Antiphospholipid Hughes Syndrome Research Articles

A glimpse into the history of description of the antiphospholipid syndrome.

Prior to 1983, several landmark reports prepared the stage for a detailed description of the Antiphospholipid (Hughes) syndrome (APS). Formerly depicted as lupus-like, APS exhibits a wide spectrum of symptoms that overlap with Sjogren's, Hashimoto, and other autoimmune diseases. In this review, we take a glimpse into the history of description of APS, discussing the events that led to its recognition as one of the most common autoimmune diseases and the enormous impact of that recognition in the rheumatology field.

The relationship between social support and health-related quality of life in patients with antiphospholipid (hughes) syndrome

Objective: Antiphospholipid (Hughes) syndrome (APS) is recognised as a systemic autoimmune disease defined by recurrent thromboembolic events and/or pregnancy morbidity. Little is known about the psychological burden of this long-term condition. This study aims to explore the relationship between social support and health-related quality of life (HRQoL) in patients with APS.Methods: A total of 270 patients with a clinical diagnosis of APS participated in a cross-sectional online questionnaire survey. Data included demographics, disease-related information, social support and HRQoL.Results: Both perceived and ideal social support were associated with HRQoL in APS. Patients reported receiving insufficient social support. Perceived emotional support was related to physical functioning (B = 7.77, p = .006, 95% CI: 2.25, 13.29); perceived instrumental support was associated with bodily pain (B = 17.52, p < .001, 95% CI: 11.15, 23.90) and perceived informational support with physical and social functioning (B = −6.30, p = .05, 95% CI: −12.52, −0.08; B = 8.06, p = .02, 95% CI: 1.17, 14.94). Ideal emotional support was related to physical and social functioning (B = 5.80, p = .04, 95% CI: 0.26, 11.34; B = 7.53, p = .04, 95% CI: 0.55, 14.51); ideal instrumental support was associated with mental health (B = 4.73, p = .03, 95% CI: 0.38, 9.07) and ideal informational support with vitality (B = 5.85, p = .01, 95% CI: 1.23, 10.46).Conclusion: Social support was linked to HRQoL in patients with APS. Insufficient social support was associated with limitations in various HRQoL domains. Increasing social support especially through provision of disease-specific education might contribute to improving HRQoL in patients with APS. Patient-tailored interventions addressing psychosocial aspects of living with APS are needed to improve patients’ psychological and physical status.

Antiphospholipid (Hughes) syndrome: description of population and health-related quality of life (HRQoL) using the SF-36

Antiphospholipid (Hughes) syndrome (APS) affects mainly women 15 to 50 years of age and is responsible for approximately 20% of strokes in people <40 years. Little is known about the psychological burden of this long-term condition. We investigated HRQoL in APS. We conducted a cross-sectional survey involving 270 members of the Hughes Syndrome Foundation worldwide. Data included HRQoL (SF-36), demographics, and APS-related self-reported major issues. Response rate was 60%. T-tests indicated significantly worse mean scores for seven of the eight domains of the SF-36 in secondary antiphospholipid syndrome (SAPS) compared to primary antiphospholipid syndrome (PAPS), e.g. bodily pain t(263) = 6.10 p < 0.001 except for mental health t(267) = 1.95 p = 0.053. PAPS appeared to be associated with poorer HRQoL in most mental health domains but overall better physical domains compared to systemic lupus erythematosus (SLE) alone. SAPS appeared to have a more adverse impact on HRQoL compared to PAPS and SLE. Major issues identified: pain and fatigue, lack of health care professional/public awareness, and medication unpredictability. HRQoL in PAPS appears to be generally better than SLE and SAPS in physical domains, but poorer in mental domains. APS patients might need more social support in terms of information and awareness of the condition to improve their coping strategies.

