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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Arthritis Care Res (Hoboken). Author manuscript; available in PMC 2013 February 1.
Published in final edited form as:
PMCID: PMC3263318

A Longitudinal Study of the Impact of Incident Organ Manifestations and Increased Disease Activity on Work Loss among Persons with SLE

Edward Yelin, Ph.D., Chris Tonner, M.P.H., Laura Trupin, M.P.H., Stuart A. Gansky, Dr.P.H., Laura Julian, Ph.D., Patricia Katz, Ph.D., Jinoos Yazdany, M.D., M.P.H., Rachel Kaiser, M.D., M.P.H., and Lindsey A. Criswell, M.D., M.P.H.



There is increasing evidence of the impact of SLE on employment, but few studies have had sufficient sample size and longitudinal follow-up to estimate the impact of specific manifestations or of increasing disease activity on employment.


Data derive from the UCSF Lupus Outcomes Study, a longitudinal cohort of 1204 persons with SLE sampled between 2002 and 2009. Of the 1204, 484 were working at baseline and had at least one follow-up interview. We used the Kaplan-Meier method to estimate the time between onset of thrombotic, neuropsychiatric, or musculoskeletal manifestations or of increased disease activity and work loss, and Cox proportional hazards regression to estimate the risk of work loss associated with the onset of specific manifestations, the number of manifestations, and increased activity, with and without adjustment for sociodemographic, employment, and SLE duration.


By four years of follow-up, 57%, 34%, and 38% of those with thrombotic, musculoskeletal, and neuropsychiatric manifestations, respectively, had stopped working as had 42% of those with increased disease activity. On a bivariable basis, the risk of work loss was significantly higher among persons 55–64, and those with increased disease activity and each kind of manifestation. In multivariable analysis, older age, shorter job tenure, thrombotic and musculoskeletal manifestations, greater number of manifestations, and high levels of activity increased the risk of work loss.


Incident thrombosis and musculoskeletal manifestations, multiple manifestations, and increased disease activity are associated with the risk of work loss in SLE.


There is a growing literature establishing the profound impact of SLE on employment, including at least two review articles (1, 2) [Scofield, 2008 #2018], one of which was a meta-analysis of the prevalence of work loss and of the risk factors for such loss (1). In the studies reviewed in the meta-analysis, half of persons with SLE had stopped working within a decade after diagnosis. Sociodemographics, including lower levels of education, minority race/ethnicity, and advanced age, and disease factors, including longer duration, higher levels of activity and such symptoms as pain and fatigue, presence of anxiety, depression and neurocognitive involvement were associated with work loss.

Relatively few studies, however, have provided systematic estimates of the impact of specific SLE manifestations on employment either because of sample sizes too small to permit assessment of more than one manifestation at a time as well as adjustment for potential confounding factors, lack of longitudinal follow-up, or both. The existing literature does highlight the importance of cognitive impairment and other forms of neuropsychiatric involvement (36) and the impact of musculoskeletal, renal, and lung manifestations (4, 7, 8). No studies were identified which evaluated the impact of thrombotic events which play a crucial role in the outcomes of SLE. The present study uses up to seven years of longitudinal follow-up data. Based on our previous finding from a prospective analysis showing the importance of SLE status on work outcomes relative to working conditions, including physical demands of jobs [Yelin, 2009 #1835], wee hypothesize that, among employed subjects, the hazards for job loss would be higher among those who incur an incident SLE-related manifestation or an increase in disease activity. The examination of the impact of changes in participants’ health over a study period can help identify risk factors that are important to measure repeatedly during follow-up



We use the UCSF Lupus Outcomes Study (LOS), a longitudinal cohort of persons with this condition, to estimate the time from incident specific organ manifestations, including thrombotic, neuropsychiatric, and musculoskeletal, and increases in disease activity until work loss among those employed at the outset of the LOS We also describe the sociodemographic, SLE, and employment characteristics associated with an elevated hazard of such work loss.

Data Source

The LOS has included 1204 persons with SLE sampled from clinical environments (n=472, 39%), and such community-based resources as support groups, websites, and newsletters (n=732, 61%). The enrollment occurred between 2002 and 2009.

