syndrome de la tête tombante: à propos de deux cas.

PURPOSE: The dropped head syndrome is characterized by an abnormal bending of the head to the body, mainly affecting old people. It corresponds to an alteration of the cervical extensor muscles, revealing in some cases a neuromuscular disease. In some cases, the etiology of this syndrome remains unknown. EXEGESIS: We report here two cases with dropped head syndrome. The first clinical case concerned a 78-year old man, presenting a dropped head syndrome revealing a myasthenia. The syndrome disappeared with specific therapy. The second clinical case was a dropped head syndrome developed in the context of severe depressive syndrome in a 71-year old woman. The etiological screening did not reveal any underlying disease. Counteracting the syndrome was successfully obtained with early physiotherapy. CONCLUSION: The dropped head syndrome can reveal a general disease such as myasthenia or amyotrophic lateral sclerosis. Therefore, investigation needs first to eliminate underlying diseases. If no etiology is found, the dropped head syndrome is considered of an unknown neuromuscular origin or a psychosomatic disease. In this latter case, physiotherapy may be beneficial.

[Rheumatoid arthritis and cystic fibrosis]. / Polyarthrite rhumatoïde et mucoviscidose.

INTRODUCTION: Inflammatory arthropathies are rare complications of cystic fibrosis (CF). We describe three cases of rheumatoid arthritis (RA) occurring in patients with this disease. OBSERVATIONS: Among the 100 patients under the care of the adult CF centre in Lille 3 presented with RA. This developed at the ages of 17, 44 and 19 years with a FEV1 of 53%, 42% and 94% respectively. They were 2 women and 1 man, with CFTR gene mutation delta F508 (1 homozygote and 2 heterozygotes) and positive sweat tests. They were colonised with Staphylococcus aureus, and rheumatoid factor and/or anti CCP antibodies were positive. The appearance and progression of RA were associated with exacerbations of bronchial infection and deterioration of respiratory function. In 2 patients the RA was continuously progressive despite intensive treatment involving high dose cortico-steroids, methotrexate (ineffective) followed by leflunomide (complicated by intractable respiratory infection). CONCLUSION: There is an increased incidence of RA in our patient population with CF. The new serum markers of RA including anti CCP are of diagnostic interest. The evolution of the two diseases is related and seems to be dependent on the level of infection leading to therapeutic problems.

Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population.

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs. 2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR-SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3'-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively. 3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17-18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer. 4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.

Rheumatoid arthritis and schizophrenia: a negative association at a dimensional level.

There is wide evidence for a decreased risk of rheumatoid arthritis in patients with schizophrenia. Nevertheless, very few studies have looked at the risk of schizophrenia in a group of patients with rheumatoid arthritis. We prospectively investigated, with the SCL-90R, 220 consecutive outpatients with rheumatoid arthritis and 196 consecutive outpatients with various medical conditions, half of them suffering from psoriatic arthritis (a medical condition close to rheumatoid arthritis). The SCL-90R appears to be a valuable tool to distinguish patients with schizophrenia from the outpatients of our sample, the former having more "paranoid ideation" (p = 0.004) and more "psychoticism" (p < 0.001) than the latter. The "paranoid ideation" dimension was significantly lower (25% decrease) in the sample of patients with rheumatoid arthritis compared to the combined control group (p = 0.005), ratings under the median value being more frequent in the former group (p = 0.025). Confounding factors might not explain this difference according to the regression logistic analysis performed. As patients with rheumatoid arthritis have a lower score of paranoid ideation than controls in our sample, even after controlling for age, gender and severity of the disease, these data represent further evidence for a decreased risk of schizophrenia in individuals with rheumatoid arthritis.

Factors influencing bone loss in rheumatoid arthritis: a longitudinal study.

OBJECTIVES: To assess the occurrence of bone loss in rheumatoid arthritis (RA) and to determine the factors influencing bone loss (particularly the usefulness of bone turnover markers) over an 18-month period. METHODS: A total of 51 patients were studied, 6 men and 45 females (of whom 35 were menopausal). Their mean age was 56 +/- 10 years and the mean RA duration was 12 +/- 10 years. Twenty-eight (55%) were receiving corticosteroids (10 mg/day for a mean duration of 6 +/- 5 years). Several clinical and biological parameters reflecting disease activity or severity were recorded both at the 0 and 18-month investigations. Bone turnover was assessed at baseline by measuring the serum levels of 4 biological markers. Three of them reflected bone formation, i.e., procollagen type I C-terminal propepeptide (PICP), procollagen type I N-terminal propeptide (PINP) and osteocalcin (OC). The fourth, procollagen type I-C terminal telopeptide (ICTP), reflected bone resorption. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry both at the lumbar spine (LS) and femoral neck (FN) at baseline and 18 months later. RESULTS: Bone loss occurred both at the LS: 2.1%, [95% CI: 0.8%-3.4%, P < 0.005] and femoral neck: 3.1%, [95% CI: 1.1%-5.1%, P < 0.005]. Bone loss was markedly increased for postmenopausal women at the FN: 5.3% [95% CI: 2.9%-7.6%, P < 0.005]. Bone loss was not statistically significantly different between users and non-users of steroids. Bone loss at the LS was significantly correlated with both osteocalcin (r = 0.51, P < 0.01) and ICTP levels (r = 0.32, P < 0.05). FN bone loss was correlated with the osteocalcin level only (r = 0.34, P < 0.05). Fast losers (bone loss at the LS above the median) had higher OC (P < 0.01) and ESR (P < 0.05) levels at baseline as compared with slow losers (bone loss at the LS below the median). CONCLUSION: Bone loss occurs in RA particularly at the FN and seems to be influenced by increased bone turnover and high levels of inflammation.