Postural tachycardia syndrome (POTS) and other autonomic disorders in antiphospholipid (Hughes) syndrome (APS)

Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder that has been shown to cause a large number of cardiac and neurological manifestations. Two recent studies have demonstrated abnormalities in cardiovascular autonomic function testing in APS patients without other cardiovascular or autoimmune disease. However, an association between autonomic disorders such as postural tachycardia syndrome and APS has not previously been described. Data were obtained by retrospective chart review. We identified 15 patients who have been diagnosed with APS and an autonomic disorder. The median age of the patients at the time of data analysis was 39 years. The autonomic disorders seen in these patients included postural tachycardia syndrome, neurocardiogenic syncope and orthostatic hypotension. The majority of patients (14/15) were female and the majority (14/15) had non-thrombotic neurological manifestations of APS, most commonly migraine, memory loss and balance disorder. Many also had livedo reticularis (11/15) and Raynaud's phenomenon (nine of 15). In some patients, the autonomic manifestations improved with anticoagulation and/or anti-platelet therapy; in others they did not. Two patients with postural tachycardia syndrome who failed to improve with the usual treatment of APS have been treated with intravenous immunoglobulin with significant improvement in their autonomic symptoms. We believe that autonomic disorders in APS may represent an important clinical association with significant implications for treatment.

A Systematic Literature Review of the Association of Lipoprotein(a) and Autoimmune Diseases and Atherosclerosis

Objective. To investigate the association of lipoprotein(a) and atherosclerosis-related autoimmune diseases, to provide information on possible pathophysiologic mechanisms, and to give recommendations for Lp(a) determination and therapeutic options. Methods. We performed a systematic review of English language citations referring to the keywords “Lp(a)” AND “autoimmune disease” AND “atherosclerosis,” “Lp(a)” AND “immune system” OR “antiphospholipid (Hughes) syndrome (APS)” OR “rheumatoid arthritis” OR “Sjögren's syndrome” OR “systemic lupus erythematosus” OR “systemic sclerosis” OR “systemic vasculitis” published between 1991 and 2011 using Medline database. Results. 22 out of 65 found articles were identified as relevant. Lp(a) association was highest in rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE), moderate in APS and lowest in systemic sclerosis (SSc). There was no association found between Lp(a) and systemic vasculitis or Sjögren's syndrome. Conclusion. Immune reactions are highly relevant in the pathophysiology of atherosclerosis, and patients with specific autoimmune diseases are at high risk for CVD. Elevated Lp(a) is an important risk factor for premature atherosclerosis and high Lp(a) levels are also associated with autoimmune diseases. Anti-Lp(a)-antibodies might be a possible explanation. Therapeutic approaches thus far include niacin, Lp(a)-apheresis, farnesoid x-receptor-agonists, and CETP-inhibitors being currently under investigation.

Neuropsychiatric Involvement in Systemic Lupus Erythematosus:Current Therapeutic Approach

The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their usefulness in the treatment of neuropsychiatric SLE. This article reviews the clinical approach to therapy in patients with SLE and neuropsychiatric involvement.

Hughes syndrome (the antiphospholipid syndrome): 25 years old

The antiphospholipid (Hughes) syndrome (APS) is a unique thrombotic disorder, causing both arterial and venous thrombosis, linked to the presence of antibodies directed against phospholipid-protein complexes. The first papers describing the syndrome were published in 1983 and, over the next two years, a series of publications described in detail the various clinical manifestations of the syndrome. Laboratory standardisation workshops were also set up and, in 1984, the first "world" symposium on APS was held. The international APS conferences have continued to grow in numbers and in stature. The APS has already had an impact in obstetrics, in medicine, in psychiatry, and in surgery. The approximate figure of 1 in 5 is a useful guide -- 1 in 5 of all young strokes, 1 in 5 recurrent miscarriages, 1 in 5 DVTs. More precise data will become available in the worlds of epilepsy, migraine, Alzheimer's, and MS. The advent of newer "biologic" immunosuppressives such as rituximab may offer help in selected cases. Intravenous immunoglobulin has proved successful, especially in the emergency setting.

Syndrome X (angina pectoris with normal coronary arteries) and myocardial infarction in patients with anti-phospholipid (Hughes) syndrome