To be enrolled in the LOS, participants had to have a diagnosis of SLE confirmed by medical record review by a rheumatologist or nurse working under a rheumatologist’s supervision. The principal data collection for the LOS is an annual structured telephone interview that collects information on demographic and socioeconomic characteristics; status of SLE, including a validated measure of activity, the Systemic Lupus Activity Questionnaire (SLAQ) (9, 10); specific manifestations; general health and functional status; medications; a complete inventory of health care encounters in the twelve months prior to interview; kind and extent of health insurance; and employment status. Prior publications have listed the specific measures collected within each of these major categories of variables (3, 11).

For the present analysis, we omitted those among the 1204 LOS participants not working at their baseline LOS interview (n=658, 54.7%), those aged 65 or older (n=16, 1.3%), those with only one LOS interview due to death, decline of further participation, or loss-to-follow-up (n=43, 3.6%), and those with missing data on any variable used in the analysis (n=4, 0.3%), yielding a total of 483 participants.

SLE Manifestations

Thrombotic Manifestations

Thrombotic events included deep vein thrombosis; pulmonary embolism; stroke; myocardial infarction; retinal vein thrombosis; other blood clots; or second or third trimester miscarriage, according to the criteria defined in previous LOS analyses(12). LOS participants were classified as having an incident thrombotic manifestation if they had reported any of the above events since their prior interview. Thus, an incident event here was not necessarily the first thrombosis experienced by the participant. We did not have access to complete medical records to validate all self-reported thrombotic events. However, we were able to validate thrombotic events that occurred prior to the baseline interview using medical records originally obtained to determine study eligibility. Using these records to document self-reported events on the baseline interview, self-report of thrombosis had 97% specificity and 68% sensitivity with regard to the record data. The low sensitivity is likely due to the long recall period for these events (often more than 10 years prior to the baseline interview). In order to address whether a shorter recall period increased the sensitivity of self-reported events, we compared the interview data to the medical records for the 55 LOS participants for whom we had a record of a thrombotic event in the medical charts that was contemporaneous with the interviews. Among these participants, all but six accurately reported the thrombotic event found in the charts, yielding an improved sensitivity of 89%.

Neuropsychiatric Manifestations

The definition of neuropsychiatric manifestations is based on new onset of clinically significant symptoms of depression, cognitive dysfunction, or seizures. We used a cut-point of 24 on the Center for Epidemiological Studies Depression Scale(CESD)(13), which has been established as an appropriate indicator for this population(14). Cognitive dysfunction was defined by a z-score of less than or equal to −1.5 compared to population normative data on one or more of three measures of cognitive functioning, including the Hopkins Verbal Learning Test-Learning Index, Hopkins Verbal Learning Test –Delayed Recall Index, or Controlled Oral Word Association (15, 16). Participants were classified as having an incident neuropsychiatric manifestation in an interview wave if they had one or more of the following: worsening depression defined as a CESD score of 24 or greater after at least one lower score; no cognitive dysfunction in previous interviews and presence of cognitive dysfunction in the current interview; or, report of a seizure in the year prior to the current interview.

Musculoskeletal Manifestations

Musculoskeletal manifestations were defined as a report of severe muscle pain, muscle weakness, pain or stiffness in joints, or swelling in joints in the three months prior to interview; these items derive from the SLAQ (9). Participants were classified as having an incident musculoskeletal manifestation in an interview wave if they reported “no” or “moderate” symptoms from the 4 musculoskeletal conditions in the previous interview and reported “severe” symptoms in at least one of the conditions in the current interview.

Renal Manifestations

Renal manifestations were defined by the report of having a kidney biopsy or starting dialysis since the prior interview. Among the LOS participants in the study sample, i.e., those who were employed and under age 65 at baseline, 106 (22%) met this criterion prior to the start of the study. However, only 30 participants had an incident renal manifestation as defined here since the baseline interview year. As such, renal manifestations were not included in the present analysis because we lacked statistical power to estimate the relationship of these manifestations to employment.

Increases in Disease Activity

In the LOS, disease activity, as indicated above, was measured by the SLAQ self-report measure. An increase in disease activity was defined as an increase of 0.5 standard deviations of the mean SLAQ score, consistent with the definition proposed by Norman and colleagues for a clinically meaningful change (10, 17).

Employment Measures

The annual telephone surveys include employment measures from the Current Population Survey (CPS), the source of the monthly employment statistics in the U.S. (18). In the CPS, persons are defined as employed only if they report being employed, on temporary leave but with a job, or working for pay or profit in the week prior to interview. For those not working according to this definition, information is collected on the month in which the individual stopped working. For respondents for whom the precise date of work loss was not available, we assumed that work cessation occurred at the midpoint between consecutive interviews, a common approach in life table analyses.

