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M Mosca,
M Govoni,
P Tomietto,
M Aringer,
D Boumpas,
R Cervera,
F Conti, D D'Cruz,
A Doria,
D De La Fuente, [......],
Y Shoenfeld,
G M Steup-Beekman,
M Szmyrka-Kaczmarek,
C Tani,
A Tincani,
A G Tzioufas,
R Voll,
W Bencivelli,
F Salaffi,
S Bombardieri
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ABSTRACT: The creation of a physician-administered questionnaire to screen patients with Systemic Lupus Erythematosus (SLE) for the presence of symptoms suggestive of neuropsychiatric involvement (NPSLE).
The development of the questionnaire followed three phases. First, a list of manifestations was prepared based on the ACR case definitions for NPSLE. A first questionnaire was constructed including 119 items. To reduce their number, a Delphi analysis was carried out and a second questionnaire with 62 questions was developed. This questionnaire was administered to 139 patients with SLE (58 with NPSLE: 29 active, 29 inactive; and 81 without NPSLE: 39 active, 42 inactive). Questions relevant to the screening of patients were selected on the basis of the receiver operating characteristic (ROC) curve analysis.
Twenty-seven questions concerning central nervous system and psychiatric manifestations were found to be relevant; the remaining could be eliminated without significantly affecting AUC. The area under the ROC curve (AUC) was 0.69 (95% CI 0.61-0.78). A score above 17 was considered as suggestive of the presence of NPSLE with a sensitivity of 92.9% (95% CI 85.1-97.3 %) and specificity of 25.4% (95% CI 14.7-39.00 %).
This questionnaire could represent a 'core set' of questions that could help in clinical practice to identify patients with neuropsychiatric symptoms requiring further evaluation.
Lupus 02/2011; 20(5):485-92. · 2.34 Impact Factor
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D A Isenberg,
E Allen,
V Farewell, D D'Cruz,
G S Alarcón,
C Aranow,
I N Bruce,
M A Dooley,
P R Fortin,
E M Ginzler, [......],
M Khamashta,
J T Merrill,
O Nived,
M Petri,
R Ramsey-Goldman,
G Sturfelt,
M Urowitz,
D J Wallace,
C Gordon,
A Rahman
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ABSTRACT: To compare the British Isles Lupus Assessment Group (BILAG) 2004, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) flare index (SFI) and physician's global assessment (PGA) in assessing flares of disease activity in patients with systemic lupus erythematosus (SLE).
Sixteen patients with active SLE were assessed by a panel of 16 rheumatologists. The order in which the patients were seen was randomised using a 4×4 Latin square design. Each patient's flare status was determined at each assessment using the BILAG 2004 activity index; the SFI and a PGA. A group of five specialists designated each patient into severe, moderate, mild or no flare categories.
The rate of complete agreement (95% CI) of the four individual examining physicians for any flare versus no flare was 81% (55% to 94%), 75% (49% to 90%) and 75% (49% to 90%) for the BILAG 2004 index, SELENA flare instrument and PGA, respectively. The overall agreement between flare defined by BILAG 2004 and the SFI was 81% and when type of flare was considered was 52%. Intraclass correlation coefficients (95% CI), as a measure of internal reliability, were 0.54 (0.32 to 0.78) for BILAG 2004 flare compared with 0.21 (0.08 to 0.48) for SELENA flare and 0.18 (0.06 to 0.45) for PGA. Severe flare was associated with good agreement between the indices but mild/moderate flare was much less consistent.
The assessment of flare in patients with SLE is challenging. No flare and severe flare are identifiable but further work is needed to optimise the accurate 'capture' of mild and moderate flares.
Annals of the rheumatic diseases 01/2011; 70(1):54-9. · 8.11 Impact Factor
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J T Merrill,
R Burgos-Vargas,
R Westhovens,
A Chalmers, D D'Cruz,
D J Wallace,
S C Bae,
L Sigal,
J-C Becker,
S Kelly,
K Raghupathi,
T Li,
Y Peng,
M Kinaszczuk,
P Nash
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ABSTRACT: To evaluate abatacept therapy in patients with non-life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis.
