Double trouble: myocardial infarction with non-obstructive coronary arteries as a presentation of Hughes syndrome in monozygotic twins.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a recently described, clinically significant entity, with prevalence rates ranging from 1% to 14% and a mean of 6% of all patients with myocardial infarction. Antiphospholipid syndrome (APS; Hughes syndrome) is characterized by the presence of antiphospholipid antibodies associated with thrombosis (arterial and/or venous) and/or pregnancy morbidity and could be the cause of MINOCA. Data on genetic predisposition to APS are scarce. The present study describes a unique case of monozygotic twin brothers who, at a young age, developed the same clinical presentation of APS. The diagnosis of APS was later confirmed, along with a diagnosis of systemic lupus erythematosus in one brother.

The cutaneous manifestations are significantly related to cerebrovascular in a Serbian cohort of patients with Hughes syndrome.

Objectives To investigate a possible relationship between cerebrovascular, such as stroke and transient ischaemic attack, and various cutaneous manifestations (livedo reticularis, skin ulcerations, pseudovasculitis lesions, superficial cutaneous necrosis and digital gangrene) in antiphospholipid syndrome (APS). This report is based on a Serbian cohort of APS patients. Methods A total of 508 antiphospholipid syndrome APS patients were assessed: 360 with primary (PAPS) and 148 with APS associated with SLE (SAPS). Antiphospholipid antibodies analysis included detection of anti-cardiolipin (IgG/IgM), anti-ß2glycoprotein I (IgG/IgM) and positive lupus anticoagulant test. Results The prevalence of cutaneous manifestations in our cohort was significantly higher in the SAPS group (76.4% vs. 27.2%, p = 0.0001). In both groups, the most common manifestation was livedo reticularis. The majority of cutaneous manifestations were significantly associated with cerebrovascular events in SAPS and PAPS. Cutaneous manifestations were independent predictors of transient ischaemic attack and stroke in PAPS patients (odds ratio 2.850, 95% confidence interval 1.562-5.202, p = 0.001, odds ratio 1.832, 95% confidence interval 1.024-3.277, p = 0.041, respectively). Conclusion In this cross-section analysis of a large cohort of Serbian APS patients, there was a strong relationship between cutaneous and cerebrovascular manifestations, suggesting a more cautious approach regarding neurological symptoms, especially in PAPS patients with cutaneous manifestations present.

Tomography and blood vessels in Hughes syndrome.

Antiphospholipid antibody syndrome (APS) or Hughes syndrome is a multisystem autoimmune disorder that is characterized by venous and arterial thrombosis and/or pregnancy complications (miscarriage and fetal death, preeclampsia, placental insufficiency, and fetal growth restriction), and positive serologic tests for anticardiolipin antibodies (aCL), lupus anticoagulant (LA), or antibodies against beta2-glycoprotein I (anti-ß2GPI) either of IgG or IgM isotype. APS is characterized by accelerated atherosclerosis that, together with an increased tendency toward thrombosis, leads to the occurrence of various vascular events. Timely diagnosis of vascular changes, preferably in the subclinical phase, is required both because of their severity and the high mortality rate. Detection of arterial and venous changes is performed by various invasive and noninvasive diagnostic methods. Computed tomographic angiography (CTA) seems to be the most precise method with low exposure time, giving clinicians an opportunity for early diagnosis and timely treatment of APS patients.

Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS).

