Arthritis Care & Research

Vol. 63, No. S11, November 2011, pp S112–S117

DOI 10.1002/acr.20623
© 2011, American College of Rheumatology
MEASURES OF PATHOLOGY AND SYMPTOMS

Measures of Disease Activity and Damage in

Pediatric Systemic Lupus Erythematosus
British Isles Lupus Assessment Group (BILAG), European Consensus Lupus Activity
Measurement (ECLAM), Systemic Lupus Activity Measure (SLAM), Systemic Lupus
Erythematosus Disease Activity Index (SLEDAI), Physician’s Global Assessment of
Disease Activity (MD Global), and Systemic Lupus International Collaborating
Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI; SDI)
BIANCA LATTANZI,1 ALESSANDRO CONSOLARO,1 NICOLETTA SOLARI,1 NICOLINO RUPERTO,2
ALBERTO MARTINI,1 AND ANGELO RAVELLI1

INTRODUCTION measures scored items and abnormalities must be attrib-

Although the presentation, clinical symptoms, and labora-
tory findings of pediatric systemic lupus erythematosus
(SLE) are similar to those that are seen in adults, children
and adolescents with SLE differ from adults in terms of
the frequency and severity of disease activity and damage
features as well as in the treatment approaches used by
their attending physicians. Furthermore, assessment of
pediatric patients with SLE should take into account the
disease and physical/mental age–related issues that are
associated with growth and development. For these rea-
sons, it cannot be assumed a priori that the clinical mea-
sures developed for adults are suitable for children and
adolescents. Therefore, outcome measures used in adults
need to be subjected to critical evidence-based evaluation
of their measurement properties in children and adoles-
cents.
Because the general characteristics of disease activity
and damage measures used in SLE are addressed in an-
other article in this issue of Arthritis Care & Research, our
review will focus on the available information specific to
pediatric SLE and the critical appraisal of the value of each
instrument to pediatric rheumatologists dealing with chil-
dren and adolescents with SLE. As a general rule, in all
1
Bianca Lattanzi, MD, Alessandro Consolaro, MD, Nico-
letta Solari, MD, Alberto Martini, MD, Angelo Ravelli, MD:
Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini,
and Università degli Studi di Genova, Genova, Italy; 2Nico-
lino Ruperto, MD, MPH: Istituto di Ricovero e Cura a Car-
attere Scientifico G. Gaslini, Genova, Italy.
Address correspondence to Angelo Ravelli, MD, Pediatria
II, Istituto G. Gaslini, Largo G. Gaslini 5, 16147 Genova,
Italy. E-mail: angeloravelli@ospedale-gaslini.ge.it.
Submitted for publication February 2, 2011; accepted in
revised form May 23, 2011.
utable to SLE.
BRITISH ISLES LUPUS ASSESSMENT GROUP
(BILAG)
Psychometric Information
Validity. In a prospective observational 12-month study
of 21 patients with systemic lupus erythematosus (SLE),
the renal BILAG score was found to be able to differen-
tiate between patients with nephritis (n ⫽ 10) and patients
without nephritis (n ⫽ 11) (1).
Ability to detect change. Excellent responsiveness to
change in disease activity was documented, by means of
effect size, effect size index, standardized response mean,
responsiveness statistic, and relative efficiency index, in
a comparative study with the Systemic Lupus Erythema-
tosus Activity Measure and the Systemic Lupus Erythem-
atosus Disease Activity Index that involved 35 newly-
diagnosed patients (2). In a study of 98 patients who were
seen every 3 months for up to 7 visits (n ⫽ 623 total visits),
the minimum clinically important difference (MCID) for
clinically important improvement or worsening, based on
physician’s or parent’s rating of the disease course be-
tween visits, was small. Using the standard error of mea-
surement approach, the MCID value was 2 (3). The MCID
is defined as “the smallest difference in a score of a disease
measure of interest that patients perceive as beneficial and
that would mandate, in the absence of side effects, a
change in the patient management” (4).
