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Biomedical subjects

M A Khamashta

Publications and source records attributed to M A Khamashta.

At least 37 records · Page 2Linked to original sources
PubMed2004

Renal artery stenosis in hypertensive patients with antiphospholipid (Hughes) syndrome: outcome following anticoagulation.

OBJECTIVE: We have demonstrated a point prevalence of 26% renal artery stenosis in patients with antiphospholipid syndrome (APS) and uncontrolled hypertension. We describe the effect of anticoagulation on blood pressure control and renal function. METHODS: We studied 23 patients retrospectively with renal artery stenosis (RAS). Fourteen received oral anticoagulation for more than 1 yr (target International Normalized Ratio (INR) of 3.0-4.5). Five patients had primary APS. Patients were divided into two groups based on their INR (< 3.0 and > or = 3.0). Nine patients had repeat magnetic resonance angiography (MRA) or an angiogram of the renal arteries after 2 yr. RESULTS: Only 8/14 patients managed to maintain their INR > or = 3.0 (median INR 3.1, range 2.8-3.7) while six had a INR < 3.0 (median INR 1.9, range 1.2-2.4). Patients with a median INR < 3.0 had poorly controlled blood pressure and there was significant deterioration in mean serum creatinine values (Wilcoxon's test, P < 0.03). Nine patients underwent follow-up renal artery imaging. Three of nine patients with an INR < 3.0 (median INR 1.9) had re-stenosis and a fourth developed bilateral renal artery stenosis. Five patients with INR > or = 3.0 (median INR 3.1) did not show re-stenosis of the renal arteries; their renal function was stable and blood pressure was well controlled. One other patient with secondary APS (mixed connective tissue disorder) with INR > 3.0 showed recanalization of the stenosed renal artery. CONCLUSION: Anticoagulation with INR maintained > or = 3.0 helped to control the blood pressure and prevent the progression of renal disease.

Anticoagulants↗
PubMed2004

Anti-C1q antibodies in nephritis: correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus.

OBJECTIVE: To investigate antibodies to complement 1q (anti-C1q) and investigate the correlation between anti-C1q titres and renal disease in systemic lupus erythematosus (SLE). METHODS: 151 SLE patients were studied. In patients with biopsy proven lupus nephritis (n = 77), activity of renal disease was categorised according to the BILAG renal score. Sera were tested for anti-C1q by enzyme immunoassay. Serum samples were randomly selected from 83 SLE patients who had no history of renal disease, and the positive and negative predictive value of the antibodies was studied. RESULTS: Patients with active lupus nephritis (BILAG A or B) had a higher prevalence of anti-C1q than those with no renal disease (74% v 32%; relative risk (RR) = 2.3 (95% confidence interval, 1.6 to 3.3)) (p<0.0001). There was no significant difference in anti-C1q prevalence between SLE without nephritis and SLE with non-active nephritis (BILAG C or D) (32% v 53%, p = 0.06) or between active and non-active nephritis (74% v 53%, p = 0.06). Patients with nephritis had higher anti-C1q levels than those without nephritis (36.0 U/ml (range 4.9 to 401.0) v 7.3 U/ml (4.9 to 401.0)) (p<0.001). Anti-C1q were found in 33 of 83 patients (39%) without history of renal disease. Nine of the 33 patients with anti-C1q developed lupus nephritis. The median renal disease-free interval was nine months. One patient with positive anti-C1q was diagnosed as having hypocomplementaemic urticarial vasculitis syndrome during follow up. CONCLUSIONS: Anti-C1q in SLE are associated with renal involvement. Monitoring anti-C1q and their titres in SLE patients could be important for predicting renal flares.

Adolescent↗
PubMed2004

Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale.

OBJECTIVE: To validate the Lupus Activity Index in Pregnancy (LAI-P) scale as a diagnostic tool for lupus flares during pregnancy and the puerperium. METHODS: The LAI-P is a modified activity scale specific for pregnancy. Thirty-eight pregnant women with systemic lupus erythematosus (SLE) were prospectively followed in 3 clinics specific for lupus in pregnancy. On each visit, LAI-P was calculated. A modified physician global assessment (m-PGA) scale was used as gold standard (0 = no activity, 1 = mild-moderate activity, 2 = severe activity). A change > or = 0.25 in LAI-P was predefined as a flare according to previous studies in nonpregnant patients. For the purposes of the study, each visit was considered as an independent case. RESULTS: During the study period, 158 visits took place for a total 621 patient-weeks. Sensitivity to change was high (standardized response mean for LAI-P = 1.6). We found a significant association between LAI-P and m-PGA (P < 0.002 in all regression models performed). Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.98, 0.88, and 0.99. Positive and negative likelihood ratios were 49 and 0.07, respectively. CONCLUSIONS: LAI-P has a high sensitivity to changes in lupus activity, a significant correlation with m-PGA, and high sensitivity, specificity, predictive values, and likelihood ratios for diagnosing SLE flares during pregnancy and the puerperium.