In a 12-month, multicenter, exploratory, phase IIb randomized, double-blind, placebo-controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (∼10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper.
A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference -3.5 [95% CI -15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period).
Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non-life-threatening manifestations of SLE. The increased rate of SAEs requires further assessment.
Arthritis & Rheumatism 10/2010; 62(10):3077-87. · 7.87 Impact Factor
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ABSTRACT: In recent decades, many research groups have focused on the role of viral infections in the etiopathogenesis of systemic lupus erythematosus (SLE), the so-called "viral hypothesis". The main candidates are herpes viruses such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), which have a high seroprevalence in the general population. However, a viral causal agent of SLE has not yet been discovered, although many interesting clinical findings on the complex interactions between viruses and SLE have been made. This review analyzes 88 cases of acute viral infections in adult patients with SLE and identifies situations in which viral infections influenced the diagnosis, prognosis or treatment of SLE. We also propose clinical guidelines for the management of these infections in patients with SLE.
Minerva medica 12/2009; 100(6):437-46. · 0.90 Impact Factor
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C-S Yee,
D A Isenberg,
A Prabu,
K Sokoll,
L-S Teh,
A Rahman,
I N Bruce,
B Griffiths,
M Akil,
N McHugh, D D'Cruz,
M A Khamashta,
P Maddison,
A Zoma,
C Gordon
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ABSTRACT: To assess the reliability of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 index in routine practice and its ability to capture disease activity as compared with the British Isles Lupus Assessment Group (BILAG)-2004 index.
Patients with systemic lupus erythematosus from 11 centres were assessed separately by two raters in routine practice. Disease activity was assessed using the BILAG-2004 and SLEDAI-2000 indices. The level of agreement for items was used to assess the reliability of SLEDAI-2000. The ability to detect disease activity was assessed by determining the number of patients with a high activity on BILAG-2004 (overall score A or B) but low SLEDAI-2000 score (<6) and number of patients with low activity on BILAG-2004 (overall score C, D or E) but high SLEDAI-2000 score (>or=6). Treatment of these patients was analysed, and the increase in treatment was used as the gold standard for active disease.
93 patients (90.3% women, 69.9% Caucasian) were studied: mean age was 43.8 years, mean disease duration 10 years. There were 43 patients (46.2%) with a difference in SLEDAI-2000 score between the two raters and this difference was >or=4 in 19 patients (20.4%). Agreement for each of the items in SLEDAI-2000 was between 81.7 and 100%. 35 patients (37.6%) had high activity on BILAG-2004 but a low SLEDAI-2000 score, of which 48.6% had treatment increased. There were only five patients (5.4%) with low activity on BILAG-2004 but a high SLEDAI-2000 score.
SLEDAI-2000 is a reliable index to assess systemic lupus erythematosus disease activity but it is less able than the BILAG-2004 index to detect active disease requiring increased treatment.
Annals of the rheumatic diseases 07/2008; 67(6):873-6. · 8.11 Impact Factor
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ABSTRACT: PURPOSE: The antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis, and pregnancy morbidity in association with antiphospholipid antibodies. Since its classical description 22 years ago, the clinical spectrum of APS has embraced the realms of obstetrics, nephrology, cardiology, neurology, gastroenterology, angiology and now, possibly orthopaedics. This is not surprising given that this disease can affect virtually any organ system and blood vessel of any size and nature. Just as venous thrombosis may affect limbs and internal organs, arterial thrombosis has been shown to affect organs such as the brain, eye, heart, kidney, liver and may also involve the skeleton. CURRENT KNOWLEDGE AND KEY POINTS: In this review, we describe the orthopedic aspects of APS recently reported, bone metatarsal fractures, osteonecrosis and more exceptional complications, ie algodystrophy and bone marrow necrosis. We briefly discuss postulated pathogenesis and possible implications of anticoagulation. FUTURE PROSPECTS AND PROJECTS: This data need further confirmation. They may suggest complementary physiopathologic and therapeutic implications.