Critical Appraisal of Overall Value to the
Pediatric Rheumatology Community
Strengths. The BILAG is the most comprehensive of the
SLE activity measures. It is the only SLE activity index that

S112
Activity and Damage in Pediatric SLE
aims specifically to show activity in individual organs/
systems. It is the only transitional index, with each item
that is present being recorded as new, the same, worse or
improving, rather than just present or absent (5). Although
initially the developers of the index did not intend to
create a cumulative score, a numerical scoring scheme was
developed for the 2004 version (6).
Caveats and cautions. With 86 items, it is the longest of
the lupus activity tools. It remains to be established
whether a different numeric conversion table should be
developed for the pediatric population because of the dif-
ferences in the extent of disease features between pediatric
and adult SLE. It does not include immunologic tests.
Clinical usability. The BILAG is a reliable and valid
instrument for measuring clinical disease activity in pedi-
atric patients with SLE in standard clinical practice. It
enables an accurate assessment of disease activity in indi-
vidual organs/systems and detection of new activity or
flare in one or more systems, and in which system(s).
Furthermore, it helps determine when a change in therapy
is needed. However, performing the BILAG is time con-
suming and requires training, which may limit its appli-
cability in routine care.
Research usability. The BILAG is best suited when the
assessment of the actual level or change over time in
disease activity in individual organs/systems is the pri-
mary objective of the study. The excellent responsiveness
to change seen in pediatric studies supports its use as a
response measure in clinical trials in children and adoles-
cents with lupus, particularly when the efficacy of a med-
ication on single-organ involvement (e.g., nephritis, skin
disease) is under scrutiny.
Advantages/disadvantages of the different versions of
the BILAG. There are 2 versions of the BILAG: the original
BILAG and the BILAG-2004 (5,6). An advantage of the
2004 version is that its numerical scoring system may
overcome the inability to give an overall score in the
original BILAG (7). All studies performed in pediatric SLE
have used the original version of the index.
EUROPEAN CONSENSUS LUPUS ACTIVITY
MEASURMENT (ECLAM)
Psychometric Information
Validity. The ECLAM (8) was found to have construct
validity and to perform similarly to the Systemic Lupus
Erythematosus Disease Activity Index (SLEDAI) in pre-
dicting disease damage and the need for steroids in 66
newly diagnosed patients with pediatric systemic lupus
erythematosus (SLE) (9). In a multinational study that in-
cluded 557 patients who underwent a baseline visit, at
the time of an active phase of disease requiring a major
therapeutic intervention, and a subsequent visit after 6
months, the ECLAM was found to possess significant abil-
ity to discriminate patients who were improved or not
improved at 6 months, based on the physician’s or parent’s
assessment of the child’s response to therapy. In the same
study, the ECLAM was found to have good construct va-
lidity, i.e., it was moderately correlated with the Physi-
S113
cian’s Global Assessment of Disease Activity and pre-
dicted strongly the child’s response to therapy (10). The
ECLAM was subsequently found to predict improvement
according to the evaluation of the participants in the con-
sensus conference that led to the development of the pro-
visional criteria for the evaluation of response to therapy
in pediatric SLE (11).
Ability to detect change. The ECLAM was found to be
very responsive to change in disease activity and slightly
more responsive than the SLEDAI in 66 newly diagnosed
patients with pediatric SLE. Responsiveness statistics
included effect size, effect size index, standardized re-
sponse mean (SRM), and relative efficiency index (9). In
a study of 98 patients who underwent a total of 623 visits,
the minimum clinically important difference (MCID) for
clinically important improvement or worsening, based
on physician’s or parent’s rating of the disease course
between visits, was small. Using the standard error of
measurement approach, the MCID value was 1 (3). In a
multinational study that included 557 patients who un-
derwent a baseline visit, at the time of an active phase of
disease requiring a major therapeutic intervention, and a
subsequent visit after 6 months, the ECLAM was found
to be strongly responsive to change in disease activity
(SRM 1.3). In the same study, the ECLAM was found to be
slightly more responsive and less skewed than the SLEDAI
(10).
