Lupus

PRIMER
Author addresses
1
Department of Rheumatology, St. George’s, University of
London, Cranmer Terrace, London SW17 0RE, UK.
2
Rheumatology Research Group, Institute of Inflammation
and Ageing, College of Medical and Dental Sciences,
University of Birmingham, Birmingham, UK.
3
Mary Kirkland Center for Lupus Research, Hospital for
Special Surgery, New York, New York, USA.
4
University of Toronto Lupus Clinic, Toronto Western
Hospital, Centre for Prognosis Studies in the Rheumatic
Diseases, Toronto, Ontario, Canada.
5
Unit for Clinical Therapy Research, Inflammatory Diseases
(ClinTRID), Karolinska Institutet, Stockholm, Sweden.
6
Autoimmune Diseases Research Unit, Department of
Internal Medicine, BioCruces Health Research Institute,
Hospital Universitario Cruces, University of the Basque
Country, Bizkaia, Spain.
7
The London Lupus Centre, London Bridge Hospital,
London, UK.
on ethnic origin and can be associated in ~15% of these
patients with the antiphospholipid syndrome, which
presents as recurrent pregnancy loss and/or arterial or
venous thrombosis 8 . In addition, patients with SLE are at
risk for accelerated cardiovascular disease (CVD), which
also contributes to damage accrual and mortality 9 .
Mortality from SLE improved in the second half
of the twentieth century, with 10‐year survival at
60% in the 1950s to >90% in the 1980s. The improvement
in survival reached a plateau in the 1980s and
1990s despite improvements in diagnosis and treatment.
This may be owing to increasing levels of SLEassociated
damage accrual and morbidity that occur
with increasing lifespan 10 .
Measuring disease activity in routine clinical care
remains challenging because of disease heterogeneity.
Serological markers are in routine clinical use but do
not adequately predict flares or activity in all patients;
however, some clinical associations are important 11 .
Global disease activity indices, such as the SLE Disease
Activity Index 2000 (SLEDAI‐2K), and organ-specific
scales, such as the British Isles Lupus Assessment Group
(BILAG) index, are used in clinical trials but are not
routine bedside measures 12 .
This Primer explores the nature of SLE and its causes
and effects on patient well-being in more detail. In addition,
the approaches to management and an outlook on
future directions are discussed.
Epidemiology
SLE is a global disease associated with an increased
risk of premature death. The number of people who
have SLE, the age of onset and the mortality risk varies
consider ably between countries 13 . The best information
we have on the incidence, prevalence, mortality and
morbidity outcome are from Europe and North America;
less data are available from Africa, South America, Asia
and Australia (TABLE 1). Given that the disease is least
common in children (before puberty), many studies only
report data from adult populations 14 . Annual incidence
rates in the United States range from 2 to 7.6 per 100,000
and prevalence varies even more widely from 19 to
159 per 100,000 depending on the defin ition of SLE
used, methods of case ascertainment, age standardization
and the racial and ethnic background of the
population 15,16 . Similarly, figures for Europe show
considerable vari ation with annual incidence rates
between 1 and 4.9 per 100,000 and prevalence ranging
from 28 to 97 per 100,000 (REFS 17,18).
SLE is more common in women than in men and
affects women particularly between puberty and menopause
14 . The female/male ratio of 3/1 in children shifts
to about 9/1 between puberty and menopause, but is
up to 15/1 in some studies 19,20 . SLE is more common in
certain racial and ethnic groups 15,20 (TABLE 1). People of
African origin, particularly those who have migrated to
North America or Europe, have a higher incidence and
prevalence of SLE than those of white north European
origin. These individuals also tend to develop the disease
at a younger age, have a higher risk of renal involvement
and of serious renal complications (end-stage renal disease)
15,16,21 . In a study in Georgia, USA, black women
had higher prevalence rates than white women (196.2
per 100,000 versus 59 per 100,000, respectively) 15 . There
is a high incidence of SLE in black people of African-
Caribbean origin 20,22 , Native Americans, (including
Alaska Natives) 23 and Indigenous Australians 24,25 .
Although populations of people with Chinese backgrounds
have been reported to have an increased prevalence
of SLE 26 , lower regional rates have been reported
from Korea 27,28 .
Mortality in patients with SLE has improved over
the past 30 years but remains considerably higher than
in people from the same geographical area without
SLE, with a standardized mortality ratio of 3 in a metaanalysis
29 . People of African, Chinese and Hispanic
origin with SLE have an increased frequency of SLEassociated
renal complications (that is, lupus nephritis)
— one of the strongest predictors of an increased
mortality risk 30,31 . As a result, mortality risk due to active
SLE and associated renal disease is highest in patients
of these ethnicities and/or from low socioeconomic
backgrounds 22,30,31 . Other explanations for the variability
in mortality risk between different populations are
different beliefs and perceptions about the condition as
well as the availability of and adherence to treatments 13 .
Furthermore, infection constitutes another important
and common cause of death in patients with SLE
worldwide (a standardized mortality ratio of 5) 29 . CVD
is strongly associated with premature death later in the
disease course and in those who develop the disease at
an older age (>40 years) 32 .
Mechanisms/pathophysiology
SLE is caused by an autoimmune reaction in which
the innate and adaptive immune systems direct an
inappro priate immune response to nucleic acidcontaining
cellular particles. However, the production
of anti bodies against these nucleic acids (antinuclear
antibodies (ANAs)) is fairly common in the general
popu lation and not all people who have ANAs develop
SLE, suggesting that other mechanisms must promote
2 | 2016 | VOLUME 2 www.nature.com/nrdp
©2016 Mac mill an Publishers Li mited. All ri ghts reserved.