La Revue de Médecine Interne 03/2007; 28(2):103-7. · 0.61 Impact Factor
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ABSTRACT: The primary systemic necrotizing vasculitides are a severe group of diseases, which untreated have a high mortality. The majority respond to treatment with high dose steroids and cyclophosphamide, however a significant proportion of those treated suffer morbidity due to the side effects of these agents, and a number of patients are refractory to treatment. We review and discuss alternative and emerging treatment options for patients who fail or cannot tolerate conventional therapy. An interesting subgroup of patients with systemic vasculitis and antiphospholipid antibodies provides an additional diagnostic and therapeutic challenge. We review what is known about this subgroup, and suggest screening for antiphospholipid antibodies in all patients with systemic vasculitis.
Lupus 02/2006; 15(3):143-7. · 2.34 Impact Factor
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ABSTRACT: Altered function of selectin glycoprotein adhesion molecules may modulate severity and organ-specific manifestations of autoimmune and inflammatory disease via changes in leukocyte trafficking. Serum concentrations of selectin molecules have been suggested as useful biomarkers in systemic lupus erythematosus (SLE). We identified increased levels of soluble L-selectin (sL-selectin), but not soluble E-selectin (sE-selectin) in 278 European-Caucasian lupus patients compared to 230 healthy siblings (P=0.002). sL-selectin levels were markedly elevated in patients with IgG antiphospholipid autoantibodies (P=0.002), suggesting that perhaps sL-selectin defines a subgroup of lupus with vasculopathy. sL-selectin level was also influenced by two L-selectin polymorphisms: 665C>T, F206L in the epidermal growth factor-like domain (P=0.015) and rs12938 in the 3'-untranslated region (P=0.06). Having shown increased sL-selectin levels in lupus patients, we used genetics to investigate whether this was a secondary phenomena or the result of an underlying genetic mechanism. The inheritance of nine single-nucleotide polymorphisms (SNP) spanning the selectin locus was tested in 523 UK simplex SLE families. No association with SLE, or related phenotypes, was evident with any single SNP, or haplotype in family-based tests of association. Selectin polymorphisms are, therefore, unlikely to be independent factors in SLE susceptibility.
Genes and Immunity 08/2005; 6(5):422-9. · 3.87 Impact Factor
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D A Isenberg,
A Rahman,
E Allen,
V Farewell,
M Akil,
I N Bruce, D D'Cruz,
B Griffiths,
M Khamashta,
P Maddison,
N McHugh,
M Snaith,
L S Teh,
C S Yee,
A Zoma,
C Gordon
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ABSTRACT: To devise a more discriminating version of the British Isles Lupus Assessment Group (BILAG) disease activity index and to show that it is reliable.
A nominal consensus approach was undertaken by members of BILAG to update and improve the BILAG lupus disease activity index. The index has been revised following intense consultations over a 1-yr period. It has been assessed in two real-patient exercises. These involved patients with diverse clinical features of SLE, including gastrointestinal, hepatic and ophthalmic problems, which the earlier versions of the index did not fully take into account. Reliability in terms of the ability to differentiate patients was assessed by calculating intraclass correlation coefficients. The level of agreement between physicians was determined by calculating the ratio of estimates of the standard error (SE) attributable to the physicians to the SE attributable to the patients.
Good reliability and high levels of physician agreement were observed in one or both exercises in the constitutional, mucocutaneous, neurological, cardiorespiratory, renal, ophthalmic and haematological systems. In contrast, the musculoskeletal system did not score as well, although providing more clear-cut glossary definitions should greatly improve the situation.
Some significant changes in the BILAG disease activity index to assess patients with SLE are proposed. The process of demonstrating validity and reliability has started with these two exercises assessing real patients. Further validation studies are under way. BILAG 2004 is likely to be valuable in clinical trials assessing new therapies for the treatment of SLE, as it provides a more comprehensive system-based disease activity measure than has been available previously.