BACKGROUND: Ferritin is an iron storage protein considered also as an acute phase reactant with high levels in various inflammatory conditions. Recently, a plausible role for ferritin in the pathogenesis of immune-mediated and especially autoimmune diseases has been suggested. However, the link between ferritin and the antiphospholipid syndrome (APS) has been rarely explored. Therefore, in the current study we evaluated ferritin levels and their correlation to clinical and serological manifestations in patients with APS. We further analyzed ferritin levels among patients with the catastrophic variant of APS (cAPS). METHODS: Ferritin levels were determined in serum samples of 176 APS patients and 98 matched healthy controls according to age and sex (LIAISON, DiaSorin, Italy). APS samples were further analyzed for antiphospholipid (anti-cardiolipin, anti- beta-2-glycoprotein, lupus anticoagulant) and anti-infectious antibodies (CMV, EBV, rubella, toxoplasma, HBV) (LIAISON, DiaSorin, Italy). Clinical, serological and demographic manifestations were recorded. An additional analysis of ferritin levels among 14 patients with cAPS was performed. RESULTS: Hyperferritinemia was present in 9% vs. 0% of APS patients and controls, respectively (p < 0.001). Among patients with APS, ferritin levels correlated with venous thrombosis, cardiac, neurological, and hematological manifestations and the presence of anti-CMV-IgM antibodies. Hyperferritinemia was present in 71% of cAPS patients, and ferritin levels among this subgroup were significantly higher compared with APS-non-cAPS patients (816 ± 847 ng/ml vs. 120 ± 230 ng/ml, p < 0.001). CONCLUSIONS: Herein, we found that hyperferritinemia correlates with the presence of APS, its clinical manifestations and specifically with the catastrophic variant of this disease. Hyperferritinemia was also linked with anti-CMV antibodies among patients with APS. These associations allude to a pathogenic role of ferritin in the pathogenesis of APS, and the plausible role of ferritin as a marker of ensuing cAPS, although further studies are needed to elucidate these associations.

Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study.

Repeated thromboses are the most frequent clinical manifestation of antiphospholipid syndrome (APS) in the presence of antiphospholipid antibodies (aPL). The objective of this study was to observe the prevalence and localization of thrombosis, and to investigate the importance of aPL type and level for thrombosis-related events in patients diagnosed with APS. These are the first results of patients enrolled in Serbian National Cohort Study which comprises 256 patients: 162 with primary antiphospholipid syndrome (PAPS) and 94 with APS associated with systemic lupus erythematosus (SLE). aPL analysis included detection of aCL (IgG/IgM), ß(2)GPI, and lupus anticoagulant. Thrombosis was diagnosed in 119 (46.5%) patients, with higher prevalence in PAPS compared with SLE patients (51.2% and 38.3%, respectively, p = 0.045). There was similar prevalence of arterial thrombosis in PAPS and SLE groups (34.6% and 34%, respectively, p = 0.932) although venous thrombosis was more frequent in PAPS (25.9% and 8.5%, respectively, p = 0.001). Thrombosis was observed in 92 (55.8%) patients who had more than one type of antibody (category I), in 13 (41.9%) patients with category IIa, in 19 (46.3%) patients with category IIb, and in 73 (44.2%) patients with category IIc (p = 0.10). The patients with thrombosis were older than those without thrombosis (49.8 and 39.8 years, respectively, p = 0.001). Overall, older age was a risk factor for thrombosis. The prevalence of venous thrombosis was higher in the PAPS group, but with lower frequency than in literature data. Any aPL type and level is a risk factor for thrombosis.

Avidity of anti-ß2-glycoprotein I antibodies in patients with antiphospholipid syndrome.

Antibodies against ß(2)-glycoprotein I (anti-ß(2)GPI) are one of the hallmarks of the antiphospholipid syndrome (APS). However, they are heterogenic regarding their epitope specificity, pathogenic mechanisms and their avidity. In the current study we present some outstanding issues about avidity of anti-ß(2)GPI antibodies. Our results confirmed that high avidity anti-ß(2)GPI are associated with thrombosis and APS, while in low avidity anti-ß(2)GPI group non-APS (predominantly systemic lupus erythematosus) patients prevailed.

Pulmonary events in antiphospholipid syndrome: influence of antiphospholipid antibody type and levels.

