Michelle Petri

Cardiac involvement in systemic lupus erythematosus

Pericarditis is the most common cardiac abnormality in systemic lupus erythematosus (SLE) patients, but lesions of the valves, myocardium and coronary vessels may all occur. In the past, cardiac manifestations were severe and life threatening, often leading to death. Therefore, they were frequently found in post-mortem examinations. Nowadays cardiac manifestations are often mild and asymptomatic. However, they can be frequently recognized by echocardiography and other noninvasive tests. Echocardiography is a sensitive and specific technique in detecting cardiac abnormalities, particularly mild pericarditis, valvular lesions and myocardial dysfunction. Therefore, echocardiography should be performed periodically in SLE patients. Vascular occlusion, including coronary arteries, may develop due to vasculitis, premature atherosclerosis or antiphospholipid antibodies associated with SLE. Premature atherosclerosis is the most frequent cause of coronary artery disease (CAD) in SLE patients. Efforts should be made to control traditional risk factors as well as all other factors which could contribute to atherosclerotic plaque development.

HOPKINS LUPUS PREGNANCY CENTER: 1987 TO 1996

This article discusses lupus and pregnancy from experiences at the Hopkins Lupus Pregnancy Center. This center has made important strides in the understanding of lupus flares, maternal morbidity, and causes of preterm birth and pregnancy loss in lupus pregnancy.

Hopkins Lupus Cohort: 1999 Update

The Hopkins Lupus Cohort is a decade-long prospective study, now numbering 800 patients with systemic lupus erythematosus. In this article, predictors of disease activity, disease damage (including accelerated atherosclerosis and antiphospholipid antibody syndrome) and health status are reviewed.

Cyclophosphamide for lupus during pregnancy.

Severe systemic lupus erythematosus often requires the use of cyclophosphamide in women of reproductive age. As cyclophosphamide is generally avoided during pregnancy because of its teratogenic risk, its impact on fetal survival is poorly understood. This is a case series of lupus patients exposed to cyclophosphamide during pregnancy. We reviewed pregnancies in patients with lupus seen at a large university hospital between October 1986 and September 2003. The pregnancies were evaluated prospectively for cyclophosphamide exposure, lupus activity, and fetal outcome. Comparison was made between pregnancies with severe lupus requiring cyclophosphamide and those that did not. We identified four pregnancies with cyclophosphamide exposure. Two pregnancies were inadvertently exposed to cyclophosphamide early in the first trimester; both resulted in first trimester miscarriages. Two patients were administered cyclophosphamide for severe lupus nephritis and thrombocytopenia during the second trimester. Soon after the administration of cyclophosphamide, both pregnancies ended with fetal demise. Pregnancies exposed to cyclophosphamide for severe lupus flare resulted in a higher rate of fetal losses than pregnancies with severe lupus but not requiring the drug (100% versus 31.25%). In conclusion we present four pregnancies exposed to cyclphosphamide, each ending with pregnancy loss. Based on our experience, the survival of the fetus is strongly in doubt when cyclophosphamide is required to treat lupus in the mother.

Systemic Lupus Erythematosus and Pregnancy

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong female predilection. Pregnancy remains a commonly encountered but high-risk situation in this setting. Both maternal and fetal mortality and morbidity are still significantly increased despite improvements in outcomes. Maternal morbidity includes higher risk of disease flares, preeclampsia and other pregnancy-related complications. Fetal issues include higher rates of preterm birth, intrauterine growth restriction, and neonatal lupus syndromes. Treatment options during pregnancy are also limited and maternal benefit has to be weighed against fetal risk. A coordinated approach, with close monitoring by a multidisciplinary team, is essential for optimal outcomes.