Rheumatology 08/2005; 44(7):902-6. · 4.06 Impact Factor
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ABSTRACT: The antiphospholipid (Hughes) syndrome (APS), is characterized by arterial and/or venous thrombosis and pregnancy morbidity in association with antiphospholipid antibodies (aPL). Since its classical description 21 years ago, the clinical spectrum of Hughes syndrome has embraced the realms of obstetrics, nephrology, cardiology, neurology, gastroenterology and now, possibly orthopaedics. This is not surprising, given that this disease can affect virtually any organ system and blood vessel of any size and nature. Just as venous thrombosis may affect limbs and internal organs, arterial thrombosis has been shown to affect organs such as the brain, eye, heart, kidney, liver and may also involve the skeleton. In this review, the skeletal aspects of Hughes syndrome, postulated pathogenesis and possible implications of anticoagulation will be discussed. Finally, the approach to APS patients undergoing orthopaedic surgery shall also be outlined.
Lupus 02/2005; 14(5):339-45. · 2.34 Impact Factor
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ABSTRACT: Antiphospholipid syndrome in association with vasculitis is highlighted in this report. The combination of thrombotic and inflammatory processes resulted in endocarditis, aneurysm formation and thrombosis. To our knowledge this is the first presentation of a large vessel aneurysm in these conditions. Anticoagulation and immunosuppression are the treatment modalities of choice.
Lupus 02/2005; 14(11):914-7. · 2.34 Impact Factor
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ABSTRACT: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial.
To study the immunological and demographic factors associated with the development of LN.
A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing.
Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes.
Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN.
Annals of the Rheumatic Diseases 07/2003; 62(6):556-60. · 8.73 Impact Factor
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Ricard Cervera,
M Abarca-Costalago,
D Abramovicz,
F Allegri,
P Annunziata,
A O Aydintug,
M R Bacarelli,
F Bellisai,
I Bernardino,
E Biernat-Kaluza, [......],
R A Sinico,
J Smolen,
A Tincani,
G Tokgöz,
A Urbano-Márquez,
C Vasconcelos,
J J Vázquez,
M Veronesi,
J Vianni,
J Vivancos
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ABSTRACT: The "Euro-Lupus Cohort" is composed by 1,000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium - the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.
Annales de medecine interne 01/2003; 153(8):530-6.
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Lupus 02/2002; 11(11):699-703. · 2.34 Impact Factor
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ABSTRACT: Many patients diagnosed with autoimmune rheumatic disease cannot be categorised easily into one of the established clinical entities such as systemic lupus erythematosus, dermatomyositis, or systemic sclerosis. The term "overlap syndrome" has been increasingly used to identify such patients and is useful in terms of clarifying prognosis and facilitating disease management. This article reviews overlap syndrome in autoimmune rheumatic disease, with particular emphasis on the associated serological markers.
Journal of Clinical Pathology 06/2001; 54(5):340-7. · 2.31 Impact Factor
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QJM: monthly journal of the Association of Physicians 03/2001; 94(2):114-5. · 2.33 Impact Factor
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ABSTRACT: To examine normal and psoriatic skin and synovial tissue from patients with psoriatic arthritis (PsA) for evidence of monocyte chemotactic protein-1 (MCP-1) mediated T cell chemotaxis.
Peripheral blood (PB), synovial fluid (SF), normal and psoriatic skin, and synovial biopsies were obtained from patients with PsA (n = 19) and compared to samples from normal (n = 5) and disease (n = 5) controls (NC, DC). Immune cell populations in PB and SF samples were assessed by immunofluorescent labeling and flow cytometry, levels of soluble MCP-1 were determined by quantitative ELISA, and immunohistochemistry was used to detect T cell subsets and macrophages and MCP-1 protein in frozen skin and synovial tissue sections.
CD8+ but not CD4+ T cells were elevated in SF compared to PB, and the majority of these cells expressed CD45RO. Plasma MCP-1 levels in PsA were elevated relative to NC. MCP-1 levels were significantly higher than paired plasma samples in patients with recent onset (< 6 mo) synovitis (n = 10). A positive correlation was observed between synovial T cell numbers and MCP-1 levels in SF. MCP-1 protein was present in all tissues examined, but most intense expression was observed in synovium.
Elevated concentrations of MCP-1 concomitant with memory T cell infiltration in PsA SF suggests that MCP-1 mediated chemotaxis is involved in the recruitment of T lymphocytes into the synovial compartment of patients with PsA.
