Ricard Cervera

EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs

Objectives To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations. Methods The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design. Results Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD. Conclusions Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

Association of antibodies against phospholipids with heart valve disease in systemic lupus erythematosus

A prospective echocardiographic study was carried out on 132 consecutive patients with systemic lupus erythematosus (SLE) derived from three European university medical centres. The prevalence of valvular lesions in patients with SLE was 22.7% compared with 2.9% in a control group of 68 healthy volunteers. 50 SLE patients had antibodies against phospholipids. The prevalence of valve vegetations (8/50 [16%]) and of mitral regurgitation (19/50 [38%]) was significantly higher among the SLE patients with antiphospholipids than among those without (1 and 10/82 [1.2% and 12%], respectively). During follow-up of the patients with valvular lesions, haemodynamically significant clinical valve disease developed in 6 but surgery was required in only 1; 9 had cerebrovascular occlusions; and 7 died, although no death was due directly to the cardiac involvement. Thus, valvular heart disease, particularly affecting the mitral valve, is common in patients with SLE, and the presence of antibodies against phospholipids is associated with a higher prevalence of valvular abnormalities in these patients.

Cardiac disease in systemic lupus erythematosus: prospective study of 70 patients.

A prospective two dimensional and Doppler echocardiographic study of 70 consecutive patients with systemic lupus erythematosus (SLE) and 40 controls was carried out. Forty patients (57%) were found to have echocardiographic disturbance. Valvular abnormalities were detected in 31 patients (44%) and in only two controls (5%). Mitral valve abnormalities were the most common findings (23/70 (33%)) with mild or moderate regurgitation the most frequent lesion (16% and 9% respectively). Three patients (4%) had a morphological echocardiographic pattern suggestive of non-infective verrucous vegetations affecting the mitral valve. No patient had haemodynamically significant clinical valve disease. Pericardial effusion was identified in 19 patients (27%), of whom 14 had mild and clinically silent disease. Myocardial abnormalities were found in 14 patients (20%), but clinical features of myocardial dysfunction were present in only one. Patients with antiphospholipid antibodies were found to have an increased prevalence of endocardial lesions, mainly valvular regurgitation. It is concluded that the inclusion of echocardiography in a study protocol of patients with SLE can identify an important subset of patients with cardiac abnormalities, many of which are clinically silent. In addition, the association of antiphospholipid antibodies with endocardial lesions suggests that these antibodies may have a prominent role in the pathogenetic mechanisms of heart valve disease in SLE.

The lung in the antiphospholipid syndrome

Patients with antiphospholipid syndrome (APS) may develop a broad spectrum of pulmonary disease. Pulmonary thromboembolism and pulmonary hypertension are the most common complications, but microvascular pulmonary thrombosis, pulmonary capillaritis, and alveolar haemorrhage have also been reported. Clinicians should seriously consider these types of vascular injury when evaluating patients with APS who present with dyspnoea, fever, and infiltrates on chest radiography.

Failure of intravenous immunoglobulin to prevent congenital heart block: Findings of a multicenter, prospective, observational study

OBJECTIVE Congenital heart block (CHB) is presumed to be caused by transplacental passage of maternal immunoglobulin against Ro and La ribonucleoproteins. The recurrence rate in subsequent pregnancies following the birth of a child with CHB is approximately 19%. The purpose of this study was to determine whether intravenous immunoglobulin (IVIG) therapy could prevent the development of CHB in the fetuses of high-risk pregnant women. METHODS A total of 24 pregnancies in 22 women who had a previous pregnancy in which CHB developed, were over the age of 18 years, were <12 weeks pregnant, and had anti-Ro, anti-La, or both antibodies were monitored in this multicenter, prospective, observational study. Fifteen patients received infusions of IVIG. The 9 pregnancies in the remaining 7 patients served as controls. IVIG was administered at a dose of 400 mg/kg at weeks 12, 15, 18, 21, and 24 of pregnancy. Echocardiograms were performed at least every 3 weeks from week 15 to week 30 of gestation. Electrocardiograms were obtained at birth. The outcome measure was the development of third-degree CHB detected by fetal echocardiogram. RESULTS CHB developed in 3 babies among the 15 pregnancies in the treatment group (20%) and in 1 baby among the 9 pregnancies in the control group (11%). CHB was detected at weeks 18, 23, and 26, respectively, in the 3 babies in the treated group and at week 19 in the baby in the control group. Three of the affected pregnancies ended in termination; 2 for reasons related to the fetal disease and 1 for reasons related to both maternal (severe pulmonary hypertension) and fetal disease (at 21 weeks of gestation). CONCLUSION IVIG at the dose and frequency used in this study was not effective as prophylactic therapy for CHB in high-risk mothers.