Critical Appraisal of Overall Value to the
Pediatric Rheumatology Community
Strengths. It has been suggested that the ECLAM may be
preferable to the SLEDAI for measuring disease activity
because of its superior quantitative properties (9). The
ECLAM has the potential advantage over the Systemic
Lupus Activity Measure and SLEDAI of using the entire
range of possible scores, which means that scores are less
skewed.
Caveats and cautions. It has been argued that face va-
lidity of the ECLAM may be inferior to that of the SLEDAI
because items are not exactly defined, the time frame dur-
ing which symptoms are regarded as “evolving” is unclear,
the decrease in the complement levels necessary to be
scored as “significantly reduced compared to the last ob-
servation” (attribute 12b) is not well defined, and there is
a lack of a clearly defined time frame during which symp-
toms have to occur to be included in a certain measure-
ment of disease activity (9).
Clinical usability. The ECLAM is reasonably short and
simple, which makes it feasible for use in standard clinical
practice. Factors potentially hampering its application
include unclear definition of items and time frames, and
complexity of calculation of the total disease activity
score, which is not equal to the simple sum of the domains
scores.
Research usability. The ECLAM has demonstrated good
construct, discriminative and predictive ability, and excel-
lent responsiveness to change over time in patients with
pediatric SLE and is, therefore, a valid instrument for the
assessment of disease activity in both clinical research and
therapeutic trials.
S114
SYSTEMIC LUPUS ACTIVITY MEASURE
(SLAM)
Psychometric Information
Validity. SLAM (12) use in childhood-onset systemic
lupus erythematosus (SLE) was assessed in a comparative
study using the Systemic Lupus Erythematosus Disease
Activity Index (SLEDAI), British Isles Lupus Assessment
Group (BILAG), and SLAM in a pediatric population of
35 patients (2). In a multinational study that included
557 patients who underwent a baseline visit, at the time of
an active phase of disease requiring a major therapeutic
intervention, and a subsequent visit after 6 months, the
SLAM was found to possess significant ability to discrim-
inate patients who were improved or not improved at 6
months based on the physician’s or parent’s assessment of
the child’s response to therapy (10).
Ability to detect change. Excellent responsiveness to
change in disease activity has been documented, by
means of effect size, effect size index, standardized re-
sponse mean (SRM), responsiveness statistic, and relative
efficiency index in a comparative study with BILAG and
SLEDAI that involved 35 newly-diagnosed patients (2).
In a study of 98 patients who underwent a total of 623
visits, the minimum clinically important difference
(MCID) for clinically important improvement or worsen-
ing, based on physician’s or parent’s rating of the disease
course between visits, was small. Using the standard error
of measurement approach, the MCID value was 4 (3). In
a multinational study that included 557 patients who
underwent a baseline visit, at the time of an active phase
of disease requiring a major therapeutic intervention, and
a subsequent visit after 6 months, the SLAM was found
to be strongly responsive to change in disease activity
(SRM 1.3) (10).
Critical Appraisal of Overall Value to the
Pediatric Rheumatology Community
Strengths. The SLAM and the latest version, SLAM-R,
include more systemic features than the SLEDAI. They
assess subjective symptoms (fatigue, arthralgias, myalgias),
which may increase their correlation with parent/patient
self assessment of function and general health. All items
are weighted, which enables an accurate grading of clini-
cal and laboratory abnormalities by severity. A compre-
hensive set of laboratory tests is incorporated.
Caveats and cautions. Inclusion of many subjective
items, which may not be related directly to disease activ-
ity, may detract from the validity of the index. The SLAM
gives equal weighting to different levels of severity of
organ disease activity without considering the significance
of the organ involved. It does not include immunologic
tests.
Clinical usability. The SLAM was found to be very
user friendly in a comparative study with BILAG and
SLEDAI (2). Item grading makes this index potentially
more flexible than the SLEDAI for monitoring of changes
in disease over time in standard clinical practice. How-
ever, the SLAM is longer and somewhat more complex
than the SLEDAI.
