Autoimmunity Reviews 2 (2003) 119–125

The epidemiology of autoimmune diseases

Glinda S. Coopera,*, Berrit C. Stroehlab
a
Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA
b
CODA, Inc., Durham, NC, USA

Received 15 October 2002; accepted 18 November 2002

Abstract

Autoimmune diseases are among the leading causes of death among young and middle-aged women in the
United States. Incidence rates vary among the autoimmune diseases, with estimates ranging from less than one
newly-diagnosed case of systemic sclerosis to more than 20 cases of adult-onset rheumatoid arthritis per 100 000
person-years. Prevalence rates range from less than 5 per 100 000 (e.g. chronic active hepatitis, uveitis) to more
than 500 per 100 000 (Grave disease, rheumatoid arthritis, thyroiditis). At least 85% of thyroiditis, systemic
¨
sclerosis, systemic lupus erythematosus, and Sjogren disease patients are female. Although most diseases can occur
at any age, some diseases primarily occur in childhood and adolescence (e.g. type 1 diabetes), in the mid-adult
years (e.g. myasthenia gravis, multiple sclerosis), or among older adults (e.g. rheumatoid arthritis, primary
systemic vasculitis). Ethnic and geographic differences in incidence of specific autoimmune diseases have been
documented, but specific groups may be at higher risk for some diseases and lower risk for other diseases. The
incidence of type 1 diabetes increased but the rates of rheumatoid arthritis declined over the past 40 years. Thus
although there are commonalities, there are also important demographic differences between diseases. Disease-
specific research, as well as studies that focus on potentially related diseases, needs to be conducted.
䊚 2003 Elsevier Science B.V. All rights reserved.

Keywords: Epidemiology; Incidence; Prevalence; Secular trends; Demographics

1. Introduction The commonality between them, however, is the

Epidemiology can be described as the study of
the distribution, and the determinants of the distri-
bution, of disease within a population. Autoim-
mune diseases as a group represent a diverse
collection of diseases in terms of their demograph-
ic profile and primary clinical manifestations w1x.
*Corresponding author. Tel.: q1-919-541-0799; fax: q1-
919-541-2511.
E-mail address: cooper1@niehs.nih.gov (G.S. Cooper).
damage to tissues and organs that arises from the
response to self-antigens. Research (laboratory-
based and epidemiologic) generally focuses on an
individual disease although there is evidence of
some common genetic and environmental risk
factors across diseases w2,3x.
Autoimmune diseases are generally thought of
as being relatively rare, but their effects on mor-
tality and morbidity are quite high. Autoimmune
diseases are among the leading causes of death
among young and middle-aged women (ages -

