First described in the early 1980s, antiphospholipid syndrome (APS) is a unique form of acquired autoimmune thrombophilia in which patients present with clinical features of recurrent thrombosis and pregnancy morbidity and persistently test positive for the presence of antiphospholipid antibodies (aPL). At least one clinical (vascular thrombosis or pregnancy morbidity) and one lab-based (positive test result for lupus anticoagulant, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) criterion have to be met for a patient to be classified as having APS. However, the clinical spectrum of APS encompasses additional manifestations that can affect many organs and cannot be explained exclusively by patients being in a prothrombotic state; clinical manifestations not listed in the classification criteria (known as extra-criteria manifestations) include neurologic manifestations (chorea, myelitis and migraine), haematologic manifestations (thrombocytopenia and haemolytic anaemia), livedo reticularis, nephropathy and valvular heart disease. Increasingly, research interest has focused on the development of novel assays that might be more specific for APS than the current aPL tests. This Review focuses on the current classification criteria for APS, presenting the role of extra-criteria manifestations and lab-based tests. Diagnostic approaches to difficult cases, including so-called seronegative APS, are also discussed.

Diagnosing antiphospholipid syndrome: 'extra-criteria' manifestations and technical advances

Both systemic lupus erythematosus (SLE) and its treatments can contribute to increased mortality rates. The focus of this review is recent studies on mortality and comorbidities during the last 5 years from around the world. The authors conducted a literature review, using PUBMED, for articles relating to SLE mortality with a specific focus on literature published within the last 5 years. Our analysis found that while mortality in SLE patients continues to improve, there are differences in survival based on ethnicity, socioeconomic status, age, and gender. The most common cause of mortality is cardiovascular disease, followed closely by infection and severe disease activity. To conclude, while there have been significant advances in the treatment of SLE and its associated comorbidities, increased mortality remains a major concern in patient management.

Mortality in Systemic Lupus Erythematosus: an Updated Review.

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is a complex condition that remains poorly understood, and includes heterogeneous manifestations involving both the central and peripheral nervous system, with disabling effects. There are several models to improve NPSLE diagnosis when a neurological syndrome is present. In the last couple of years, the growing knowledge of the role of cytokines and antibodies in NPSLE, as well as the development of new functional imaging techniques, has brought some insights into the physiopathology of the disease, but their validation for clinical use remains undetermined. Furthermore, besides the classic clinical approach, a new tool for screening the 19 NPSLE syndromes has also been developed. Regarding NPSLE therapeutics, there is still no evidence-based treatment approach, but some data support the safety of biological medication when classic treatment fails. Despite the tendency to reclassify SLE patients in clinical and immunological subsets, we hope that these data will inspire medical professionals to approach NPSLE in a manner more tailored to the individual patient.

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Neuropsychiatric Systemic Lupus Erythematosus Involvement: Towards a Tailored Approach to Our Patients?

Hypothyroidism among SLE patients: Case-control study.

Antiphospholipid syndrome (APS) is an autoimmune antibody-mediated condition characterized by thrombotic events and/or pregnancy morbidity in association with persistent positivity to antiphospholipid antibodies (aPL). The nervous system is frequently affected, as intracranial vessels are the most frequent site of arterial pathology. Over the course of years, many other neurological conditions not included in the diagnostic criteria, have been associated with APS. The pathogenic mechanisms behind the syndrome are complex and not fully elucidated. aPL enhance thrombosis, interfering with different pathways. Nevertheless, ischemic injury is not always sufficient to explain clinical features of the syndrome and immune-mediated damage has been advocated. This may be particularly relevant in the context of neurological complications. The reason why only a subgroup of patients develop non-criteria nervous system disorders and what determines the clinical phenotype are questions that remain open. The double nature, thrombotic and immunologic, of APS is also reflected by therapeutic strategies. In this review we summarize known neurological manifestations of APS, revisiting pathogenesis and current treatment options.

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Antiphospholipid Syndrome and the Neurologist: From Pathogenesis to Therapy.