Lattanzi et al
Research usability. The SLAM has shown excellent
psychometric properties in validation analyses in patients
with pediatric SLE and is therefore well suited for use in
clinical research and therapeutic trials.
SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE
ACTIVITY INDEX (SLEDAI)
Psychometric Information
Validity. The SLEDAI (13) was found to have construct
validity and to perform similarly to the European Consen-
sus Lupus Activity Measurement (ECLAM) in predicting
disease damage and the need for steroids in 66 newly
diagnosed patients with pediatric systemic lupus erythem-
atosus (SLE). In a multinational study that included 557
patients who underwent a baseline visit, at the time of an
active phase of disease requiring a major therapeutic in-
tervention, and a subsequent visit after 6 months, the
SLEDAI was found to possess significant ability to dis-
criminate patients who were improved or not improved at
6 months based on the physician’s or parent’s assessment
of the child’s response to therapy (10).
Ability to detect change. Excellent responsiveness to
change in disease activity has been documented, by means
of effect size, effect size index, standardized response
mean (SRM), responsiveness statistic, and relative effi-
ciency index, in a comparative study with the British Isles
Lupus Assessment Group (BILAG) and Systemic Lupus
Activity Measure (SLAM) that involved 35 newly-diag-
nosed patients (2). In a study of 98 patients who under-
went a total of 623 visits, the minimum clinically impor-
tant difference (MCID) for clinically important
improvement or worsening, based on physician’s or par-
ent’s rating of the disease course between visits, was small.
Using the standardized error of measurement approach,
the MCID value was 2 (3). In a multinational study that
included 557 patients who underwent a baseline visit, at
the time of an active phase of disease requiring a major
therapeutic intervention, and a subsequent visit after 6
months, the ECLAM was found to be strongly responsive
to change in disease activity (SRM 1.1) (10).
Critical Appraisal of Overall Value to the
Pediatric Rheumatology Community
Strengths. The SLEDAI includes only 24 items, which
makes it the shortest of the lupus activity tools. The
SLEDAI gives more points to renal disease than does the
SLAM (up to 16 points versus a maximum of 8 points),
which makes it potentially more responsive in patients
who relapse with renal disease primarily.
Caveats and cautions. The SLEDAI is the only lupus
activity tool that does not include subjective items, such as
fatigue, joint pain, etc. This makes it potentially less suit-
able in capturing patient-relevant disease changes. Indi-
vidual items are not graded for severity. It has been argued
that the SLEDAI may not capture sufficiently worsening of
an already existing feature or detect partial improvement.
However, the 2000 modification of the index (SLEDAI-2K)
Activity and Damage in Pediatric SLE
enables recording ongoing disease activity, as well as new
or deteriorating disease activity (14).
Clinical usability. The SLEDAI was found to be the
quickest measure to complete in a comparative study with
BILAG and SLAM (2). In the clinical setting, it may be the
preferable lupus activity tool because it is concise and easy
to complete.
Research usability. The SLEDAI has shown excellent
psychometric properties in validation analyses in patients
with pediatric SLE and is, therefore well suited for use in
clinical research and therapeutic trials.
Advantages/disadvantages of the different versions of
the SLEDAI. There are 3 versions of the SLEDAI: the
original SLEDAI (13), the SLEDAI-2K (14), and the MEX-
SLEDAI (15). In the original version, the items rash, alo-
pecia, mucous membrane lesions, and proteinuria are
scored only if they represent their first occurrence or a
recurrence (or a recent increase for proteinuria), whereas
in the SLEDAI-2K version these items are simply scored
when present. This change in the 2K version was made to
reflect ongoing disease activity in the affected organ sys-
tems. The MEX-SLEDAI has the advantage of avoiding the
cost of immunologic laboratory tests because it does not
include anti– double-stranded DNA antibodies and com-
plement levels. All studies performed in pediatric SLE
have used the original version of the SLEDAI, except for
the study by Brunner et al (3), which was based on the
SLEDAI-2K version.
