ARTHRITIS & RHEUMATOLOGYVol. 66, No. 2, February 2014, pp 242–245DOI 10.1002/art.38240© 2014, American College of Rheumatology

EDITORIAL

Updates in US Systemic Lupus Erythematosus Epidemiology: Tales of Two Cities

Christie Michels Bartels1 and Rosalind Ramsey-Goldman2

While contemporary US and international sys-temic lupus erythematosus (SLE) consortia (1–3) havegreatly advanced our knowledge regarding the disease,many argue that such registries suffer from referral biasand do not accurately represent the spectrum of diseaseat the population level. In contrast, population-basedcohort studies encompass the spectrum of mild throughsevere cases of SLE and can estimate incidence andprevalence. Yet identifying the full range of cases forthis disease across a given population requires multipledata sources with precisely interpreted clinical, labora-tory, and even pathology data. These factors have madeSLE one of the most challenging diseases to researchthrough epidemiologic or administrative data (4). More-over, the few existing US population-based SLE cohortssummarized in a 2009 review (5) are now largely out-dated or had described SLE prevalence and incidencerates in small, homogeneous, geographic regions (6,7).Those studies reported widely varying rates of SLE,likely related, at least in part, to differences in method-ology. Updating contemporary lupus population-basedepidemiology is critically important to framing the currentpublic health burden and status of SLE care in the US.

SLE is a disease with substantial direct andindirect costs over the patient’s lifespan (8,9) and withwell-known health disparities. Important health dispari-ties, including higher renal complications and mortalityrates, have been noted in groups defined by low socio-economic status, black race, Hispanic ethnicity, or Asianethnicity (1,3,10–12). Prior reports from US referralcohorts representing some of these vulnerable popula-

tions are criticized for missing mild cases and patientswith limited access to care. To include such cases, it isimportant to have a broad definition of case ascertain-ment and to search multiple points of entry into thehealth care system, ranging from tertiary centers tocommunity clinics and hospitals, or even laboratory andpathology services. To date, the lack of a comprehen-sively defined population-based “denominator” to accu-rately represent the number of SLE cases in the US haslimited our ability to answer many important questions.For example, without accurate numbers of existing SLEcases, it has been difficult to adequately quantify theburden of SLE in the US, let alone reassess health dis-parities and SLE quality of care on a population level (13).

Two reports in this issue of Arthritis & Rheuma-tology, one by Lim et al (14) and the other by Somerset al (15), describe collaborative studies offering much-needed updates on the epidemiology of SLE in the US.Among the key contributions of their work are thepivotal partnerships with the Centers for Disease Con-trol and Prevention (CDC) and their respective statehealth departments. These groups cooperated under astate public health surveillance exemption to HealthInsurance Portability and Accountability Act (HIPAA)to facilitate comprehensive regional searches for SLEcases. Both groups of investigators ascertained all pedi-atric and adult cases of SLE encountered between 2002and 2004 in hospitals, dermatology, nephrology, andrheumatology clinics, pathology and laboratory centers,and the US Renal Data System for end-stage renaldisease (ESRD). The results of these two studies werederived from two comparable urban populations, At-lanta and Detroit and their surrounding areas, and theyprovide contemporary data on SLE incidence and prev-alence in these regions.

These rigorous studies update the epidemiologicdata on SLE with improved precision, highlighting themagnitude of the disease burden, including importanthealth disparities for SLE patients. Using parallel meth-ods, Lim (14) and Somers (15) found nearly identicalSLE rates of 5.6 versus 5.5 incident SLE cases per

Dr. Bartels’ work was supported by the NIH (NationalInstitute of Arthritis and Musculoskeletal and Skin Diseases grantK23-AR-062381).

1Christie Michels Bartels, MD, MS: University of Wisconsin,Madison; 2Rosalind Ramsey-Goldman, MD, DrPH: NorthwesternUniversity, Feinberg School of Medicine, Chicago, Illinois.

Address correspondence to Christie Bartels, MD, MS, De-partment of Medicine, Rheumatology Division, University of Wiscon-sin, 1685 Highland Avenue, Room 4132, Madison, WI 53705-2281.E-mail: cb4@medicine.wisc.edu.

Submitted for publication October 3, 2013; accepted in re-vised form October 15, 2013.

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100,000 person years and 73 versus 72.8 prevalent casesper 100,000. Not surprisingly, both studies confirmheightened SLE incidence and severity in young blackwomen, including far more cases of ESRD. Althoughmany renal diseases disproportionately burden blackAmericans due to a combination of genetic factors (10),comorbidities, and socioeconomic challenges (1,11), thefinding of 3–7-fold higher rate of ESRD in young blackwomen with lupus documents the need to prioritizerheumatology care quality and research agendas tominimize this adverse outcome. Moreover, these regis-tries also offer an excellent platform from which toaddress the remaining questions regarding other organ-specific manifestations and disease outcomes over time.

When compared to each other, the differentialfindings of these two studies also merit investigation. Forinstance, a bimodal peak in incidence age, including alater peak for those 60–69 years old, was observed byLim and colleagues but not Somers and colleagues.Based upon reports of later-onset disease among Euro-pean descendants (16–18), one might have predictedthat the Somers group would also have seen a latedisease peak, given a proportionally larger white popu-lation base in Detroit than in Atlanta, although a latepeak also occurred in black patients in the Lim study.This contrast raises questions regarding whether thereare regional variations in access to care or care-seekingamong older adults influencing the incidence rates oflate-onset SLE in these cities. Alternatively, competingmortality risks could have decreased the rates of late-onset SLE in Detroit, genetics or environmental triggerscould account for more frequent late-onset SLE inAtlanta, or other unknown factors could explain thesedifferences.