Adult↗
PubMed2004

Association of HLA-DM polymorphism with the production of antiphospholipid antibodies.

OBJECTIVE: To investigate whether variation in the HLA-DM gene is important in producing a group of pathogenic autoantibodies-antiphospholipid antibodies (aPL)-on the basis that HLA class II restricted antigen presentation is involved in the production of aPL. METHODS: HLA-DMA and DMB polymorphisms were genotyped by polymerase chain reaction combined with restriction enzyme digestion in 51 white patients with primary antiphospholipid syndrome (APS), 82 with systemic lupus erythematosus (SLE) (42 with APS and 40 without APS), and 109 healthy white controls. The association with the aPL profile was examined. RESULTS: The distribution of DMA alleles in APS patients and in patients with APS associated with SLE was significantly different from that in controls by 4x2 chi(2) test with 3 degrees of freedom (p = 0.035 and 0.011, respectively), but it was not different between SLE patients without APS and controls. The allelic distribution of DMA was also different between patients with IgG class anticardiolipin antibody or those with lupus anticoagulant (LA) and controls (p = 0.012 and 0.007, respectively) and between patients with and without LA among SLE patients (p = 0.035). All these differences included the increase in DMA*0102 in the former groups. CONCLUSIONS: The results suggest that HLA-DMA*0102 or its linked gene(s) form one of the genetic risks for the production of aPL.

Adult↗
PubMed2004

Antiphospholipid antibodies, systemic lupus erythematosus, and non-traumatic metatarsal fractures.

BACKGROUND: Stress fractures are common in military recruits and athletes and are thought to be secondary to stress and overuse. Less often they are associated with metabolic disorders such as osteoporosis, hypophosphataemia, and diabetes mellitus. OBJECTIVE: Analysis of 19 patients with systemic lupus erythematosus and antiphospholipid antibodies presenting consecutively with foot pain. All had metatarsal fractures (six bilateral) without any obvious history of trauma. RESULTS: 13 of the 19 patients had antiphospholipid syndrome. Among the whole group, 13 had normal bone mineral density, one had osteopenia, and five others had osteoporosis as defined by WHO criteria; 10 had received steroids, mostly in low dosage; 13 were receiving warfarin. There was no evidence that a metabolic bone abnormality was a unifying factor in the pathogenesis. CONCLUSIONS: Atraumatic metatarsal stress fractures may occur in SLE, particularly in association with the antiphospholipid syndrome. The pathogenesis of these fractures remains uncertain but microinfarcts in the metatarsal bones are a possible cause.

Adult↗
PubMed2004

Evaluation of systemic lupus erythematosus activity during pregnancy.

Due to our increasing knowledge on the pathophysiological basis of autoimmunity and the development of combined medical-obstetric clinics, pregnancy is becoming common among women with systemic lupus erythematosus (SLE). However, whether lupus worsens during pregnancy continues to be a controversial issue. SLE assessment during pregnancy is sometimes difficult due to physiological changes during this period, and common tools for measuring lupus activity during pregnancy were not available until recently. Several lupus activity scales in common use have been adapted for pregnancy [systemic lupus erythematosus in pregnancy activity index (SLEPDAI), modified lupus activity measurement (m-SLAM) and lupus activity index in pregnancy (LAI-P)]. All of them take into account the influence of pregnancy on clinical manifestation and common biochemical tests. LAI-P also accounts for specific manifestations of antiphospholipid syndrome in order not to score them as due to SLE activity. LAI-P has recently been validated for use in SLE pregnancy and could be used in future studies. However, daily assessment and management of individual pregnant women with lupus still relies on the clinical skills of attending physicians.

Female↗
PubMed2003

Prevalence and clinical correlations of antibodies against six beta2-glycoprotein-I-related peptides in the antiphospholipid syndrome.

Two-hundred ninety five patients with the antiphospholipid syndrome (APS) were studied for the presence of antibodies against six anti-beta2GPI-related peptides Abs. The prevalence of a wide spectrum of clinical and laboratory parameters of APS was evaluated in all patients, and correlated with the presence of each anti-beta2GPI peptide antibody. The rates of the various antipeptides Abs ranged from 18.0 to 63.7%. Altogether, 87.1% of the patients had antibody reactivity against at least one of the six beta2GPI-related peptides. A high degree of simultaneous reactivity against several beta2GPI-peptides was found. Positive and negative correlations were found between several antipeptides Abs and the rates of thrombosis and fetal loss. Our results point to a heterogeneous activity of antiphospholipid Abs in APS patients, directed, often concurrently, against various epitopes of the beta2GPI molecule. Evaluation of APS patients for the presence of specific antipeptides Abs may be of a value in predicting the risk for future thrombotic and obstetrical complication, as well as for specific therapeutic purposes.

