REVIEWAntiphospholipid syndrome associated with infections: clinical and microbiological characteristics
Introduction
The detection of antiphospholipid antibodies (aPL), namely the lupus anticoagulant (LA) or anticardiolipin antibodies (aCL), is of considerable interest because of their importance in the pathogenesis of clotting in the antiphospholipid syndrome (APS) (Asherson, 1988; Asherson et al., 1989). However, aPL were originally detected in human serum almost 100 years ago when a complement fixation test was first used for the diagnosis of syphilis (Wasserman, 1907) and the Venereal Disease Research Laboratory (VDRL) test was described (Michaelis, 1907). A phospholipid, called cardiolipin was the major tissue extract utilized in performing these tests. It was subsequently found that the VDRL was not specific for syphilis but was also found in autoimmune diseases such as systemic lupus erythematosus (SLE).
In 1983, at the Hammersmith Hospital, cardiolipin was used for the first time as the antigen in solid-phase aPL specific assays (Harris et al., 1983). Since then, many infections have been found to be associated with aPL positivity, although a pathogenic role for these antibodies was not usually obvious except in a few isolated cases. Over recent years it has been emphasized and reported in several articles that a large variety of infections (Table 1) may not only “trigger” the production of these antibodies but also appear to be followed by clinical manifestations of APS itself (Cervera et al., 2004). This has been particularly seen in patients with catastrophic APS.
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Hepatitis C virus (HCV)
Elevated levels of aCL were found by Ordi-Ros et al. (2000) in 3.3% of patients with HCV infection and these were all beta-2 glycoprotein I (β2GPI)-independent. Higher frequencies (22%) were observed by Prieto et al. (1996) and these authors related the presence of thrombocytopenia, portal hypertension and prior thrombotic events to elevated titres of aCL. Sthoeger et al. (2000) found elevated levels of aCL in 44% of patients but once again no relationship to any APS-related clinical
Bacterial infections
Many bacterial infections demonstrate aPL. However, these elevations are usually not associated with thrombotic events. Of interest, however, is that, although β2GPI dependence is usually negative in this group, in leprosy patients the aCL may be β2GPI dependent such as is found with autoimmune diseases, particularly in the multibacillary type of leprosy patients (Fiallo et al., 1998). Lucio's phenomenon is a rare manifestation of leprosy in which the histopathological findings are related to
The catastrophic antiphospholipid syndrome
This unusual and potentially fatal subset of the APS was first defined in 1992 (Asherson, 1992). Since then, more than 300 patients have been reported (Cervera et al., 2005). “Triggering” factors have become apparent and these have included trauma, withdrawal of anticoagulation, carcinoma and also infections (Asherson, 1999). Infections preceding the appearance of catastrophic APS were reported in eight patients from Mexico (Rojas-Rodríguez et al., 1999). A larger analysis of patients with this
Conclusions
A wide variety of infections can be associated with thrombotic events in patients with APS, including the potentially lethal subset termed catastrophic APS. There is clearly a disproportionately larger number of patients who have developed catastrophic APS following infection than those observed in the simple/classic APS, considering the small number of catastrophic APS patients documented in the literature (around 300) as opposed to the several thousand with simple/classic APS. This emphasizes
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Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature
2017, IDCasesCitation Excerpt :A lupus anticoagulant was again positive 65 (normal range: 27–41 s) 3 months’ after discharge. A probable association and a causal relationship between infections and APS have been well reported, and various organisms have been implicated [3]. A “two hit” model has been proposed to explain the pathogenesis of thrombosis of APS [4,5].
The role of infectious diseases in the catastrophic antiphospholipid syndrome
2015, Autoimmunity ReviewsCitation Excerpt :It is possible to identify the triggering factor for CAPS in 60% of cases [3], infection being the most common (22–50%). Other factors are surgery (10%), discontinuation of anticoagulation therapy (8%), oral contraceptives (7%), obstetric complications (7%) and neoplastic diseases (5%) [3–6,9,18,25,26]. Several factors can be present in the same patient: infection with anticoagulation withdrawal followed by a surgical procedure, or a biopsy in a patient with neoplasia [3].
Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant
2015, Thrombosis ResearchCitation Excerpt :However, on multivariate analysis, aspirin treatment was not found to have an effect on thrombosis incidence. Isolated LAC positivity might be explained with conditions as cancer [27] and infections or chronic illness [28]. These findings further support the current guidelines on LAC testing [14], in which it is stated that testing should be limited to young patients.
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