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ABSTRACT: Biological therapies are based on the administration of various types of synthetic molecules related to the immune response. Their use has spread in recent years to the field of systemic autoimmune diseases, particularly to systemic lupus erythematosus (SLE). Until 2011, these diseases were not included in the therapeutic indications approved by international regulatory agencies. Therefore, the use of biological therapies was restricted to clinical trials and to compassionate use for cases refractory to standard treatments (off-label use), which require the approval of the Health Ministry. In 2011, belimumab, a human monoclonal antibody that specifically binds to the soluble form of the protein human B lymphocyte stimulator BlyS, was approved for use in patients with SLE. Because the clinical information on the use of this new drug in patients with SLE has only been obtained from the results of randomized trials, the Study Group of Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine (SEMI) has developed therapeutic guidelines. These guidelines are based on the current scientific evidence on the use of belimumab in SLE patients in the clinical practice.
Revista Clínica Española 12/2012; · 2.01 Impact Factor
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ABSTRACT: Antibodies to prothrombin in solid phase (aPT) and those to phosphatidiyserine-prothrombin complex (aPS/PT) have been suggested to strongly correlate with the presence of lupus anticoagulant (LA). As their clinical diagnostic value and true relationship with the LA remains elusive, we designed this study to evaluate the prevalence and significance of aPT and aPS/PT in a large cohort of patients with and without LA. Samples from 257 patients were included. aPT and aPS/PT were tested by ELISA. LA was tested as per the current criteria from the ISTH Subcommittee on LA-Phospholipid-dependent antibodies. aPS/PT and aPT were found in 51% and 32% of LA-positive (LA+ve) patients and in 22% and 28% of LA-negative (LA-ve) patients, respectively. Thrombosis, particularly venous thrombosis was associated with IgG aPT in the LA+ve group (p=0.0006) and in the LA-ve group (p=0.017). Antibodies to phosphatidylserine-prothrombin, either IgG and IgM were associated with thrombosis in general (p=0.0003) in particularly with venous thrombosis in the LA+ve group (p<0.0001 for IgG and p=0.025 for IgM; respectively) and the LA-ve group (p=0.028, 0.02 and 0.001, respectively). Further multivariate logistic regression analysis showed that LA and of IgG and/or IgM aPS/PT were independent risk factors for thrombosis and pregnancy loss. In conclusion, aPS/PT, but not aPT, are more frequently found in patients with LA. Their association with thrombosis seems to be independent of the presence of LA.
Thrombosis and Haemostasis 12/2012; 109(2). · 5.04 Impact Factor
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ABSTRACT: The value of testing for aPE in venous thrombosis and fetal death is in constant debate. We evaluated if testing for aPE has a diagnostic value in patients with SLE. PATIENTS AND METHODS: We included 224 patients. aPE were tested by an in-house ELISA using FCS. RESULTS: aPE were found in 41% of the patients. IgG and IgM aPE were more frequently found along with other aPL than in those negative for aPL (p=0.003 and p=0.01). IgG aPE were more frequently found in patients with definite APS than in those without (p=0.003). aPE were more frequent in patients with thrombosis than in those without, particularly the IgG isotype (p=0.03). When subdividing between venous and arterial thrombosis, only an association between IgG aPE with venous thrombosis was retained (p=0.01). Titres of IgG aPE were significantly higher in patients with arterial or those with venous thrombosis, when compared to the patients without thrombosis (p=0.004 and p=0.001). Titres of IgM aPE were higher in patients with arterial thrombosis when compared to those without (p=0.014). No associations were found between the presence of aPE and/or pregnancy morbidity. The presence of aPE did not correlate with that of any other aPL. After multivariate analysis all clinical associations failed to retain significance. CONCLUSIONS: aPE are frequently seen in SLE and do not correlate with other routinely tested aPL. Although more prevalent, aPE is not an independent risk factor for thrombosis or pregnancy morbidity in patients with SLE.
