Biomedical subjects
Publications and source records attributed to Y Allanore.
Neurological involvement is uncommon in systemic sclerosis. Most of the reported cases concern trigeminal neuropathy or peripheral nerve entrapment. We report a third case of brachial plexopathy, presumably related to vasculitis, in a patient with systemic sclerosis, which improved after cyclophosphamide therapy.
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Dactylitis and calcaneitis developed in a patient with untreated sarcoidosis of the skin and lungs. Radiographs showed a defect in the second phalanx of the left middle finger. Radiographs of the feet were normal, but magnetic resonance imaging demonstrated a defect in the left calcaneus. Methylprednisolone therapy (1 g per day for 3 consecutive days) induced a dramatic improvement within 48 hours. Low-dose oral glucocorticoid therapy was given subsequently. One year later, a recurrent episode of dactylitis responded promptly to the same regimen. Maintenance therapy was given, and no further recurrences were noted during the four-year follow-up. Sarcoid bone lesions are uncommon and arise selectively in the small bones of the hands and feet. Involvement of the calcaneus is exceedingly rare, and its treatment is not standardized. In our patient, glucocorticoid therapy combined with methotrexate and hydroxychloroquine were effective in controlling the disease.
OBJECTIVE: To investigate nitric oxide (NO) production and inducible NO synthase expression by cultured peripheral blood mononuclear cells (PBMC) in patients with systemic sclerosis (SSc). METHODS: Eighteen patients with SSc were compared with two control groups: 16 patients with rheumatoid arthritis (RA) and 23 patients with mechanical sciatica. Nitrate was determined by fluorimetry in plasma and by spectrophotometry in supernatants. Inducible NO synthase (iNOS) was detected in cultured PBMC by immunofluorescence, immunoblotting and flow cytometry with or without treatment of the cells with interleukin (IL) 1beta+ tumour necrosis factor alpha (TNF-alpha), IL-4 or interferon gamma (IFN-gamma) from day 1 to day 5. RESULTS: NO metabolite concentrations were lower in SSc patients (mean+/-s.e.m. 34.3+/-2.63 micromol/l) than in RA (48.3+/-2.82 micromol/l; P<0.02) and sciatica (43.3+/-5.24 micromol/l; P<0.03) patients. iNOS was detected in cultured monocytes in all three groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. CONCLUSIONS: The concentrations of NO metabolites are decreased in SSc patients and the metabolism of these compounds in PBMC is altered. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may have therapeutic implications.
We investigated nitric oxide (NO) production and inducible NO synthase (iNOS) expression by cultured peripheral blood mononuclear cells (PBMC) in systemic sclerosis (SSc). Eighteen patients with SSc were compared to two control groups: 16 rheumatoid arthritis patients (RA) and 23 mechanical sciatica patients. The sum of nitrites and nitrates was determined by fluorimetry in sera and spectrophotometry in supernatants. Inducible iNOS was detected in cultured PBMC by immunofluorescence, immunoblot and flow cytometry with or without IL-1 beta + TNF alpha, IL-4 or IFN gamma from day 1 to day 5. NO metabolite concentrations in the plasma were lower in SSc (34.3 mumol/l +/- 2.63 SEM) than in RA (48.3 mumol/l +/- 2.2; p < 0.02) and sciatica (43.3 mumol/l +/- 5.24; p < 0.03) patients. iNOS was detected in cultured monocytes in the 3 groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. The concentrations of NO metabolites are decreased in SSc patients and the induction of iNOS in PBMC is delayed. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may suggest therapeutic implications.
BACKGROUND: Rheumatoid arthritis and insulin-dependent diabetes mellitus are both autoimmune disorders of unknown etiology. We report the case of a patient who developed the two diseases simultaneously. CASE REPORT: A 64-year-old man with no remarkable medical history developed insulin-dependent diabetes disclosed by ketoacidosis that occurred 3 weeks after onset of a bilateral symmetrical polyarthritic syndrome characteristic of rheumatoid arthritis. DISCUSSION: These two disorders share common susceptibility of subjects with MHC class II molecules HLA DRB1*04. Immunological studies have also shown a common Th1 type cytokine-secretion pattern in both diseases. Epidemiological studies have not however clearly demonstrated a link between them.
