Ma Khamashta

Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients.

We report a 10-year follow-up on 52 patients with raised levels of anticardiolipin antibodies (aCL) who were first seen at our tertiary referral centre in 1986. The clinical and serological features of these 52 patients are described. Thirty-one patients had the antiphospholipid syndrome (APS) in 1986. Nine of these patients (29%) had further thrombotic events during the follow-up period. Of the other 21 aCL positive patients without clinical manifestations of APS, 11 (52%) developed the syndrome over this period. Five patients (10%) died during the follow-up. Close monitoring of patients with connective tissue diseases and aCL is essential as the likelihood of developing antiphospholipid syndrome is high.

Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes.

Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with cardiolipin binding activity were subsequently eluted from these platelets. Total phospholipids extracted from platelets inhibited aCL activity, and the specific phospholipids bound were shown to be phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. It is concluded that aCL antibodies can bind phospholipids in platelet membranes but pertubation of the membrane must first occur.

The Euro-Phospholipid project: epidemiology of the antiphospholipid syndrome in Europe.

The Euro-Phospholipid project started in 1999 with a multicentre, consecutive and prospective design. A total cohort of 1000 patients with antiphospholipid syndrome (APS), derived from 13 countries (Belgium, Bulgaria, Denmark, France, Germany, Greece, Hungary, Israel, Italy, the Netherlands, Portugal, Spain and United Kingdom), has been followed since then. This project allowed the identification of the prevalence and characteristics of the main clinical and immunological manifestations at the onset and during the evolution of APS and demonstrated that it is possible to recognize more homogeneous subsets of clinical significance. Patients with APS associated with systemic lupus erythematosus (SLE) had more episodes of arthritis, livedo reticularis and more frequently exhibited thrombocytopenia and leucopenia. Female patients had more episodes of arthritis and livedo reticularis – both connected with the higher prevalence of migraine and SLE-related APS in women, while male patients had more myocardial infarction, epilepsy and lower limb arterial thrombosis. Childhood onset patients presented more episodes of chorea and jugular vein thrombosis, whereas older onset patients were more frequently male and had more strokes and angina pectoris, but less frequently livedo reticularis.

The Euro-lupus project: epidemiology of systemic lupus erythematosus in Europe

The Euro-lupus project provides updated information on the epidemiologic characteristics of systemic lupus erythematosus (SLE) at the change of the millennium and defines several clinical and immunological prognostic factors. The Euro-lupus cohort is composed of 1000 patients with SLE who have been followed prospectively since 1991. Among other findings, this project has shown that a) the age at onset of the disease, the gender and the autoantibody pattern, among other factors, modify the disease expression and define some specific SLE subsets; b) most of the SLE inflammatory manifestations are less common after long-term evolution of the disease, thus probably reflecting the effect of therapy as well as the progressive remission of the disease in many patients and c) a more prominent role of thrombotic events is becoming evident affecting both morbidity and mortality in SLE.

Chorea in systemic lupus erythematosus: association with antiphospholipid antibodies.

Chorea is a rare manifestation of systemic lupus erythematosus (SLE). In this report the clinical features of two cases of chorea associated with SLE are presented. Of special interest were the raised titres of antiphospholipid antibodies in both cases. The possible pathogenic role of these antibodies is briefly discussed.

Treatment of menorrhagia associated with oral anticoagulation: efficacy and safety of the levonorgestrel releasing intrauterine device (Mirena coil).

Menorrhagia is common in women receiving oral anticoagulation. In healthy women, reductions of up to 90% of menstrual loss have been described with the levonorgestrel releasing intrauterine device (LNG-IUS). However there is no data about the use of LNG-IUS in women receiving oral anticoagulation and so we assessed the efficacy and safety of LNG-IUS in this setting. Patients with menorrhagia who used LNG-IUS and warfarin were contacted by post and asked to complete a questionnaire assessing the extent and duration of menstrual bleeding, quality of life and treatment satisfaction. The questionnaire was sent to 23 patients and returned by 17. The amount of bleeding was reduced with the LNG-IUS in 10 (58.8%) women; amenorrhea occurred in four (23.5%), no change in blood loss in one (5.9%) and greater blood loss in two (11.8%) patients. The number of sanitary pads used was less in 12 (70.6%) patients; same in one (5.9%) patient, more in two (11.8%) patients and two (11.8%) did not remember. Five patients (29.4%) had shorter duration of bleeding, four (23.5%) had amenorrhoea, four (23.5%) had longer periods and four (23.5%) had same duration by subjective assessment. Eight (47.1%) patients felt very satisfied, four (23.5%) felt satisfied, two (11.8%) felt dissatisfied with the treatment, one felt very dissatisfied (5.9%) and two (11.8%) did not respond to the question. This small study suggests LNG-IUS is effective in reducing the duration and amount of menstrual bleeding in women with menorrhagia associated with oral anticoagulation. We feel the use of LNG-IUS is a major advance in reducing menorrhagia in women on oral anticoagulation as the previous alternative-hysterectomy-is associated with an increased risk of thrombosis and bleeding

Update on immunotherapy for systemic lupus erythematosus—what's hot and what's not!

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.

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-β2-glycoprotein I (aβ2GPI), 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 aβ2GPI was present in one patient from each group. All IgA aβ2GPI were present together with IgG and/or IgM aβ2GPI. 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 aβ2GPI are not useful in identifying additional women with APS and pregnancy morbidity.

Water intoxication induced by low-dose cyclophosphamide in two patients with systemic lupus erythematosus:

Cyclophosphamide(CY) is an alkylating agent used to treat a variety of autoimmune disorders.Water intoxication is a well-known complication of high-dose intravenous (i.v.) CY, but is rare in patients treated with low dose i.v. CY. We describe two patients with lupus nephritis and water intoxication following low dose i.v. CY. The first patient was treated with oral prednisolone and azathioprine for eight weeks with inadequate response and persistent renal inflammatory activity. Eight hours after the first i.v. CY pulse she had a grand mal seizure. The second patient had WHO class III lupus nephritis, and after a single i.v. CY pulse developed vomiting, diarrhoeaand grand mal seizures.They were both fluid-restrictedand their serum sodium levels returned to normal. In conclusion, even at low doses i.v. CY may induce hyponatremiarelated to inappropriateantidiuretichormone secretion. This potentially life-threateningcomplication of i.v. CY could be minimized by avoidance of overhydrationfollowing pulse i.v. CY.

Antiphospholipid antibodies in patients with scleroderma: prevalence and clinical significance

Antiphospholipid antibodies (aPL) are detected in a variety of autoimmune disorders, most commonly systemic lupus erythematosus, but also in some infectious diseases, lymphoproliferative disorders, and even in apparently healthy people. Although a wide prevalence of aPL in systemic sclerosis has been reported (between 0 and 41%), most studies have focused on anticardiolipin antibodies (aCL) and very little is known about other aPL in this disease. We determined the prevalence and clinical significance of aCL, antibodies to β2-glycoprotein I (anti-β2GPI), and antibodies to phosphatidylserine-prothrombin complex (aPS-PT) in 25 patients with scleroderma (18 with limited and 7 with diffuse scleroderma, as defined by LeRoy et al 1) (table 1). Twenty four patients were female (median age 50 years (range 28–70), median disease duration 3 years (range 1–20)). …