Additional employment measures included job tenure (number of years at current job) and the type of industry in which the participant worked, categorized as government, including education; goods producing industries; professional, technical, scientific, and media services; retail, wholesale, and finance; and other service industry jobs.

Measures of Health Status and Sociodemographics

In addition to the specific SLE manifestations described above, health status measures included disease duration (years since diagnosis), a measure of general health (ranging from excellent to poor), and a global assessment of disease activity (on a 10 point scale). Sociodemographic variables included age, categorized as 18–34, 35–54, and 55 – 64; gender; race/ethnicity, dichotomized to white non-Hispanic vs. all others; and education, categorized as high school graduate or less, some college, and baccalaureate degree or greater.

Estimating the Onset of Incident Manifestations or Increases in Disease Activity

As mentioned, we hypothesize that among employed subjects the hazards for job loss would be higher among subjects who have an incident SLE-related manifestation or an increase in disease activity. Specifically, we examined whether having such events during the interview period immediately preceding job loss would increase the hazards of job loss. Since our data is collected longitudinally, we were able to assess at each interview if a patient reported having an incident SLE manifestation or increase in disease activity since their prior interview (on average 12 months). Because the reports of incident manifestations correspond to the prior 12 month interval and the report of job loss is an exact date, we assigned the manifestations variable from the interview immediately preceding the job loss date in the following way. First we calculated the midpoint between the dates of interview with first reported of job loss or censorship and and the prior interview. When the job loss date was before the midpoint of interview dates, the manifestation value from the prior interview was assigned; if the job loss date was at or after the midpoint interview dates, the value from the latter interview date was assigned. These assignments may have resulted in some cases being misclassified. For example, if an individual reported stopping work in the tenth month of the year prior to the interview that individual would be assigned the manifestation value from that same interview. It may be possible however, that the manifestation occurred during the eleventh or twelfth month of that interview period, after the time of job loss. However, results of a sensitivity analysis in which we assigned the manifestation data from the prior interview whenever job loss occurred at after or at the midpoint of the year did not differ appreciably from the results presented below. Because the neuropsychiatric manifestations and increase in disease activity measures were based on a change in scores from one year to the next rather than discrete events, we assigned the end of the year in which the change occurred as the point of incidence for these manifestations.

Statistical Analysis

We calculated the time until first reported work loss among persons with SLE who met the criterion for employment in the baseline interview and subsequently developed incident manifestations or an incident increase in disease activity. Thus, we focused on the impact of specific incident manifestations or the number of such manifestations or increases in activity on work loss among those employed prior to the incidence of each of three manifestations or increased activity. In all analyses, we excluded those who were 65 years of age or older at baseline.

We first used the Kaplan-Meier method to compare the employment trajectories in LOS participants who experienced the SLE manifestations under study. We estimated the proportion working in each month following the incident manifestations or increase in disease activity. In these analyses, individuals who continued to be employed were censored observations, as were individuals who reached age 65 without work loss. For all observations, the length of time until work loss is measured not since study entry, but from the point of the first incident manifestation in each category. For this reason, not all observations are carried through for the entire time period, as reflected in Figure 1, below.

Figure 1
Time Until Work Loss Among Persons with Incident Thrombosis, Musculoskeletal or Neuropsychiatric Manifestations or Increase in Disease Activity

We next estimated bivariable Cox proportional hazard regressions to ascertain the relative impact of the specific incident manifestations, number of manifestations, or increases in disease activity and other variables on the risk of work loss. Because we were interested in the immediate effect of an incident manifestation on employment status, we used a time-dependent approach (19) in which the risk of job loss is evaluated based on the incident manifestation value from the interview immediately preceding the job loss or censorship. In multivariable Cox regressions, we also included sociodemographic measures (age, gender, race/ethnicity, and education), job characteristics (job tenure and industry), and disease duration. We did not include the general health status or global disease activity measures in these models, as we viewed them as potentially part of the pathway from manifestation to job loss and thus would be inappropriate to include in a multivariable model. To control for changing economic circumstances, we included the the year of baseline employment as a continuous variable

In the analysis of the impact of manifestations, the multivariable Cox regression included the specific time-dependent manifestations, i.e. thrombotic, musculoskeletal, and neuropsychiatric. In a separate Cox regression analysis, we substituted the number of the foregoing manifestations (with zero manifestations as the reference); this regression included the same variables listed above. The analysis of the impact of an increase in disease activity was done separately from the analysis of specific manifestations since there was considerable overlap between the SLAQ and the musculoskeletal manifestation measure. This analysis included only 342 participants, rather than 483, because the SLAQ score was only begun in the second wave of LOS data collection after its validity had been established.