OBJECTIVE: This prospective clinical study examined the association between subclasses of antiphospholipid antibodies (aPL) and pulmonary manifestations in antiphospholipid syndrome (APS). METHODS: The cohort involved 329 patients: 214 patients with primary APS (PAPS) and 115 patients with secondary APS (SAPS). aPL analysis included detection of serum anticardiolipin antibodies [aCL (IgG/IgM)], ß2 glycoprotein I [ß2GPI (IgG/IgM)], and lupus anticoagulant (LA). RESULTS: In SAPS, high aCL IgG levels (> 100 PLU/mL) were more common in major pulmonary arterial thrombosis (p = 0.006) and medium aCL IgG levels (41-99 PLU/mL) in adult respiratory distress syndrome (ARDS; p = 0.047) and fibrosing alveolitis (p = 0.002). aCL IgG antibodies were more common in SAPS (p = 0.037). In PAPS, fibrosing alveolitis was more common in patients with medium ß2GPI IgM levels (p = 0.0001). LA correlated with pulmonary embolism (p = 0.03) and microthrombosis (p = 0.03) in SAPS, and with pulmonary microthrombosis (p = 0.03) in PAPS. Males were more likely to develop secondary pulmonary hypertension when diagnosed with PAPS (p = 0.019). CONCLUSION: Certain classes of aPL are associated with distinct pulmonary manifestation, indicating their predictive role and importance in diagnosis and treatment of APS.

Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression.

BACKGROUND AND AIMS: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, obstetric complications and the presence of anti-phospholipid antibodies such as anti-ß2GPI-Abs. These antibodies may set off the coagulation cascade via several mechanisms, including the induction of tissue factor (TF) expression. Vitamin D has recently emerged as an immunomodulator that might exert an anti-thrombotic effect. Therefore, we studied serum vitamin D levels in a cohort of APS patients, as well as the effect of vitamin D in an in vitro model of APS-mediated thrombosis. METHODS: Serum vitamin D levels were measured in 179 European APS patients and 141 healthy controls using the LIAISON chemiluminescent immunoassay, and the levels were evaluated in conjunction with a wide spectrum of clinical manifestations. In an vitro model, anti-ß2GPI antibodies were purified from four patients with APS to evaluate the expression of TF in activated starved human umbilical vein endothelial cells. The effect of vitamin D (1,25-dihydroxyvitamin D, 10 nm) on anti-ß2GPI-Abs mediated TF expression was analysed by immunoblot. RESULTS: Vitamin D deficiency (serum level ≤15 ng/ml) was documented in 49.5% of our APS patients versus 30% of controls (p<0.001) and was significantly correlated with thrombosis (58% vs 42%; p<0.05), neurological and ophthalmic manifestations, pulmonary hypertension, livedo reticularis and skin ulcerations. In vitro vitamin D inhibited the expression of TF induced by anti-ß2GPI-antibodies. CONCLUSIONS: Vitamin D deficiency is common among APS patients and is associated with clinically defined thrombotic events. Vitamin D inhibits anti-ß2GPI-mediated TF expression in vitro. Thus, vitamin D deficiency might be associated with decreased inhibition of TF expression and increased coagulation in APS. Evaluation of vitamin D status and vitamin D supplementation in APS patients should be considered.

EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: A EULAR task force was composed of experts representing 11 European countries, consisting of eight rheumatologists, four clinical immunologists, one rheumatologist/clinical immunologist, one infectious disease physician, one nephrologist, one paediatrician/rheumatologist and one clinical epidemiologist. Key questions were formulated and the eligible spectrum of AIIRD, immunosuppressive drugs and vaccines were defined in order to perform a systematic literature review. A search was made of Medline from 1966 to October 2009 as well as abstracts from the EULAR meetings of 2008 and 2009 and the American College of Rheumatology (ACR) meetings of 2007 and 2008. Evidence was graded in categories I-IV, the strength of recommendations was graded in categories A-D and Delphi voting was applied to determine the level of agreement between the experts of the task force. RESULTS: Eight key questions and 13 recommendations addressing vaccination in patients with AIIRD were formulated. The strength of each recommendation was determined. Delphi voting revealed a very high level of agreement with the recommendations among the experts of the task force. Finally, a research agenda was proposed. CONCLUSION: Recommendations for vaccination in patients with AIIRD based on the currently available evidence and expert opinion were formulated. More research is needed, particularly regarding the incidence of vaccine-preventable infectious diseases and the safety of vaccination in patients with AIIRD.

Prolactin's role in the pathogenesis of the antiphospholipid syndrome.

