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Expert Review of Clinical Immunology

ISSN: 1744-666X (Print) 1744-8409 (Online) Journal homepage: http://www.tandfonline.com/loi/ierm20

Epidemiology of systemic lupus erythematosus

Guillermo J. Pons-Estel, Manuel F Ugarte-Gil & Graciela S. Alarcón

To cite this article: Guillermo J. Pons-Estel, Manuel F Ugarte-Gil & Graciela S. Alarcón (2017):Epidemiology of systemic lupus erythematosus, Expert Review of Clinical Immunology, DOI:10.1080/1744666X.2017.1327352

To link to this article: http://dx.doi.org/10.1080/1744666X.2017.1327352

Accepted author version posted online: 04May 2017.Published online: 16 May 2017.

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REVIEW

Epidemiology of systemic lupus erythematosusGuillermo J. Pons-Estel a,b, Manuel F Ugarte-Gil c,d and Graciela S. Alarcón e,f

aDepartment of Autoimmune Diseases, Institut Clinic de Medicina I Dermatologia, Hospital Clinic, Barcelona, Catalonia, Spain; bDivision ofRheumatology and Autoimmune Diseases, Sanatorio Parque, Grupo Oroño, Rosario, Argentina; cServicio de Reumatología, Hospital NacionalGuillermo Almenara Irigoyen, EsSalud, Lima, Perú; dSchool of Medicine, Universidad Científica del Sur, Lima, Perú; eDivision of Clinical Immunologyand Rheumatology, School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA; fDepartment of Medicine, School ofMedicine, Universidad Peruana Cayetano Heredia, Lima, Perú

ABSTRACTIntroduction: Systemic lupus erythematosus (SLE) is a disease distributed worldwide, which occurs inboth genders, and across racial/ethnic and age groups; however, higher rates are observed in adults, inwomen and in non-Caucasians. Genetic, environmental, sociodemographic and methodological issuesare responsible not only for these differences but for the variable course and outcome of the disease.Non-Caucasians have a more severe disease with a higher risk for early mortality and damage accrual.Males also have a more severe disease; however, a negative impact of male gender on lupus outcomeshas not been firmly established. Childhood-onset is associated with a more severe disease; moreover, itis also associated with higher damage and diminished survival; finally, late-onset lupus is mild but it isassociated with higher damage accrual and a diminished survival.Areas covered: In this review, we discuss the incidence and prevalence of SLE, the impact of age,gender and race/ethnicity in SLE and in the survival of those affected.Expert commentary: Age, gender and race/ethnicity impact disease expression in SLE patients; despiteimprovements in survival, mortality in SLE remains almost three times higher than in the generalpopulation.

ARTICLE HISTORYReceived 12 February 2017Accepted 2 May 2017

KEYWORDSSystemic lupuserythematosus; epidemiology;incidence; prevalence; age;gender; race /ethnicity;survival /mortality

1. Introduction

Systemic lupus erythematosus (SLE) is a complex multisyste-mic autoimmune disease characterized by a wide spectrum ofclinical manifestations, overabundance of immunological andlaboratory abnormalities and a variable course and outcome.Epidemiological data available to date derives primarily fromdescriptive, observational and experimental studies, whichhave used a set of classification criteria to include patientswith similar clinical and laboratory abnormalities. Population-based studies have, for the most part, validated the informa-tion from the other studies.

In 1982, the American College of Rheumatology (ACR)developed and validated a set of classification criteria toachieve a consistent definition of SLE for the purpose ofboth, research and epidemiological surveillance; these criteriawere updated, albeit never validated in 1997 [1] and arecurrently used for case definition [2,3]. In 2012, the SystemicLupus International Collaborating Clinics (SLICC) group under-took a revision of the ACR criteria with the aim of establishinga more precise and clinical relevant set; in fact, clinical rele-vance was gained and sensitivity increased but not so speci-ficity when compared with the 1997 revised ACR criteria [4].While the applicability of this new criteria set is to be defined,different groups have evaluated their performance in classify-ing real-life patients; these studies have shown that at leastthe SLICC criteria exhibit similar specificity, better sensitivity

and fewer misclassifications than the ACR criteria [5–7]. TheSLICC criteria clearly offer some advantages over the ACRcriteria as they can classify as lupus patients those withbiopsy-proven nephritis in the presence of autoimmunity mar-kers [antinuclear antibodies (ANAs) and/or anti-dsDNA antibo-dies]. In addition, heightened clinical relevance has beenachieved with the inclusion of manifestations such as alopeciaand neurological manifestations other than psychosis andseizures. Finally, integument manifestations have beengrouped under acute and chronic cutaneous lupus. In sum-mary, the SLICC classification criteria seem to perform betterthan the revised 1997 ACR criteria in terms of sensitivity, but atthe cost of losing some specificity [8].

2. Lupus worldwide

Using for the most part the ACR criteria (1982 or 1997), theoverall incidence rates for SLE have varied from approximately0.3–23.7 per 100,000 person-years [9,10] whereas prevalencerates have ranged from 6.5 to 178.0 per 100,000. Data for themost salient incidence and prevalence studies are summarizedin Table 1.

The variations observed in these rates across the worldmost likely represent differences in patients’ characteristicssuch as age, gender, ethnic/racial background, socioeconomicstatus (SES), geographic region and national origin and envir-onmental exposures. However, differences in case

CONTACT Graciela S. Alarcón galarcon@uab.edu 832 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294-3408, USA

EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 2017https://doi.org/10.1080/1744666X.2017.1327352

© 2017 Informa UK Limited, trading as Taylor & Francis Group

Table1.

Dataon

system

iclupu

serythematosus

(SLE)incidenceandprevalence

arou

ndtheworld.

Coun

try/

geog

raph

ical

Area

Authors[reference]

Case

defin

ition

(ACR

1982,A

CR1997,o

rother)

Stud

ytype

No.

ofpatients

Ethn

icdistrib

ution

Age

(years)

Gender

Stud

yperio

d

Incidence(cases

per

100.000person

s-years)(F/M

)

Overallprevalence

(cases

per100.000

inhabitants)

(F/M

)

Europe

Denmark/Funen

Voss

etal.[11]

ACR1982

Centralp

opulationregistry

Hospitalrecords

(autoimmun

etest

+)

Physicians

survey

127

C≥15

11%-M

1980–1994

3.6(NA/NA)

21.7

(37.9/4.7)

Denmark/Funen

Laustrup

etal.[12]

ACR1982

Centralp

opulationregistry

Hospitalrecords

(+autoimmun

etest)

Physicians

survey

109

C≥15

NA

1995–2003

1(NA/NA)

28.3

(NA/NA)

Estonia

Otsaet

al.[13]

ACR1982

ICD-10

Estonian

health

insurancefund

database

677

All

≥15

NA

2006–2010

1.5–1.8(NA/NA)

39–48(NA/NA)

Denmark

Hermansenet

al.[14]

ICD-10

Nationalp

atient

registry

1644

Alle

thnicities

≥18

14%-M

1995–2011

2.3(4.0/0.7)

NA

Finland

Helve

[15]

NA

Hospitalrecords

Causeof

deathregistries

NA

Alle

thnicities

NA

NA

1976–1978

NA

28

Finland,

all

region

sElfvinget

al.[16]

ACR1997

ICD-10

Nationalh

ealth

insurance

566

Alle

thnicities

All

13%-M

2000–2007

1.7(2.9/0.5)

NA

France,all

region

sArnaud

etal.[17].