Adolescent↗
PubMed2003

Central nervous system involvement in the antiphospholipid (Hughes) syndrome.

The antiphospholipid (Hughes) syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disorder or secondary to a connective tissue disease, most frequently systemic lupus erythematosus. Central nervous system (CNS) involvement is one of the most prominent clinical manifestations of APS, and includes arterial and venous thrombotic events, psychiatric features and a variety of other non-thrombotic neurological syndromes. In this review we focus on the common and some of the less common CNS manifestations that have been reported in association with antiphospholipid antibodies.

Antiphospholipid Syndrome↗
PubMed2003

Prevalence and associations of an abnormal ankle-brachial index in systemic lupus erythematosus: a pilot study.

BACKGROUND: Accelerated atheroma is a well recognised complication of systemic lupus erythematosus (SLE). Its aetiology is multifactorial and several methods may be used to detect early signs of atheroma. METHODS: Patients aged </=55 years were screened using the ankle-brachial index (ABI). Ninety one patients aged </=55 years and fulfilling the revised American College of Rheumatology criteria for SLE were studied. The ABI was measured using a contour wrapped 12 cm cuff attached to a mercury sphygmomanometer and an 8 MHz Doppler probe in the arms and legs; a ratio of <1 was considered abnormal. RESULTS: The mean (SD) age of the patients was 39.0 (9.2) years. Of the 91 patients studied, 34 (37%) had an abnormal ABI. Only one patient was mildly symptomatic. Abnormal ABI correlated with age but not with disease duration, cumulative steroid dosage, ECLAM score, or any other traditional risk factors for atherosclerosis. In comparison with population studies, the prevalence of an ABI<1 in the patients with SLE with a mean age of 39 years was similar to that in adults aged over 80. CONCLUSION: In this pilot study, patients with SLE with a mean age of 39 years had a high prevalence of an abnormal ABI. The ABI is a simple non-invasive tool for the early detection of accelerated atheroma in SLE.

Adult↗
PubMed2003

Renal artery stenosis in the antiphospholipid (Hughes) syndrome and hypertension.

BACKGROUND: Hypertension is common in the antiphospholipid (Hughes) syndrome (APS) and its cause is poorly understood. Anecdotal evidence suggests that renal artery stenosis (RAS) may be a relevant and treatable cause of hypertension. OBJECTIVE: To investigate the prevalence of RAS in patients with APS and hypertension. PATIENTS AND METHODS: Three groups of patients were evaluated: (1) 77 patients with positive antiphospholipid antibodies (aPL) (60 secondary APS, 11 primary APS, and 6 with aPL only) and uncontrolled hypertension who were receiving two or more antihypertensive drugs; (2) 91 patients (</=50 years) attending hypertension clinics;(3) 92 normotensive healthy, potential renal transplant donors. Magnetic resonance renal angiography was used to image the renal arteries in all three groups. RESULTS: Group 1: 20/77 (26%) patients had evidence of RAS (16 unilateral and 4 bilateral). Sixteen patients (80%) had smooth well defined stenoses in the proximal third of the renal artery. Three further patients had irregular arteries without distinct stenosis. Group 2: 7/91 (8%) hypertensive patients had RAS (chi(2)=10.3, p<0.001 v group 1). Group 3: 3/92 (3%) healthy donors had RAS (chi(2)=18.2, p<0.0001 v group 1). CONCLUSION: A significantly increased prevalence of RAS (26%) was found in patients with APS and hypertension, compared with relatively young (</=50 years) hypertensive controls and healthy potential donors.

Adult↗
PubMed2003

Value of IgA anticardiolipin and anti-beta2-glycoprotein I antibody testing in patients with pregnancy morbidity.

