Elisabeth J. M. Zirkzee

Neuropsychiatric manifestations in patients with systemic lupus erythematosus: epidemiology and radiology pointing to an immune-mediated cause

Background Different pathogenetic pathways have been proposed for neuropsychiatric (NP) manifestations in systemic lupus erythematosus (SLE). Objective To describe the patient characteristics of a large cohort of patients with SLE with NP manifestations (NPSLE) in a single centre and to review whether these and other data are compatible with immune-mediated mechanisms. Methods A total of 212 patients were identified from MRI scans of the brain ordered for suspected NPSLE. Data were collected from the medical records. NP syndromes were classified according to the American College of Rheumatology (ACR) nomenclature and case definitions. Results 155 patients fulfilled the criteria for SLE. In 102 patients NP manifestations were attributed to SLE itself (primary NPSLE) whereas, in the remaining patients, the NP symptoms were due to other causes. The median age at the time of SLE diagnosis in patients with primary NPSLE was 27.5 years and the median duration prior to NPSLE was 2.8 years. Forty patients (39%) had a NP manifestation in the first year of the disease. Cerebrovascular disease, cognitive dysfunction, seizures and headache were the most prevalent syndromes. In 47% of patients with primary NPSLE the MRI scan of the brain showed no abnormalities. Conclusions Most NP manifestations in SLE occur early in the disease. This finding, as well as data from quantitative imaging studies and recent pathological studies, point to an immune-mediated pathogenesis.

Prospective Study of Clinical Phenotypes in Neuropsychiatric Systemic Lupus Erythematosus; Multidisciplinary Approach to Diagnosis and Therapy

Objective. To describe clinical phenotypes in neuropsychiatric systemic lupus erythematosus (NPSLE). Methods. Data were prospectively collected in the Leiden NPSLE referral clinic, where patients suspected of having NPSLE are assessed in a standardized multidisciplinary manner. In consensus meetings, all medical specialists agreed on therapeutic strategy based on the suspected pathogenetic mechanism of NPSLE in the individual patient. An algorithm illustrates the process of decision-making during the consensus meeting. Clinical phenotypes are described, classified by pathogenetic mechanism. Results. One hundred consecutive patients were evaluated, of whom 71 had SLE (29 patients did not fulfill ≥ 4 American College of Rheumatology criteria) and 46 had NPSLE. Primary NPSLE was diagnosed in 38 patients (53%) and could be differentiated in 21 patients (55%) with inflammatory NPSLE who were advised on immunosuppressive therapy, 12 patients (32%) with ischemic NPSLE who were advised on anticoagulant therapy, and 5 patients (13%) with undefined NPSLE who were advised symptomatic treatment only. Cognitive dysfunction and higher level of disease activity were associated with inflammatory NPSLE. Although presence of immunoglobulin G anticardiolipin antibodies and abnormalities on magnetic resonance imaging (MRI) were associated with ischemic NPSLE, abnormalities on MRI lacked specificity to distinguish phenotypes. A history of renal disease and use of corticosteroids were associated with secondary NPSLE. Conclusion. We describe multidisciplinary consensus as a standard for diagnosing and defining phenotypes in NPSLE. These phenotypes show specific characteristics, which can be used to support diagnosis and guide therapeutic decisions. Clinical phenotyping and selection of patients becomes increasingly important when advances in experimental science lead to new targets for therapy in NPSLE.

Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most common pharmacological treatments used in NPSLE, based on both a literature search and our expert opinion. The extent to which new drugs in the advanced development of SLE, or the blockade of new targets, may impact future treatment of NPSLE will also be discussed.

Needs and preferences regarding health care delivery as perceived by patients with systemic sclerosis