1568-9972/03/$ - see front matter 䊚 2003 Elsevier Science B.V. All rights reserved.
PII: S 1 5 6 8 - 9 9 7 2 Ž 0 3 . 0 0 0 0 6 - 5
120 G.S. Cooper, B.C. Stroehla / Autoimmunity Reviews 2 (2003) 119–125
65 years) in the United States w4x. The chronic
nature of many of these diseases results in a
significant impact in terms of medical care utili-
zation, direct and indirect economic costs, and
quality of life.
2. Incidence and prevalence of autoimmune
diseases
Jacobson et al. recently summarized available
studies pertaining to the incidence and prevalence
of specific autoimmune diseases w1x. Data on at
least one of these rates were available for 19 of
the 24 selected diseases. Table 1 summarizes this
analysis, with additional information from studies
of Addison disease w5x, adult-onset type 1 diabetes
w6,7x, juvenile rheumatoid arthritis w8,9x, systemic
sclerosis (scleroderma) w10x, Sjogren
¨ disease w11x
and Wegener granulomatosis and systemic vascu-
litis w12,13x published since this report. The esti-
mated incidence (number of newly diagnosed
cases per year) ranged from less than 1 per
100 000 person-years (e.g. chronic active hepatitis,
myasthenia gravis, primary biliary cirrhosis, scle-
roderma) to more than 20 per 100 000 person-
years (adult-onset rheumatoid arthritis, thyroiditis).
The prevalence (number of people with the disease
at a specific time) ranged from less than 5 per
100 000 (e.g. chronic active hepatitis, uveitis,
Wegener granulomatosis) to more than 500 per
100 000 (Grave’s disease, rheumatoid arthritis,
thyroiditis). The estimated total (summed across
diseases) incidence (90 per 100 000 person-years)
and prevalence (f3%) may be viewed as conser-
vative estimates since there are no data available
for some diseases and since the list does not
include some conditions (e.g. psoriasis, antiphos-
pholipid syndrome).
Data pertaining to adult-onset type 1 diabetes is
particularly sparse and difficult to interpret because
of changes in the definition and classification of
this disease over time. Recent studies from Europe
examine incidence of type 1 diabetes diagnosed at
ages 15–29 years w6x or 15–39 years w7x. Esti-
mates ranged from 4.9 to 13.4 per 100 000 person-
years across countries.
2.1. Demographic patterns with respect to disease
incidence
Almost all autoimmune diseases disproportion-
ately affect women (Table 1). In some diseases
(e.g. thyroiditis, scleroderma, systemic lupus ery-
¨
thematosus, Sjogren disease), 85% or more of
patients are female. The disparity by sex is smaller
in other diseases (e.g. 60–75% female patients in
multiple sclerosis, rheumatoid arthritis). A rela-
tively equal risk between males and females is
seen in some childhood onset autoimmune diseases
(e.g. type 1 diabetes) but in other diseases (e.g.
juvenile rheumatoid arthritis) a female predomi-
nance is seen. The recent studies of adult-onset
diabetes indicate a higher risk among men com-
pared with women w6,7x.
There are notable differences in the age distri-
bution among autoimmune diseases. Although
most diseases can occur at any age, there are clear
peaks of onset (Table 2). The mean age of two
childhood onset diseases, juvenile rheumatoid
arthritis w8,9x and type 1 diabetes w14,15x is
approximately 8–10 years. Recent population-
based studies of systemic lupus erythematosus
w16–19x and of scleroderma w20x provide evidence
that these diseases may occur later than had been
reported in earlier studies in more selected popu-
lations. Other diseases that generally occur
between ages 30 and 50 years include myasthenia
gravis w21x, multiple sclerosis w22,23x, and Grave
disease w24x. An older age at diagnosis (40–70
years) is seen in myositis w25x, thyroiditis w24x,
¨
Sjogren disease w11x, rheumatoid arthritis w26,27x,
Wegener granulomatosis w12x and other types of
systemic vasculitis w13x. Data are not available
concerning the full age distribution of adult-onset
type 1 diabetes.
Differences between the sexes in age at diag-
nosis or onset of specific autoimmune diseases
have been noted. These age differences may pro-
vide evidence of different disease pathways. Sys-
temic lupus erythematosus occurs 5–10 years
earlier among women compared with men but this
difference may be limited to white patients w17x.
In contrast, hyperthyroidism occurs earlier among
men (mean age 35 and 48 years, respectively, for
 G.S. Cooper, B.C. Stroehla / Autoimmunity Reviews 2 (2003) 119–125 121

Table 1
Incidence, prevalence, and sex distribution of autoimmune diseases

Disease Incidence Prevalence Percent

per 100 000 per 100 000 female
person-years (%)
Addison diseasea 0.6 14.0 93
Chronic active hepatitis 0.7 0.4 88
Glomerulonephritis
Primary 3.6 40.0 32
IgA 2.4 23.2 67
Diabetes (type 1)
Age -20 12.2 192.0 48
Age 20 and upa 8.1 No data 35
Grave diseaseyhyperthyroidism
All ages 13.9 1151.5 88
Ages 10–19 No data 106.9 67
Multiple sclerosis 3.2 58.3 64
Myasthenia gravis 0.4 5.1 73
Myocarditis
All ages 0.1 No data 45
Ages -15 4.1 No data 44
Pernicious anemia No data 150.9 67
Polymyositisydermatomyositis 1.8 5.1 67
Primary biliary cirrhosis 0.9 3.5 89
Rheumatoid arthritis
Juvenile (age -16)a 17 148 68
Adult 23.7 860.0 75
Systemic sclerosis (scleroderma) 1.4 4.4 92
¨
Sjogren disease 3.9b 14.4 94
Systemic lupus erythematosus 7.3 23.8 88
Thyroiditisyhypothyroidism
Ages )19 21.8 791.7 95
Ages 10–19 No data 532.1 83
Uveitis 18.9 1.7 50
Vitiligo No data 400.2 52
Wegener granulomatosisa 1.0 3.0 51
Primary systemic vasculitisa 2.0 14.5 43
Total 90 3225 80
a
Except as noted, data from Jacobson et al. w1x.
b
Additional data sources: Addison w5x, adult-onset type 1 diabetes w6,7x, juvenile rheumatoid arthritis w8,9x, systemic sclerosis
¨
w10x, Sjogren disease incidence w11x, Wegener granulomatosis w12,13x, primary systemic vasculitis w13x.

