Ronald A. Asherson

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 catastrophicAPS 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 pre-symposium 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 catastrophicAPS must have three clear aims: to treat any precipitating factors (prompt use of antibioticsif 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.

The Catastrophic Antiphospholipid Syndrome

The addition of the word “catastrophic” to the term antiphospholipid syndrome (APS) was proposed 20 years ago by Ronald Asherson when he published an editorial in The Journal of Rheumatology describing a group of patients who develop multiple thrombosis in a short period of time and with a much worse prognosis than that attributed to patients with classic APS [1]. Since then, many cases have been published reporting patients with this devastating variant of the APS.

Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients.

The antiphospholipid syndrome (APS), originally defined as the combination of venous or arterial thrombotic events, recurrent fetal loss, and, frequently, a moderate thrombocytopenia in association with antiphospholipid antibodies (aPL), was subsequently greatly expanded to include diverse conditions, for example, heart valve lesions, adrenal insufficiency, and pulmonary syndromes such as acute respiratory distress syndrome (ARDS), “capillaritis,” and pulmonary alveolar hemorrhage, among others (16, 17). It was then realized that several “microangiopathic syndromes” also existed, as opposed to large vessel occlusive disease. Single organs, such as the kidneys, heart, skin, and brain, have been affected by this “thrombotic microangiopathy” in the context of the “classic” or “simple” APS. The temporal occurrence of thrombotic events in patients with this classic APS usually extends over months or years. In 1992, the existence of a new “subset” was described in which multiple vascular occlusive events, usually affecting small vessels supplying organs and presenting over a short period of time, were the outstanding features. This subset was termed the “catastrophic” APS. Although large vessel occlusions were also present, their prevalence did not in any way approach that in patients with the classic APS. The occlusions occurred over days to several weeks, and more than 50% of patients usually succumbed despite seemingly adequate therapy, including anticoagulation, steroids, etc. (6). In 1998, a comprehensive review article with the clinical and laboratory description of 50 such patients was published (8). In the present paper we describe the clinical and serologic features of the largest series of patients with catastrophic APS hitherto reported, including 30 new cases from interested physicians in many different countries, as well as a comprehensive literature review of 50 additional recently published case reports with this syndrome. This new series, comprising a total of 80 patients, enables us to analyze further and clarify not only the clinical importance of this syndrome, but also its pathogenesis. 0025-7974/01/8006-0355/0 MEDICINE® 80: 355-77, 2001 Vol. 80, No. 6 Copyright

Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome

PURPOSE AND PATIENTS AND METHODS Antiphospholipid antibodies, lupus anticoagulant antibodies to cardiolipin, and a false-positive result on testing for syphilis have been linked to thrombotic vascular occlusions, particularly in patients with systemic lupus erythematosus (SLE) or lupus-like disease, i.e., patients not fulfilling four American Rheumatism Association criteria for the classification of SLE. The clinical and serologic features of 35 patients with cerebrovascular disease (strokes/transient ischemic attacks) who demonstrated antibodies to phospholipids are presented. Complete histories were obtained from all 35 patients, and all underwent routine physical examinations, radiography, electrocardiography, computed tomographic brain scanning, and immunologic studies. Psychometric tests were performed in nine patients. RESULTS The strokes were often multiple and were followed by multi-infarct dementia in nine patients. Of particular interest were 10 patients in whom the presence of antiphospholipid antibodies was the major and often the sole immunologic disturbance present. Several of these patients were antinuclear antibody-negative, and the antinuclear antibodies, when present, were usually of a low titer (1:40 to 1:160). These patients conform to a group classified as having a primary antiphospholipid syndrome. CONCLUSION Antiphospholipid antibodies are strongly associated with cerebrovascular occlusions in patients with SLE as well as in those with lupus-like disease and the primary antiphospholipid syndrome. All patients with any of these conditions who present with vascular events should be screened for these antibodies, as their occurrence may have a bearing on future therapy.