ICD-10

French

natio

nala

dministrative

databases

27,369

Alle

thnicities

All

12%-M

2010

3.3(5.5/0.9)

47(79.1/11.8)

Germany

Brinks

etal.[18]

ICD-10

Federalstatisticalofficedataset

845

Alle

thnicities

All

19.5%-

M2002

NA

36.7

(55.4/15.4)

Germany

Brinks

etal.[19]

ICD-10

Federalstatisticalofficedataset

845

Alle

thnicities

All

19.5%-

M2002

NA(1.9/0.9)

NA

Greece,

Northwest

Alam

anos,etal.[20]

ACR1982

Hospitalrecords

Physicians

survey

178

Alle

thnicities

All

11.8%-

M1982–2001

2.1(3.7/0.5)

39.5

(69.3/9.5)

Iceland

Gud

mun

dsson,

etal.[21]

ACR1982

Hospitalrecords

Physicians

survey

76Alle

thnicities

NA

NA

1975–1984

3.3(5.8/0.8)

35.9

(62.0/7.2)

Ireland

,Northern

Gou

rleyet

al.[22]

NA

Clinicalrecords

Physicians

survey

415

C(414)

AS(1)

All

8.1% (422)

1992–1993

NA

25.4

(46.5/4.3)

Italy,Florence

Benu

ccie

tal.[23]

ACR1997

Clinicalrecords

Patient

evaluatio

n23

C(22)

AF(1)

≥18

0%-M

2002

NA

71.0

Italy,Ferrara

Govon

ietal.[24]

ICD-9 ACR1982

Hospitalrecords

Clinicrecords

201

C≥16

10.0%-

M1996–2002

2.6

57.9

(100.1/12.0)

Italy,Valtrom

pia

Tsioni1et

al.[25]

ACR1997

Hospitalrecords

Clinicrecords

44C(38)

A(3)

I(2)

C/A(1)

All

11.0%-

M2009–2012

2.0(3.9/0)

39.2

(68.8/9.0)

Norway,A

rtic

Region

Nossent

[26]

ACR1982

Hospitalrecords

Mortalitydataset

83C

≥16

12.0%-

M1978–1996

2.6(4.6/0.6)

44.9

Russian

Federatio

nNason

ovet

al.[9]

ACR(NA)

Hospitalrecords

79C(72)

AS(1)

6Unkno

wn

≥18

2.5%

-M2010

1.4(NA)

9(15.8/0.5)

Sweden,Sou

thNived

etal.[27]

ACR1982

Hospitalrecords

65C

NA

NA

1981–1982

4.8(7.6/2.0)

38.9

(64.8/11.7)

Sweden,Sou

thStåhl-H

alleng

renet

al.[28]

ACR

Hospitala

ndclinicalrecords

379

NA

NA

NA

1986–1991

4.1

68.0

Sweden,Sou

thJonsson,

etal.[29]

NA

Hospitala

ndclinicalrecords

Physicians

survey

39NA

NA

NA

1981–1986

4.0(5.4/1.0)

NA

Sweden,A

llSimardet

al.[30]

ICD7–10

Patient,d

rugandpo

pulatio

nregistry

Mortalityregistry

7929

(Lenient)

5939

(Strict)

Alle

thnicities

All

15%-M

13%-

M

2010

NA

85(144/25)

46(79/12)

(Con

tinued)

2 G. J. PONS-ESTEL ET AL.

Table1.

(Con

tinued).

Coun

try/

geog

raph

ical

Area

Authors[reference]

Case

defin

ition

(ACR

1982,A

CR1997,o

rother)

Stud

ytype

No.

ofpatients

Ethn

icdistrib

ution

Age

(years)

Gender

Stud

yperio

d

Incidence(cases

per

100.000person

s-years)(F/M

)

Overallprevalence

(cases

per100.000

inhabitants)

(F/M

)

Sweden,Lun

dIngvarsson

etal.[31]

ICD10

Hospitala

ndclinicalrecords

174

Alle

thnicities

>15

15%-M

1981–2006

1981–

1995

1996–

2006

3.9 5.0

2.8

55 65

Spain,

Lugo

Alon

soet

al.[32]

ICD-9 ACR1982

Hospitala

ndclinicalrecords

150

Alle

thnicities

≥15

15.3%-

M1987–2006

3.6(5.9/1.1)

17.5

(29.2/5.8)

Spain,

Asturias

Lopezet

al.[33]

ACR1982

Hospitala

ndclinicalrecords

367

CAll

11.7%-

M1998–2002

2.2(3.6/0.5)

34.1

(57.9/8.3)

Turkey,H

avsa

Cakıret

al.etal.[34]

ACR1982

Commun

itysurvey

andho

spital

records

8All

All

10%-M

NA

NA

59(104/12)

Turkey,Thrace

Pamuk

etal.[35]

ICD10

Hospitalrecords

331

All

≥15

7.3%

-M2003–2014

4.4(8.4/0.6)

51.7

(97.7/7.0)

UK,

England

andWales

Hochb

erg[36]

ICD-9

Nationalm

orbidity

survey

20All

All

0%-M

1981–1982

NA

6.5(12.5/2.0)

UK, N

ottin

gham

Hop

kinson

etal.[37]

NA

Hospitala

ndclinicalrecords

Physicians

survey

147

C AC AS

NA

NA

1989–1990

4(6.5/1.5)

24.6

(45.4/3.7)

UK,

Birm

ingh

amJohn

sonet

al.[38]

ACR1982

Hospitala

ndclinicalrecords

Physicians

survey

242

C(155)

AC(50)

AS(36)

≥18

6.2%

-M1991

3.8(6.8/0.5)

27.7

(49.6/3.6)

UK,

allcou

ntries

Rees

etal.[39]

ICD-10

ACR1982

Clinicalpracticeresearch

datalink

7732

Alle

thnicities

All

14.0%-

M1999 2012

5.1 4.6

64.9 97.0

Ukraine

Nason

ovet

al.[9]