Differences in the prevalence of some specificSLE classification criteria and manifestations are alsonotable when comparing the two studies (Table 3 in theLim et al study [14] and Table 2 in the Somers et al study[15]). Renal disease in general was 6–7 times higher inblack patients among prevalent SLE cases in Atlanta,compared with 3 times higher in black patients amongprevalent SLE cases in Detroit. This difference in renaldisease between the two urban regions again raisesquestions regarding whether higher renal disease inAtlanta reflects population genetics, environmental trig-gers, or differences in regional care, all of which deservefurther study. In contrast, lower photosensitivity amongthe prevalent SLE patients in Atlanta compared toDetroit (25.5% versus 48%) might partly reflect racedifferences, but otherwise appears counterintuitive, rais-ing questions regarding interobserver reliability or doc-

umentation variation versus other causal explanations.Even antinuclear antibody positivity varied between thestudies (82% in Atlanta versus 94% in Detroit), raisingquestions regarding ascertainment, assay methods, orinterpretation versus other causal explanations. Assess-ment of these and other regional variations may provequite helpful when comparing long-term outcomes, in-cluding survival reports, from the different registries.

While offering expanded information regardingthe contemporary epidemiology of SLE in the US, thesetwo studies also have some limitations, many of whichwere noted by the authors. First, although the Detroitand Atlanta population demographics intentionallyoversampled at-risk black Americans, they underrepre-sented other racial and ethnic groups, such as Asian andHispanic populations, who are also known to be at riskof SLE (1,12). Simple capture of race using census-typequestions likely misses important mixed race/ethnicitycharacteristics (19). Moreover, while SLE patients aregenerally referred to rheumatologists, dermatologists, ornephrologists, the decision not to include primary careclinics, while logistically understandable, might underre-port milder cases or those with the least followup and/oraccess to care. However, capture–recapture estimatesusing alternative data sources, including clinical labora-tories, facilitated the estimation of the numbers ofmissing cases. While these authors and their teams are tobe applauded for their exhaustive efforts to comprehen-sively identify cases, one also may ask whether popula-tions in the nonresponding specialty clinics, hospitals, orlaboratories, which appeared to be more frequent in theSomers study, differed from the clinic populations thatwere studied. Last, as described in a recent report byBernatsky et al (20,21), the short followup period of 3years in both studies may systematically overestimate theincidence and underestimate the prevalence in contrastto periods of �5 years. Fortunately, future observationsare planned for both registries, and overall, the strengthsof these studies by far outweigh these limitations.

These important CDC-sponsored studies offer anexcellent vantage point for examining SLE in the US andin fact raise several research and public health policyquestions. Lim and Somers and their respective col-leagues have provided an excellent example of how tofind and count SLE cases in order to create a reliableSLE denominator for their respective regions. Addi-tional CDC-sponsored investigations are under way inManhattan, NY, San Francisco, CA, and with the IndianHealth Service to examine US populations with largerrepresentations of Hispanic, Asian, and Native Ameri-can patients that will likely complement the present data

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(http://www.cdc.gov/arthritis/funded_science/current/lupus_registries.htm). Future research that incorporatesgenetic admixture perspectives (19,22) or other effortsto capture the heterogeneity of the US populationbeyond traditional race/ethnicity categories will alsoadvance our epidemiologic understanding of SLE. Like-wise, the impact of age at SLE onset could be more fullyexamined, given that both of the present studies in-cluded pediatric SLE patients, but their SLE course wasnot separately described. It also remains timely andrelevant to ask whether using the recently publishedSystemic Lupus International Collaborating Clinics(SLICC) SLE classification criteria would capture adifferent spectrum of SLE cases compared to the Amer-ican College of Rheumatology modified 1982 SLE clas-sification criteria and expert diagnosis (23).

More broadly, the present studies have estab-lished a reliable SLE denominator for use in populationcohort studies examining strategies to detect, reverse,and prevent SLE complications (24). Population-basedSLE cohorts could offer platforms for observationalstudies, for example, examining the impact of vaccina-tion strategies on the mitigation of infectious complica-tions of SLE. Alternatively, one could compare neigh-borhood context and health care experienced by thosewith good and poor outcomes (25). Variations in lupuscare quality could be critically examined (13). Qualityof care process measures, such as “retention in care,”a measure first developed in research on the humanimmunodeficiency virus and indicating the proportion ofpatients receiving regular quarterly clinical care or treat-ment, could similarly assess rates of lapsed SLE care atthe population level (26). Retention in care may bean important potentially modifiable mediator of healthdisparities outcomes and an opportunity to improvehealth in vulnerable SLE patients.

Important health care policy questions alsoemerge from the work of Lim and Somers and theircolleagues. Given the early peak onset of SLE in youngwomen in their early 30s and the high rates of uninsuredstatus affecting up to 1 in 3 young individuals in the US(27), rheumatology clinics may need to promote individ-ual use of new insurance exchanges and advocate foralternatives for those not eligible for such care. Under-standing more about the public health burden of SLEthrough reliable prevalence figures will also help toinform rheumatology workforce needs and drug therapypolicies as new SLE treatments emerge. Last, comparingthese US studies with international studies might furtherbuild SLE knowledge and enhance care quality (28).

We have much to ponder in the tales of these two

cities with regard to SLE care in the US and much toenvision regarding future research and health care policyagendas necessary to improve the lives of all patientswith SLE irrespective of where they reside.

ACKNOWLEDGMENTS

The authors thank Drs. Carolyn Bell and Sasha Ber-natsky for critical review of the manuscript.

AUTHOR CONTRIBUTIONS

Drs. Bartels and Ramsey-Goldman drafted the article, revisedit critically for important intellectual content, and approved the finalversion to be published.

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