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Biomedical subjects

M De Bandt

Publications and source records attributed to M De Bandt.

At least 19 recordsLinked to original sources

Lessons for lupus from tumour necrosis factor blockade.

Systemic lupus erythematosus (SLE) is a systemic non-organ specific autoimmune disease associated with multiple autoantibodies targeting autoantigens from the nucleus. Given the complex pathophysiology of SLE and the role of TNF alpha in that disease, modulation of TNF alpha (in SLE or non-SLE patients) using TNF blockers could either be detrimental or beneficial in some patients. In this review we will focus on lupus autoantibodies and clinical manifestations after TNF blockade in SLE patients and conversely on drug-induced-SLE in non-SLE patients. Some hypotheses regarding the mechanism of induction of autoantibodies in RA patients treated with TNF blockers are proposed.

Apoptosis↗

Clinical practice decision tree for the choice of the first disease modifying antirheumatic drug for very early rheumatoid arthritis: a 2004 proposal of the French Society of Rheumatology.

OBJECTIVE: To elaborate a clinical practice decision tree for the choice of the first disease modifying antirheumatic drug (DMARD) for untreated rheumatoid arthritis of less than six months' duration. METHODS: Four steps were employed: (1) review of published reports on DMARD efficacy against rheumatoid arthritis; (2) inventory of the information available to guide DMARD choice; (3) selection of the most pertinent information by 12 experts using a Delphi method; and (4) choice of DMARDs in 12 clinical situations defined by items selected in step 3 (28 joint disease activity score (DAS 28): < or =3.2; >3.2 and < or =5.1; >5.1; rheumatoid factor status (positive/negative); structural damage (with/without)-that is, 3 x 2 x 2). Thus, multiplied by all the possible treatment pairs, 180 scenarios were obtained and presented to 36 experts, who ranked treatment choices according to the Thurstone pairwise method. RESULTS: Among the 77 items identified, 41 were selected as pertinent to guide the DMARD choice. They were reorganised into five domains: rheumatoid arthritis activity, factors predictive of structural damage; patient characteristics; DMARD characteristics; physician characteristics. In the majority of situations, the two top ranking DMARD choices were methotrexate and leflunomide. Etanercept was an alternative for these agents when high disease activity was associated with poor structural prognosis and rheumatoid factor positivity. CONCLUSIONS: Starting with simple scenarios and using the pairwise method, a clinical decision tree could be devised for the choice of the first DMARD to treat very early rheumatoid arthritis.

Antirheumatic Agents↗

Crowned dens syndrome misdiagnosed as polymyalgia rheumatica, giant cell arteritis, meningitis or spondylitis: an analysis of eight cases.

BACKGROUND: The crowned dens syndrome, related to microcrystalline deposition in the peri-odontoid articular and abarticular structures, is mainly responsible for acute or chronic cervical pain. PATIENTS: We report eight cases of crowned dens syndrome with atypical presentations mimicking giant cell arteritis, polymyalgia rheumatica, meningitis or discitis. The clinical and radiological aspects of these cases are presented and discussed. RESULTS: For all patients, fever, cervical stiffness, headaches and biological inflammatory syndrome were reported. For three patients, impairment of general condition, occipito-temporal or mandible pain and weakness with inflammatory pain of the shoulder girdle was suggestive of giant cell arteritis and/or polymyalgia rheumatica, leading to temporal artery biopsy and/or long-term steroid treatment. Recurrence of clinical symptoms when tapering steroids was noted. In two cases, previous breast carcinoma led to the initial diagnosis of metastatic spondylitis. For three patients with vomiting, nausea and Kernig's and/or Brudzinski's sign, the first diagnosis was meningitis, leading to unhelpful lumbar puncture. In all cases, diagnosis of crowned dens syndrome once evoked, was confirmed by cervical CT scanning and dramatic improvement with non-steroidal anti-inflammatory drugs or colchicine. CONCLUSION: This under-recognized entity must be considered as a differential diagnosis of meningitis and discitis, but also of giant cell arteritis and polymyalgia rheumatica, as well as a possible aetiology for fevers of unknown origin. CT scanning is necessary for diagnosis. Clinicians should be aware of such misleading clinical presentations.

Aged↗

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.