ACR(NA)

Hospitalrecords

45C

≥18

11.1%-

M2010

0.3

14.9

(23.8/3.7)

North

America

USA

,California

Fessel

[40]

NA

Inpatient

andou

tpatient

records

NA

NA

NA

NA

1965–1973

7.6

50.8

USA

,Baltim

ore

Hochb

erg[41]

ICD-8 ARA1971

Hospitalrecords

302

AA(223)

C(79)

All

13.0%-

M1970–1977

4.6

NA

USA

,Rochester

Michetet

al.[42]

NA

NA

25Alle

thnicities

NA

NA

1950–1979

1.8(2.5/0.9)

40(53.8/19.0)

USA

,Rochester

Uramotoet

al.[43]

ACR1982

Hospitala

ndclinicalrecords

48Mostly

CAll

NA

1980–1992

5.6(9.4/1.5)

130

USA

,Pittsburgh

McCarty

etal.[44]

ICD-9 ACR1982

Hospitala

ndclinicalrecords

191

C,AA

,OAll

7.9%

-M1985–1990

2.4

NA

USA

,Rural

Wisconsin

Nalew

ayet

al.[45]

ICD-9 ACR1982

Hospitala

ndclinicalrecords

117

Mostly

CAll

NA

1991–2001

5.1(8.2/1.9)

78.5

(131.5/24.8)

USA

,Arizon

aBalluzet

al.[46]

ACR1982

Hospitala

ndclinicalrecords

Popu

latio

nsurvey

20Mostly

HAll

NA

1997

NA

103

USA

,Southeastern

Michigan

Somerset

al.[47]

ICD-9 ACR1997

SNOMED

Hospitala

ndclinicalrecords

Medicaidclaims

USrenald

atasystem

2139

AA(1219)

C(820)

H(39)

All

8.5%

-M2002–2004

5.6(9.3/1.6)

72.1

(128.7/12.4)

USA

,Southeastern

Michigan

Hou

seyel

al.[48]

ACR1997

Hospitala

ndclinicalrecords

2296

AR+CH

(54)

AA(1356)

C(886)

All

8.9%

-M2002–2005

7.6(13.6/2.7)

3.7(6.2/1.1)

8.8(14.2/2.3)

62.6

(120.5/16.2)

52.3

(93.8/10.0)

120.1(200.0/

20.8)

USA

,Olmsted

Coun

ty,

Minnesota

Ung

prasertet

al.[49]

ICD-9 ACR1997

SLICC

Hospitala

ndclinicalrecords

44(ACR

)58

(SLICC

)84%

C7%

AA5%

AS2%

AI

≥18

NA

1993–2005

ACR3.7

SLICC4.9

NA (Con

tinued)

EXPERT REVIEW OF CLINICAL IMMUNOLOGY 3

Table1.

(Con

tinued).

Coun

try/

geog

raph

ical

Area

Authors[reference]

Case

defin

ition

(ACR

1982,A

CR1997,o

rother)

Stud

ytype

No.

ofpatients

Ethn

icdistrib

ution

Age

(years)

Gender

Stud

yperio

d

Incidence(cases

per

100.000person

s-years)(F/M

)

Overallprevalence

(cases

per100.000

inhabitants)

(F/M

)

USA

,Alaska,

Phoenixand

Oklahom

a

Feruccie

tal.[50]

ICD-9 ACR1997

Indian

health

servicenatio

nald

ata

warehou

se285

AI(155)

AN(130)

All

11.9%-

M2007–2009

7.4(40.4/-)

178(271/54)

USA

,47States

and

Washing

ton

DC

Feldman

etal.[10]

ICD-9

Medicaidanalyticextract

34,339

AA(13,236)

H(4,767)

A(1,452)

NA(515)

C(12,436)

18–65

6.7%

-M2000–2004

23.7

(30.5/4.9)

143.7(192.2/31.8)

USA

,Georgia

Lim

etal.[51]

ICD-9 ACR1997

Hospitala

ndclinicalrecords

1320

(1156p)

AAp(889)

Cp(251)

All

9.8% p-M

2002–2004

5.6(9.4/1.7)

74.4

(131.3/14.9)

USA

,Haw

aii

Kurahara,etal.[52]

ACR1982

Hospitala

ndclinicalrecords

69All

≤18

NA

1993–2002

NA

18.3–25.7

Canada,

Manito

baPeschekenet

al.[53]

ACR1997

Region

alarthritiscenter

database

Hospitala

ndclinicalrecords

49 208

NA

NA

NA C

1980–1996

2.0–7.4

0.9–2.3

42.3 20.6

Canada,A

lberta

Barnabeet

al.[54]

ICD-9

Administrativedatabases

Hospitala

ndclinicalrecords

NA

FirstNations

Non

–First

Nations

NA

NA

1994–2007

NA

NA(322/32)

NA(271/32)

Canada,Q

uebec

Bernatsky,et

al.[55]

ICD-9

Quebechealth

insurancebo

ard

Hospitala

ndclinicalrecords

2455

NA

All

NA

1989–2003

3.0

32.8

(44.7regression

mod

el)

Canada,N

ova

Scotia

Hanly,etal.[56]

7individu

alcase

defin

ition

sHospitala

ndclinicalrecords

373

NA

NA

22.1%-

M2000–2010

2.9–25.5

17.2–92.0

Mexico

Peláez-Ballestas

etal.[57]

ACR1997

COPC

ORD

15NA

≥18

NA

2005

NA

70(90/40)

Mexico,

Southeastern

Alvarez-Nem

egyeie

tal.[58]

ACR1997

COPC

ORD

3NA

≥18

NA

2005

NA

70

Central

Americaan

dCa

ribb

ean

Island

Barbados

Flow

eret

al.[59]

ACR1997

Hospitala

ndclinicalrecords

226

AC(98%

)All

6.0%

-M2000–2009

6.8(12.2/0.8)

84.1

(152.6/10.1)

Cuba,H

avana

Reyes-Llerenaet

al.[60]

ACR1997

COPC

ORD

2NA

≥15

0%-M

2006

NA

60Cu

racaoisland

Nossent

[61]

ICD-9 ACR1982

Hospitalrecords

Deadcertificates

94AC

All

11.7%-

M1980–1989

4.6(7.9/1.1)

47.6

(83.8/8.5)

Martin

ique

island

Deligny

etal.[62]

ACR1982

Hospitalrecords

Mortalityregistry

286

ACAll

7.37%-

M1990–1999

4.7(8.5/0.7)

64.2

(115.0/9.2)

SouthAmerica

Argentina,

Buenos

Aires

Scolniket

al.[63]

ACR1997

Hospitalrecords

75C(75)

All

16.2%-

M1998–2008

6.3(8.9/2.5)

58.6

(83.2/23.0)

Brazil,Minas

Gerais

Senn

aet

al.[64]

ACR1997

COPC

ORD

3All

≥16

33.3%-

MNA

NA

98(110/90)

Brazil,Natal

Vilaret

al.[65]

ACR1997

Hospitala

ndclinicalrecords

43AL

(6)

M(4)

C(33)

≥16

11.6%-

M2000

8.7(14.1/2.2)

NA

Peru,Tam

boViejo-

Cieneguilla

Gam

boaet

al.[66]

ACR1997

COPC

ORD

3All

≥18

NA

2004

NA

50

Venezuela,

Mon

agas

Granado

set

al.[67]

ACR1997

COPC

ORD

1NA

≥18

NA

2011

NA

70 (Con

tinued)

4 G. J. PONS-ESTEL ET AL.

Table1.

