Evaluation of systemic lupus erythematosus activity during pregnancy

Due to our increasing knowledge on the pathophysiological basis of autoimmunity and the development of combined medical-obstetric clinics, pregnancy is becoming common among women with systemic lupus erythematosus (SLE). However, whether lupus worsens during pregnancy continues to be a controversial issue. SLE assessment during pregnancy is sometimes difficult due to physiological changes during this period, and common tools for measuring lupus activity during pregnancy were not available until recently. Several lupus activity scales in common use have been adapted for pregnancy [systemic lupus erythematosus in pregnancy activity index (SLEPDAI), modified lupus activity measurement (m-SLAM) and lupus activity index in pregnancy (LAI-P)]. All of them take into account the influence of pregnancy on clinical manifestation and common biochemical tests. LAI-P also accounts for specific manifestations of antiphospholipid syndrome in order not to score them as due to SLE activity. LAI-P has recently been validated for use in SLE pregnancy and could be used in future studies. However, daily assessment and management of individual pregnant women with lupus still relies on the clinical skills of attending physicians.     

New-onset systemic lupus erythematosus during pregnancy

Few studies have been published focusing on the clinical features of new-onset systemic lupus erythematosus (SLE) during pregnancy. This study examined the clinical characteristics of SLE during pregnancy or puerperium. The clinical characteristics and serological parameters of 48 patients with onset of SLE during pregnancy were retrospectively compared with those of age-matched new-onset SLE patients who were diagnosed in a period of more than 12 months without pregnancy (n?=?65) and age-matched preeclampsia patients (n?=?48). SLE tended to occur during the first and second trimesters (33 and 42 %, respectively). Lupus nephritis (LN) and severe thrombocytopenia were more commonly seen in new-onset SLE during pregnancy than in patients without pregnancy (68.8 vs 35.4 % and 25 vs 9.2 %, respectively, p?<?0.05). However, pregnant patients had lower frequency of fever, arthritis, arthralgia, alopecia, oral ulcer, and hypocomplementemia than the nonpregnant controls (p?<?0.05). Compared to LN patients without pregnancy (n?=?23), LN patients with pregnancy (n?=?33) had more prominent proteinuria and nephrotic syndrome (p?<?0.05). On the other hand, when compared to patients with preeclampsia, patients with new-onset SLE during pregnancy had early onset of symptoms during gestation and were characterized by presence of fever, malar lesion, autoantibodies, hypocomplementemia, hyperuricemia, active urinary sediment, and multi-organ involvement. In conclusion, patients with their first onset of lupus during pregnancy generally have more severe disease with higher prevalence of renal and platelet involvement.     

Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale

OBJECTIVE: To validate the Lupus Activity Index in Pregnancy (LAI-P) scale as a diagnostic tool for lupus flares during pregnancy and the puerperium. METHODS: The LAI-P is a modified activity scale specific for pregnancy. Thirty-eight pregnant women with systemic lupus erythematosus (SLE) were prospectively followed in 3 clinics specific for lupus in pregnancy. On each visit, LAI-P was calculated. A modified physician global assessment (m-PGA) scale was used as gold standard (0 = no activity, 1 = mild-moderate activity, 2 = severe activity). A change > or = 0.25 in LAI-P was predefined as a flare according to previous studies in nonpregnant patients. For the purposes of the study, each visit was considered as an independent case. RESULTS: During the study period, 158 visits took place for a total 621 patient-weeks. Sensitivity to change was high (standardized response mean for LAI-P = 1.6). We found a significant association between LAI-P and m-PGA (P < 0.002 in all regression models performed). Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.98, 0.88, and 0.99. Positive and negative likelihood ratios were 49 and 0.07, respectively. CONCLUSIONS: LAI-P has a high sensitivity to changes in lupus activity, a significant correlation with m-PGA, and high sensitivity, specificity, predictive values, and likelihood ratios for diagnosing SLE flares during pregnancy and the puerperium.     