Thrombosis Research 10/2012; · 2.44 Impact Factor
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ABSTRACT: Objectives: To evaluate the clinical accuracy of antiphospholipid antibody (aPL) specificities both, individually and/or in combination, in a wide cohort of systemic lupus erythematosus (SLE) patients in an attempt to identify a panel of tests that may provide the best accuracy for diagnosing antiphospholipid syndrome (APS). Patients and Methods: This study included 230 patients (218 women, mean age 42.7±11.9 years, mean disease duration 12.2±8.7years), all fulfilling the 1982 criteria for SLE. All patients were tested for lupus anticoagulant (LA), anti-cardiolipin (aCL), anti-β(2) glycoprotein I (anti-β2GPI), solid phase anti-prothrombin (aPT), anti-phosphatidylserine/prothrombin (aPS/PT), and anti-phosphatidylethanolamine (aPE) antibodies. Sensitivity, specificity and predictive values were calculated. The diagnostic accuracy for each combination of tests was assessed by ROC and their area under the curve analysis as well as by the Youden's index (YI). Results: Testing for 6 aPL derived in 23 possible combinations of results. Among them, LA+ anti-β(2) GPI+aPS/PT had the best diagnostic accuracy for APS as a whole, and individually for both thrombosis and pregnancy loss (AUC 0.712, OR3.73 [95% CI 1.82-5.38],p=0.0001,YI= 0.32 and AUC 0.709 OR3.75[95% CI 2.13-6.62],p=0.0001,YI=0.37 and AUC 0.677, OR4.82[95%CI 2.17-10.72],p=0.0007,YI= 0.38;respectively) and the best specificity when compared to all the other obtainable combination of tests. Triple positivity for LA+anti-β(2) GPI+aPS/PT was more strongly associated with clinical events (thrombosis and/or PL) when compared to double or single positivity (OR23.2[95%CI 2.57-46.2]vs.OR7.3[95%CI 2.21-25.97],OR5.7[95%CI 2.12-17.01]or OR3.11[95%CI 1.56-7.8] for single positivity for LA, aPS/PT and anti-β(2) GPI, respectively). Conclusions: Combining LA, anti-β(2) GPI and aPS/PT improves the diagnostic power and helps in stratifying the risk for each patient, according to their aPL profile. © 2012 International Society on Thrombosis and Haemostasis.
Journal of Thrombosis and Haemostasis 10/2012; · 5.73 Impact Factor
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F Conti,
C Alessandri,
M Sorice,
A Capozzi,
A Longo,
T Garofalo,
R Misasi,
D Bompane,
G R V Hughes, M A Khamashta,
G Valesini
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ABSTRACT: In clinical practice it is possible to find patients with clinical signs suggestive of anti-phospholipid syndrome (APS) who are persistently negative for the routinely used anti-phospholipid antibodies (aPL). Therefore, the term proposed for these cases was seronegative APS (SN-APS). We investigated the clinical usefulness of thin-layer chromatography (TLC) immunostaining in detecting serum aPL in patients presenting clinical features of SN-APS. Sera from 36 patients with SN-APS, 19 patients with APS, 18 patients with systemic lupus erythematosus (SLE), 20 anti-hepatitis C virus (HCV)-positive subjects and 32 healthy controls were examined for aPL using TLC immunostaining. Anti-β(2) -glycoprotein-I, anti-annexin II, anti-annexin V and anti-prothrombin antibodies were tested by enzyme-linked immunosorbent assays (ELISA). Eahy926, a human-derived endothelial cell line, was incubated with immunoglobulin (Ig)G fraction from SN-APS patients and analysis of phospho-interleukin (IL)-1 receptor-associated kinase (IRAK) and phospho-nuclear factor (NF)-κB was performed by Western blot, vascular cell adhesion molecule 1 (VCAM-1) expression by cytofluorimetric analysis and supernatants tissue factor (TF) levels by ELISA. TLC immunostaining showed aPL in 58·3% of SN-APS patients: anti-cardiolipin in 47·2%, anti-lyso(bis)phosphatidic acid in 41·7% and anti-phosphatidylethanolamine in 30·5%. Six of 36 patients showed anti-annexin II. Incubation of Eahy926 cells with IgG from SN-APS induced IRAK phosphorylation, NF-κB activation, VCAM-1 surface expression and TF cell release. TLC immunostaining could identify the presence of aPL in patients with SN-APS. Moreover, the results suggest the proinflammatory and procoagulant effects in vitro of these antibodies.