PHYSICIAN’S GLOBAL ASSESSMENT OF
DISEASE ACTIVITY (MD GLOBAL)
Psychometric Information
Validity. In a multinational study that included 557
patients who underwent a baseline visit, at the time of an
active phase of disease requiring a major therapeutic in-
tervention, and a subsequent visit after 6 months, the MD
Global demonstrated a strong ability in discriminating pa-
tients who were improved or not improved at 6 months
based on the physician’s or parent’s assessment of the
child’s response to therapy. The discriminative ability of
the MD Global as well as its ability to predict response to
therapy were comparable to that of the European Consen-
sus Lupus Activity Measurement (ECLAM). The baseline-
to-6 month change in the MD Global was moderately cor-
related with the change in the ECLAM, physical summary
score of the Child Health Questionnaire, and parent global
assessment of the patient’s overall well-being, and poorly
correlated with the change in the 24-hour proteinuria (10).
The MD Global was subsequently found to predict im-
provement according to the evaluation of the participants
in the consensus conference that led to the development
of the provisional criteria for the evaluation of response
to therapy in pediatric systemic lupus erythematosus
(SLE) (11).
Ability to detect change. In a multinational study that
included 557 patients who underwent a baseline visit, at
the time of an active phase of disease requiring a major
therapeutic intervention, and a subsequent visit after 6
S115
months, the MD Global was found to be the most respon-
sive measure, together with the ECLAM and the Systemic
Lupus Activity Measure (SLAM; standardized response
mean 1.3 for all 3 measures) (10). In a study of 98 patients
who underwent a total of 623 visits, the minimum clini-
cally important difference (MCID) for clinically important
improvement or worsening, based on physician’s or par-
ent’s rating of the disease course between visits, was small.
Using the standard error of measurement approach, the
MCID value was 1. The change-corrected agreement of
activity index with a stable course was greater for the MD
Global than for the ECLAM, SLAM, and Systemic Lupus
Erythematosus Disease Activity Index (3).
Critical Appraisal of Overall Value to the
Pediatric Rheumatology Community
Strengths. The MD Global is the simplest and most fea-
sible of the physician-reported disease activity measures.
Furthermore, its statistical performances were found to be
comparable to those of the composite disease activity
tools.
Caveats and cautions. The MD Global is a broad mea-
sure of SLE activity and, therefore, may not detect with
sufficient reliability improvement or worsening of disease
activity in individual organs/systems. Use of the 10-cm
horizontal line visual analog scale (VAS) to rate the MD
Global may lead to inaccuracies in assessing disease re-
mission. Due to the relative aversion to extremes that is
often seen when using such VAS, very low values (0.1 or
0.2 cm) are frequently obtained when the assessor actually
intended to mark the end of the line. It has been suggested
that the 21-circle VAS format may be less skewed and less
affected by ceiling effect and has the potential advantage of
increasing the accuracy of assessment of clinical remission
(16).
Clinical usability. The simplicity and ease of the MD
Global makes it well suited for use in monitoring the
course of disease activity over time in standard clinical
practice.
Research usability. The MD Global has shown excellent
psychometric properties in patients with pediatric SLE
and is therefore well suited for use in clinical research and
therapeutic trials.
SYSTEMIC LUPUS INTERNATIONAL
COLLABORATING CLINICS/AMERICAN
COLLEGE OF RHEUMATOLOGY DAMAGE
INDEX (SLICC/ACR DI; SDI)
Psychometric Information
Validity. Several studies have shown that the SDI is a
valid and reliable instrument to capture damage in pa-
tients with pediatric systemic lupus erythematosus (SLE)
(17–21). Accumulated damage, measured with the SDI,
was found to be predicted by cumulative disease activity
over time and to be correlated with the frequency of severe
disease flares in the first 3 years of followup. Item weight-
ings for the SDI using Rasch analysis were not found to
S116
lead to an important clinical improvement (22). Rasch
analysis is a psychometric approach that has been used to
assess and improve rheumatology scales by generating ap-
propriate item weightings (23). The presence of accumu-
lated damage, measured with the SDI, was found to affect
significantly the health-related quality of life, particularly
in the physical domain in patients with pediatric SLE (24).