Increased levels of serum prolactin have been reported in patients with various autoimmune diseases and have been associated with lupus disease activity. Currently, there is a lack of data regarding hyperprolactinaemia in patients with the antiphospholipid syndrome. Hence, this study was carried out in order to evaluate the prevalence and clinical significance of hyperprolactinaemia in antiphospholipid syndrome. A total of 172 European patients with antiphospholipid syndrome and 100 geographically and sex-matched healthy controls were included in the study; none had obvious causes of hyperprolactinaemia. All patients underwent clinical assessment for disease manifestations, in addition to laboratory assessment for serum prolactin, antiphospholipid antibodies and some other biomarkers of autoimmune diseases. The tests were performed utilizing the LIAISON® Analyzer (DiaSorin, Sallugia Italy). Hyperprolactinaemia was detected in 21/172 patients with antiphospholipid syndrome and 0/100 controls (p < 0.001). This significant difference was present in both genders and was obvious even after subgrouping the patients into primary and secondary antiphospholipid syndrome. When clinical features were compared, hyperprolactinaemia was associated with reproductive failure, including early and late pregnancy loss (p < 0.05), as well as intrauterine growth retardation (p < 0.05). Hyperprolactinaemia was negatively related to arthralgias, venous thrombosis, pulmonary microthrombosis, pulmonary hypertension in both primary antiphospholipid syndrome and antiphospholipid syndrome secondary to other diseases, and to neurological manifestations in primary antiphospholipid syndrome (p<0.05). The data indirectly imply that prolactin may play a role in the pathogenesis of antiphospholipid syndrome, especially antiphospholipid syndrome-related reproductive failure.

Restricted specificity of anti-ribosomal P antibodies to SLE patients in Israel.

OBJECTIVE: Anti-ribosomal P antibodies (aRib-P Ab) are highly specific for systemic lupus erythematosus (SLE), but their correlatation with disease activity and manifestations including renal, hepatic and central nervous system (CNS) involvement is still controversial. The aim of our study was to evaluate the prevalence of aRib-P Ab and their correlation with clinical manifestations and anti-dsDNA antibodies in SLE patients from Israel. METHODS: Elevated titers of aRib-P Ab utilizing the ELISA method were analyzed in 141 sera samples from 44 SLE patients, 20 Familial Mediterranean Fever (FMF) patients, 22 primary antiphospholipid syndrome (PAPS) patients, 12 patients with infections, and 43 healthy individuals. The SLEDAI score was utilized for assessing SLE disease activity. RESULTS: Elevated titers of aRib-P Ab were present in 11% of SLE patients (n = 6). The mean SLEDAI was 7 (range: 3-10). No statistically significant association was observed between the presence of aRib-P Ab and disease manifestations present in the SLEDAI. The 6 SLE patients had renal disease (n = 1), leucopenia (n = 1), rash (n = 3), and CNS involvement manifested as psychosis (n = 1) or depression (n = 1). Elevated titers of anti-dsDNA antibodies were found in 50% of patients with elevated titers of aRib- P Ab. Patients with PAPS, FMF, infections or healthy controls did not harbor elevated titers of aRib-P Ab. CONCLUSION: Elevated titers of aRib-P Ab were restricted to SLE patients. We confirm previously reported associations of aRib-P Ab reactivity with disease activity and elevated anti-dsDNA Ab titers. No significant correlation with a specific manifestation described on the SLEDAI score was established in this small cohort of patients.

Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients.

The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616-0.837 and AUC 0.824, p˂0.001, 95 % CI 0.690-0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.

Livedo reticularis is a marker for predicting multi-system thrombosis in antiphospholipid syndrome.

OBJECTIVE: Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients with anti-phospholipid syndrome (APS) and reported to be present in association with valvular heart pathology and strokes (i.e. Sneddon's syndrome). METHODS: In a cohort of APS patients we investigated the possible association of LR with various clinical aspects of APS such as pregnancy morbidity, central nervous system (CNS) and cardiac manifestations. RESULTS: Livedo reticularis was found in 50/308 (16%) of APS patients, and there was a significant association with cerebrovascular accidents (CVA), migraines and epilepsy (p = 0.01, 0.002, and 0.02 respectively). A similar association was also detected between LR, and the presence of cardiac valve thickening and vegetations (p = 0.001). No association with venous thrombosis, recurrent fetal loss, IUGR or toxemia was found. CONCLUSION: Livedo reticularis is a frequent cutaneous manifestation in patients with APS. Its high association with cardiac and CNS thrombosis may suggest that LR-APS patients compose a subset at higher risk for thrombosis, and thus may require a closer follow-up and a more aggressive anticoagulation.

