OBJECTIVE\nTo develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE).\n\n\nMETHODS\nAn international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests.\n\n\nRESULTS\nCase definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed.\n\n\nCONCLUSION\nThe American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the clinical association of antiphospholipid autoantibodies (aPL) with a syndrome of hypercoagulability that can affect any blood vessel, irrespective of type or size. Involvement of larger vessels, such as arteries or veins, manifests in the form of thrombosis or embolism, whereas involvement of smaller vessels, including capillaries, arterioles, and venules, manifests as thrombotic microangiopathy. Virtually any organ in the body, including the kidney, can be affected. Here, we review the basic principles and recent advances in our understanding of APS, and discuss the broad spectrum of renal diseases that have been observed in association with this syndrome. We also discuss the impact that APS may have on pre-existing renal disease as well as current recommendations for treatment of APS.

The antiphospholipid syndrome.

VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

ACOG practice bulletin: Clinical management guidelines for obstetrician-gynecologists

Background: Antimalarial drugs (AM), chloroquine (CQ) and hydroxychloroquine (HCQ), are frequently withdrawn in lupus patients with either severe or remitting disease. However, additional effects beyond immunomodulation have been recently described. Our aim was to analyse all the published evidence of the beneficial and adverse effects of AM therapy in SLE. Methods: Systematic review of the English literature between 1982-2007 using MEDLINE and EMBASE. Randomised controlled trials (RCTs) and observational studies were selected. Case reports were excluded except for toxicity reports. The GRADE system was used to analyse the quality of the evidence. Results: 95 articles were included in the systematic review. We have found high evidence that AM prevent lupus flares and increase long-term survival of SLE patients; moderate evidence of protection against irreversible organ damage, thrombosis and bone mass loss .Toxicity related to AM is infrequent, mild and usually reversible, with HCQ having a safer profile. In pregnant women, we have found high evidence that AM, particularly HCQ, decrease lupus activity without harming the baby. On the other hand, evidence supporting an effect on severe lupus activity, lipid levels and subclinical atherosclerosis was weak. Individual papers suggest effects in preventing the evolution from SLE-like to full-blown SLE, influencing vitamin D levels and protecting lupus patients against cancer. Conclusion: Given the broad spectrum of beneficial effects and the safety profile, HCQ should be given to most patients with SLE during the whole course of the disease, irrespective of its severity, and be continued during pregnancy.

https://ard.bmj.com/content/annrheumdis/early/2009/08/28/ard.2008.101766.full.pdf

Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review

SUMMARY The objective was to determine whether the frequency of flare in systemic lupus erythematosus (SLE) patients is increased during pregnancy and the pucrpcrium. Seventy-eight pregnancies in 68 SLE patients attending the lupus pregnancy clinic, at St Thomas' Hospital, during the last 5 yr were included. The pregnancy period and 8 weeks post-delivery were considered. This group was compared with a control group of 50 consecutive, non-pregnant, age-matched SLE patients attending our weekly lupus clinic. Additionally, 43 of the pregnant patients carried on attending the lupus clinic for the year after puerperium, and their course was compared with themselves during pregnancy. SLE activity was assessed using the Lupus Activity Index (LAI) score. An increase St0.26 in the score was considered as a flare of the disease. Pregnancy and control groups were homogeneous for age, race, disease duration and distribution of autoantibodie s. Sixty-five per cent of the patients flared during pregnancy and/or the puerperium and 42% flared in the control group {P = 0.015).The rates of flare per patient/month were 0.082 ± 0.004 for the pregnancy group and 0.039 ±0.003 for the control group (P < 0.001). The 43 patients whose course was controlled after the puerperium flared more frequently during pregnancy than thereafter (McNemar test, P = 0.003). The rates of flare per patient/month were 0.093 ± 0.006 during pregnancy and the puerperium, and 0.049 ± 0.004 after the puerperium (P «= 0.0015). Kidney and central nervous system involvement was not different between the pregnancy and control groups. In terms of frequency of flares, there was no difference in any of the groups between patients taking and not taking steroids. We conclude that SLE tends to flare during pregnancy. Flares are maximal during the second and third trimester and the puerperium. Flares are not more severe than in non-pregnant patients, and most of the flares can be managed conservatively. Prednisolone does not prevent flares. IN recent years, pregnancy has become an important management focus in systemic lupus erythematosus (SLE) patients. The fertility rate in SLE women is normal [1], improvement in patients' care has provided longer periods of remission and a better quality of life, and the advent of combined obstetric-medical clinics has ameliorated the course and outcome of pregnancy. Clearly, the relationships between SLE and pregnancy are complex, and increasing evidence points to an important role of sex hormones in immunity. Increased prolactin levels have been demonstrated in mice and humans during SLE flares [2-4]. Changes in sex hormone levels during pregnancy and the puerperium are more apparent than in any other period of life. During the last 5 yr, we have prospectively followed a large number of patients with SLE, primary antiphospholipid syndrome and other autoimmune conditions, who have attended our lupus pregnancy clinic at St Thomas' Hospital. In order to assess the interaction of pregnancy and lupus, we have studied 78 pregnancies in SLE patients. We include in our data our experience of lupus in the puerperium.

Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies

Objective To study the maternal and fetal outcome in treated antiphospholipid syndrome (APS) pregnancies. Methods Sixty pregnancies in 47 APS patients (11 primary and 36 secondary) were followed in a multidisciplinary clinic. Patients testing antiphospholipid antibody positive and having a history of recurrent miscarriages were treated with low-dose aspirin (75 mg) daily. Patients with APS and a previous history of thrombotic events were treated with subcutaneous unfractionated or low molecular weight heparin and low-dose aspirin (75 mg) daily. Results The live birth rate increased from 19% of their previous non-treated pregnancies to 70% despite a high incidence of obstetric and fetal complications: pre-eclampsia (18%), prematurity (43%), fetal distress (50%) and intrauterine growth retardation (31%). Two predictors of fetal outcome were observed: the previous obstetric history and the presence of thrombocytopenia. Seven pregnancies (12%) were complicated by thrombotic events during pregnancy or during the puerperium. There were no thrombotic events in those receiving a low molecular weight heparin regimen. Conclusion Close obstetric monitoring by a multidisciplinary team and the use of antithrombotic therapy was effective in reducing the fetal wastage in APS pregnancies despite a high incidence of obstetric and fetal complications.

A study of sixty pregnancies in patients with the antiphospholipid syndrome.

Venous thromboembolic disease remains the commonest cause of maternal death. The management of thromboprophylaxis in high risk women during pregnancy is contentious. Low molecular weight heparins (LMW) have theoretical advantages compared with unfractionated heparin and warfarin but have been poorly studied in pregnancy. We report on the use of LMW heparin (Fragmin) as thromboprophylaxis in thirty four high risk pregnancies. All the women had a previous thrombosis or a thrombosis in their current pregnancy +/- a recognised thrombophilic state (eleven had the antiphospholipid syndrome). Fragmin was given subcutaneously to maintain trough anti-Xa activity of 0.15-0.2 U/ml and 2 h post injection levels of 0.4-0.6 U/ml. The levels were checked monthly during pregnancy. Most women required 5,000U Fragmin once daily during the first trimester unless they were greater than 100 kg at the start of pregnancy. The mean time for dosage increase was 20.5 week (S.D. 8.2). 26/34 pregnancies (76%) required 5,000 twice daily at the end of pregnancy. Epidural anaesthesia was managed by omitting Fragmin dose or inserting the needle 6 hours after the previous Fragmin injection. There were no thromboembolic events thrombocytopenias or excessive haemorrhage. One woman had osteoporotic vertebral collapse post partum, she had no other risk factors for osteoporosis. LWM heparin (Fragmin) appears to be efficacious in preventing recurrent thromboembolic disease in pregnant women at high risk, but it is notable that osteoporotic fractures occurred post partum in one woman. Further trials are required to determine optimal dosage and safety.

Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies

OBJECTIVE: To study maternal and fetal outcome of pregnancy in patients with lupus who were exposed to hydroxychloroquine (HCQ). METHODS: The case records of women (n = 33) exposed to HCQ during their pregnancies (n = 36) and of 53 control patients from a single lupus pregnancy centre were reviewed to determine lupus activity, obstetric experience, and infant outcome. RESULTS: HCQ was not apparently teratogenic. Lupus activity and obstetric outcome in the two groups were similar. CONCLUSION: HCQ continuation is probably safe during pregnancy in patients with lupus, but there is no obvious advantage in commencing treatment.

https://ard.bmj.com/content/annrheumdis/55/7/486.full.pdf

N. M. M. Buchanan

Papers

Increased rate of lupus flare during pregnancy and the puerperium: a prospective study of 78 pregnancies

A study of sixty pregnancies in patients with the antiphospholipid syndrome.

Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies

Hydroxychloroquine and lupus pregnancy: review of a series of 36 cases.

Obstetric outcome in systemic lupus erythematosus