Steroid hormones and disease activity during pregnancy in systemic lupus erythematosus

OBJECTIVES: To analyze the variation of steroid hormone levels during pregnancy in patients with systemic lupus erythematosus (SLE). Moreover, to investigate whether, during gestation, there is any relationship between steroid concentration and SLE activity. METHODS: Seventeen consecutive pregnant SLE patients and 8 matched healthy pregnant controls were studied prospectively. Disease activity was evaluated by European Consensus Lupus Activity Measure (ECLAM) score modified for pregnancy. The following hormones were evaluated: testosterone, 17beta-estradiol (estradiol), cortisol, dehydroepiandrosterone sulfate (DHEAS), and progesterone. RESULTS: Disease activity score significantly varied during pregnancy and postpartum (P< 0.05), being decreased in the third trimester and increased in the second trimester and postpartum. Serum levels of all steroids varied significantly during pregnancy and the postpartum period both in patients and in healthy subjects. In SLE patients, estradiol, progesterone, and DHEAS concentrations were found to be significantly reduced compared with controls. Serum level profiles of estradiol and progesterone were different from those observed in controls. No differences in the steroid levels were observed between patients taking prednisone 5 mg/day, apart from cortisol, which was, as expected, lower in the latter group. CONCLUSIONS: The major hormonal alteration observed during pregnancy in SLE patients was an unexpected lack of estrogen serum level increase, and, to a lesser extent, progesterone serum level increase, during the second and-even more-the third trimester of gestation. This lack of increase probably was due to placental compromise. Therefore, these steroid hormone variations may result in a lower humoral immune response activation, probably related to a change in the estrogen/androgen balance, that in turn could account for the decrease in disease activity observed during the third trimester in pregnant SLE patients.     

Organ-specific systemic lupus erythematosus activity during pregnancy is associated with adverse pregnancy outcomes

Systemic lupus erythematosus (SLE) is a disease of reproductive-age women, and thus questions regarding how disease influences pregnancy outcomes arise. We investigated whether five specific types of SLE activity during the 6 months before conception or during pregnancy (nephritis, cytopenias, skin disease, arthritis, serositis) were associated with adverse pregnancy outcomes. We performed a retrospective cohort study of pregnancy outcomes among women with SLE at the Brigham and Women’s Hospital Lupus Center. Adverse pregnancy outcomes included pre-eclampsia, pre-term delivery, elective termination due to SLE, spontaneous miscarriage at weeks 12–20, and stillbirth. SLE and obstetric history, laboratories, and medications were obtained from electronic medical records. Generalized linear mixed models adjusting for potential confounders were used to identify predictors of any adverse pregnancy outcome. Most pregnancies resulted in a live term delivery (76.5 %). After adjustment for Hispanic ethnicity, prior adverse pregnancy outcome and medication use 6 months before conception, nephritis during pregnancy (odds ratio (OR) 3.6, 95 % confidence interval (CI) 1.0–12.8), cytopenias during pregnancy (OR 3.9, 95 % CI 1.3–11.4), and serositis during pregnancy (OR 5.9, 95 % CI 1.0–34.0) were significantly associated with adverse pregnancy outcome. Specific types of SLE disease activity during pregnancy were related to adverse pregnancy outcome. Nephritis, cytopenias, and serositis carried a higher risk of adverse pregnancy outcome, suggesting that these abnormalities should be carefully monitored during pregnancy.     

Evaluation of the clinical activity of systemic lupus erythematosus

It is difficult to measure clinical disease activity in systemic lupus erythematosus because many organs can be involved simultaneously and the corresponding symptoms are not easy to quantify. Disease activity is poorly defined and there is no consensus on what disease activity means or how it should be measured. More than 60 systems have been devised but none of them is commonly used because they do not have the 3 characteristics necessary for such a tool: validity, reliability and sensitivity. Three recent systems, BILAG (British Isles Lupus Assessment Group), SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) and SLAM (Systemic Lupus Activity Measures) are very valid. Comparisons of their reproducibility are in progress; however, more information is needed concerning their sensitivity and the feasibility of making these systems easy to manage for physicians.     