Critical Appraisal of Overall Value to the
Pediatric Rheumatology Community
Strengths. The SDI (25,26) enables a detailed and com-
prehensive assessment and cumulative organ/system dam-
age in pediatric patients with SLE. It constitutes an impor-
tant tool to monitor over time the development of damage
due to active inflammation, medication side effects, and
comorbid conditions. Regular use of the SDI ensures har-
monization of long-term studies of pediatric patients into
adulthood.
Caveats and cautions. It has been argued that the SDI
does not cover all forms of damage that children or ado-
lescents with SLE may develop over time, particularly
effects on growth and development (27). Incorporation of
growth retardation and pubertal delay in a modified pedi-
atric version of the SDI has been advised. Furthermore, a
redefinition of the item cognitive impairment has been
proposed to facilitate its applicability in younger patients.
Since some SDI items, such as myocardial infarction, pan-
creatic insufficiency, claudication, gastrointestinal stric-
ture, ruptured tendons, and malignancy, are rarely seen in
children and adolescents with SLE, the utility of their
assessment in pediatric SLE has been questioned (27). To
avoid confusion between active inflammation and irre-
versible damage, in order to be scored in the SDI an item
needs to be present for 6 months (except damage items that
are theoretically nonreversible). Thus, the SDI covers, by
definition, only irreversible damage and does not take
into account the ability of children to recover and regen-
erate to a greater degree than adults. For instance, avascu-
lar necrosis may have a potential for regeneration and
remodeling of bone lesions in children if better control of
disease without the use of steroids is achieved and if
normal growth velocity is restored. Furthermore, children
have an exceptional capacity for neurologic recovery that
adults lack, and full recovery may occur months to years
later (28). It has also been argued that since steroid-
induced diabetes mellitus may be reversible, the presence
of steroid-induced diabetes mellitus for 6 months or more
may not represent a true permanent damage (29).
To overcome the limitations of the SDI, a modified pe-
diatric version, (Ped-SDI) has been proposed (27). As com-
pared with the original SDI, the pediatric version includes
2 additional items: growth failure and delayed puberty.
The glossary of terms for the items of the original SDI was
maintained, with the sole exception of the indication that
in younger children proteinuria should be adjusted for
height and weight. A specific definition for the new items
growth failure and delayed puberty was provided. At vari-
ance from the original SDI, which defines damage as an
irreversible change in an organ or system, it was taken into
Lattanzi et al
account that some forms of damage are potentially revers-
ible in pediatric patients.
Modifications to the pediatric version of the SDI sug-
gested subsequently are to rename the item growth failure
as “reduced final height,” to reflect the really irreversible
outcome, and to alter the definition of pubertal delay to
mean a significant lack of pubertal progression to indicate
permanent damage to the hypothalamic-pituitary axis.
Furthermore, the modification of the definition of the item
of gonadal failure has been advised, as gonadal failure
defined as secondary amenorrhea before the age of 40 years
is not easily applied to adolescent girls, whose menstrual
cycles may be irregular as a normal physiologic variant for
the first 2 years after menarche (29).
Clinical usability. The pediatric version of the SDI en-
ables an accurate assessment and monitoring of the main
forms of cumulative organ/system damage that can occur
in pediatric patients with SLE. It is simple and easy to
complete and score. Regular (i.e., yearly) completion of the
SDI provides clinicians with an important tool to follow
the course of organ/system damage from the pediatric age
into adulthood (30).
Research usability. Application of the SDI and its pe-
diatric version in pediatric patients with SLE has shown
that the index is valid for use in observational cohort
studies and long-term outcome surveys. It may also be
valuable in the prediction of outcome.