Adult↗

[Crowned dens syndrome: three new cases].

INTRODUCTION: Crowned dens syndrome is due to a microcrystalline infringement (hydroxyapatite or calcium pyrophosphate) of the retro-odontoidal ligament of atlas, often leading to the erroneous diagnosis of meningitis or spondylitis. We report on three new cases diagnosed from 1996 to 1999. EXEGESIS: The patients complained of cervicalgies, headaches or fever. The initially evoked diagnoses were meningitis, spondylodiscitis or endocarditis. Clinical exam found meningism and an inflammatory syndrome in all patients. Analysis of the cerebro-spinal fluid realised in two cases was normal. The diagnosis of crowned dens syndrome was assessed in two cases by cervical CT scan of C1/C2. In the third case, chondrocalcinosis of a wrist allowed this diagnosis. We report a probably non fortuitous case of crowned dens syndrome associated with genetic hemochromatosis. A non steroidal anti-inflammatory treatment allowed a dramatic regression of clinical symptoms. CONCLUSION: This entity should be better known; it can mimick numerous diagnosis and be responsible for fever in the long course.

Aged↗

[Outcome of pregnancies in lupus: experience at one center].

We determined the outcome of all pregnancies in SLE patients in our lupus cohort between 1991 and 1997. The women were advised that pregnancy was acceptable if the disease had been inactive for 6 months (SLEDAI < or = (4 at 2 serial examinations) and daily prednisone dose was below 10 mg. Patients were advised against pregnancy in case of active nephritis or neurolupus. In case of antiphospholipid antibodies, patients were treated with aspirin or heparin if previous fetal losses were documented. In case of anti-SSA ab, patients were monitored with ultrasound and given dexamethasone in case of atrioventricular block. Fifty-nine pregnancies were registered among 31 women: mean age at diagnosis of SLE was 25.3 +/- 3.7 years (range: 17-31); mean disease duration before pregnancy 4.4 +/- 3 years (0-14); mean ACR score 5.4 +/- 1.5 (4-9). Seven patients had ACL ab, 8 had anti-SSA ab. Pregnancies ended in: 13 early spontaneous abortions (9 not related to disease flare up, 4 related to SAPL); 7 elective abortions (patient decision in 5 cases, severe lupus flare up in 2); one in utero death; 19 full term births (> 38 weeks); and 19 preterm births. Cesarean section was performed in 11 cases (6 for fetal distress, dystocia and previous ceasarian; 5 for active lupus). Severe sepsis occurred in one premature infant who died at the age of 1 week. Intrauterine growth retardation was observed in 11 cases, mean APGAR score was 8.9 +/- 1.43. Child development was normal in all cases except one child with mild mental retardation. Severe lupus flare ups occurred in 6 cases, of which 4 were pregnancies in unadvised situations. Six mild flare ups were documented in the post partum. One fatal case of neonatal lupus with AVB was observed. In conclusion, in our experience, the live birth rate is similar to the general population and the risk of lupus flare up is low when the above mentioned criteria are applied. Systematic increase of steroid dose at pregnancy onset does not seem to be necessary. The high rate of prematurity remains a problem to be solved.

Adult↗

Angiogenesis: general mechanisms and implications for rheumatoid arthritis.

In rheumatoid arthritis, the vascular endothelium is among the key targets for circulating mediators of inflammation and controls the trafficking of cells and molecules from the bloodstream toward the synovial tissue. Local blood vessel proliferation allows the pannus to develop and grow, thereby promoting cartilage and bone destruction and joint remodeling. Angiogenesis, the production of new capillaries from preexisting blood vessels, is a key process in rheumatoid arthritis that involves multiple substances such as cytokines, chemokines, growth factors, cell adhesion molecules, proteinases, proteinase inhibitors, and matrix proteins. In animal models of arthritis, angiogenesis inhibitors have been found to improve clinical and radiological outcomes, opening up the possibility of therapeutic applications in humans. Before this possibility is realized, the steady accumulation of data on the mechanisms that regulate angiogenesis will have to continue until a clear picture of angiogenesis is formed.

Angiogenesis Inducing Agents↗

Anti-proteinase-3 (PR3) antibodies (C-ANCA) recognize various targets on the human umbilical vein endothelial cell (HUVEC) membrane.