(Con

tinued).

Coun

try/

geog

raph

ical

Area

Authors[reference]

Case

defin

ition

(ACR

1982,A

CR1997,o

rother)

Stud

ytype

No.

ofpatients

Ethn

icdistrib

ution

Age

(years)

Gender

Stud

yperio

d

Incidence(cases

per

100.000person

s-years)(F/M

)

Overallprevalence

(cases

per100.000

inhabitants)

(F/M

)

Asia

Asian-Pacific

region

Jakeset

al.[68]

ACR1997

System

aticreview

NA

Alle

thnicities

All

NA

1973–2006

0.9–3.1(1.4–5.4/

0.4–0.8)

4.3–45.3

(7.7–68.4/

0.8–7.0)

China,An

hui

Zouet

al.[69]

ACR1997

Patient

evaluatio

n471

ASAll

8.7%

-M2009–2010

NA

37.6

(70.3/6.4)

China,Hon

gKong

Mok

etal.[70]

ACR1992

Hospitalrecords

442

ASAll

9%-M

2000–2006

3.1(5.4/0.8)

NA

Iran,

Zahedan,

Sanand

ajand

Tuyserkan

Davatchie

tal.[71]

NA

COPC

ORD

NA

All

≥15

NA

2004–2012

NA

60

Iran,

Tehran

Davatchie

tal.[72]

NA

COPC

ORD

3All

≥15

0%-M

2004–2005

NA

40(80/0)

Iran,

Sanand

ajMog

himie

tal.[73]

NA

COPC

ORD

NA

C(Kurdish)

≥15

NA

2011–2012

NA

50Japan,

Okinawa

Isekie

tal.[74]

NA

Hospitalrecords

566

ASNA

9%-M

1972–1991

0.9–2.8(1.4–4.7/

0.4–0.8)

4.3–37.7

(7.7–68.4/

0.8–7.0)

Japan

Kameda[75]

NA

Hospitalrecords

108

ASNA

NA

1975–1977

1.0

10.8

Kazakhstan

Nason

ovet

al.[9]

ACR(NA)

Hospitalrecords

525C

47AS

≥18

3.8%

-M2010

1.6

20.6

Malaysia,Ku

ala

Lumpu

rWanket

al.[76]

ACR1982

Hospitalrecords

539

ASAll

7%-M

1974–1990

NA

43

Saud

iArabia,

Al-Qaseem

Al-Arfaj

etal.[77]

ACR

Commun

itysurvey

2NA

NA

NA

1992

NA

19.3

SouthKorea

Juet

al.[78]

ICD-10

ACR1982

Health

insurancereview

9,000–11,000

All

All

NA

2004–2006

NA

18.8–21.7

UnitedArab

Emirates,Al

Ainregion

Dhanh

anie

tal.[79]

ICD-9 ACR1982

SLICC

Hospitalrecords

16All

NA

18.8%-

M2009–2012

8.6(14.1/3.2)

103(188.5/20.3)

Ocean

iaAu

stralia

Anstey

etal.[80]

NA

Hospitalrecords

Physicians

survey

22Ab

origines

NA

NA

1984–1991

1152.6

(100.0/5.25)

Australia

Bossingh

am[81]

ACR1982

Hospitalrecords

Physiciansurvey

180

Aborigines

(26)

Non

-Ab

origines

(86)

All

9.3%

-M1996–1998

NA

45.3

(overall)

92.8

(Abo

rigines)

NA:

notavailable;ICD:Internatio

nalC

lassificatio

nof

Diseases;SN

OMED

:systematized

nomenclatureof

medicinecodesforpatholog

yrepo

rts;CO

PCORD

:Com

mun

ityOriented

Prog

ram

fortheCo

ntrolofR

heum

aticDiseases;C:

Caucasian;

A:African;A

A:African-American;A

C:Afro-Caribbean;A

S:Asian;

AI:A

merican

Indian;A

N:A

laskaNative;AR

:Arab;

CH:C

haldean;

H:H

ispanics;I:Ind

ians.

EXPERT REVIEW OF CLINICAL IMMUNOLOGY 5

ascertainment (self-reported, physician diagnosed, inclusion ofserologic tests), study type and time at which the study wasconducted may also explain these differences.

Childhood SLE incidence and prevalence rates are consid-erably lower than adult rates. The annual incidence rate of SLEin children (<16 years) has been reported to be less than 1 per100,000 persons in studies from Europe and North America[82]. In China, the prevalence of childhood SLE was estimatedas 6.3 per 100,000 [83]. Nationwide Medicaid claims data fromadult SLE patients reveal the following incidence and preva-lence rates by age group (18–29, 30–49, and 50–64) 14.3/27.9/29.7 and 78.9/200.3/292.4 per 100,000 inhabitants, respec-tively [10].

It is widely known that SLE is much more common inwomen than in men with a ratio close to 9:1. In the afore-mentioned Medicaid study the incidence and prevalence ofSLE was six times higher in women (30.5 and 192.2, respec-tively) than in men (4.9 and 31.8, respectively) [10]. Markeddifferences in incidence and prevalence SLE rates accordingto ethnic group have been observed. Overall, non-Caucasians experience higher rates than Caucasians. Thiswas nicely illustrated in a population base study performedin the Metropolitan Districts of Birmingham and Solihull,England [38] in 1992. In this study, the overall incidenceand prevalence rates were 11.9 and 111.8 for Afro-Caribeans, 11.5 and 46.7 for Asians and 2.5 and 20.7 forCaucasians [38]. Whereas SES does not appear to impactthe incident of SLE, Feldman et al. found that patients withlow SES exhibited the highest prevalence rate (167.9 per100,000) in the Medicaid study [10]. This may suggest thatin addition to genetics, occupational (particularly to silicadust), environmental (exposures hazardous wastes and airpollution) and psychosocial stress that are more common inlow SES neighborhoods may be responsible for the higherprevalence of SLE in this group of patients.

