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Systemic Lupus Erythematosus

Cynthia Aranow, Betty Diamond, Meggan Mackay

Systemic lupus erythematosus (SLE) is a systemic autoimmune mortality, and response to therapy are also modulated by ethnicity,
disease characterized by the production of autoantibodies and and all studies support observations of increased disease activity,
a broad spectrum of clinical manifestations. It most commonly damage, and mortality in nonwhite populations (Table 51.2). 4
presents in women during their childbearing years. Although
the etiology of SLE is unknown, both genetic and environmental Mortality
factors contribute to loss of self-tolerance. Current therapeutic Increased awareness leading to earlier diagnoses, availability and
modalities are antiinflammatory and immunosuppressive. use of immunosuppressive agents, and improved treatment for
comorbid diseases have contributed to a dramatic decrease in
EPIDEMIOLOGY mortality over the last half-century, with a 5-year survival rate
5
of 50% in the 1950s to 96–99% in the past 5 years. Despite this
The American College of Rheumatology (ACR) classification increase in survival, lupus patients continue to suffer significant
(Table 51.1), created initially to classify this disease with multiple morbidity and mortality related to disease and medication effects.
diverse manifestations, has undergone several revisions in efforts Compared with the general population, risk of death is reported
1
to improve sensitivity and specificity of the criteria. The revised as 2–5 times higher in lupus patients, with standardized mortality
1997 classification scheme is the most widely accepted instrument rates as high as 6.7 and 7.8 in SLE cohorts with lupus nephritis.
for “diagnosing” lupus; however, these criteria do not represent Overall, mortality is modulated by gender, ethnicity, race, geo-
the full spectrum of disease. Patients fulfilling 4 out of the 11 graphical location, disease comorbidity, age at diagnosis, and
criteria are classified with SLE with approximately 95% certainty, the presence of lupus nephritis or end-stage renal disease.
although many individuals who meet only two or three criteria Generally, highest mortality rates are associated with male sex,
may also be considered as having SLE. More recently, the Systemic black race, and active lupus nephritis. The leading causes of
Lupus International Collaborating Clinics (SLICCs) have proposed death include cardiovascular disease, infection, and active SLE;
and validated a revised classification scheme that seeks to improve the order of frequency depends on the population reported. A
sensitivity and specificity by inclusion of a broader range of bimodal distribution of death has been well recognized; early
immunological and clinical criteria. A patient will satisfy the deaths often result from infections or active disease, whereas
SLICCs classification of SLE if there is biopsy-proven lupus deaths occurring later in the course of disease are frequently
nephritis with an autoantibody (antinuclear antibody [ANA] or attributed to end-stage organ damage and cardiovascular disease,
anti-dsDNA) or if a minimum of 4 predefined criteria are met usually in the setting of inactive disease. Both cardiovascular
(1 of these 4 criteria must be clinical, and one must be immu- disease and organ failure are associated with damage accrued
2
nological). During the childbearing years, the ratio of women from recurrent SLE disease activity and medication effects.
to men with lupus is approximately 9 : 1. This ratio is less in
younger and older populations, supporting a role for hormonal DAMAGE
factors in disease induction. The majority of lupus presents during
adulthood; approximately 20% of cases are in the pediatric With improved survival, the impact of comorbid conditions has
population. Recent studies suggest that age at diagnosis may be become increasingly important. Patients may accrue irreversible
increasing in some populations; mean ages at diagnosis reported damage over time resulting from active disease and/or toxicities
since 2002 range from 31 years in Martinique and Brazil to 51.7 of medications. The SLICCs/ACR Damage Index (SDI) is a validated
years in Wisconsin (United States) and 47 years in Sweden. instrument to measure damage. Damage accumulates over time
Lupus occurs throughout the world; susceptibility is linked and is associated with poorer quality of life as well as increased
to race and ethnicity as well as environmental exposures. World- morbidity and mortality. Renal, musculoskeletal, and cardiac
wide incidence rates vary from 1.9–8.7/100 000, and prevalence domains are important contributors to damage. There is increased
3
rates vary from 19.3–207/100 000; however, incidence rates in awareness of cardiovascular disease in SLE. As discussed below
African Americans, African Caribbeans, Hispanics, and Asians (cardiac involvement: coronary artery disease), events attributable
are approximately three times greater than in Caucasians. to atherosclerotic disease occur significantly more frequently in
Although epidemiological data are scant, it appears that the lupus cohorts compared with their age-matched controls. Tradi-
incidence of SLE in Africa is lower. Data from animal models tional risk factors, e.g., hypertension, hyperlipidemia, physical
suggest this may be a consequence of a protective effect of malaria inactivity, and impaired glucose control, are enriched in lupus
infection. Clinical manifestations, disease activity, damage accrual, patients. However, the risk of cardiovascular events continues to

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