Prolactin and gonadal hormones during pregnancy in systemic lupus erythematosus

We performed prospective hormonal studies in 9 patients (5 active and 4 inactive) with systemic lupus erythematosus (SLE) during pregnancy (Weeks 10 to 37). Nine healthy pregnant women and 5 patients with rheumatoid arthritis (RA) were used for comparison. Serum prolactin (PRL), testosterone and estradiol (E2) levels were determined by RIA. The patients with SLE showed higher serum PRL levels, the difference being statistically significant at Week 20, and reaching the highest levels at Weeks 30 to 40 (p = 0.05 when compared to healthy pregnant women). The 5 patients with active SLE had the highest serum PRL levels; one of these had fetal wastage. In active SLE the serum testosterone and E2 levels were decreased significantly from Weeks 10 to 30 compared with controls (p = 0.001). In patients with RA serum PRL levels, although higher than in controls, did not differ significantly, nor did the lower testosterone and E2 levels. We conclude that gonadal hormones and PRL changes observed in SLE are present also during pregnancy and may be related to fetal wastage and reactivation of disease.     

An overview on systemic lupus erythematosus pregnancy

A systemic lupus erythematosus (SLE) pregnancy is no longer regarded as unacceptable, with an early diagnosis, a mild disease condition, and good interdisciplinary collaboration ensuring intense surveillance of pregnant SLE patients. The key point is a sufficiently long period of disease quiescence before conception. A low dose of prednisone is preferable during pregnancy. Nevertheless, 20% of disease flare-up still happens interpartum or postpartum, even in such well-planned pregnancies, although usually with only mild severity. Pregnancy during an active disease stage, especially active nephritis, should always be avoided. Substantial renal function damage may occur, and there is a relatively high prevalence of preeclampsia, which may further compromise the mother as well as the fetus. It is well documented that antiphospholipid syndrome and antiphospholipid antibodies are strongly associated with fetal wastage. Low-dose aspirin or heparin is indicated for a favorable fetal outcome. Women with positive anti-SSA and/or anti-SSB should be aware of the danger of congenital heart block in their infants. Cytotoxic drugs applied in the early stage of pregnancy are dangerous to the fetus. A rather long-term follow-up is required to make a precise evaluation of the maternal SLE influence on the offspring.     

Successful management of systemic lupus erythematosus nephritis flare-up during pregnancy with tacrolimus

Systemic lupus erythematosus (SLE) is one of the common autoimmune disorders that affect women during their childbearing years. Disease activity frequently increases during pregnancy and the postpartum period, representing a challenge for both the patient and the treating physician(s). We report a case of successful management of lupus nephritis flare in the first trimester. The patient developed bilateral leg edema and nephrotic-range proteinuria of 5 g/day. She was treated with steroids and tacrolimus, which resulted in the induction of remission during pregnancy. The patient reached full-term with no maternal or fetal complications. This case indicates that tacrolimus, which is convenient to use and has limited adverse effects, may represent a potential safe and effective treatment option for SLE nephritis during pregnancy.     

Clinical and serological risk factors of systemic lupus erythematosus outcomes during pregnancy