Clinical & Experimental Immunology 03/2012; 167(3):429-37. · 3.36 Impact Factor
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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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M Mosca,
C Tani,
M Aringer,
S Bombardieri,
D Boumpas,
R Cervera,
A Doria,
D Jayne, M A Khamashta,
A Kuhn,
C Gordon,
M Petri,
M Schneider,
Y Shoenfeld,
J S Smolen,
R Talarico,
A Tincani,
M M Ward,
V P Werth,
L Carmona
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ABSTRACT: The assessment of systemic lupus erythematosus (SLE) patients in routine clinical practice is mainly based on the experience of the treating physician. This carries the risk of unwanted variability. Variability may have an impact on the quality of care offered to SLE patients, thereby affecting outcomes. Recommendations represent systematically developed statements to help practitioners in reducing variability. However, major difficulties arise in the application of recommendations into clinical practice. In this respect, the use of quality indicators may raise the awareness among rheumatologists regarding potential deficiencies in services and improve the quality of health care. The aim of this study was to develop a set of quality indicators (QI) for SLE by translating into QIs the recently developed EULAR Recommendations for monitoring SLE patients in routine clinical practice and observational studies. Eleven QIs have been developed referring to the use of validated activity and damage indices in routine clinical practice, general evaluation of drug toxicity, evaluation of comorbidities, eye evaluation, laboratory assessment, evaluation of the presence of chronic viral infections, documentation of vaccination and of antibody testing at baseline. A disease specific set of quality assessment tools should help physicians deliver high quality of care across populations. Routine updates will be needed.
Autoimmunity reviews 01/2011; 10(7):383-8. · 6.37 Impact Factor
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C N Pisoni,
A Brucato,
A Ruffatti,
G Espinosa,
R Cervera,
M Belmonte-Serrano,
J Sánchez-Román,
F G García-Hernández,
A Tincani,
M T Bertero,
A Doria,
G R V Hughes, M A Khamashta
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ABSTRACT: Congenital heart block (CHB) is presumed to be caused by transplacental passage of maternal immunoglobulin against Ro and La ribonucleoproteins. The recurrence rate in subsequent pregnancies following the birth of a child with CHB is approximately 19%. The purpose of this study was to determine whether intravenous immunoglobulin (IVIG) therapy could prevent the development of CHB in the fetuses of high-risk pregnant women.
A total of 24 pregnancies in 22 women who had a previous pregnancy in which CHB developed, were over the age of 18 years, were <12 weeks pregnant, and had anti-Ro, anti-La, or both antibodies were monitored in this multicenter, prospective, observational study. Fifteen patients received infusions of IVIG. The 9 pregnancies in the remaining 7 patients served as controls. IVIG was administered at a dose of 400 mg/kg at weeks 12, 15, 18, 21, and 24 of pregnancy. Echocardiograms were performed at least every 3 weeks from week 15 to week 30 of gestation. Electrocardiograms were obtained at birth. The outcome measure was the development of third-degree CHB detected by fetal echocardiogram.
CHB developed in 3 babies among the 15 pregnancies in the treatment group (20%) and in 1 baby among the 9 pregnancies in the control group (11%). CHB was detected at weeks 18, 23, and 26, respectively, in the 3 babies in the treated group and at week 19 in the baby in the control group. Three of the affected pregnancies ended in termination; 2 for reasons related to the fetal disease and 1 for reasons related to both maternal (severe pulmonary hypertension) and fetal disease (at 21 weeks of gestation).
IVIG at the dose and frequency used in this study was not effective as prophylactic therapy for CHB in high-risk mothers.