Table 1 displays the characteristics of the 483 persons with SLE who were working in the year they enrolled in the LOS. A majority were 35–55 years of age, 91% were female, and two-thirds were white not of Hispanic origin. Nearly 90% of these employed LOS respondents attended at least some college. Nevertheless, nearly one in five lived in a household whose income is 125% or less of the Federal Poverty Level. Self-reported disease activity at baseline was 3.5 (on a 0–10 scale); average disease duration was 10.8 years (range 0–46 years), and just over one-quarter reported fair or poor health status. As of the baseline interview in the LOS, respondents who were working had been in their jobs an average of 6.6 years (range 0–43 years). Forty-two percent had jobs in government, another 17% worked in the professional or media sector, and a similar percentage were in retail, wholesale, or finance companies. Only 13% were in service industries not elsewhere classified (e.g. restaurant and hotel workers) and 10% were in goods producing industries. During the follow-up period, 160 respondents (33%) left work; job loss occurred an average of 29 months (range 5–75) after the baseline interview. Follow-up time for the entire study sample was 46±27 month (range 5– 87).

Table 1
Baseline Characteristics and Incident SLE Manifestations among Employed LOS Participants, ages 18–64

Figure 1 presents the results of the Kaplan-Meier estimates of time from incident manifestations or increased disease activity to work loss. Incident thrombotic events were reported by 59 (12%) of employed LOS participants, 170 (35%) experienced incident musculoskeletal manifestations, and 179 (37%) met study criteria for incident neuropsychiatric symptoms. A total of 34% had one type of manifestation, while 24% had two or three. Of the 342 participants included in the disease activity analysis, 54% experienced a clinically meaningful increase in SLAQ scorFor participants with thrombotic events or increased disease activity, there was a marked drop in employment in the first 12 months. These two groups continued to have a steep decline in employment for at least four years, ending with employment rates near 40%. Individuals with incident neuropsychiatric or musculoskeletal manifestations had less steep immediate declines in employment. Nevertheless, by the study’s end, only about half of these individuals were still employed. For the study population as a whole, 66% remain employed throughout the study period.

The Cox proportional hazard regressions indicated that sociodemographics, work, and SLE characteristics all contributed to the risk of work loss (Table 2). On a bivariable basis, older age, each of the three types of incident manifestations, the number of manifestations, and both baseline and increased SLAQ score were each associated with increased risk of work loss (first column). The hazard ratio (3.2, 95% CI 1.8, 5.8) associated with thrombotic events was particularly pronounced. In the multivariable analysis of the impact of manifestations (second column), older age continued to be associated with work loss, while longer job tenure was associated with a decreased risk (HR 0.9 per 5 years, 95% CI 0.7, 0.97). Among the specific manifestations, the risk of work loss associated with thrombosis remained unchanged, while the risks associated with incident musculoskeletal manifestations decreased somewhat (HR 1.7, 95% 1.2, 2.5), and the hazard ratio associated with neuropsychiatric manifestations was no longer significant (HR 1.5, 95% CI 0.96,2.2). The third column of the table displays the hazard ratios associated with the number of manifestations rather than the specific manifestations present. The risk of work loss increases with a greater number of manifestations; the hazard ratio associated with one type of manifestation was 1.5 (95% CI 1.0, 2.2), while the ratio associated with having two or three types was 2.6 (95% CI 1.4, 4.6). The last column of Table 2 analyzes the impact of increases in SLAQ score on the risk of work loss and indicates that those with a clinically meaningful increase in disease activity had a hazard ratio for work loss of 1.7 (95% CI 1.1, 2.7), after adjusting for their disease activity at baseline.

Table 2
Hazard and 95% Confidence Intervals by SLE Manifestations and Disease Activity, with and without Adjustment for Sociodemographics, Health, and Employment Characteristics


The onset of SLE typically occurs in adolescence or early adulthood. The age of onset often limits the ability of individuals with this condition to gain a stable toehold in the economy, and in the LOS cohort, less than half were employed at baseline. We had previously reported on the work dynamics of persons with SLE, showing both that rates of employment were relatively low compared to an age-matched population and that this was the result of lower rates of work entry prior to age 55 (8, 11). In the present analysis, longer job tenure protected against work loss, highlighting the importance of maintaining employment in existing jobs.