This study aims to examine the needs and preferences regarding the delivery of health care services and information provision and their determinants in patients with systemic sclerosis (SSc). A questionnaire was sent to 77 SSc outpatients, comprising 27 items on health care needs within the domains physical, psychological, social support, employment/daily activities, or other health problems and 13 items on information needs. Moreover, the patients’ preferences regarding the provision of health care services and information were listed. Additional assessments included sociodemographic characteristics, physical functioning (SSc Health Assessment Questionnaire), and quality of life (SF-36). Sixty-four patients (83%) returned the questionnaire. Twenty-six patients (41%) reported one or more unmet health care needs, with the highest proportions of patients with unmet needs seen in the physical (28%) and psychological (20%) domain. The highest percentages of patients with information needs were observed for medical subjects (20–28%). A lower mental component summary scale score and younger age were associated with the presence of at least one health care need in the psychological domain. Worse physical functioning, a diagnosis of diffuse SSc and having a partner were associated with higher information need score. A yearly, standardized multidisciplinary assessment program was most frequently mentioned as a preferred, but not yet existing health care model (59%) and the rheumatologist as a preferred source of information supply (75%). Unmet health care and information needs are common among SSc patients. To improve SSc health care, more attention should be paid to health care services for specific physical and psychological problems and medical information supply by the rheumatologist. In addition, the development of new models of care, such as a yearly, standardized multidisciplinary diagnostic program seems warranted.

Measuring educational needs among patients with systemic lupus erythematosus (SLE) using the Dutch version of the Educational Needs Assessment Tool (D-ENAT).

Objective The Educational Needs Assessment Tool (ENAT) was developed in the United Kingdom (UK) to systematically assess the educational needs of patients with rheumatic diseases. The aim of the present study was to describe the educational needs of Dutch patients with systemic lupus erythematosus (SLE) by means of a Dutch version of the ENAT (D-ENAT). Methods The D-ENAT was sent to a random sample of 244 SLE patients registered at the outpatient clinic of a university hospital. D-ENAT consists of 39 items in seven domains. The D-ENAT domain scores range from 0–16 to 0–28 (higher scoring equals higher educational needs) depending of the number of items in the domain. A total D-ENAT score (0–156) is calculated by summing all 39 items. In addition, age, disease duration, gender, educational level, present information need (yes/no) and the extent of information need (1–4: nothing–everything) were recorded. Univariate regression analysis was used to examine the D-ENAT’s potential determinants. Results The response rate was 122 out of 244 (50%). The mean (% of maximum score) educational needs scores were 56% for ‘D-ENAT total score’, 62% for ‘Self-help measures’, 60% for ‘Disease process’, 58% for ‘Feelings’, 56% for ‘Treatments’, 50% for ‘Movement’, 49% for ‘Support systems’ and 46% for ‘Managing pain’. Being female was significantly associated with higher scoring on the D-ENAT total score (β 23.0; 95% CI 5.9, 40.3). Conclusion SLE patients demonstrated substantial educational needs, especially in the domains: ‘Self-help measures’, ‘Disease process’ and ‘Feelings’. The validity and practical applicability of the D-ENAT to make an inventory of SLE patients’ educational needs requires further investigation.

Cluster Analysis of an Array of Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

Cluster Analysis of an Array of Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

FRI0402 Cluster Analysis of an ARRAY of Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus (NPSLE)