Several environmental factors may influence SLE occur-rence; in a population-based study performed in general resi-dents in rural areas of China, multiple environmental factors,including birth conditions, sweet food, cooking oil, fruit con-sumption, sunlight exposure, quality of sleep, physical activ-ities, drinking water, residence, negative life events, hepatitis Bvaccine, age of menarche, and age at birth of first child werefound to affect SLE rates [69].

SLE has been described worldwide, however, it seems to beinfrequent in the African continent but surprisingly commonin African descendants (Afro-Caribbean, African-American andAfro-Latin-American) around the world. A possible explanationcomes from the ‘prevalence gradient’ hypothesis, which sug-gest that Africans descendants present a genetic backgroundand environmental exposures that are different than in theirnative countries and predispose them to present higher SLEincidence rates; in turn, African patients living in their nativecountries may experience competing causes of death whichmay diminish the incidence of SLE; furthermore, prevalence isaffected by reduced survival for patients inadequately treated[84]. It should also be stressed that there are no good qualityprevalence data published from West Africa, assumptions areusually made from a United Kingdom study of immigrantwomen which revealed a SLE prevalence three-times higher

among them than in Caucasian but not as high as in patientsof Afro-Caribbean origin [85].

It is important to clarify that most of the previous studiesdiffer in their recruitment methodology. While some only useinpatient and outpatient medical records based on the ACRcriteria [38] others use international classification of disease(ICD) codes, drugs prescriptions and cause of death registriesleading to important variability in SLE prevalence and incidentrates [30]. Variations on prevalence rates as a function of thedefinition used can be appreciated in a Swedish population-based study were the overall prevalence of SLE ranged from46 and 85 per 100,000 inhabitants depending on the strictnessof the case definition used [30]. Similarly, differences can beobserved as a function of the criteria used; for example,Ungprasert et al. established that the adjusted incidence inpatients living in Olmsted County, Minnesota, was statisticallyhigher using the SLICC than the ACR criteria (4.9 vs. 3.7 per100,000 person-years, p = 0.004) [49].

Some temporal variation in the incidence and prevalenceof SLE has been observed. Uramoto et al. demonstrated in aUS population-based study, that SLE has more than tripledover the past 40 years [43]. This increase likely reflects not onlyan actual increase in disease occurrence but a more accurateascertainment of cases, the inclusion of milder cases of SLEand the widespread use of antinuclear antibody testing. Incontrast to this study, a recent retrospective cohort studyutilizing a UK clinical practice research datalink shows adecline in the annual SLE incidence of 1.8% while in contrastthe prevalence increase from 64.9 per 100,000 in 1999 to 97.04in 2012 [39].

The prevalence estimates increased with time during the1990s. This was suggested to be due to recording a relapsing-remitting disease within a longitudinal database, rather thanan actual increase in prevalence [86]. However, one of theincidence studies found a small but non-significant increasein the incidence of SLE in females over time and studies inother European countries have found an increased temporaltrend [11,20].

3. Factors that affect the course of SLE

3.1. Impact of age

Age is one of the major factors affecting the clinical manifes-tations and prognosis of SLE patients. SLE may develop at anyage, although its peak incidence occurs during the reproduc-tive age years; in the majority of adult and pediatric cohortsthe mean age at diagnosis has varied from 24 to 32 and 12 to17 years, respectively [87,88].

There is no consensus regarding the appropriate cut offage defining ‘pediatric’ or ‘childhood onset lupus’, with moststudies using either 16 or 18 years. Childhood onset lupus(cSLE) represents 10–20% of all SLE cases. As with adults,Caucasian children experience lower SLE incidence and pre-valence rates and milder disease, characterized predominantlyby malar rash, thrombocytopenia, and a low incidence of renaldisease than non-Caucasian children [89].

Clinical manifestations of adult and cSLE are identical,although children, overall, experience a higher frequency of

6 G. J. PONS-ESTEL ET AL.

renal, neurologic and hematologic involvement than theiradult counterparts. Renal involvement can be present in 81%of children compared with 46% of adults [90] and is often apresenting feature occurring within 2 years from disease onsetin 90% of the patients; histological class distribution of lupusnephritis in children is similar than in adults [91].

cSLE patients show more pronounced disease activity thanadults as reported by Ramírez-Gómez et al. in a study compar-ing Latin American SLE inception cohorts of children (N = 230)and adults (N = 948); the median SLE Disease Activity Indexwas 13 [interquartile range 8–19) in cSLE and 11(interquartilerange 7–17) in adults] and the difference was statisticallysignificant (p < 0.01) [92]. The most pronounced differencesin disease activity between adult SLE and cSLE pertain to therenal and neurologic organ systems [93]. Control of diseaseactivity is likely to result in a greater requirement of oralcorticosteroids (over 90%), intravenous methylprednisoloneand immunosuppressive medications [90,91]. Disease activityand exposure to corticosteroids at high doses and for longertime than in adults contribute to greater damage accrual incSLE. Brunner et al. compared Canadian children and adult SLEinception cohorts, demonstrating significantly higher meanSLICC damage index scores (SDIs) in the children (1.7 vs.0.76; p = 0.008). The observed frequency of overall damagein cSLE fluctuates between 39% and 65%, with mean SDIscores of 0.6–2.3 after a median follow-up of 4.1–6.8 years.The most frequently affected organ systems in cSLE are themusculoskeletal, renal, ocular and neuropsychiatric systems[90,91,94].

The 5-year survival rates in juvenile SLE patients in theWestern world are now 94–100%; however, the 10-year survi-val rate remains disappointing at only 81–92% in juvenile SLE[95,96] with lower rates (65%) in Asian patients with asso-ciated renal involvement [97]. Moreover, juvenile SLE con-tinues to carry a higher mortality risk than adult SLE which iseven evident in adolescents compared to adults as reported inthe LUMINA cohort [90].

On the contrary, late-onset lupus (age 50 years and above)tends to have a more insidious onset, the very first manifesta-tions being non-specific (arthralgias, weakness, fatigue, myal-gias, weight loss, pyrexia, or loss of cognitive function). Majororgan system involvement (renal and neuropsychiatric) is lessfrequent, lower degrees of disease activity are observed, yetthese patients tend to have a poor outcome, in terms of bothdamage accrual and mortality [98].