OBJECTIVE: To determine the cumulative incidence and the point prevalence of atopy in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A standardized questionnaire was sent to 300 RA patients. Questions concerned previous or present characteristics of atopy (hay fever, asthma and constitutive eczema) and RA. RA patients were matched with genetically unrelated controls (sister- or brother-in-law, neighbour or friend). The same questionnaire (except for questions about RA) was sent to the control subjects. In cases of atopy, patients, controls and the treating physicians were contacted by a physician to check the validity of the responses. RESULTS: Paired responses were obtained in 173 cases. Information about atopy was obtained for 69 other RA patients. The characteristics of RA were similar for patients who responded and those who did not respond. The frequency of atopy was significantly lower in RA patients than in controls, both for cumulative incidence (RA 7.5%, controls 18.8%; P: < 0.01) and point prevalence (RA 3.5%, controls 16.2%; P: < 0.0001). The clinical manifestations of atopy stopped before the onset of RA in eight of the 17 RA patients with an allergic condition, and there was no subsequent relapse. No effect of RA treatment could account for the remission of atopy. CONCLUSION: These data support the concept that atopy protects against the future development of RA and that the two diseases could counterbalance one another.
OBJECTIVE: To determine, for the first time, plasma levels of general fibronectin (Fn) and two spliced isoforms, Ed-A and Ed-B, in patients with spondyloarthropathy (SpA) in comparison with rheumatoid arthritis (RA) patients and healthy volunteers (HV). METHODS: Plasmas (EDTA) as well as clinical data, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected in two groups of 10 patients fulfilling the European Spondylarthropathy Study Group criteria for SpA or the 1987 American College of Rheumatology criteria for RA. Plasmas of 21 blood donors served as controls. Plasma levels of Fns were determined by using an in-house immunocapture ELISA, using monoclonal antibodies (MAbs) against general Fn and its isoforms. RESULTS: Total Fn plasma levels were significantly higher in the SpA group (mean+/-S.D.=1387+/-569 mg/l) than in the RA group (684+/-196 mg/l; P=0.02) and in HV (303+/-211 mg/l; P<0.0001). Ed-A Fn levels appeared higher in SpA (23+/-10.4 mg/l) and RA (32.5+/-16.5 mg/l) groups than in the HV group (2.8+/-0.9 mg/l; P=0.0003 and P<0.0001, respectively), without a significant difference between SpA and RA groups. Ed-B Fn levels were higher in SpA (6.9+/-2.1 mg/l) than in RA (3.2+/-1.9 mg/l; P=0. 02) and HV (1.1+/-0.8 mg/l; P=0.0003) groups. No significant correlation was observed in SpA patients between each Fn level and clinical activity, ESR or CRP levels. CONCLUSIONS: This study showed an increase in plasma levels of Fn and Ed-B Fn in SpA patients compared with RA patients and HV, which could not be attributed solely to systemic inflammation. It may be hypothesized that Ed-A and Ed-B Fn might reflect local turnover in inflamed tissues, and that Ed-B Fn might be particularly involved in the musculoskeletal inflammatory process of SpA.
UNLABELLED: 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. CONCLUSION: 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.
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OBJECTIVE: To identify risk factors associated with disease activity, in a group of patients with spondyloarthropathy (SpA) living in France. METHODS: Patients fulfilling the ESSG or Amor criteria for SpA were enrolled in a cross sectional multicenter study. Disease activity was assessed using a French version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Univariate and multivariate analyses were used to identify a link between BASDAI and disease characteristics, genetic factors, and environmental factors such as infectious events, mental stress, working conditions, and dietary factors. RESULTS: We studied 293 patients. On multivariate analysis, BASDAI appeared to be mainly linked to disease duration (negative correlation), the absence of sacroiliitis, and the "frequency of meals taken out of home" (negative correlation). CONCLUSION: Disease activity in a French population of patients with SpA appeared to be linked mainly to a shorter disease duration and a peripheral pattern of arthritis, as well as to dietary habits. The underlying links between this last environmental factor and disease activity remained hypothetical and could only reflect a nontested social factor.