IntroductionSLE is an important risk factor for mother and fetus during pregnancy.Aim of the workTo identify clinical and serological risk factors that may cause poor maternal and fetal outcomes in pregnant systemic lupus erythematosus (SLE) patients.Patients and methodsForty selected SLE pregnant women (group A) versus 35 non-pregnant SLE patients (group B). SLE disease activity index (SLEDAI) and flares were evaluated for both groups. Laboratory investigations included double stranded DNA, anticardiolipin antibodies (aCL), and complements (C3 & C4). SLE pregnant patients were followed up in the second and third trimesters by ultrasonography and fetal Doppler were done to assess fetal outcome. Risk factors for poor maternal and fetal outcome were recorded.ResultsSLEDAI was increased in both groups more in group A. Lupus flares were increased during pregnancy as it occurred in (62.5%) of group A compared to (37.14%) in group B where severe flares were more frequent in group A. Gestational hypertension and active SLEDAI were found statistically significant for poor maternal outcome. Fetal outcome included full term 37.5%, prematurity 25%, intra-uterine growth retardation (IUGR) 22.5%, stillbirth 12.5%, abortion 7.5% and congenital heart block (CHB) 2.5%. Factors significantly associated with poor fetal outcome were severe flares and active renal disease where fetal loss significantly associated with aCL antibodies. Full term was more common in patients with no flares.ConclusionThese data demonstrate that pregnancy in SLE patients should be considered as a high-risk pregnancy and conception should be planned during a quiescent period. Close monitoring for optimal disease control of flares, lupus nephritis, gestational hypertension and aCL antibodies is recommended.     

Antimalarial drugs, systemic lupus erythematosus and pregnancy

Antimalarial drugs containing the 4-amino quinoline radical are used to help control disease activity in discoid lupus erythematosus and systemic lupus erythematosus (SLE). Many patients with these complaints are young women, some of whom will become pregnant. The use of these substituted 4-amino quinoline compounds in pregnancy is controversial. We studied the full obstetric histories of 8 women with SLE who had taken either chloroquine phosphate or hydroxychloroquine sulphate (Plaquenil) throughout the entire length of at least 1 pregnancy. These 8 women had 14 pregnancies while receiving antimalarial drugs. Fetal wastage was high in these patients, regardless of antimalarial therapy, and was almost 100% in patients who were clinically active. Six normal full term spontaneous deliveries resulted from these pregnancies with clinically healthy normal babies born despite exposure to antimalarial therapy throughout the pregnancies.     

Lymphocyte responses in systemic lupus erythematosus in pregnancy

There is a high incidence of pregnancy loss in patients with systemic lupus erythematosus (SLE). This may be due to clinically undetectable exacerbations of the disease. Two case reports are presented in which the patients' lymphocyte responses were assessed throughout pregnancy. The results obtained suggest that monitoring lymphocyte responses may be a useful indicator of disease activity in pregnancy.     

Devic's neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus.

Neuropsychiatric forms of systemic lupus erythematosus (SLE) vary, most commonly consisting of seizures, psychiatric disturbances, or focal central nervous deficits. This is a new case of neuromyelitis optica or Devic's syndrome during the course of SLE. Few reports of this association exist in the literature. Our objective is to report this unique case of Devic's neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus. A 28-year-old woman had been diagnosed as having SLE with cutaneous and articular involvement in 1987 when she was 17 years old. She was treated with a synthetic antimalarial agent associated with corticosteroids. In 1994, during the fourth month of pregnancy, she had signs of transverse myelitis with a sensory level at T6 associated with an optic neuropathy suggesting a Devic's syndrome. The patient was managed by plasmapheresis sessions and intravenous corticosteroids. Transverse myelitis recurred postpartum and three years later at the same thoracic level. Management by bolus administration of a steroid and cyclophosphamide resulted in remission again. There have only been around a dozen reports in the literature of patients who had both Devic's neuromyelitis optica and SLE. Magnetic resonance imaging is contributive to diagnosis and therapeutic follow-up, showing spinal cord lesions with increased intensity on T2-weighted sequences. Although the clinical course of the present patient has been favourable so far, the prognosis of this neurologic disease is generally considered to be poor with elevated mortality.     

Transverse myelitis occurring during pregnancy in a patient with systemic lupus erythematosus.