Numerous studies suggest that C-ANCA are directly pathogenic in vasculitis by activating leucocytes (oxidative burst, enzyme release, endothelial cytotoxicity, etc.). We and others have shown that C-ANCA can also directly activate HUVEC, but the precise target on HUVEC is unknown. We show in this study that C-ANCA recognize various targets on the HUVEC membrane (different from PR3 in our model), leading to secondary cell activation. Polyclonal affinity-purified C-ANCA recognized targets on the unfixed endothelial membrane in fluorescent ELISA, flow cytometry, and immunoprecipitation studies. C-ANCA did not react with Fcgamma receptors. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments showed that HUVEC did not express PR3. The targets of polyclonal and monoclonal anti-PR3 antibodies on the endothelial membrane were not the same. Some epitopes were lost after trypsin-EDTA digestion and formaldehyde fixation of cells, whereas anti-PR3 targeted unfixed HUVEC. This suggests that anti-PR3 react with the endothelial membrane and recognize conformational epitopes shared with PR3. Endothelial cells may thus participate in the inflammation associated with Wegener's granulomatosis and contribute to the emergence of clinical manifestations.

Antibodies, Antineutrophil Cytoplasmic↗

Anti-heat shock protein 70 kDa and 90 kDa antibodies in serum of patients with rheumatoid arthritis.

OBJECTIVES: Stress proteins (HSPs) are highly conserved immunodominant antigens found in various species. The purpose of this study was to assess the prevalence and prognostic significance of antibodies to HSC 70 kDa and HSP 90 kDa in three groups of patients with longstanding rheumatoid arthritis (RA) defined based on the severity of articular erosions. METHODS: 73 patients with longstanding (> 6 years) RA whose HLA-DR genotype was known were divided in three groups according to Larsen's score and compared with 47 recent onset (<1 year) RA patients and with control groups composed of patients with other inflammatory diseases (n=137) or of normal controls (n=48). IgGs and IgMs to HSC 70 kDa and HSP 90 kDa were determined using an ELISA with purified bovine HSC 70kDa or HSP 90 kDa. RESULTS: Concentrations of IgGs and IgMs to HSC 70 were significantly increased in 41.1% and 42.5% of longstanding RA patients, respectively. Corresponding figures for IgGs and IgMs to HSP 90 were 39.7% and 56%. IgMs to HSC 70 and HSP 90 were less frequent in recent onset RA (19% and 13% respectively). Among the groups with other inflammatory diseases, only the MCTD group exhibited high frequencies of IgGs to HSC 70 (80%) and HSP 90 (85%). DRB1*0401 positive RA patients (n=23) were not more likely to have increased concentrations of antibodies to HSC 70 kDa or HSP 90 kDa than other RA patients (DR4 positive but DRB1*0401 negative, or DR1 positive, n=31; or negative for both DR4 and DR1, n=14). IgGs to HSP 90 kDa were significantly more frequent (p<0.05) in longstanding RA patients whose Larsen's score was 4 or more (57%) than in those whose Larsen's score was 2 or 3 (39.4%) or less than 2 (16%). No associations were found between Larsen's score and IgGs or IgMs to HSC 70 kDa or IgMs to HSP 90 kDa. A significant correlation was demonstrated between IgGs to HSP 90 kDa and two other serological markers for RA, rheumatoid factor, and anti-Sa antibody; there were no correlations with antikeratin antibody, antiperinuclear factor, or anti-RA 33. CONCLUSION: IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA

Adolescent↗

Classification of an intermediate group of patients with antiphospholipid syndrome and lupus-like disease: primary or secondary antiphospholipid syndrome?