Association of antibodies against phospholipids with heart valve disease in systemic lupus erythematosus

A prospective echocardiographic study was carried out on 132 consecutive patients with systemic lupus erythematosus (SLE) derived from three European university medical centres. The prevalence of valvular lesions in patients with SLE was 22.7% compared with 2.9% in a control group of 68 healthy volunteers. 50 SLE patients had antibodies against phospholipids. The prevalence of valve vegetations (8/50 [16%]) and of mitral regurgitation (19/50 [38%]) was significantly higher among the SLE patients with antiphospholipids than among those without (1 and 10/82 [1.2% and 12%], respectively). During follow-up of the patients with valvular lesions, haemodynamically significant clinical valve disease developed in 6 but surgery was required in only 1; 9 had cerebrovascular occlusions; and 7 died, although no death was due directly to the cardiac involvement. Thus, valvular heart disease, particularly affecting the mitral valve, is common in patients with SLE, and the presence of antibodies against phospholipids is associated with a higher prevalence of valvular abnormalities in these patients.

Catastrophic Antiphospholipid Syndrome.

This paper reports one case of successfully treated patients suffering from a rare entity, the catastrophic antiphospholipid syndrome (CAPS). Management of this patient is discussed in detail.

Chorea in the antiphospholipid syndrome. Clinical, radiologic, and immunologic characteristics of 50 patients from our clinics and the recent literature.

&NA; Abbreviations used in this article: aCL, anticardiolipin antibodies; ANA, antinuclear antibody; aPL, antiphospholipid antibodies; APS, antiphospholipid syndrome; CT, computed tomography; DVT, deep vein thrombosis; LA, lupus anticoagulant; MRI, magnetic resonance imaging; OC, oral contraceptives; SLE, systemic lupus erythematosus.

The lung in the antiphospholipid syndrome

Patients with antiphospholipid syndrome (APS) may develop a broad spectrum of pulmonary disease. Pulmonary thromboembolism and pulmonary hypertension are the most common complications, but microvascular pulmonary thrombosis, pulmonary capillaritis, and alveolar haemorrhage have also been reported. Clinicians should seriously consider these types of vascular injury when evaluating patients with APS who present with dyspnoea, fever, and infiltrates on chest radiography.

Long term outcome of catastrophic antiphospholipid syndrome survivors

Background: Catastrophic antiphospholipid syndrome (APS) is defined as life threatening multiple organ thromboses developing simultaneously or over a short period. The survival rate of catastrophic APS is about 50%, but the long term outcome of patients who survive is unknown. Objective: To determine the long term outcome of patients with catastrophic APS and provide further information on patients who survived. Patients and methods: The clinical characteristics and outcomes of 130 patients with catastrophic APS have been reported previously. Six new cases were recently added to this series. Based on these publications, the authors who reported patients who had survived were contacted. Each author was asked (a) what treatment they gave their patients after the catastrophic APS; (b) if their patients had any further thrombosis. Results: 63/136 (46%) patients died at the initial event. Of the remaining 73 patients, information was available for 58 (79%). Thirty eight (66%) patients did not develop further APS related events during an average follow up of 67.2 months. Eleven (19%) patients developed further APS related events but were still alive. No patients developed further catastrophic APS. Nine (16%) patients died: due to multiple organ failure (three patients); myelofibrosis (one); pneumonia (one); and APS related events (four). Conclusion: Sixty six per cent of patients who survive an initial catastrophic APS event remained symptom free with anticoagulation during an average follow up of 67.2 months. Twenty six per cent of the survivors developed further APS related events and the mortality rate of these patients was about 25%.

Anticardiolipin antibodies: occurrence in Behçet's syndrome.

Anticardiolipin antibodies have recently been described in association with arterial and venous thrombosis, and with neurological symptoms, in connective tissue diseases. In a study of 70 patients with Behçets syndrome 13 patients had these antibodies. Of these 13 patients eight had a history of either retinal vascular pathology, cerebral infarction, or thrombophlebitis. The association of retinal vascular disease and the presence of anticardiolipin antibodies was statistically significant.