Patients with clinical features of angina pectoris in the absence of coronary artery pathology have remained an enigma to clinicians. Previous data has suggested that almost 20% of women with symptoms suggestive of angina had abnormal stress induced ischaemia. This phenomenon is more commonly observed in women than in men. 1 Anti-phospholipid (Hughes) syndrome (APS) is an autoimmune disease of unknown aetiology characterized by arterial and/or venous thromboses, pregnancy losses and the presence of anti-phospholipid antibodies (aPL). 2 Although thrombosis and pregnancy loss are the cardinal features of APS, heterogeneous clinical features such as cardiac valve involvement, livedo reticularis and low platelets are also described. 3 There is accumulating evidence to suggest that there is an increased risk of accelerated atherosclerosis in patients with primary APS as well as APS associated with SLE. 4 Since the description of the APS (Hughes) syndrome in 1983, a number of cardiac manifestations have been described in association with APS, 5,6 including cardiac valvular abnormalities (Libman‐Sacks endocarditis). The syndrome has been implicated in coronary artery disease in young adults and coronary artery bypass graft occlusions. 7 Vaarala 8 described an increased prevalence of myocardial infarction (MI) in patients with aPL. Hamsten et al. 9 found an association between the presence of aPL and recurrent cardiovascular events in young survivors of MIs. Although typical MI with occluded coronary arteries is well described in patients with APS, there are a number of reports describing anginal chest pain and MI with normal coronary arteries in patients. In 2002, we described a patient with syndrome X and Hughes syndrome, suggesting that MI in APS may be associated with normal coronary arteries. 10 Further anecdotal

The point prevalence of an abnormal ankle-brachial index in antiphospholipid antibody negative patients with livedo reticularis: a controlled study

Livedo reticularis (livedo) is characterised by reticular cyanotic cutaneous discolouration surrounding a pale central area. Physiological livedo, also known as cutis marmorata, is common in young women on exposure to...

The presence of anticardiolipin antibodies in adults may be influenced by infections in infancy

There has been limited success defining environmental factors important in the development of antiphospholipid (Hughes) syndrome (APS). Recent work suggests that the perinatal environment may be important in the development of other autoimmune diseases. We measured anticardiolipin antibodies (aCL) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with aCL positivity in adult life. aCLs were measured using an ELISA in 1384 individuals from the Hertfordshire cohort study. We investigated associations between the presence of aCL and early growth and infectious exposure in infancy in men and women. ELISA positive aCL (IgM and IgG) was present in 22 (3%) men and 15 (2%) women. Using the highest octile of aCL results, in men higher birth weight (per lb of birth weight: OR 1.18, 95% CI 1.02-1.36, P = 0.02) and diarrhoeal infection in the first year of life (OR 2.55, 95% CI 1.10, 5.92, P = 0.03) were associated with an increased likelihood of being aCL positive. In women, diarrhoeal infection in the first year of life was also associated with an increased likelihood of aCL positivity (OR 2.23, 95% CI 1.01, 4.91, P = 0.05). For IgG titre in men, significant relationships were found with sharing a bedroom (regression coefficient 1.13; 95% CI 1.05, 1.22; P = 0.02) and diarrhoea in the first year (coefficient 1.25; 95% CI 1.00, 1.56; P = 0.05). A developing immune system when exposed to the infectious environment may influence the likelihood of producing aCL in adult life.

Vasculopathy and arterial stenotic lesions in the antiphospholipid syndrome

The antiphospholipid (Hughes) syndrome (APS) is characterized by recurrent arterial or venous thromboembolism, or pregnancy loss, in association with antiphospholipid antibodies. These antibodies may be associated with premature or accelerated atherosclerosis and emerging evidence supports the concept of a vasculopathy in the APS that may lead to arterial stenotic lesions, possibly contributing to vascular occlusions and pregnancy morbidity.

Hughes Syndrome, the Antiphospholipid Syndrome: A New Chapter in Neurology

The importance of cerebral disease in patients with the antiphospholipid (Hughes) syndrome (APS) is now becoming more widely recognized. The range of neuropsychiatric manifestations of APS is comprehensive and includes focal symptoms attributable to lesions in a specific area of the brain as well as diffuse or global dysfunction. Patients with APS frequently present with strokes and transient ischemic attacks, but a wide spectrum of other neurologic features, also including nonthrombotic neurological syndromes, has been described in association with the presence of antiphospholipid antibodies. In this review, we attempt to highlight the large variety of the neurological features of APS.