OBJECTIVE: (1) To classify an intermediate group of patients (IntAPS) with antiphospholipid syndrome (APS) and lupus-like disease either as primary (PAPS) or secondary APS (SAPS) and to discuss 2 different classifications. (2) To compare patients of a division of rheumatology with either PAPS or SAPS. METHODS: Patients with APS and patients with systemic lupus erythematosus (SLE) followed at the Department of Rheumatology, University Hospital Bichat, Paris, from 1987 to 1996 were analyzed. A chart review and a standardized telephone interview in 1997 completed the data of this study. RESULTS: (1) We found a total of 108 patients with APS: 22 with PAPS, 69 with SAPS, and 17 with IntAPS. The group of IntAPS did not differ from PAPS in any clinical or laboratory signs with the exception of antibodies to dsDNA and to extractable nuclear antigen (ENA). Between IntAPS and SAPS, there were several significant differences in clinical signs of SLE (malar rash, discoid rash, arthralgia) and in laboratory values (leukocytopenia). (2) Comparison of PAPS and SAPS showed statistically significant differences for positive Coombs' test, leukocytopenia, lymphocytopenia, antinuclear antibodies, antibodies to dsDNA and to ENA, and hypocomplementemia. CONCLUSION: The mainstay of the diagnosis of APS is the clinical event of thrombosis or miscarriage in the presence of antiphospholipid antibodies. Less important are laboratory values, which may help to differentiate PAPS from SAPS in order to initiate adequate therapy (e.g., anticoagulation in the first and additional corticosteroids in the second). Patients with IntAPS are more likely to be integrated into the group of PAPS than in the group of SAPS; therefore, special exclusion criteria for PAPS are not appropriate.

Adult↗

Clinical usefulness of antibodies to U1snRNP proteins in mixed connective tissue disease and systemic lupus erythematosus.

OBJECTIVES: To determine whether the anti-68 kDaU1snRNP antibody is associated with mixed connective tissue disease and not with SLE; to evaluate correlations between anti-U1snRNP titers and disease activity; and to look for associations between anti-U1snRNP specificities and specific clinical features. PATIENTS AND METHODS: 40 patients with a positive double diffusion test for anti-68 kDa U1snRNP were studied, including 21 with mixed connective tissue disease, 14 with systemic lupus erythematosus and five with other connective tissue diseases. IgGs to 68 kDa U1snRNP were assayed using an ELISA. Clinical features, disease activity and antibody test findings were evaluated longitudinally in nine patients. RESULTS: Both proportions of patients with anti-68 kDa U1snRNP and titers of IgG to 68 kDa U1snRNP were similar in the mixed connective tissue disease and systemic lupus erythematosus groups. Patients with mixed connective tissue disease were significantly more likely to have anti-A U1snRNP or anti-C U1snRNP than those with systemic lupus erythematosus (P < 0.03 and P < 0.04, respectively). No significant correlations were found between any of the features of mixed connective tissue disease (e.g., Raynaud's phenomenon, myositis, or sausage digits) and a specific anti-U1snRNP antibody. During follow-up (mean, seven years; range, 1-25 years), changes occurred in the anti-U1snRNP profile and in the anti-68 kDa U1snRNP titer. These changes were not correlated with disease activity. CONCLUSIONS: IgGs to 68 kDa U1snRNP are not associated with a specific pattern of anti-RNP-positive connective tissue disease. No useful information can be gained by monitoring anti-68 kDa U1snRNP IgG titers over time. A Western blot profile including anti-A U1snRNP or anti-C U1snRNP indicates a high likelihood of U1snRNP-associated mixed connective tissue syndrome (MCTD).

Adolescent↗

[Extra-articular manifestations of rheumatoid polyarthritis].

Rheumatoid arthritis is mainly a chronic and disabling articular disease. If most patients do well (because of limited form or efficient treatment), in some cases they present with extra-articular rheumatoid arthritis. The clinical manifestations of extra-articular rheumatoid arthritis are wide, ranging from common and benign manifestations such as rheumatoid nodules to severe events such as Felty's syndrome or systemic vasculitis. The incidence of systemic rheumatoid arthritis seems cumulative over the course of the chronic disease, and the severity of individuals lesions when fully developed can be of major importance and even life threatening. A classification of the main features of extra-articular rheumatoid arthritis is given (even if not perfect), and the clinical manifestations are described.

Adult↗

Systemic sclerosis and sarcoidosis, a report of five cases.

We report on five cases of associated systemic sclerosis and sarcoidosis (associated connective tissue diseases). The special peculiarities of this association are emphasized with a review of the literature (14 other cases reported). The clinical aspects, the prognosis, the role of silica, the likelihood of a chance association and the need (in our opinion) to reconsider the name 'sarcoidosis' are discussed.

Adult↗