Background Neuropsychiatric complaints in systemic lupus erythematosus (SLE) patients present a challenge to the clinician due to the lack of specific diagnostic tests. To date, reports on the associations between specific autoantibodies and distinct NPSLE syndromes are conflicting. New multiplex technologies for the detection of autoantibodies have emerged in the last years and it has been noted that they might be helpful diagnosing SLE. We hypothesized that a cluster of autoantibodies could be associated with a specific NPSLE syndrome or with focal or diffuse NPSLE manifestations. Objectives Our aim was to analyse a microarray kit of autoantibodies and the antiphospholipd (aPL) autoantibodies status in a prospective well-defined cohort of NPSLE patients. Furthermore, we aimed to identify the relationship between clusters of these autoantibodies and NPSLE syndromes. Methods We included 133 SLE patients with neuropsychiatric symptoms attending the Leiden NPSLE clinic. The serum samples of all patients were analysed using the FIDIS connective profile kit (Theradiag), a semi-quantitative homogeneous fluorescent based microparticles immunoassay for the simultaneous detection of anti-SSA, anti-SSB, anti-TRIM21, anti-Sm, anti-Sm/RNP, anti-Jo1, anticentromere, anti-Ribosomal-P, anti-dsDNA, anti-Histone, anti-PmScl and anti-PCNA. Furthermore, anticardiolipin (aCL) IgG and IgM antibodies and lupus anticoagulant (LAC) status were available from the clinical evaluation. We performed hierarchical cluster analyses using R software (version 3.0.2) on 1. all autoantibodies from the microarray kit and 2. all autoantibodies from the microarray kit plus the aPL antibodies, and we analysed their associations with NPSLE diagnosis, the American College of Rheumatology (ACR) NPSLE syndromes and groups of focal/diffuse NPSLE manifestations. Statistical significance was defined as p<0.05. Results In 81 (61%) patients a diagnosis of NPSLE was established. In the first cluster analysis we identified three clusters of autoantibody profiles (No specific autoantibodies, DNA/Ro/La and Sm/RNP), however an association with NPSLE diagnosis or with NPSLE syndromes was not found. In the second cluster analysis, after inclusion of aPL antibodies, we identified four clusters of autoantibody profiles (1 - No specific autoantibodies, 2 - DNA/Ro/La, 3 - Sm/RNP, 4 - DNA/LAC/aCL). In this case the frequency of major focal syndromes in cluster 4 (DNA/LAC/aCL) was significantly greater than in other clusters (p=0,008). With respect to the individual NPSLE syndromes we found an association for cerebrovascular disease (p=0,002), seizure (p=0,016) and myelopathy (p=0,019) with cluster 4 (DNA/LAC/aCL). Conclusions Our study failed to show an association between autoantibodies retrieved by multiplex testing or clusters of these autoantibodies and NPSLE. We have found an association between a cluster of autoantibodies (DNA/LAC/aCL) and major focal NPSLE syndromes. From all the autoantibodies used in daily practice, only LAC and aCL are indispensable in the NPSLE diagnostic work-up. References To CH, Petri M. Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?. Arthritis Rheum. 2005;52:4003-10. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3289

SAT0218 Clinical phenotypes in NPSLE; data from the leiden NPSLE clinic

Background Therapeutic decisions in NPSLE are made on a patient-by-patient basis guided by the severity of symptoms and the suspected underlying pathogenetic mechanism. Evidence for therapeutic decisions is scanty as is data on clinical phenotypes in NPSLE. Objectives To describe clinical phenotypes per suspected pathogenetic mechanism in NPSLE. Methods The Leiden NPSLE clinic is a tertiary referral centre that evaluates patients suspected of NPSLE and leads to a prospectively collected database. Standardized evaluation including serological, imaging, clinical and neuropsychological testing is followed by a multidisciplinary consensus meeting. Diagnosis and therapeutic decisions based on the suspected pathogenetic mechanism are made by consensus of all participating medical specialists. We describe clinical phenotypes with sociodemographic and clinical characteristics per pathogenetic mechanism. Results One hundred consecutive patients were evaluated in the Leiden NPSLE clinic. Three clinical phenotypes could be differentiated in primary NPSLE; 55% inflammatory NPSLE in patients who were advised immunosuppressive therapy, 32% ischemic NPSLE in patients who were advised anticoagulant therapy and 13% undefined NPSLE in patients who were advised symptomatic treatment. Age and disease duration in each group were 42 and 8, 47 and 9, 45 and 2 years, respectively. MRI abnormalities were present in 72%, 100% and 80% of respective phenotypes and SLEDAI scores were 10, 7 and 6. IgG anticardiolipin antibodies and lupus anticoagulans were present in respectively 33% and 48% of inflammatory and in 58% and 67% of ischemic NPSLE and were absent in undefined NPSLE patients. Twenty-five percent of ischemic NPSLE-patients reported transient ischemic attacks oppose to none in other groups. Cognitive dysfunction was present in 62% of inflammatory, 50% of ischemic and 20% of undefined NPSLE patients. As a fourth group secondary NPSLE was recognized in 11% of patients, in this group 75% of patients had a renal disorder and 88% of patients used steroids. Conclusions To the best of our kowledge this is the first prospective evaluation of a standardized multidisciplinary assessment of neuropsychiatric symptoms in SLE-patients. A remarkable feature of inflammatory NPSLE is a high SLEDAI and high prevalence of cognitive dysfunction. Whereas in ischemic NPSLE IgG anticardiolipin antibodies and lupus anticoagulans are highly prevalent and patients are distinguished by the report of TIA’s, also in this group all patients had abnormalities on MRI of the brain. Disclosure of Interest None Declared