Because SLE is a heterogeneous condition, it stands to reason that the work prospects of persons with this condition may differ depending on the mix of the manifestations experienced. We were able to describe the patterns of employment associated with incident thrombotic, musculoskeletal, and neuropsychiatric manifestations. Thrombotic events appeared to have a particularly profound impact on employment, even after adjustment for potential confounders in the multivariable Cox regressions. Prior work has demonstrated that thrombotic events are associated with decreased quality of life (20), mortality (21), and irreversible organ damage (22). Although musculoskeletal and neuropsychiatric manifestations were also associated with the risk of work loss in the bivariable analysis, the addition of covariates to the multivariable models reduced their effect slightly. The risk of work loss increased with the number of incident manifestations experienced. A clinically meaningful increase in disease activity was also associated with the risk of work loss.

The Kaplan-Meier analysis revealed distinct differences in the trajectory of employment among the four types of manifestations studied, with thrombotic events and increased disease activity leading to steeper declines in employment in comparison to neuropsychiatric and musculoskeletal manifestations. However, for all of these groups, the net loss in employment was quite substantial, and appears to be greater than for the remainder of the study participants.

Both the Cox regression and Kaplan-Meier analyses highlight the importance of tight monitoring of risk factors for thrombosis to prevent the onset of such manifestations. We have previously reported that monitoring for cardiovascular events occurred in less than a third of persons in the LOS and was tied to the conjoint effects of poverty, absence of health insurance, and the specialty of physicians seen for SLE(23). However, since some thrombotic events are associated with preventable behaviors such as smoking, or treatable conditions such as hypertension or high cholesterol, they may be amenable to prevention. Therefore, more effective monitoring may have the added benefit of helping those with jobs stay employed.

This study was able to reliably describe the employment history of those with incident manifestations because of the large sample size and annual data collection. The annual data collection occurred through self-report in structured telephone surveys, raising the possibility of reporting bias particularly for more complex medical events, such as thromboses. In the validation analysis on retrospectively reported events, however, we were able to accurately estimate the occurrence of thrombotic events with 68% sensitivity and 96% specificity; limiting the analysis to documented events contemporaneous with the LOS interviews increased the sensitivity to 89%. Moreover, it is likely that misclassification with respect to these manifestations would have led to an underestimate of the true effect of incident thrombotic events on job loss. We may also have underestimated the true incidence of neuropsychiatric manifestations, as we categorized stroke as a thrombotic rather than neuropsychiatric event; we were only able to capture the most common behavioral neuropsychiatric events; and we were unable to adequately asses other central nervous system and peripheral nervous system SLE manifestations. While thromboses are discrete events, the incidence of neuropsychiatric manifestations is dependent on artificially derived cutpoints in continuous measures. However, we chose very conservative thresholds for depression and cognitive dysfunction, but it may be that even mild cognitive impairment conferred effects on employment (1, 3) and, in general population studies, milder levels of depression have been indistinguishable from major depression in the prediction of some outcomes. All of this may have led to an underestimation of the employment effect due to neuropsychiatric manifestations. Despite the large sample, the LOS participants included in this analysis experienced too few severe renal events during the follow-up period to allow for a reliable estimate of renal manifestations. Another limitation is that we may not have been able to capture the full employment impact of incident manifestations that occurred in the same year as work loss if we incorrectly assumed that the work loss occurred before the onset of the manifestation. However, as noted above, the results proved insensitive to an alternative assignment of the interval between incident manifestations and work loss.

In summary, we have found that incident thrombotic events are associated with a relatively high risk of acute work loss, while the development of musculoskeletal manifestations and neuropsychiatric events is associated with more delayed work loss. Moreover, we have demonstrated that increases in disease activity are prospectively associated with work loss in individuals with SLE. These findings add to our understanding of employment outcomes in persons with SLE. Interventions geared toward decreasing the risk factors for work loss identified in this study have potential to improve employment outcomes in SLE.

Significance and Innovation

  • SLE manifestations, especially thrombotic events, and increased disease activity are associated with a high risk of work loss. Efforts on the part of clinicians and patients to control disease activity or prevent thromboses may have the added benefit of maintaining employment.
  • These findings are innovative in that the sample size and lengthy follow-up allow for reliable estimates of risk of work loss associated with specific SLE manifestations.


Grant Support: NIAMS P60 AR053308 and R01 AR056476 and California State Lupus Fund


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