Myelopathy is a well recognised but infrequent neurological manifestation of systemic lupus erythematosus (SLE). The case of a 27 year old woman with SLE of seven years' duration who developed a spastic paraparesis during her second pregnancy is reported. Magnetic resonance imaging did not show any intrinsic abnormality of the spinal cord. Anticardiolipin antibody was weakly positive and C4 was low. The patient responded dramatically to steroids.     

Patterns of disease activity in systemic lupus erythematosus

OBJECTIVE: To describe patterns of systemic lupus (SLE) disease activity over time. METHODS: Disease activity was measured in a prospective cohort of 204 consecutive SLE patients followed up quarterly for 2.0-7.5 years (911 person-years of followup). Physician's global assessment (PGA) and modified SLE Disease Activity Index (M-SLEDAI; omitting serology) scores were plotted against time for each patient. Definitions for disease activity patterns were developed by consensus using these plots, and the proportion of total follow-up time represented by each pattern was calculated. RESULTS: Three patterns of SLE activity were apparent: relapsing-remitting (RR), chronic active (CA), and long quiescent (LQ). The CA pattern was the most frequent for both the PGA and M-SLEDAI, representing 58% and 40% of total person-years, respectively. The least common pattern was LQ (PGA 16%, M-SLEDAI 25%), while the RR pattern was intermediate in frequency (PGA 26%, M-SLEDAI 35%). Average disease activity during RR periods tended to be mild, while that during CA periods was more likely to be moderately severe. The most common discrepancy between instruments was that the PGA depicted CA when the M-SLEDAI showed an RR pattern. The M-SLEDAI did not appear to capture mild degrees of activity. CONCLUSION: SLE activity was readily classified into 1 of 3 patterns: RR, CA, or LQ. The CA pattern was most common, suggesting that significant morbidity may arise from persistent disease activity. These findings may have important implications regarding the choice of outcome measures in SLE clinical trials, since comparison of flare rates may not account for chronic disease activity.     

Reduced prostacyclin activity in systemic lupus erythematosus.

When fresh rabbit aorta is incubated with plasma, prostacyclin, a potent inhibitor of platelet aggregation, is normally released. Plasma obtained from 2 patients with systemic lupus erythematosus (SLE) inhibited prostacyclin activity, while plasma from 22 other patients with SLE and 40 normal control subjects showed normal activity. Absence of prostacyclin activity did not appear to correlate with the clinical severity of the underlying disease. The possible association of this finding and the presence of thrombotic lesions in both patients is discussed.     

Regulation of coagulo-fibrinolytic activity and lupus anticoagulants in systemic lupus erythematosus

We determined the following coagulo-fibrinolytic activities in 24 patients with systemic lupus erythematosus (SLE) and 20 healthy adults: prothrombin time (PT), activated partial thromboplastin time (A-PTT), factor VIII: coagulant activity), von Willebrand factor antigen (vWF: Ag), antithrombin-III (AT-III), plasminogen (PLG), alpha 2 plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (PIC), protein C (PC: activity and antigen concentration), and protein S (PS: total PS and free PS). PLG, AT-III, PC antigen concentration and total PS were significantly decreased in ten female controls as compared with ten male controls. Therefore, we used the ten healthy females as controls and excluded two male SLE patients in the analysis of the correlations of coagulo-fibrinolytic activities with lupus anticoagulant (LA), clinical and laboratory features in 22 female patients with SLE. In the SLE patients, PT was significantly shortened, while A-PTT was prolonged. PLG, PC activity and antigen, and total PS were significantly increased, and free PS levels were decreased in SLE. The shortened PT and decreased free PS suggest hypercoagulable states in SLE patients. A significant prolongation of A-PTT and a decrease of F VIII activity were observed in the six LA-positive SLE patients, and the results were considered as known effects of LA. Furthermore, vWF: Ag, AT-III and PC antigen levels were significantly increased in the LA-positive patients as compared with LA-negative patients. These changes indicate both vascular endothelial cell damages and a compensatory increase in coagulation inhibitors in the LA-positive patients.