Epilepsy and seizures are reported among the neurological manifestations of antiphospholipid syndrome (APS) at a prevalence rate of approximately 8%, which is nearly 10 times the prevalence of epilepsy in the general population. The association of seizures with antiphospholipid antibodies (aPL) is even more significant in the presence of systemic lupus erythematosus (SLE). In this review, we discuss the epidemiological, pathophysiological, laboratory, clinical, and radiological aspects of this association, and derive suggestions on when to consider testing for aPL in epileptic patients and how to manage seizures secondary to APS based on literature data. Epilepsy due to APS should be considered in young patients presenting with seizures of unknown origin. Temporal lobe epilepsy seems to be particularly prevalent in APS patients. The pathogenesis is complex and may not only involve micro-thrombosis, but also a possible immune-mediated neuronal damage. Patients with seizures and positive aPL tend to develop thrombocytopenia and livedo racemosa more frequently compared with those without aPL. Magnetic resonance imaging (MRI) remains the imaging modality of choice in these patients. The presence of SLE and the presence of neurological symptoms significantly correlate with the presence of white matter changes on MRI. In contrast, the correlation between aPL positivity and the presence of white matter changes is very weak. Furthermore, MRI can be normal in more than 30-40% of neuropsychiatric lupus patients with or without aPL. aPL testing is recommended in young patients presenting with atypical seizures and multiple hyper-intensity lesions on brain MRI in the absence of other possible conditions. New MRI techniques can better understand the pathology of brain damage in neuro-APS. The therapeutic management of epileptic APS patients relies on anti-epileptic treatment and anticoagulant agents when there is evidence of a thrombotic event. In the absence of consensual recommendations, the decision of lifelong anticoagulation is discussed on a case-by-case basis. The anti-thrombotic benefit of hydroxychloroquine and statins is supported by several studies.

Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies?

Data on thyroid disease in Arabs with lupus is scarce. We conducted a cross-sectional and retrospective case-control study to report the prevalence of thyroid diseases in 110 Arabs with lupus who attended our Rheumatology Clinic between January 2002 and January 2007, and to delineate the clinical and immunological features of Arabs lupus patients with thyroid diseases. We found hypothyroidism in 15 (13.7%) patients. Overall, 25.6% had elevated thyroid peroxidase antibodies, 14.6% had elevated anti-thyroglobulin antibodies, and 13.7% were positive for both antibodies. Lupus patients with hypothyroidism had a significantly higher frequency of polyarthritis (OR = 9.3, CI: 2.0-41.7, P < 0.001), cutaneous manifestations (OR = 5.6, CI: 2.4-14.3, P < 0.0001), positive anti-thyroglobulin antibodies (OR = 19.9, CI: 8.38-47.4, P < 0.0001), and thyroid peroxidase antibodies (OR = 12.3, CI: 6.27-24.1, P < 0.0001) than lupus patients with normal thyroid function. Furthermore, neuropsychiatric (OR = 0.36, CI: 0.14-0.93, P < 0.05) and hematological (OR = 0.52, CI: 0.29-0.91, P < 0.05) manifestations were significantly lower in patients with hypothyroidism than in euthyroid patients. Surprisingly, the prevalence of anticardiolipin antibody immunoglobulin G (aCL IgG) (OR = 0.34, CI: 0.13-0.86, P < 0.05), lupus anticoagulant (OR = 0.02, CI: 0.001-0.35, P < 0.0001), and anticardiolipin syndrome (OR = 0.02, CI: 0.001-0.43, P < 0.0001) were significantly lower in lupus patients with hypothyroidism than in lupus patients with normal thyroid function. In conclusion, the prevalence of hypothyroidism in Arabs with lupus is comparable to that reported in the literature. Arab lupus patients with hypothyroidism have distinctive clinical and immunological features that differentiate them from euthyroid patients.

Hypothyroidism determines the clinical and immunological manifestations of Arabs with lupus.