Lupus and pregnancy

Systemic lupus erythematosus (SLE) disproportionately affects women in their reproductive age years. Pregnancy in this systemic autoimmune disease has long been associated with poor obstetric outcomes. However, the frequency of pregnancy loss in lupus has dropped to a level commensurate with that of the general US population. The outcomes of lupus pregnancies are better if conception is delayed until the disease has been inactive for at least 6 months, and the medication regimen has been adjusted in advance. Pregnancy in lupus is prone to complications, including flares of disease activity during pregnancy or in the postpartum period, preeclampsia, miscarriage, stillbirth, intrauterine growth retardation, and preterm birth. Active lupus nephritis poses the greatest risk. The recognition of a lupus flare during pregnancy may be difficult because the signs and symptoms may mimic those of normal pregnancy. Monitoring should include baseline and monthly laboratory tests, serial ultrasonography, fetal surveillance tests, and fetal m-mode echocardiography for mothers with SS-A (Ro) or SS-B (La) antibodies. In the absence of any signs or symptoms of active SLE, affected patients require no specific treatment during pregnancy. If hydroxychloroquine was in use before conception, it should be maintained throughout pregnancy. If a woman with SLE has antiphospholipid antibodies, prophylactic treatment with aspirin and/or low-molecular weight heparin is indicated to prevent fetal loss. Lupus flares during pregnancy are generally treated with hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone, and azathioprine. High-dose prednisone and cyclophosphamide are reserved for severe lupus complications but are associated with significant pregnancy-related complications and poor obstetrical outcomes.Systemic lupus erythematosus (SLE) disproportionately affects women in their reproductive age years. Pregnancy in this systemic autoimmune disease has long been associated with poor obstetric outcomes. However, the frequency of pregnancy loss in lupus has dropped to a level commensurate with that of the general US population. The outcomes of lupus pregnancies are better if conception is delayed until the disease has been inactive for at least 6 months, and the medication regimen has been adjusted in advance. Pregnancy in lupus is prone to complications, including flares of disease activity during pregnancy or in the postpartum period, preeclampsia, miscarriage, stillbirth, intrauterine growth retardation, and preterm birth. Active lupus nephritis poses the greatest risk. The recognition of a lupus flare during pregnancy may be difficult because the signs and symptoms may mimic those of normal pregnancy. Monitoring should include baseline and monthly laboratory tests, serial ultrasonography, fetal surveillance tests, and fetal m-mode echocardiography for mothers with SS-A (Ro) or SS-B (La) antibodies. In the absence of any signs or symptoms of active SLE, affected patients require no specific treatment during pregnancy. If hydroxychloroquine was in use before conception, it should be maintained throughout pregnancy. If a woman with SLE has antiphospholipid antibodies, prophylactic treatment with aspirin and/or low-molecular weight heparin is indicated to prevent fetal loss. Lupus flares during pregnancy are generally treated with hydroxychloroquine, low-dose prednisone, pulse intravenous methylprednisolone, and azathioprine. High-dose prednisone and cyclophosphamide are reserved for severe lupus complications but are associated with significant pregnancy-related complications and poor obstetrical outcomes. Target Audience: Obstetricians and Gynecologists and Family Physicians Learning Objectives: After completing the CME activity, physicians should be better able to provide preconception counseling to a woman with lupus, differentiate signs of a lupus flare from symptoms of pregnancy, differentiate preeclampsia from a flare of lupus nephritis, and differentiate the serious medical complications of pregnancy in a lupus patient.

Clinical features of systemic lupus erythematosus

Major findings in the understanding of the epidemiology of systemic lupus erythematosus and in the description and understanding of its presentation and course in individual organ systems are reviewed. The role of serologic tests as correlates of disease activity remains controversial. No consensus has been reached on the association of either corticosteroid dose or of antiphospholipid antibodies with avascular necrosis of bone. Multiple rare presentations of cutaneous lupus have been reviewed during the past year. The role of hormones in the activity of lupus and the use of hormonal agents in the treatment of lupus are rapidly expanding and contentious areas of research. Cognitive function deficit continues to be an area of great interest, with studies differing on whether psychiatric disorders or organic lupus (or both) are responsible. Finally, fatigue and the potential role of fibromyalgia as an explanation for “lupus fatigue,” are of major interest.

Predictors of incident depression in systemic lupus erythematosus

Objective. Findings from previous studies of predictors of depression among patients with systemic lupus erythematosus (SLE) have been inconsistent. The aim of our study was to identify risk factors that preceded incident depression based on a large, closely followed longitudinal cohort. Methods. Data regarding 1609 patients with SLE in the Hopkins Lupus Cohort who had no history of depression prior to cohort entry were analyzed. Demographic variables, SLE manifestations, laboratory tests, physician’s global assessment, Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), cumulative organ damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and onset of depression were recorded at enrollment and each quarterly visit. Rates of incident depression were calculated overall, and in subgroups defined by demographic and clinical variables. Adjusted estimates of association were derived using pooled logistic regression. Results. The incidence of depression was 29.7 episodes per 1000 person-years. In the multivariable analysis, these variables remained as independent predictors of incident depression: recent SLE diagnosis, non-Asian ethnicity, disability, cutaneous activity, longitudinal myelitis, and current prednisone use of 20 mg/day or higher. Global disease activity (SELENA-SLEDAI) was not a significant predictor after controlling for prednisone use. Conclusion. Depression in SLE is multifactorial. Higher-dose prednisone (≥ 20 mg daily) is 1 important independent risk factor. Global disease activity is not a risk factor, but cutaneous activity and certain types of neurologic activity (myelitis) are predictive of depression. The independent effect of prednisone provides clinicians with an additional incentive to avoid and reduce high-dose prednisone exposure in SLE.

1998 UPDATE ON ANTIPHOSPHOLIPID ANTIBODIES

The field of antiphospholipid antibodies continues to evolve, with major contributions from both clinical research and laboratory studies. Antiphospholipid antibodies remain one of the more common causes of acquired hypercoagulability, both in patients with systemic lupus erythematosus and in patients who have no known connective tissue disease. In recent years, great progress has been made in identifying the protein targets. In addition, knowledge of the clinical syndrome that we call antiphospholipid antibody syndrome has also progressed. Finally, new insights into treatment continue to be gained from clinical trails.

Gene Expression and Pharmacodynamic‐Induced Changes in 1,760 SLE Patients from Two Phase III Trials of B Cell Activating Factor Blockade with Tabalumab

To characterize baseline gene expression and pharmacodynamically induced changes in whole blood gene expression in 1,760 systemic lupus erythematosus (SLE) patients from 2 phase III, 52‐week, randomized, placebo‐controlled, double‐blind studies in which patients were treated with the BAFF‐blocking IgG4 monoclonal antibody tabalumab.