Differences in understanding and application of 1987 ACR criteria for rheumatoid arthritis and 1991 ESSG criteria for spondylarthropathy. A pilot survey.

OBJECTIVES: To determine areas of agreement and disagreement among experts in the interpretation of the published criteria for RA (ACR) and spondylarthropathies ( ESSG). METHODS: Thirty-two experts (16 from France and 16 from 10 other countries) replied anonymously to a mailed questionnaire. RESULTS: Tenosynovitis and 'sausage-like' painless swelling of the toes were considered as criteria for RA by 18 and 14 experts, respectively. The definition of symmetry differed widely among experts (symmetry of only one group of joints was sufficient for 13). Twenty-five experts considered erosions of other joints than the wrists and fingers as a criterion for RA, 17 thought that fulfilment of criteria could be achieved cumulatively, and 19 would appreciate clarifications of the current criteria. Among possible clarifications for RA, it was frequently recommended that morning stiffness and nodules be eliminated and that new marker antibodies, X-rays of the feet, and exclusion criteria be added. Twenty-three of the 29 experts who gave an opinion (79%) agreed with the notion of SP in the absence of axial signs and sacroiliitis, 26/31 (84%) indicated that a patient can have both RA and SP, and 19/30 (63%) thought that RA and SP could be regarded as syndromes more than diseases. Only 5/32 experts relied more on the criteria than on their clinical judgement in diagnosing RA. CONCLUSIONS: There would seem to be a needfor the optimisation of RA and ESSG criteria, particularly within the context of early arthritis.

Treatment of severe, recalcitrant reflex sympathetic dystrophy: assessment of efficacy and safety of the second generation bisphosphonate pamidronate.

The objective of the study was to assess the efficacy and the safety of pamidronate (APD) in recalcitrant reflex sympathetic dystrophy (RSD). Ten women and 13 men with a mean (+/-standard deviation, SD) age of 44 +/- 11 years were included. The involved sites were: the ankle (n = 10), the foot (n = 7), the hand (n = 3), the hip (n = 2), the knee (n = 2) and the shoulder (n = 1). Some patients had more than one site involved. Mean (+/-SD) duration of the disease was 15 +/- 13 months. RSD was in pseudo-inflammatory phase in 16 patients and in ischaemic phase in 7 patients. RSD was post-traumatic in 17 cases; 11 patients have been previously treated unsuccessfully by sympathetic blockades. APD was administered intravenously (perfusion) to a dose of 1 mg/kg/day during 3, 2 or one day. Fourteen patients received APD during 3 consecutive days whereas 7 patients have been treated during 2 consecutive days and 2 patients only during 1 day mainly due to adverse events. Efficacy was assessed by a decrease of pain = visual analogic scale (VAS, 0-100 mm) and verbal scale (PVS, range 0-3). Moreover, the patient and the observer have estimated the efficacy of the treatment on a verbal scale (EVS, range 0-3). Measurements of these parameters were performed immediately before the treatment and 7, 30, 60 and 90 days later. The maximum duration after treatment was 9 months. A significant decrease of VAS and PVS were observed between D0 and D30 (p = 0.0002 and p = 0.0002 respectively), D0 and D60 (p = 0.0004, p = 0.0004 respectively), and D0 and D90 (p = 0.00003, p = 0.0001 respectively). A significant increase of EVS was only observed between D0 and D90 (p = 0.03). Adverse events were noted in 14 patients: transient fever (n = 6), venous inflammation (n = 2), transient symptomless hypocalcaemia (n = 3), nausea (n = 1), lymphopenia (n = 1), transient hypertension (n = 1). These results suggest an efficacy of APD in recalcitrant RSD. Double-blind placebo controlled studies are required to back up these preliminary results.

Dialysis-related beta 2 microglobulin-amyloid arthropathy. Improvement of clinical symptoms after a switch of dialysis membranes.

Amyloidosis containing beta 2 microglobulin (beta 2m) and joint pains are frequent complications of long-term hemodialysis. In a prospective study the authors planned to act on dialysis arthropathies (DA) by improving beta 2m depuration: for 8 patients suffering from DA we replaced usual cuprophane membranes (CU) by high permeability polyacrylonitrile membranes (PAN). DA was diagnosed on the presence of severe disabling arthralgias in the absence of any other obvious etiology, and on the presence of at least 3 among 6 criteria. The efficacy of the switch of DM was assessed on 6 criteria including the patient's own evaluation at the end of the study and a joint pain severity index. Clinical evaluation and beta 2m measurement were carried out at the start of the trial and after a mean duration of dialysis on PAN of 6 months. An improvement in joint symptomatology and a decrease of joint severity index were noted in the 8 cases. Our results suggest that the change of DM has a favorable influence on DA. This improvement could result either from a better beta 2m depuration or from a better biocompatibility of PAN than the CU previously used.