The Journal of Rheumatology 10/2000; 27(10):2432-43. · 3.69 Impact Factor
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ABSTRACT: To determine the prevalence and associations of antiendothelial cell antibodies (AECA) in a well characterized cohort of patients with idiopathic inflammatory myopathies (IIM).
Clinical characteristics, AECA, and myositis-specific autoantibodies were assessed by standard methods in 56 subjects with IIM.
AECA were found in 20/56 patients with IIM, were seen in all the major clinical and serologic IIM groups, and were found in 10/15 patients with interstitial lung disease (ILD) (chi squared 6.5, p<0.01 with Yates' correction, relative risk 2.7, specificity 86% and sensitivity 50%). Antisynthetase antibodies, also associated with ILD as described (chi squared = 26.5, p<0.001 with Yates' correction, relative risk 8.7, specificity 95%, sensitivity 77%), did not correlate with the presence of AECA.
AECA appear to be present in all forms of IIM and are markers for ILD that are independent of anti-synthetase autoantibodies. AECA may be a useful serologic marker for ILD in IIM.
The Journal of Rheumatology 02/2000; 27(1):161-4. · 3.69 Impact Factor
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ABSTRACT: To establish the relationship between T cell responses to integrin coreceptor stimulation and B cell hyperreactivity as measured by pathologic autoantibody production.
Peripheral blood mononuclear cells from 42 patients with SLE according to the American Rheumatism Association criteria were examined for their ability to adhere to plate-immobilised fibronectin. Co-stimulation assays were performed on the same cells using anti-CD3 antibody alone or co-immobilised with an anti-beta1-integrin antibody. Proliferative responses were measured by 3[H]thymidine pulsing on day 3 and activation was determined using a commercial protein kinase C assay, the protocol being established by our group in association with Promega. Beta-integrin expression was established by FACS analysis.
An impaired PKC response to integrin-mediated activation was found in T-lymphocytes from 6/21 (29%) SLE patients, which correlated significantly with an absence of anti-dsDNA antibody in patient sera, irrespective of prednisolone treatment. Integrin co-stimulation of TcR/CD3-induced proliferation and T cell adhesion to fibronectin were also impaired among 5/21 (24%) and 6/15 (40%) patients studied, respectively.
We hypothesise that the integrity of beta1-integrin signalling pathways may influence pathological antibody production in SLE by affecting T-lymphocyte activation and interactions between T- and B-lymphocytes.
Lupus 02/1999; 8(1):39-51. · 2.34 Impact Factor
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ABSTRACT: To examine 3 soluble circulating T cell antigens: interleukin 2 receptors (sIL-2r), CD4 (sCD4), and CD8 (sCD8) with von Willebrand factor antigen levels (vWF:Ag) and antiendothelial cell antibodies (AECA) as indices of endothelial involvement in patients with Wegener's granulomatosis (WG).
We studied 23 patients with WG, of whom 11 had active disease with renal involvement, and 20 healthy controls. sIL-2r, sCD4, sCD8, vWF:Ag, and AECA were measured by ELISA.
Median sIL-2r levels in patients were higher than controls (789.5 vs. 551 U/ml, p<0.01). sCD4 levels were higher in patients: 17.0 vs. 15.2 U/ml (p<0.005) and correlated with sIL-2r levels. sIL-2r and sCD4 levels correlated with disease activity scores, antineutrophil cytoplasmic antibodies (ANCA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and neutrophil counts. sCD8 levels were also higher: 260.5 vs. 127 U/ml (p<0.001) and correlated with CRP levels but not with disease activity. vWF:Ag levels were elevated in patients (median 296% vs. controls 109%; p<0.001) and correlated with disease activity, ESR, CRP, ANCA titers, and serum creatinine levels. AECA levels did not differ from controls (5% vs. 7%).
Circulating levels of sIL-2r, sCD4, sCD8, and vWF:Ag are elevated in active WG, indicating T cell and endothelial activation. sIL-2r, sCD4, and vWF:Ag are potentially useful disease activity markers.
The Journal of Rheumatology 02/1999; 26(1):103-9. · 3.69 Impact Factor
