Hughes syndrome crosses boundaries
Introduction
The recognition that a number of manifestations of systemic lupus erythematosus (SLE) have a thrombotic rather than inflammatory basis can be considered one of the most important recent contributions to clinical Rheumatology and Immunology. The ‘anticardiolipin syndrome’ described by Graham Hughes in the early 1980s [1], subsequently changed to antiphospholipid syndrome (APS) — or Hughes syndrome — proved to be a frequent condition in patients with lupus [2], but also present in others without SLE or other classifiable autoimmune disease. In these cases it was called the ‘primary’ antiphospholipid syndrome (PAPS) [3].
Now almost 20 years old, APS has crossed boundaries between many fields of medicine. Clinical manifestations bring together rheumatologists, neurologists, obstetricians, hematologists, cardiologists, nephrologists, etc. The full spectrum of this syndrome is still to be defined.
Significant advances in the diagnosis and management of patients with APS have been made. However, there is not complete consensus in very important questions such as use of tests alternative to anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) assays, treatment of pregnancy failure or intensity of anticoagulant therapy, among other examples. These and other issues will be briefly discussed in this review.
Section snippets
Classification criteria
A panel of experts joining the 8th International Symposium on antiphospholipid antibodies (aPL) at Sapporo [4] has recently established the preliminary criteria for the classification of definite APS (Table 1). Clinical criteria include arterial, venous and/or small vessel thrombosis as well as recurrent (three or more) miscarriage, one fetal death or prematurity due to severe pre-eclampsia or placental insufficiency. Laboratory criteria only consider aCL at medium–high titers or LA, any of
Antiphospholipid antibody testing
The laboratory is crucial in the identification of patients with APS. Clinical suspicion based on recurrent thrombosis, miscarriage or other features of APS must be always confirmed by positive tests that detect the presence of aPL. Ideally, these tests must have high sensitivity and specificity. Also, standardisation and a high level of intra and inter-laboratory agreement is desirable, hence patients tested at different times and places do not exhibit different results.
The two more
Clinical features
‘Classical’ clinical features associated with APS include recurrent thrombosis and pregnancy losses. APS is unique among thrombophilias in causing arterial and venous thrombosis with similar frequency. Recurrent thrombosis is common in untreated patients with APS, frequently taking place in the same vascular bed (arterial or venous) as the initial event [11]. Women with APS may experience a high rate of pregnancy failure. Although early miscarriage is common, APS is characterised by the
Therapy
Therapy of Hughes syndrome is based on anticoagulant and antiaggregant drugs [32]. Corticosteroids play only a marginal role in the management of APS-limited to haematological manifestations such as thrombocytopenia and haemolytic anaemia and life-threatening conditions such as catastrophic APS and myelopathy [33]. Early attempts at suppressing aPL production by immunosuppressive treatment were not beneficial [34].
The optimal treatment for recurrent pregnancy losses in APS is still debated.
References (40)
- et al.
Anti-β2-glycoprotein I antibodies in women with recurrent spontaneous abortion, unexplained fetal death, and antiphospholipid syndrome
Am J Obstet Gynecol
(1999) - et al.
Anticardiolipin antibodies in an unselected stroke population
Lancet
(1994) - et al.
Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian registry
Am J Med
(1996) Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone
Am J Obstet Gynecol
(1996)- et al.
Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial
Am J Obstet Gynecol
(2000) - et al.
and the Duration of Anticoagulation Study Group. Anticardiolipin antibodies predict early recurrence in thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy
Am J Med
(1998) The anticardiolipin syndrome
Clin Exp Rheumatol
(1985)- et al.
Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients
Medicine (Baltimore)
(1989) - et al.
The ‘primary’ antiphospholipid syndrome: major clinical and serological features
Medicine
(1989) - et al.
International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome
Arthritis Rheum
(1999)
Validation of the Sapporo criteria for antiphospholipid syndrome
Arthritis Rheum
Anticardiolipin testing
Lupus anticoagulant measurement
Criteria for the diagnosis of lupus anticoagulant: an update
Throm Haemost
Antiphospholipid antibody-negative syndrome-other phospholipids
A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis
Arch Intern Med
Systemic lupus erythematosus and antiphospholipid syndrome during pregnancy: maternal and fetal complications and their management
Isr Med Assoc J
Anticardiolipin antibodies in acute non-hemorrhgic stroke seen within six hours after onset
Acta Neurol Scand
β2-glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction. The Honolulu heart program
Stroke
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Annexin A2, autoimmunity, anxiety and depression
2016, Journal of AutoimmunityCitation Excerpt :The antiphospholipid syndrome (APS) is an auto-immune disorder, manifested by thromboembolic events (arterial and venous), recurrent spontaneous abortions, and elevated titers of circulating antiphospholipid antibodies (aPL) (reviewed in Ref. [1]). While APS is clinically defined by its association with hypercoagulability [2], many patients have neurological manifestations in the absence of overt strokes and these include seizures, ocular disturbances, dementia, migraine, transverse myelitis, chorea (as reviewed [3]) epilepsy, depression [4] and cognitive decline [5,6]. Similarly, in a mouse model of the disorder, animals develop behavioral abnormalities despite lack of ischemic injury [7–9].
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