https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1538-7836.2006.01753.x

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).

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 higher frequency of stroke and angina pectoris, but a lower frequency of livedo reticularis, than the remaining patients. Conclusion. APS may affect any organ of the body and display a broad spectrum of manifestations. An association with SLE, the patient's sex, and the patient's age at disease onset can modify the disease expression and define specific subsets of APS.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.10187

Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the clinical association of antiphospholipid autoantibodies (aPL) with a syndrome of hypercoagulability that can affect any blood vessel, irrespective of type or size. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or embolism, whereas involvement of smaller vessels, including capillaries, arterioles, and venules, manifests as thrombotic microangiopathy. Virtually any organ in the body, including the kidney, can be affected. Here, we review the basic principles and recent advances in our understanding of APS, and discuss the broad spectrum of renal diseases that have been observed in association with this syndrome. We also discuss the impact that APS may have on pre-existing renal disease as well as current recommendations for treatment of APS.

The antiphospholipid syndrome.

Background The antiphospholipid-antibody syndrome is a thrombophilic disorder in which venous or arterial thrombosis, or both, may occur in patients with antiphospholipid antibodies. The optimal treatment of these patients is unclear. We assessed the efficacy of warfarin, low-dose aspirin, or both in the secondary prevention of thrombosis in patients with the syndrome. Methods One hundred forty-seven patients (124 [84 percent] of whom were female) with the antiphospholipid-antibody syndrome and a history of thrombosis were studied retrospectively. The syndrome was primary in 62 patients and was associated with systemic lupus erythematosus in 66 patients and lupus-like disease in 19. Each patient's history was reviewed. Results One hundred one patients (69 percent) had a total of 186 recurrences of thrombosis. The median time between the initial thrombosis and the first recurrence was 12 months (range, 0.5 to 144 months). Treatment with high-intensity warfarin (producing an international normalized ratio o...

The Management of Thrombosis in the Antiphospholipid-Antibody Syndrome

Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature

Comparison of the primary and secondary antiphospholipid syndrome: A European multicenter study of 114 patients☆

A prospective echocardiographic study was carried out on 55 patients with the recently described 'primary' antiphospholipid syndrome derived from three university medical centres. The prevalence of valvular lesions in patients with this syndrome was 38% compared with 4% in a control group of 55 healthy volunteers (P < 0.001). Mean age of patients with valve was 42 ± 12 years and of those without, 30 ± 10 years (P < 0.05). One patient had a morphologic echocardiographic pattern suggestive of non-infective verrucous mitral endocarditis. Twenty patients had a two-dimensional or Doppler echocardiographic pattern of significant valvular dysfunction —either regurgitation or stenosis—without evidence of vegetations. Mitral and aortic regurgitation were the most common lesions in these patients. During follow-up of patients with valvular disease, haemodynamically significant clinical valve disease developed in four and surgery was required in one. Eleven patients had cerebrovascular occlusions. Thus, valvular hea...

High Prevalence of Significant Heart Valve Lesions in Patients with the 'Primary' Antiphospholipid Syndrome

Using an ELISA, anti-endothelial cell antibodies (AECA) have been found in sera obtained at the time of renal biopsy in 46 out of 57 patients (81%) with systemic lupus erythematosus (SLE) and nephritis (mean binding index (BI) = 84% +/- 52.8) compared with 22 out of 50 SLE patients (44%) without nephritis (mean BI = 45% +/- 35.9). Seventy normal human sera had a mean BI of 10% +/- 9.8. The highest levels were seen in patients with diffuse proliferative glomerulonephritis (WHO grade IV) and in patients with proteinuria and nephrotic syndrome. When the biopsies were assessed for activity and chronicity scores, AECA were associated with active renal lesions (P less than 0.001). AECA levels correlated with low complement levels but not with anti-DNA antibodies to extractable nuclear antigens (ENA), anti-cardiolipin or anti-neutrophil cytoplasmic antibodies. The presence of AECA conferred a positive predictive value of 0.68 for the presence of nephritis. Twenty-five patients had active vasculitis at the time of assay and the highest AECA values were seen in patients with both nephritis and vasculitis. No correlation was seen with serum immunoglobulin levels and immune complexes did not bind significantly to the endothelial surface. The possible role of these antibodies as a marker in lupus nephritis is discussed.

Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis.

We carried out a prospective study of the prevalence and characteristics of anticardiolipin antibodies (aCL) and migraine on 103 consecutive patients with systemic lupus erythematosus (SLE) derived from three European referral university centers. We also included a control group of 58 patients with migraine not associated with SLE. We interviewed all patients using a data collection form designed to provide a complete record of the clinical characteristics of headache. Fifty-four (52%) patients with SLE suffered recurrent headache. We diagnosed migraine in 32 patients, tension headache in 21, and cluster headache in one. Thirty (29%) patients with SLE had aCL. Migraine was present in five patients with aCL and in 27 patients without aCL (17% versus 37%, p = 0.07). No migraine control patient had aCL. Our study highlights the frequency of headache in SLE, but does not support an association between the presence of aCL and migraine in this disease.

Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus

During a 6-month period, 100 patients with systemic lupus erythematosus (SLE) were consecutively studied for the presence of antithyroid antibodies and thyroid disease Overall, the prevalence of antithyroid antibodies was similar in patients with SLE (21%) and controls (16%) However, antithyroglobulin antibodies were found in 11% of patients with SLE and only 2% of controls (p = 0009) The levels of antimicrosomal antibodies were also different (median levels: SLE = 400; controls = 100) but this difference did not reach statistical significance We found a significant correlation between thyroid stimulating hormone (TSH) levels and the levels of both the antithyroglobulin dilutions (p less than 005) and the antimicrosomal dilutions (p less than 005) This was not seen in the controls A higher frequency of clinical thyroid disease was seen in patients with SLE with thyroid antibodies (5/21; 3 hypothyroid, 2 hyperthyroid) than in those without these antibodies (1/79; p = 0001) Levels of antithyroid antibodies correlated with clinical or subclinical (marked by elevations of TSH) thyroid disease Patients with SLE with these antibodies were significantly older (mean age 475 +/- 13 years) than those without antithyroid antibodies (mean age 375 +/- 12 years; p less than 0001) Antithyroid antibodies define a subset of older patients with SLE with increased prevalence of both clinical and subclinical thyroid disease

J. L. Vianna

Papers

Comparison of the primary and secondary antiphospholipid syndrome: A European multicenter study of 114 patients☆

High Prevalence of Significant Heart Valve Lesions in Patients with the 'Primary' Antiphospholipid Syndrome

Antibodies to endothelial cells in systemic lupus erythematosus: a potential marker for nephritis and vasculitis.

Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus

A prospective evaluation of antithyroid antibody prevalence in 100 patients with systemic lupus erythematosus.