Summary.  New clinical, laboratory and experimental insights, since the 1999 publication of the Sapporo preliminary classification criteria for antiphospholipid syndrome (APS), had been addressed at a workshop in Sydney, Australia, before the Eleventh International Congress on antiphospholipid antibodies. In this document, we appraise the existing evidence on clinical and laboratory features of APS addressed during the forum. Based on this, we propose amendments to the Sapporo criteria. We also provide definitions on features of APS that were not included in the updated criteria.

Objective. To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression.Methods. The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database.Results. The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean ؎ SD age of 42 ؎ 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a

Objective. Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment.Methods. In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed.Results. Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the lowdose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the Supported by the European League Against Rheumatism.

ObjectivesTo develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations. Methods The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design. Results Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1-5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fi vefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fl uid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fl uid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to refl ect an infl ammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD. Conclusions Neuropsychiatric manifestations in SLE patients should be fi rst evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly. involve the central and the peripheral nervous system and that range from overt manifestations such as stroke, seizures and psychosis, to more subtle abnormalities of cognitive function (see supplementary table S1, available online only). Multiple pathological mechanisms are implicated in NPSLE, including antiphospholipid or other autoantibodymediated vascular or neuronal injury, intrathecal production of infl ammatory mediators and accelerated atherosclerosis. Despite substantial advances in the understanding of lupus, NPSLE continues to pose diagnostic and therapeutic challenges to practising physicians. The indicated diagnostic work-up remains unclear, therapies are empiric, and the prognosis after an neuropsychiatric event is often diffi cult to determine. We sought to develop recommendations for the management of systemic lupus erythematosus (SLE) patients presenting with neuropsychiatric manifestations using an evidencebased approach followed by exper...

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.