3.2. Impact of gender

Lupus is more frequent in females than males, in particular infemales of child-bearing age, with a female:male ratio of8–15:1 [99]. In pre-puberal and late-onset lupus the ratio is2–8:1 [99]. The SLE clinical phenotype differs some betweenfemales and males; males present less frequently arthritis/arthralgia [100–107] although there are some exceptions(among Turkish patients, arthritis was found to be more fre-quent in male patients [108], photosensitivity [102,104,106–109] malar rash [101,104,107,110], oral ulcers[104,107,110,111], alopecia [102–106,108,112] and Raynaud’sphenomenon [102–108,110]; in turn, they present more

frequently discoid lesions [101,105,110], subacute cutaneouslesions [101], serositis [107–110,112], renal disease [102–104,106,107,109,113], fever [106], weight loss [106], myositis[102], lymphopenia [104,107,113], and hemolytic anemia [106]whereas the data for hematological and central nervous sys-tem manifestations are still controversial[100,103,104,107,110,112,113]. Regarding flares, they werefound to be less frequent in males in a study from China[105]. As to serological features, a lower prevalence of anti-Ro [100,105,107,110] and anti-La [107], and a higher preva-lence of anti-Smith [104], antids-DNA [104,107], Coombs posi-tivity [104], and hypocomplementemia [104,106] have beenreported in male SLE patients.

In addition, male patients present a higher frequency ofthrombosis [102,104,107], including antiphospholipid antibo-dies [104,106,107,114], antiphospholipid syndrome [102] andhypertension [104,106,109]; there is, however, some contro-versial data about a lower frequency of IgM anticardiolipin wasfound in male patients from the United Kingdom [111]).

In addition, as male SLE patients present a higher fre-quency of kidney involvement, hypertension is not uncom-mon among them which also conveys a worse prognosis; thus,it would be expected that male patients would present anincreased risk of damage and earlier mortality. In fact, in theLUMINA study [114] an association between male gender andearly damage occurrence was found; however, that has notbeen the case for studies emanating from Latin America [106],Greece [110], and China [105]. In the Hopkins Lupus cohort[104], an association between male gender and some SDIcomponents like seizures, myocardial infarction, angina,thrombosis, and kidney involvement was found.Furthermore, kidney damage [105] and cardiovascular involve-ment were found to be associated with male gender in studiesfrom Asia and Latin America [106]. In terms of mortality, thedata are still controversial; in favor of a higher mortality inmales are studies from the Hopkins [104], Duke’s [115],Germany and Toronto cohorts, and the Carolina Lupus Study[116]. However, data from the United Kingdom [111] and LatinAmerica [106,117] have not confirmed this finding. Whetherthe phenotypic differences in SLE as a function of gender aredue to differences in the genetic load is controversial[118,119].

3.3. Impact of race/ethnicity

Ethnicity is a biological and social construct, including not onlygenetic ancestry, but also cultural characteristics (language,religion, values, social behaviors, country of origin) yet it isan arbitrary definition [120]. Race is oftentimes used inter-changeable with ethnicity but it mainly refers to the biologicalfeatures of groups of people. Given that there are differencesin the clinical characteristics and prognosis among differentpopulations, it is worth evaluating the impact of race/ethnicityin SLE. Genetic ancestry influences the risk for the incidence ofSLE; for example, Amerindian ancestry is associated with anincreased number of risk alleles for SLE [121], and also with anearly age at onset [122], Amerindian and African ancestry areassociated with a higher risk for kidney involvement [122,123]and European ancestry with a lower risk [124]. Among

EXPERT REVIEW OF CLINICAL IMMUNOLOGY 7

European descendants, Southern Europeans present a higherrisk of renal involvement and auto-antibody production butwith a lower risk of discoid rash and photosensitivity; serositisand autoantibody production is associated with WesternEuropean background, compared to Eastern European; finally,Ashkenazi Jewish seem to be protected from the occurrenceof neurologic manifestations [125].

Phenotypic differences in SLE between Caucasians and not-Caucasian are depicted in Table 2. In addition, general mani-festations are less frequent in Asian patients and Aboriginalsfrom Canada than African descendants [126]. Fever is also lessfrequent in Mestizo than in African descendants [127].Cutaneous vasculitis and mononeuritis multiplex are morefrequent in Aboriginals from Canada [126]. Asians fromCanada have a lower frequency of arthritis and serositis thanpatients from the other ethnic groups (Caucasians, Africandescendants, and Canadian Aboriginals) [126]. Seizures occurmore frequently in African descendants and tend to be morefrequent in Hispanics than in Caucasians; they seem to be lessfrequent in Asians [128].

Kidney involvement is one of the most worrisome manifes-tations of SLE, and it is more frequent in Hispanics, Mestizos,African descendants and Asians [126,127,184,185]; Hispanicsand African descendants are also at higher risk of developingend-stage renal disease than Caucasians [186]. Furthermore,response to treatment in lupus nephritis is not uniform acrossdifferent ethnic groups; for example, in the entire populationof the Aspreva Lupus Management Study, mycophenolate andcyclophosphamide groups had similar rates of response, but,Hispanic patients have better rate of response to mycopheno-late mofetil than to cyclophosphamide [187].

Hispanics and African descendants experience higher levelsof disease activity as compared to Caucasians [188]; further-more, after disease onset, disease activity declines slowly inHispanics, followed by African descendants while inCaucasians it declines faster [189]. In addition, non-Caucasians (Hispanics, Asians, and African descendants)experience damage accrual more frequently and of highermagnitude [190–193]. However, this was not bore down inAsians from the SLICC cohort who experience new damageless frequently than European Caucasians [193]. In relation tothe pattern of damage, renal damage occurs more frequentlyin Hispanics, African descendants, and Asians than inCaucasians [184,191,192,194]; integument and diabetes inAfrican descendants [184,190,192], ocular in Hispanics andCaucasians [184]; gastrointestinal and malignancy inCaucasians [184] whereas ocular and cardiovascular damageoccur less frequently in Asians, compared to Caucasians [194].However, socioeconomic factors like health insurance[127,195], education level [127,192], poverty [190,192], help-lessness [195] and abnormal illness behaviors [192,195] alsoimpact on damage accrual and could explain, at least in part,the impact of ethnicity on this intermediate outcome.