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The prognosis of large granular lymphocyte proliferation with rheumatoid arthritis (pseudo-Felty's syndrome) remains uncertain. We report a case with a 15-year follow-up. To date, the patient has not developed lymphadenopathy, splenomegaly, abnormalities in erythrocyte or platelet counts, neutropenia or severe or unexplained infections. This favorable course is not ascribable to an unusual lymphocyte phenotype (CD3+, CD8+, CD57+). A beneficial effect of methotrexate therapy is possible.
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OBJECTIVES: To investigate autoantibody induction in rheumatoid arthritis (RA) patients treated with infliximab. METHODS: We included 59 refractory RA patients treated with infliximab in combination with low-dose prednisone and methotrexate or leflunomide. We tested the sera of the patients for antinuclear antibodies (ANA), rheumatoid factor (RF), anti double-stranded DNA antibodies (anti dsDNA), anti-histone and anti-extractable nuclear antigen antibodies (aENA) at baseline and before infusion at weeks 6 and 30. Infliximab, initiated at a dose of 3 mg/kg, was increased to 5 mg/kg if insufficient improvement was observed after three infusions. RESULTS: At week 6, only the frequency of anti-histone IgM antibody-positive patients had significantly increased (19 vs 42%, p = 0.009). At week 30, the frequency of patients with ANA had increased from 29% to 69% (p < 0.001), that of patients with anti-dsDNA antibodies had increased from 0% to 3% for IgG (NS) and from 0% to 32% for IgM (p < 0.001); the frequency of antihistone IgG detection had increased from 22% to 32% (p = 0.04) and that of IgM detection, from 18% to 79% (p < 0.001). No lupus-like syndrome was observed. RF decreased significantly (87 IU to 52.5 IU, from baseline to week 30; p < 0.001). No significant difference was observed between the 16 non-responders and the responders, in terms of autoantibody status at baseline and changes with infliximab therapy. CONCLUSION: Infliximab therapy lead to the selective and delayed induction of autoantibodies. This induction was not associated with clinical symptoms until week 30 and did not differ between responders and non-responders.
OBJECTIVE: To investigate the prevalence and clinical significance of antiphospholipid antibodies in patients with systemic sclerosis (SSc). METHODS: Autoantibodies against cardiolipin (aCL) and beta2-glycoprotein 1 (beta2-GPI) were detected by enzyme-linked immunoabsorbent assays (ELISAs) in successively hospitalised SSc patients admitted during a 24-month period. These patients were compared to patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA). RESULTS: 108 SSc patients were included: 61 had limited cutaneous SSc, 47 had the diffuse sub-type, 16 had primitive pulmonary arterial hypertension (PAH) and 34 had digital ulcerations. The control groups consisted of 37 RA and 38 SLE patients. The prevalence of aCL positivity was lower in SSc patients vs SLE patients (14 vs 47%; p < 0.001), lower in RA patients vs SLE patients (19 vs 47%; p < 0.001), and not different in SSc vs RA patients (14 vs 19%; NS). The mean aCL titer was also lower in SSc vs SLE patients (8+/-10 vs 15+/-20; p < 0.001). In SSc patients, positivity for aCL was associated with PAH (p = 0.009) and the aCL titer correlated with that of the von Willebrand antigen factor (r= 0.23; p = 0.045). The prevalence of anti beta2-GPI positive patients (IgG and/or IgM) was 5% in the SSc group, 18% in the SLE group and 5% in the RA group (SLE vs SSc and SLE vs RA; p = 0.005). CONCLUSION: We found that the prevalence of antiphospholipid antibodies in SSc patients was low. However, aCL antibodies were associated with PAH and endothelial injury.