Pregnancy in women with rheumatic disorders is known to be associated with risks for both the mother and fetus; however, these risks can be minimized with proper planning and careful management of the disease In the Middle East, there are specific cultural challenges that may have a negative impact on the care that women with rheumatic disorders receive There is a need for cross-collaboration between specialist physicians, improved awareness of rheumatic disorders among the general public and more open discussion with patients about the potential complications of pregnancy Women in the region are often unwilling to discuss their disease with their partner and are even less likely to seek advice regarding family planning from their physician The objective of this review is to highlight the specific challenges of pregnancy management and to discuss why establishing specialist pregnancy clinics for women with rheumatic disorders could be an effective solution Such clinics can provide high quality care before, during and after pregnancy as shown in several European and US centers Additionally, such clinics could be useful for the collection of pregnancy outcomes data from the Middle East, which may currently be lacking in the region, in order to highlight where further improvements can be made With specialist care and analysis of pregnancy outcomes, the standard of care for women with rheumatic disorders in this area could be significantly improved

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Enhancing the care of women with rheumatic diseases during pregnancy: challenges and unmet needs in the Middle East.

Background Epilepsy and seizures are commonly reported among the neurological manifestations of Antiphospholipid Syndrome (APS). Objectives To discuss the epidemiological, pathophysiological, laboratory, clinical, radiological, and therapeutic aspects of epilepsy/seizures in APS/ antiphospholipid antibody (aPL)-positive patients. Methods We searched the literature through Google Scholar and PubMed for all publications reporting on the epidemiology, pathogenesis, laboratory, imaging and associated clinical findings, and management of epilepsy/seizures in APS/aPL-positive patients. The following keywords were used: antiphospholipid, Hughes syndrome, anticardiolipin, lupus anticoagulant, anti-β2-glycoprotein I, partial, complex, generalized, and idiopathic epilepsy, seizure, and convulsion. All reports published between 1971 and 2015 were included. Results Temporal lobe epilepsy is particularly prominent in many APS cases. The prevalence of epilepsy/seizures in APS patients is approximately 8%, which is nearly 10 times the prevalence of epilepsy in the general population (0.5–1%). The pathogenesis is complex and may involve micro-thrombosis and/or immune-mediated neuronal damage. The association of seizures with aPL is more significant in the presence of SLE. Seizure patients with positive aPL tend to develop thrombocytopenia and livedo racemosa more frequently than those without aPL. The presence of SLE and the presence of neurological symptoms significantly correlate with the presence of white matter changes on MRI. In contrast, the correlation between aPL positivity and the presence of white matter changes is very weak. However, MRI can be normal in more than 30–40% of patients. New MRI techniques can better elucidate the pathology of brain damage in neuro-APS. The theurapeutic management of epileptic APS patients relies on anti-epileptic treatment and anticoagulant agents when there is evidence of a thrombotic event. The anti-thrombotic benefit of hydroxychloroquine and statins is supported by several studies. Conclusions MRI remains the imaging modality of choice. aPL testing is recommended in young patients presenting with atypical seizures and multiple hyper-intensity lesions on brain MRI in the absence of other possible conditions. In the absence of consensual recommendations, the decision of lifelong anticoagulation in epileptic APS patients is discussed on a case-by-case basis. Disclosure of Interest None declared

AB0487 Antiphospholipid Syndrome and Epilepsy: Where Do We Stand?

Behcet's disease (BD) is a systemic inflammatory disorder with a diverse spectrum of clinical manifestations including mucocutaneous, ocular, vascular, gastrointestinal, musculoskeletal, and central nervous system involvement. It was first described by Professor Hulusi Behcet. The diagnosis is clinical. The prevalence of gastrointestinal manifestations of BD is variable among countries.

J. Al Saleh

Papers

Hughes syndrome and epilepsy: when to test for antiphospholipid antibodies?

Hypothyroidism determines the clinical and immunological manifestations of Arabs with lupus.

Enhancing the care of women with rheumatic diseases during pregnancy: challenges and unmet needs in the Middle East.

AB0487 Antiphospholipid Syndrome and Epilepsy: Where Do We Stand?

Intestinal Behçet's Disease