Arthritis & Rheumatism 04/2010; 62(4):1147-52. · 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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ABSTRACT: There have been significant advances in the treatment of SLE, which have produced major impacts on morbidity and in some cases mortality. The major drugs of the last three decades in treatment of SLE have been corticosteroids, AZA, MTX and cyclophosphamide. However, these drugs have considerable toxicities, and with the increasing knowledge of the immune system, and further understanding of SLE immunopathogenesis, many groups are seeking to identify and trial novel immunotherapeutic strategies. These have included therapies aimed at influencing particular immune cells (e.g. B cells) and molecules (e.g. costimulatory molecules, cytokines) which are thought to be important in disease pathogenesis. The advantage of such therapies is that efficacy may be achieved with lower toxicity, and without wide-ranging suppression of the immune system. Success has not always been achieved by specific design of immunotherapies for SLE, and the best recent example has been the use of B-cell depletion therapy, a concept derived from its successful use in RA. In this article, we discuss those immunotherapeutic strategies that have arrived as far as clinical trials in human subjects. In addition to these relatively specific immunotherapies, we also highlight the use of mycophenolate mofetil, an anti-proliferative immunosuppressant which has had good success over the last 10 yrs, with similar early efficacy to cyclophosphamide when used as induction therapy for lupus nephritis. Data are presented on more generalized immune strategies, such as the use of stem cell transplantation and intravenous immunoglobulin.
Rheumatology (Oxford, England) 02/2009; 48(4):332-41. · 4.24 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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G K Bertsias,
J P A Ioannidis,
J Boletis,
S Bombardieri,
R Cervera,
C Dostal,
J Font,
I M Gilboe,
F Houssiau,
T Huizinga, [......],
C G M Kallenberg, M Khamashta,
J C Piette,
M Schneider,
J Smolen,
G Sturfelt,
A Tincani,
R van Vollenhoven,
D T Boumpas,
C Gordon
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ABSTRACT: To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE.
The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists.
Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken.
This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.
Annals of the rheumatic diseases 05/2008; 68(4):477-83. · 8.11 Impact Factor
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C Gordon,
G Bertsias,
J P A Ioannidis,
J Boletis,
S Bombardieri,
R Cervera,
C Dostál,
J Font,
I-M Gilboe,
F Houssiau, [......],
D Isenberg,
C G M Kallenberg, M A Khamashta,
J-C Piette,
M Schneider,
J S Smolen,
G Sturfelt,
A Tincani,
R Van Vollenhoven,
D T Boumpas
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ABSTRACT: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions.
ng a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE.
The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE.
The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications.
Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.
Annals of the rheumatic diseases 05/2008; 68(4):470-6. · 8.11 Impact Factor
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Lupus 02/2008; 17(4):271-3. · 2.34 Impact Factor
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Lupus 02/2008; 17(5):416-20. · 2.34 Impact Factor
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ABSTRACT: To determine the effects of primary antiphospholipid syndrome (PAPS)-derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays.
Anti-beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real-time PCR analysis or at the protein level by ELISA.
A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti-beta(2)GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C).
This study reveals a complex gene expression response in HUVEC to anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines, pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti-beta(2)GPI antibody-regulated genes could contribute to the vasculopathy associated with this disease.
Annals of the Rheumatic Diseases 09/2007; 66(8):1000-7. · 8.73 Impact Factor
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ABSTRACT: To assess the efficacy and tolerability of mycophenolate mofetil (MMF) in six patients with myositis refractory to conventional immunosuppressive therapy.
Six patients were identified from hospital notes. All had previously failed to respond to other immunosuppressive treatments. Efficacy was measured as changes in muscle strength, creatine kinase (CK) levels and prednisolone dose.
The mean age of the group was 49.8 +/- 9.1 yrs, 6 (100%) were female and Caucasian. Patients had failed to respond to a median of 3 (range 1-3) immunosuppressive drugs. They received MMF for a mean of 22.3 +/- 18.9 months with a mean MMF dose of 1.6 +/- 0.5 g/day. The mean initial prednisolone dose was 13.7 +/- 7.7 mg and the mean follow up dose was 8.5 +/- 4.9 mg/day (P = 0.03). CK levels were reduced from mean 2395 IU/l +/- 1202.8 to 746.6 +/- 555.8 IU/l (P = 0.03).
Our data demonstrate that MMF may be effective in myositis, previously unresponsive to conventional immunosuppressive drugs.
Rheumatology 04/2007; 46(3):516-8. · 4.06 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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Annals of the Rheumatic Diseases 11/2006; 65(10):1398-9. · 8.73 Impact Factor
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Annals of the Rheumatic Diseases 06/2006; 65(5):683-4. · 8.73 Impact Factor
