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- PATIENTS AND METHODS
Over the last 20 years, pregnancy has become a frequent event in women with systemic lupus erythematosus (SLE). During this period, the effect of pregnancy and the puerperium on lupus activity has been matter of debate. Several controlled studies have tried to address this issue with conflicting results (1–6). The reasons for this heterogeneity have been discussed elsewhere (7, 8), one of the most important being the lack of a common working definition for a “lupus flare.” Some of the studies employed lupus activity scales already in use (4–6), such as the Lupus Activity Index (LAI) or the SLE Disease Activity Index (SLEDAI), despite the fact that these scales have been validated in nonpregnant lupus populations, which also included men (9). Because some physiologic changes in pregnancy may mimic lupus activity and also may limit the validity of some clinical and biochemical findings (7), it seemed appropriate to construct lupus activity scales specific for pregnant women.
A proposal for the definition of 3 activity scales specific for pregnancy (SLE Pregnancy Disease Activity Index [SLEPDAI], Lupus Activity Index in Pregnancy [LAI-P], and modified Systemic Lupus Activity Measure [m-SLAM]) was published in 1999 (10). They were adaptations of SLEDAI, LAI and SLAM, respectively. Although the SLEPDAI has already been used in 1 research article (11), the validity of these scales as sensitive and specific tools to measure lupus activity during pregnancy has not been established. We therefore tested the usefulness of LAI-P in a multicenter, prospective study of pregnant women with lupus attending 3 combined lupus-pregnancy clinics at St. Thomas' Hospital, London, UK, the Birmingham Women's Hospital, Birmingham, UK, and the Hospital for Special Surgery, New York, NY.
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- PATIENTS AND METHODS
This study confirms that LAI-P is an accurate tool for measuring SLE activity and diagnosing lupus flares during pregnancy and the puerperium. This scale is sensitive to changes in disease activity (as measured by SRM) and has a strong association with m-PGA. Regarding the utility of LAI-P for diagnosing lupus flares, both sensitivity and specificity of LAI-P were well above 90%. This is reflected in the positive and negative likelihood ratios, which were higher than 10 and lower than 0.1, respectively.
One of the main difficulties in validating lupus activity scales is the lack of a good gold standard. Traditionally, the treating physician opinion, expressed in VAS and usually named PGA has been used to define the degree of lupus activity. Although this is rather subjective a gold standard—thus any result of validation studies using it must be taken with caution—it has been widely used (9, 20, 21). Indeed, no other available standards (patient global assessments, quality of life, etc.) have proved superior to PGA (16).
This limitation also applies to this work. In fact, because the opinion of the treating physician regarding activity usually has therapeutic consequences, there is a bias favoring scales that contain treatment items, such as the LAI-P (20). Specifically, minor increases in activity affecting only 1 organ that required changes in treatment were recognized as flares by LAI-P. False-positive results were also few, due in part to the modifications made in the original LAI to make unlikely diagnosing as lupus flare changes in anti-DNA and complement levels without any concurrent clinical manifestations. Interestingly, the utility of both immunologic tests as predictors of SLE flares has been put into question in 2 recent, well-designed studies (14, 15). Also, manifestations of APS, such as stroke and thrombocytopenia, cannot be labeled as lupus by LAI-P because its definitions specifically exclude these issues from scoring items (10). This is particularly relevant in pregnant patients, because combined lupus-pregnancy clinics receive a large number of women with APS due to obstetric complications.
The use of multiple visits per patient for some statistical calculations could have also biased our study. However, SRM values were not different when using 1 or more than 1 visit per woman, which is encouraging. Calculations of sensitivity, specificity, predictive values, and likelihood ratios may be influenced by the lack of independence of measurements. Thus, such results must be viewed as an intuitive and approximate guide of the usefulness and weakness of LAI-P, rather than as absolute values.
Almost three-quarters of women in our group were white. This may raise some doubts regarding the extension of this validation study to populations of other ethnic groups, specifically blacks, in whom lupus may be more severe. We believe that more florid lupus activity will be more easily detected by LAI-P without a concurrent decrease in specificity, thus this scale will probably be appropriate for black women with SLE.
Despite these limitations, this study represents a step forward in providing investigators a common and objective tool to unify observations regarding lupus activity during pregnancy. Indeed, 1 of our main aims was to recruit patients from several lupus-pregnancy clinics, so that the results would be more widely applicable than those from a single-center study. Although clinical management must be guided by observations beyond those recorded by any activity scale, the extended use of any of them will allow comparison of results between studies in a field in which heterogeneity in conclusions has been the rule in the past (7, 8).
Most authors today agree that women with less severe forms of lupus who have a good control of disease before conception are less likely to suffer SLE exacerbations during pregnancy and the puerperium (22). In fact, studies including unselected women with lupus (3–6) have usually found higher rates of flares than others in which women became pregnant with longstanding inactive SLE (23, 24). This was also an issue in this study, in which we observed a low proportion of women having flares (26%) as compared with older data from St. Thomas' Lupus Pregnancy Clinic (6). This reflected not only the incomplete followup of some of them (some women were enrolled late in pregnancy and those lost to followup were also included in the analysis), but also a better selection of the optimal time to become pregnant. However, determining the flare rate was not an objective of this work.
Although not validated yet, SLEPDAI has already been used in a study addressing the effect of hydroxychloroquine on SLE exacerbations in pregnant women (11). Future studies analyzing the role of other therapies, of clinical manifestations before pregnancy, of autoantibody profiles, or of the influence of hormonal changes will be able to measure SLE activity using LAI-P, which is supported by the results of this study.