Immunoreactivity and avidity of IgG anti-ß2-glycoprotein I antibodies from patients with autoimmune diseases to different peptide clusters of ß2-glycoprotein I.

The pathogenicity of antibodies against ß2-glycoprotein I (anti-ß2GPI) depends on multiple factors such as subclass type, epitope binding and avidity. Due to their large heterogeneity, their impact on antiphospholipid syndrome (APS) onset is still not fully clarified. We studied the binding characteristics of IgG anti-ß2GPI with known avidity from sera of 201 autoimmune patients (87 with APS, 67 with APS associated with systemic lupus erythematosus (SLE), 47 with only SLE) to six ß2GPI peptides corresponding to amino acid clusters on domains I-II, II, III and III-IV by indirect ELISA and evaluated their association with clinical features of APS. Peptides A (LKTPRV; domain I-II), B (KDKATF; domain IV) and C (TLRVYK; domain III) were derived from a hexapeptide phage display library previously shown to react with pathogenic monoclonal anti-ß2GPI. Peptides D (NGPANSK; domain III), E (YNPLWFV; domain II) and F (KMDGNHP; domain III-IV) represent surface amino acid clusters on ß2GPI. The percentage of patients positive for peptides were observed as follows: 30.3% for peptide D, 28.90% for B, 25.9% for C, 24.9% for E, 24.4% for F and 10.0% for A. The anti-peptide antibodies in studied serum samples were predominantly of heterogeneous avidity, followed by law avidity anti-peptide antibodies, whereas only a few were of high avidity. Positive and negative correlations were found between several anti-peptide antibodies and the rate of thrombosis. Our results indicated diverse reactivity of IgG anti-ß2GPI to different epitopes on ß2GPI. Classification of IgG anti-ß2GPI into subgroups regarding epitope specificity and avidity could represent an additional tool in understanding their pathogenicity in APS.

Disintegration and reorganization of fibrin networks during tissue-type plasminogen activator-induced clot lysis.

In this study, we investigated tissue-type plasminogen activator (tPA)-induced lysis of glutamic acid (glu)-plasminogen-containing or lysine (lys)-plasminogen-containing thrombin-induced fibrin clots. We measured clot development and plasmin-mediated clot disintegration by thromboelastography, and used scanning electron microscopy (SEM) to document the structural changes taking place during clot formation and lysis. These events occurred in three overlapping stages, which were initiated by the addition of thrombin, resulting first in fibrin polymerization and clot network organization (Stage I). Autolytic plasmin cleavage of glu-plasminogen at lys-77 generates lys-plasminogen, exposing lysine binding sites in its kringle domains. The presence of lys-plasminogen within the thrombin-induced fibrin clot enhanced network reorganization to form thicker fibers as well as globular complexes containing fibrin and lys-plasminogen having a greater level of turbidity and a higher elastic modulus (G) than occurred with thrombin alone. Lys-plasminogen or glu-plasminogen that had been incorporated into the fibrin clot was activated to plasmin by tPA admixed with the thrombin, and led directly to clot disintegration (Stage II) concomitant with fibrin network reorganization. The onset of Stage III (clot dissolution) was signaled by a sustained secondary rise in turbidity that was due to the combined effects of lys-plasminogen presence or its conversion from glu-plasminogen, plus clot network reorganization. SEM images documented dynamic structural changes in the lysing fibrin network and showed that the secondary turbidity rise was due to extensive reorganization of severed fibrils and fibers to form wide, occasionally branched fibers. These degraded structures contributed little, if anything, to the structural integrity of the residual clot, and eventually collapsed completely during the course of progressive clot dissolution. These results provide new perspectives on the major structural events that occur in the fibrin clot matrix during fibrinolysis.

Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases.

OBJECTIVES: To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD). METHODS: AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible. RESULTS: Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive. CONCLUSION: Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy.

Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjögren syndrome and other autoimmune diseases.

Neurological manifestations are known to occur in patients with autoimmune diseases, often subclinically, but autonomic nervous system (ANS) involvement has rarely been studied, and studies have shown conflicting results. We performed cardiovascular ANS assessment in 125 patients with autoimmune diseases in this case-control study, including 54 patients with systemic lupus erythematosus (SLE), 39 with rheumatoid arthritis (RA), 20 with primary Sjbgren syndrome (pSS), eight patients with polymyalgia rheumatica (PR), four patients with scleroderma (Ssc) and 35 healthy control subjects. The control group was formed to approximately match the mean age of SLE, RA and pSS patients; controls did not differ significantly by gender from the autoimmune pations. All patients with were in stable condition. Autonomic nervous system dysfunction was diagnosed by applying cardiovascular reflex tests according to Ewing, and was considered to exist if at least two tests were positive. Vagal dysfunction was established by applying three tests: Valsalva manoeuvre, deep breathing test, and heart rate response to standing. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing and handgrip test. In all cardiovascular reflex tests, frequencies of abnormal results were significantly higher among the patients than among the controls (P < 0.05). The difference between the autoimmune patients and the controls was particularly significant in sympathetic and parasympathetic tests, with P < 0.0001. No correlation was found between disease duration, clinical manifestations, cardiovascular risk factors and diseases activity on the one hand, and ANS dysfunction on the other hand. Cardiovascular autonomic dysfunction was revealed in the majority of autoimmune patients.

Autoimmune hemolytic anaemia in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a multisystem disease with recurrent thrombosis in the presence of antiphosphlipid antibodies, which may include cardiac, neurological, gastrointestinal, hematologic or cutaneous manifestations. The occurrence of autoimmune hemolytic anaemia (AIHA) in APS has not been well established. The purpose of this study was to review the occurrence of AIHA in patients with APS and its relation to other disease manifestations. Three-hundred and eight patients with APS from seven medical centers in Israel, Serbia and the Slovac Republic were included and evaluated for associations between AIHA and various manifestations of APS. AIHA was documented in 32 patients (10.4%). The odds ration for AIHA was increased in the presence of anticardiolipin antibodies and livedo reticularis (5.4 and 7.8, respectively). There was a highly significant association between AIHA and cardiac valvular vegetations and thickening (P < 0.0001), arterial thrombosis (P < 0.02), livedo reticularis (P < 0.0001) and CNS signs of epilepsy or chorea (P < 0.02 and P < 0.03, respectively). Thus, APS patients with AIHA are at risk of developing these manifestations, and should therefore be investigated for them. In addition, the occurrence of AIHA may define a subgroup of patients with a significant risk for subsequent development of SLE.

Close association between valvar heart disease and central nervous system manifestations in the antiphospholipid syndrome.

BACKGROUND: Heart valves lesions and central nervous system involvement are among the most common manifestations of the antiphospholipid syndrome (APS). OBJECTIVE: To evaluate possible interrelations between these manifestations in a large group of APS patients. METHODS: 284 APS patients were evaluated retrospectively, 159 of whom had primary APS. Cardiac-CNS associations were determined for the entire study population, and for subgroups of patients with primary APS or APS associated with systemic lupus erythematosus (SLE). RESULTS: Significant associations where found between cardiac vegetations and epilepsy (p < 0.02), and between cardiac valve thickening or dysfunction and migraine (p = 0.002). Borderline association was found between valvar vegetations and migraine (p = 0.09). A significant association was also found between all valvar lesions and stroke or transient ischaemic attacks. Subanalyses showed that patients with primary APS had significant associations between cardiac valve pathology and all CNS manifestations, while patients with APS associated with SLE had no such associations. CONCLUSIONS: The study suggests potential differences in biological behaviour between primary APS and APS associated with SLE. The presence of cardiac valve pathology may be a risk factor for several types of CNS involvement in PAPS.