As to mortality, several cohort studies have reported highermortality rates among African descendants and Hispanics com-pared to Caucasians; however, when socioeconomic factors arefactored into the analyses, ethnic group is no longer significant[115,171,196]; the exception being the Duke’s cohort in which

the rates were still higher in the non-Caucasians after adjustingfor SES [197]. In contrast, Asian patients from the Toronto cohort[198] has a similar survival rate than the rest of the members ofthe cohort (Caucasian, by and large); furthermore, SLE patientsfromHong Kong [159] had a survival rate at 5 years of 93%whichis similar to the rates observed in Caucasians worldwide. Withinethnic groups there are also some difference; for example, theAfrican descendant Gullah patients from the Sea Islands regionof South Carolina, USA have a higher frequency ofmalar rash andphotosensitivity and lower frequency of hematologic involve-ment than African descendant patients from the PROFILE cohortand the Lupus Multiplex Registry and Repository study [199]. Inaddition, Hispanics, as defined in the United States (descendantsfrom a Spanish speaking-country) are a heterogeneous group;not surprisingly, therefore, those from Texas (with a largeAmerindian ancestral background) have a more severe diseasethan Hispanics from Puerto Rico, including higher disease activ-ity, more damage accrual, more frequent renal involvement,psychosis and thrombocytopenia but less frequent cutaneousinvolvement [200]. These data taken together, suggest that evencurrent racial/ethnic group classification is rudimentary to com-pletely explain the differences in the expression and outcome ofthe disease among populations.

3.4. Mortality and survival in SLE

The survival of SLE patients has been improving over the past60 years with an increase of the five-year survival from around50% in the 1950s to around 95% in the 2000s [201]. Survivalrates for different cohorts are depicted in Table 3 This obviousimprovement may relate not only to better management ofthe disease itself and its associated comorbidities but also toan earlier diagnosis. Noteworthy, however is that the standar-dized mortality ratio (SMR) for SLE is 2.6–3.0 times higher thanin the general population; this is probably related to higherrates of cardiovascular (SMR = 2.3) and renal disease(SMR = 4.7) and of infections (SMR = 5.0) [202,203]. The SMRis even higher in cSLE (18.8) although a breakdown for cardi-ovascular, renal, and infections causes is not available [204]. Abimodal pattern of mortality has been recognized in SLE sincethe mid-1970s with patients who die early in the course of thedisease do so due to active disease and/or infections whilethose who die late in the course of the disease due so sec-ondary to cardiovascular disease and oftentimes they have aninactive disease at the time of their death [133].

Several factors have been associated with a higher mortal-ity as already discussed like age at diagnosis, gender, ethnicity,and SES factors.

As to disease-related factors, higher levels of disease activ-ity at diagnosis [152,210,211] and over time [212–217] and thepresence of damage, particularly renal, have been associatedwith increased mortality [127,163,170,211,216–220]. The pre-sence of hematologic disorders [170] (including thrombocyto-penia [142,152,159], hemolytic anemia [155,171]), neurological[221], psychiatric [107], pulmonary [107,152] and renal[107,116,152,155,163,166–168] involvement, the antiphospho-lipid syndrome and of comorbidities including coronary artery

8 G. J. PONS-ESTEL ET AL.

Table 2. Cumulative probability of survival in patients with systemic lupus erythematosus (1955–2016)a.

Ethnic group (%) Survival (%)

Author Country N C Af H As O Pub date 5-y 10-y 15-y 20-y

1955–1964Merrel and Shulman [129] USA 99 73 27 1955 51b

Kellum and Haserick [130] USA 299 ND 1964 691965–1974Estes and Christian [131] USA 150 ND 1971 77 59 48Jessop and Meyers [132] South Africa ND 1973 661975–1984Urowitz et al. [133] Canada 81 ND 1976 75 63 53Feinglass et al. [134] USA 140 ND 1976 94 82Urman and Rothfield [135] USA (NYC) 209 ND 1977 70Urman and Rothfield [135] USA (Connecticut) 156 ND 1977 93Lee et al. [136] Canada 110 95 4 1 1977 91Ginzler et al. [137] USA 1103 58 32 5 3 2 1982 77 71Feng et al. [138] Singapore 183 100 1982 70 601985–1994Malaviya et al. [139] India 181 ND 1987 68 50Wallace et al. [140] USA 609 ND 1989 79Swaak et al. [141] Netherlands 110 ND 1989 87Reveille et al. [142] USA 389 47 52 1 1990 89 84 79Gudmundsson and Steinsson [143] Iceland 69 ND 1990 84 78Worral et al. [144] UK 100 63 7 6 24 1990 88Seleznick and Fries [145]c USA 310 ND 1991 96 89Pistiner et al. [146] USA 570 72 11 8 6 3 1991 97 93Breban et al. [147] France 51 ND 1991 86 78Wong et al. [148] Hong Kong 156 100 1992 97 94Anstey et al. [149] Australia 22 ND 100 1993 60Drenkard et al. [150] Mexico 667 ND 1994 96 92Massardo et al. [151] Chile 218 ND 1994 87 791995–2004Abu-Shakra et al. [152] Canada 665 86 7 0 7 1995 93 85 79 68Ward et al. [115] USA 408 52 48 1995 82 71 63Paton et al. [153] Malaysia 102 100 1996 86 70Murali et al. [154] India 98 100 1997 77 60Jacobsen et al. [155] Denmark 513 ND 1998 91 76 64Blanco et al. [156] Spain 306 ND 1998 90 85 80Rodriguez and Gonzales-Pares [157] USA (Puerto Rico) 662 ND 2000 77Stahl-Hallengren et al. [158] Sweden ND 2000 93 83Mok et al. [159] Hong Kong 186 100 2000 93Bellomio et al. [160] Argentina 366 ND 2000 91 85Nossent et al. [161] Norway 83 100 2001 75Yeap et al. [162] Malaysia 494 100 2001 82 71Manger et al. [163] Germany 338 100 2002 97 90Kasitanon et al. [164] Thailand 349 100 2002 84 75Alamanos et al. [165] Greece 178 ND 2003 97 90Cervera et al [166,167] Europe 1000 97 2 1 2003 95 92Ruiz-Irastorza et al. [168] Spain 202 100 2004 95 91 86 69Houman et al. [169] Tunez 100 100 2004 86Pons-Estel et al. Latin America 1480 41 13 44 2 942005–2014Mok et al. [170] Hong Kong 285 100 2005 92 83 80Kasitanon et al. [171] USA 1378 56 49 5 2006 95 91 85 78Doria et al. [172] Italy 207 100 2006 96 93 76Heller et al. [173] Saudi Arabia 92 8 18 74 2007 92Funauchi et al. [174] Japan 101 100 2007 94 88 77Funauchi et al. Japan 151 100 2007 94 92Al Saleh et al. [175] United Arab Emirates 151 1 3 23 73 2008 94Al Arfaj et al. [176] Saudi Arabia 624 2 98 2009 98 97Rabbani et al. [177] Pakistan 198 ND 2009 80 77 75 75Campbell at el. [116] USA 265 65 28 7 2008 90Nossent et al. [178] Europe 200 97 3 2010 97Alonso et al. [179] España 150 100 2012 94 87 80Flower et al. [59] Barbados 183 98 2012 80Voss et al. [180] Denmark 215 94 6 2013 94 87 73Pamuk et al. [181] Turkey 428 ND 2013 96 92 89Lerang et al. [182] Norway 127 ND 2014 95 90Wu G et al. [183] China 665 100 2014 91 80

N: population; C: Caucasian; Af: African descendant; H: Hispanic; As: Asian; O: other; pub date: publication date; 5-y: 5-year survival; 10-y: 10-year survival; 15-y: 15-year survival; 20-y: 20-year survival.

aMost of the data presented were not derived from inception cohorts; thus, a survival effect bias cannot be ruled out.bFour years.cFrom first symptom.