Orthopaedic manifestations of the antiphospholipid (Hughes) syndrome

The antiphospholipid (Hughes) syndrome (APS), is characterized by arterial and/or venous thrombosis and pregnancy morbidity in association with antiphospholipid antibodies (aPL). Since its classical description 21 years ago, the clinical spectrum of Hughes syndrome has embraced the realms of obstetrics, nephrology, cardiology, neurology, gastroenterology and now, possibly orthopaedics. This is not surprising, given that this disease can affect virtually any organ system and blood vessel of any size and nature. Just as venous thrombosis may affect limbs and internal organs, arterial thrombosis has been shown to affect organs such as the brain, eye, heart, kidney, liver and may also involve the skeleton. In this review, the skeletal aspects of Hughes syndrome, postulated pathogenesis and possible implications of anticoagulation will be discussed. Finally, the approach to APS patients undergoing orthopaedic surgery shall also be outlined.

Renal manifestations of the antiphospholipid syndrome

Renal thrombotic manifestations have been reported since the earliest descriptions of the antiphospholipid (Hughes) syndrome (APS). The spectrum of clinical features associated with antiphospholipid nephropathy continues to widen. This review will highlight recent developments such as the prevalence of hypertension, livedo reticularis and renal artery stenosis as well as the ultrastructural changes seen in antiphospholipid nephropathy. The increasing risks of renal transplantation in antiphospholipid antibody positive patients is also discussed leading some authors to question whether these patients should undergo transplantation at all.

Central nervous system involvement in the antiphospholipid (Hughes) syndrome.

The antiphospholipid (Hughes) syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disorder or secondary to a connective tissue disease, most frequently systemic lupus erythematosus. Central nervous system (CNS) involvement is one of the most prominent clinical manifestations of APS, and includes arterial and venous thrombotic events, psychiatric features and a variety of other non-thrombotic neurological syndromes. In this review we focus on the common and some of the less common CNS manifestations that have been reported in association with antiphospholipid antibodies.

Behavioral and cognitive deficits occur only after prolonged exposure of mice to antiphospholipid antibodies.

The antiphospholipid (Hughes) syndrome (APS) includes systemic and central nervous system (CNS) pathology associated with antibodies to a complex of phospholipids and beta2-glycoprotein I (beta2-GPI). Beta2-GPI immunized mice develop systemic manifestations of APS and we presently examined CNS manifestations in this APS model. Female BALB/c mice were immunized once with beta2-GPI in complete Freund's adjuvant (CFA) or with CFA alone (controls). A staircase test and a T-maze alternation test were performed to test behavior and cognition in independent groups of mice 6, 12 and 18 weeks following the immunization. The APS mice developed elevated levels of antibodies against negatively charged phospholipids and beta2-GPI. Neurological impairment was detected only 18 weeks after the induction of the APS and consisted of both cognitive (53 +/- 4 vs 71 +/- 3% correct choices in the T-maze alternation for APS vs control mice, P < 0.001) and behavioral changes (higher number of rears (18 +/- 2 vs 11 +/- 1, P < 0.006) and higher number of stairs climbed (12 +/- 2 vs 7 +/- 1, P < 0.02). This is the first report of cognitive deficits in this APS model and demonstrates the time course for the development of previously described behavioral changes. The mechanism involved in these CNS manifestations remains to be elucidated.

Lipoprotein(a) oxidation and autoantibodies: a new path in atherothrombosis.

Lipoprotein(a) (Lp(a)) is considered a vascular pathogen of outstanding importance. High plasma levels of this lipoprotein are associated with premature arterial disease; however, the mechanisms involved have not been clarified. The atherosclerotic process is increasingly regarded as a chronic inflammatory reaction in the arterial wall where oxidation-mediated endothelial injury involving modified forms of low-density lipoprotein (LDL) seems to be a key event. Autoimmune pathways are involved in the progression of atherosclerosis and humoral response to oxidatively modified LDL can be considered among these pathways. A number of factors can be encountered in the pathogenesis of the accelerated arterial disease seen in patients with antiphospholipid (Hughes) syndrome (APS) and systemic lupus erythematosus (SLE). Among these, high levels of Lp(a) have been described in both and increasing evidence indicates that patients with antiphospholipid antibodies (aPL) are under oxidative stress. Recent studies suggest that the so-called 'oxidation theory of atherosclerosis' may also be applied to Lp(a). This fact makes this lipoprotein potentially suitable as a target of the immune system and antibodies reacting against oxidatively-modified Lp(a) by malondialdehyde have been recently described in APS and SLE. It is therefore likely that an immune response to the oxidized moiety of Lp(a) might be influential in the pathogenicity of this lipoprotein and, subsequently, of atherosclerosis.