men and women), but there was no difference
between sexes in age at diagnosis for hypothyroid-
ism w24x.
Differences in risk of specific autoimmune dis-
eases among countries or among ethnic groups
living in the same area have been reported. The
pattern is not consistent across autoimmune dis-
eases, however, as specific ethnic groups may be
at higher risk for some diseases but lower risk for
others w28x. The most country-specific data are
available for type 1 diabetes. Type 1 diabetes is
more common in northern European countries
compared with southern European countries; rates
in Asian countries are also low w29x. A similar
pattern is suggested for multiple sclerosis, but
smaller area variation in rates is also evident w30x.
 122
Table 2

G.S. Cooper, B.C. Stroehla / Autoimmunity Reviews 2 (2003) 119–125

Distribution of age at diagnosis of autoimmune diseases

Disease Mean or Approximate References

Median Mid-range
(mean"S.D.)a
Childhood onset
Juvenile rheumatoid arthritis 8 3–13 Peterson et al. w8x, Moe and Rygg w9x
Type 1 diabetes (age -20) 10 6–13 Rangasami et al. w14x, Kostraba et al. w15x
Mid-adult onset
Addison disease 33 15–45 ¨ and Husebye w5x
Løvas
Myasthenia gravis 40 S.D. data not given Kalb et al. w21x
Multiple sclerosis 37 25–45 Nicoletti et al. w22x, Robertson et al. w23x
Systemic lupus erythematosus 40 30–50 Uramoto et al. w16x, McCarty et al. w17x, Hopkinson et al. w18x, Johnson et al. w19x
Systemic sclerosis (scleroderma) 50 35–65 Laing et al. w20x
Grave disease 48 S.D. data not given Vanderpump et al. w24x
Late-adult onset
Dermatomyositisypolymyositis 52 S.D. data not given Marie et al. w25x
Thyroiditis 59 S.D. data not given Vanderpump et al. w24x
¨
Sjogren disease 59 43–75 Pillemer et al. w11x
Rheumatoid arthritis 58 42–74 ¨
Doran et al. w26x, Kaipiainen-Seppanen et al. w27x
Wegener granulomatosis 55 40–70 Cotch et al. w12x
Primary systemic vasculitis 63 S.D. not given Watts et al. w13x
a
Lower value is 1 standard deviation (S.D.) less than the mean and upper value is 1 S.D. greater than the mean, based on noted references.
 G.S. Cooper, B.C. Stroehla / Autoimmunity Reviews 2 (2003) 119–125
In the United States, blacks are at higher risk
compared with whites of systemic lupus erythe-
matosus w17x and scleroderma w10,20x, and age at
diagnosis is approximately 7 years younger among
blacks with these diseases compared with whites
w10,17x. An increased risk of systemic lupus ery-
thematosus has also been reported among Asian
and Afro-Caribbean immigrants in the United
Kingdom w19,31x. Incidence rates for type-1 dia-
betes among blacks and among Hispanics appear
to be lower than among whites w15,32x, and blacks
and Asians living in the United States also have a
lower risk of multiple sclerosis w33x compared
with whites. Rates for rheumatoid arthritis are
similar among whites, blacks and Hispanics w34x.
2.2. Temporal changes in incidence
For most autoimmune diseases, there is little
data concerning recent changes in incidence. Type
1 diabetes, multiple sclerosis, and rheumatoid
arthritis have been studied more extensively. The
temporal patterns with respect to incidence appear
to differ among these diseases. Several studies
have reported increasing rates of type 1 diabetes
over periods ranging from 10 to 40 years. These
data were recently reviewed by Onkamo et al.
w35x. Multiple sclerosis appears to be increasing in
some areas w22,36,37x, but there is less consistency
across studies compared with type 1 diabetes.
However, rheumatoid arthritis ( juvenile and adult-
onset) appears to have declined over this period.
This decline has been seen in studies in the Pima
Indians, a high risk population w38x and in two
areas that have established databases that enable
such analyses (the Mayo clinic-based health care
system in Olmsted County, Minnesota and popu-
lation-based registries in Finland) w8,26,39,40x. In
contrast, an analysis of the Mayo clinic data
pertaining to systemic lupus erythematosus pro-
vides some evidence of an increasing incidence in
this disease w16x.
3. Summary
There are several epidemiologic questions per-
taining to autoimmune diseases and autoantibodies
that require additional research. Basic descriptive
123
information (incidence, prevalence, age, sex, eth-
nic or racial distributions, temporal changes in
incidence) is lacking for many diseases. Although
there may be commonalities between some auto-
immune diseases (e.g. the increased risk experi-
ence by women), autoimmune diseases as a group
do not follow consistent demographic patterns.
Disease-specific research, as well as studies that
focus on potentially related diseases, needs to be
conducted.
Acknowledgments
This research was supported by the Intramural
Research Program of the National Institute of
Environmental Health Sciences and the National
Center for Minority Health and Health Disparities
of the National Institutes of Health.
Take-home messages
● As a group, autoimmune diseases have a signif-
icant impact in terms of overall prevalence and
mortality—at least 3% of the United States
population has an autoimmune disease, and
autoimmune diseases are among the leading
causes of death among young and middle-aged
women.
● Most autoimmune diseases disproportionately
affect women, with at least 65% of patients
being female. Exceptions to the female predom-
inance include type 1 diabetes (childhood- and
adult-onset disease) and the small vessel
vasculidities.
● Differences in risk of specific autoimmune dis-
eases among countries or among ethnic groups
living in the same area have been reported but
specific ethnic groups may be at higher risk for
some diseases and lower risk for others.
● The temporal pattern with respect to incidence
differs among the autoimmune diseases that
have been most extensively studied: type 1
diabetes has increased worldwide over the past
40 years but rheumatoid arthritis ( juvenile and
adult-onset) appears to have declined over this
period.
124 G.S. Cooper, B.C. Stroehla / Autoimmunity Reviews 2 (2003) 119–125
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The World of Autoimmunity; Literature Synopsis