EXPERT REVIEW OF CLINICAL IMMUNOLOGY 9

disease [217] and the hemophagocytic syndrome [107] havebeen associated with an increased risk of mortality.

Treatments used for the management of lupus are alsoknown to impact on mortality; this may reflect the severityof the disease but also the medications themselves such ashigh doses of glucocorticoids [159] and immunosuppressivedrugs [217], including cyclophosphamide. On the other hand,antimalarials have been shown to prolong survival[217,222,223], probably in a time-dependent manner [221].

4. Conclusions

Remarkable disparities worldwide are seen in the incidenceand prevalence of SLE. Genetic, environmental, sociodemo-graphic and methodological issues are responsible for thevariations observed.

cSLE is a more active disease process than the one in adultswith increased predominance of hematological, immunologi-cal and renal manifestations and more damage accrual overtime (particularly renal). An increase use of corticosteroids(longer time, higher doses) and of immunosuppressive drugsin these patients derives in a higher burden of drug toxicity.

Male SLE patients have severe involvement like lupusnephritis more frequently; conversely, they present cutaneousmanifestations and other features such us a milder disease lessfrequently. However, the association between gender anddamage accrual and mortality is not universally accepted.

Non-Caucasian patients tend to be younger at diseaseonset; they also have an increased risk of severe organ invol-vement and of damage accrual than Caucasians. Increasedmortality rates in non-Caucasian SLE patients seem to berelated primarily to SES factors.

Survival in SLE has improved steadily over the past 60 years.Older and younger age at diagnosis, lower SES and lower educa-tional level, and more severe disease, damage included, areassociated with higher mortality rates. Comorbidities, includingthe antiphospholipid syndrome and cardiovascular disease arealso associated with higher mortality rates in lupus.Immunosuppressive drugs and high doses of glucocorticoidsare associated with higher mortality rates while the use of anti-malarials prolongs survival in these patients.

5. Expert commentary

Differences in SLE epidemiology across different populationsare multifactorial in origin, with some explanatory variablesyet to be discovered. Further genetic and epigenetic SLEstudies may shed some light into this. For example, it wouldbe expected that identical SLE twins who are reared apart mayexperience differences in the expression of their disease whichmay be explained by different environmental factors. Theimpact of ethnicity in SLE could be also explained also bygenetic and environmental factors; for example, non-Caucasians, by and large, have a lower SES than Caucasianwhich may be linked to increased rate of infections, anddifferential access to adequate healthcare [224].

Younger age at disease onset could be due to a highergenetic load for SLE; thus, younger patients are expected tohave a more active disease. Older age on the other hand isassociated with less severe disease, yet older SLE patientsaccrue more damage and experience higher mortality rates.SLE is more frequent in females but male patients tend tohave more severe disease manifestations and consequentlyhigher levels of disease activity.

Mortality in SLE has dramatically improved over the years,yet lupus patients have a SMR three times higher than thegeneral population. It is expected that with new and safertreatment strategies, disease manifestations will be bettercontrolled, damage accrual less prominent and that survivalrates in SLE will continue to improve.

6. Five years view

In five years, there will be more information about genetic andepigenetic factors associated with the development of SLEand its patterns of disease expression. It is expected thatsome of these epigenetic factors would be modifiable whichwill result in reduced damage and mortality.

And, with safer medications, and new treatment strategies,like treat-to-target, damage accrual will decrease and survivalwill improve. Validation of definitions of possible treatmenttargets like remission and low disease activity state should becompleted worldwide over the next few years.

Key issues

● The overall incidence rates of SLE vary from approximately0.3 to 23.7 per 100,000 person-years whereas prevalencerates range from 6,5 to 178,0 per 100,000. There are, how-ever, temporal, racial/ethnic and gender differences.

● Childhood onset lupus represents 10–20% of all SLE cases.● The clinical manifestations of adult and children with SLE

are the same; however, children overall, experience a higherfrequency of renal, neurologic and hematologic involve-ment and higher levels of disease activity and damage.

● Male patients exhibit more severe clinical features; how-ever, gender has not been proved to be associated with aworse prognosis.

● Non-Caucasian patients tend to be younger at diseaseonset and have a more severe disease.

Table 3. Phenotypic differences in SLE as a function of racial/ethnic groupsa.

C Af H As

Age at diagnosis (years)[127,205,206]

30–40 26–35 28–33 27–35

Acute onset (%) [207,208] 22 10Cutaneous manifestationsMalar rash (%) [127,184] 63–67 45–63 59–64Photosensitivity (%) [127,184] 60–72 46–59 52–59Mucosal ulcers (%) [127,184] 41–57 43–46 40–48Discoid rash (%) [127,184,209] 11–12 20–33 6–10 6

Serositis (%) [209] 26 11Pericarditis (%) [127] 16 23 16

General manifestationsWeight loss (%) [126,127] 11–30 11–32 23 22Fever (%) [126,127] 10–60 9–59 53 17

Hematologic manifestation (%) [209] 83 58Lymphopenia (%) [127] 51 70 64

Kidney involvement (%) [126,127,184,185] 27–44 55–63 58–64 59ESRD (%) [186] 6 7 16

Hypertension (%) [127] 21 30 32aPercentage are shown only if provided in the original publications.

10 G. J. PONS-ESTEL ET AL.

● Lower socioeconomic status, more severe disease, comor-bidities and higher doses of glucocorticoids and immuno-suppressive drugs are associated with higher mortality rateswhereas antimalarials prolong patients’ survival.

Funding

The authors have received no specific funding for the preparation of thisarticle.

Declaration of interest

The authors have no relevant affiliations or financial involvement with anyorganization or entity with a financial interest in or financial conflict withthe subject matter or materials discussed in the manuscript. This includesemployment, consultancies, honoraria, stock ownership or options, experttestimony, grants or patents received or pending, or royalties.

ORCID

Guillermo J. Pons-Estel http://orcid.org/0000-0002-0647-929XManuel F Ugarte-Gil http://orcid.org/0000-0003-1728-1999Graciela S. Alarcón http://orcid.org/0000-0001-5190-9175

References

Papers of special note have been highlighted as either of interest (•) or ofconsiderable interest (••) to readers.

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