Long term outcome of catastrophic antiphospholipid syndrome survivors

Background: Catastrophic antiphospholipid syndrome (APS) is defined as life threatening multiple organ thromboses developing simultaneously or over a short period. The survival rate of catastrophic APS is about 50%, but the long term outcome of patients who survive is unknown. Objective: To determine the long term outcome of patients with catastrophic APS and provide further information on patients who survived. Patients and methods: The clinical characteristics and outcomes of 130 patients with catastrophic APS have been reported previously. Six new cases were recently added to this series. Based on these publications, the authors who reported patients who had survived were contacted. Each author was asked (a) what treatment they gave their patients after the catastrophic APS; (b) if their patients had any further thrombosis. Results: 63/136 (46%) patients died at the initial event. Of the remaining 73 patients, information was available for 58 (79%). Thirty eight (66%) patients did not develop further APS related events during an average follow up of 67.2 months. Eleven (19%) patients developed further APS related events but were still alive. No patients developed further catastrophic APS. Nine (16%) patients died: due to multiple organ failure (three patients); myelofibrosis (one); pneumonia (one); and APS related events (four). Conclusion: Sixty six per cent of patients who survive an initial catastrophic APS event remained symptom free with anticoagulation during an average follow up of 67.2 months. Twenty six per cent of the survivors developed further APS related events and the mortality rate of these patients was about 25%.

Systemic lupus erythematosus in the elderly: clinical and immunological characteristics.

Systemic lupus erythematosus (SLE) predominantly affects young women in their 20s. In 40 out of 250 (16%) patients with SLE seen in our hospital disease onset occurred after the age of 50. The interval between the time of onset and diagnosis was five years in this older group compared with three years in the younger group. Arthritis, as a first symptom, was less common in the older onset group. During the follow up a lower incidence of arthritis, malar rash, photosensitivity, and nephropathy was found in the older onset group. In contrast, this group showed an increased incidence of myositis. High titres of anti-dsDNA tended to occur less often and the incidence of anti-Ro antibodies was lower in the older onset group. These features seem to distinguish patients with older onset SLE as a particular subset.

The central nervous system in systemic lupus erythematosus

SummaryManagement of central nervous system (CNS) involvement is one of the most challenging problems in systemic lupus erythematosus. This article reviews the spectrum of CNS manifestations present in this disease, their diagnosis and pathogenesis, as well as an approach to their treatment and prognostic implications.

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.

Isotype distribution of anticardiolipin antibodies in systemic lupus erythematosus: prospective analysis of a series of 100 patients.

A prospective study of IgG and IgM isotypes of anticardiolipin antibodies (aCL) in a series of 100 patients with systemic lupus erythematosus was carried out. To determine the normal range of both isotype titres a group of 100 normal control serum samples was studied and a log-normal distribution of IgG and IgM isotypes was found. The IgG anticardiolipin antibody serum was regarded as positive if a binding index greater than 2.85 (SD 3.77) was detected and a binding index greater than 4.07 (3.90) was defined as positive for IgM anticardiolipin antibody. Twenty four patients were positive for IgG aCL, 20 for IgM aCL, and 36 for IgG or IgM aCL, or both. IgG aCL were found to have a significant association with thrombosis and thrombocytopenia, and IgM aCL with haemolytic anaemia and neutropenia. Specificity and predictive value for these clinical manifestations increased at moderate and high anticardiolipin antibody titres. In addition, a significant association was found between aCL and the presence of lupus anticoagulant. Identification of these differences in the anticardiolipin antibody isotype associations may improve the clinical usefulness of these tests, and this study confirms the good specificity and predictive value of the anticardiolipin antibody titre for these clinical manifestations.