Anti-U3 small nucleolar RNP complex in scleroderma

Sera from 220 scleroderma patients were examined for antinucleolar antibodies, anti-fibrillarin and anti-U3
small nucleolar RNP specific proteins, Mpp10 and hU3-55K (Yang et al., Arthritis Rheum 2002;48:210).
Among these patients, 59 were positive for antinucleolar antibodies, 31 had anti-fibrillarin antibody. Ten
patients had anti-hU3-55K antibodies, and they were all anti-fibrillarin positive, whereas 23 of 29 patients
having anti-Mpp10 antibodies were also anti-fibrillarin positive. The presence of either of these 3
autoantibodies were associated with diffuse rather than limited, systemic or localized scleroderma. The
highest frequency of esophageal and lung involvement was found in patients having anti-Mpp10 alone. The
presence of these autoantibodies in the more severe form of scleroderma adds another evidence for the
association between fibrillarin and small nucleolar RNPs with autoantibody response, and provides clues for
disease pathogenesis.

OxLDL antibodies in myocardial infarction

Oxidized LDL (oxLDL) is a form of LDL which saturates macrophages and turns them into foam cells
within atherosclerotic plaques. Inoue et al. (Cardiology 2002;98:13) measured anti-oxLDL titer in 39 patients
having acute myocardial infarction (AMI). Whereas upon admission with AMI, anti-oxLDL levels were
higher in patients than in controls, within 1 month their titers deceased to those observed in control subjects.
Their main conclusion was that increased anti-oxLDL titer might be a risk factor for AMI. It should be
noticed however that anti-oxLDL antibodies represent autoantibody response directed towards a huge particle
having several antigens, and therefore it is unclear whether all anti-oxLDL reactivity really possesses such a
risk factor.