OBJECTIVE: To study the prevalence of IgA antiphospholipid antibodies, particularly anticardiolipin antibodies (aCL) and anti-beta(2)-glycoprotein I (abeta(2)GPI), in a cohort of patients with pregnancy morbidity. PATIENTS AND METHODS: Serum samples from four groups of patients were studied by an in house enzyme linked immunosorbent assay (ELISA). Group I: 28 patients with primary antiphospholipid syndrome (PAPS) (median age 32.5 years, range 25-34). Twelve patients had a history of thrombosis. All were positive for IgG/M aCL or lupus anticoagulant (LA), or both. Group II: 28 patients with unexplained pregnancy morbidity (median age 35 years, range 23-48). Seven had history of thrombosis. Nine patients were positive for IgG/M aCL. None from this group fulfilled Sapporo criteria for APS. Group III: 28 patients with systemic lupus erythematosus (SLE) (median age 34 years, range 25-52). Eleven had a history of thrombosis. Twenty one patients had IgG/M aCL and/or LA, but only 19 fulfilled Sapporo criteria for APS. RESULTS: IgA aCL were found in 12, 6, and 14 patients from the groups with PAPS, unexplained pregnancy morbidity, and SLE, respectively. Most patients had these antibodies together with IgG/IgM aCL. Three patients from the group with unexplained pregnancy morbidity and two with SLE had IgA aCL alone. IgA abeta(2)GPI was present in one patient from each group. All IgA abeta(2)GPI were present together with IgG and/or IgM abeta(2)GPI. CONCLUSIONS: The prevalence of IgA aCL is high in patients with pregnancy morbidity, although IgA aCL are usually present together with IgG and/or IgM aCL. IgA abeta(2)GPI are not useful in identifying additional women with APS and pregnancy morbidity.

Abortion, Habitual↗
PubMed2003

Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis.

BACKGROUND: 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. OBJECTIVE: To study the immunological and demographic factors associated with the development of LN. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗
PubMed2003

Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis.

Venous thromboembolism (VTE) in patients suffering from the antiphospholipid syndrome (APS) has been reported in almost any location of the vessel tree and the risk of recurrences has been found in several studies to be more closely associated with the presence of lupus anticoagulant than with the positivity for anti-cardiolipin antibodies. The thrombophilic state of APS raises the problem of the secondary prophylaxis to avoid VTE recurrences. For APS patients with VTE, published data appear to support a longer warfarin treatment if compared with the standard management of antiphospholipid (aPL)-negative patients with VTE. The question of how long oral anticoagulant treatment should be continued for APS patients, however, remains unanswered. Concerning the intensity of anticoagulation, several authors recommend a target international normalized ratio (INR) between 3.0 and 4.0 to efficiently protect from VTE recurrences. A recent decision analysis study does support such a suggestion. On the contrary, in a few prospective studies regimens with lower target INRs appear to be effective, and some authors therefore recommend a target INR of between 2.0 and 3.0. Specific large and prospective trials are needed to address this question. Until such information becomes available, individualized treatment according to the patient's individual risk factors for both bleeding and thrombosis is the general practice.

Administration, Oral↗
PubMed2003

Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report.

The Committee reviewed cardiac involvement in the antiphospholipid antibody syndrome. The Committee's recommendations are: Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review). Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi: the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: the Committee has no recommendations on this aspect of cardiac disease. Pulmonary hypertension: the Committee recommends intensive anticoagulation with warfarin and clinical trials of bosentan, epoprostenol and other new agents.

Anticoagulants↗
PubMed2003

Non-stroke neurological syndromes associated with antiphospholipid antibodies: evaluation of clinical and experimental studies.

Although many types of neurological disorders and events have been described in association with antiphospholipid antibodies (aPL) and the antiphospholipid syndrome (APS), only ischaemic stroke is reasonably well established and accepted as a diagnostic criterion for the syndrome. We propose to evaluate, classify and rank the association of other neurological manifestations as possible, probable, or definite according to the data available from clinical studies and animal models. By these criteria, none of the neurological disorders or events such as epilepsy, psychiatric disease, dementia, transverse myelitis, multiple sclerosis-like disease, chorea, migraine, Guillian-Barrè syndrome, and sensory-neural hearing loss, can be definitely associated with aPL or APS.

Antibodies, Antiphospholipid↗
PubMed2003

Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines.

The term 'catastrophic' antiphospholipid syndrome (APS) is used to define an accelerated form of APS resulting in multiorgan failure. Although catastrophic APS patients represent less than 1% of all patients with APS, they are usually in a life-threatening medical situation that requires high clinical awareness. The careful and open discussion of several proposals by all participants in the presymposium workshop on APS consensus, held in Taormina on occasion of the 10th International Congress on aPL and chaired by Munther A Khamashta and Yehuda Shoenfeld (29 September 2002), has allowed the acceptation of a preliminary set of classification criteria. On the other hand, the optimal management of catastrophic APS must have three clear aims: to treat any precipitating factors (prompt use of antibiotics if infection is suspected, amputation for any necrotic organ, high awareness in patients with APS who undergo an operation or an invasive procedure), to prevent and to treat the ongoing thrombotic events and to suppress the excessive cytokine 'storm'. Anticoagulation (usually intravenous heparin followed by oral anticoagulants), corticosteroids, plasma exchange, intravenous gammaglobulins and, if associated with lupus flare, cyclophosphamide, are the most commonly used treatments for catastrophic APS patients.

Antiphospholipid Syndrome↗