DISCUSSION
All global measures of disease activity have been found to
be reliable and valid for use in children and adolescents
with SLE, and none of them has shown clearly superior
metrologic properties. The choice of a specific tool may
largely depend on the purposes of the study, the investi-
gational setting (standard clinical practice or research), or
the personal preference of the investigator. Owing to its
simplicity, feasibility, and good psychometric properties,
the MD Global should always be incorporated in the as-
sessment of disease activity either in standard clinical
practice and research. Although the SDI has proved suit-
able to assess damage in patients with pediatric SLE, it was
found to have some important limitations for use in the
pediatric age group, the chief of which is the inability to
capture some forms of damage that are unique to children
and adolescents, namely growth failure and delayed pu-
berty. Use of the modified pediatric version of the SDI in
pediatric patients with SLE is, therefore, advised.
AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it
critically for important intellectual content, and all authors ap-
proved the final version to be published.
REFERENCES
1. Marks SD, Pilkington C, Woo P, Dillon MJ. The use of the British Isles
Lupus Assessment Group (BILAG) index as a valid tool in assessing
disease activity in childhood-onset systemic lupus erythematosus.
Rheumatology (Oxford) 2004;43:1186 –9.
2. Brunner HI, Feldman BM, Bombardier C, Silverman ED. Sensitivity of
Activity and Damage in Pediatric SLE
the Systemic Lupus Erythematosus Disease Activity Index, British Isles
Lupus Assessment Group Index, and Systemic Lupus Activity Measure
in the evaluation of clinical change in childhood-onset systemic lupus
erythematosus. Arthritis Rheum 1999;42:1354 – 60.
3. Brunner HI, Higgins GC, Klein-Gitelman MS, Lapidus SK, Olson JC,
Onel K, et al. Minimal clinically important differences of disease
activity indices in childhood-onset systemic lupus erythematosus.
Arthritis Care Res (Hoboken) 2010;62:950 –9.
4. Jaeschke R, Singer J, Guyatt GH. Measurement of health status: ascer-
taining the minimal clinically important difference. Control Clin Trials
1989;10:407–15.
5. Symmons DP, Coppock JS, Bacon PA, Bresnihan B, Isenberg DA, Mad-
dison P, et al. Development and assessment of a computerized index of
clinical disease activity in systemic lupus erythematosus: members of
the British Isles Lupus Assessment Group (BILAG). Q J Med 1988;69:
927–37.
6. Yee CS, Cresswell L, Farewell V, Rahman A, Teh LS, Griffiths B, et al.
Numerical scoring for the BILAG-2004 index. Rheumatology (Oxford)
2010;49:1665–9.
7. Pope J. The revised BILAG Index with numerical scoring in systemic
lupus erythematosus: added value with some limitations. Rheumatol-
ogy (Oxford) 2010;49:1616 –7.
8. Bencivelli W, Vitali C, Isenberg DA, Smolen JS, Snaith ML, Sciuto M,
et al. Disease activity in systemic lupus erythematosus: report of the
Consensus Study Group of the European Workshop for Rheumatology
Research III: development of a computerised clinical chart and its
application to the comparison of different indices of disease activity.
The European Consensus Study Group for Disease Activity in SLE. Clin
Exp Rheumatol 1992;10:549 –54.
9. Brunner HI, Silverman ED, Bombardier C, Feldman BM. European
consensus lupus activity measurement is sensitive to change in disease
activity in childhood-onset systemic lupus erythematosus. Arthritis
Rheum 2003;49:335– 41.
10. Ruperto N, Ravelli A, Cuttica R, Espada G, Ozen S, Porras O, et al,
for the Pediatric Rheumatology International Trials Organization
(PRINTO) and the Pediatric Rheumatology Collaborative Study Group
(PRCSG). The Pediatric Rheumatology International Trials Organiza-
tion criteria for the evaluation of response to therapy in juvenile sys-
temic lupus erythematosus: prospective validation of the disease activ-
ity core set. Arthritis Rheum 2005;52:2854 – 64.
11. Ruperto N, Ravelli A, Oliveira S, Alessio M, Mihaylova D, Pasic S, et al.
for the Pediatric Rheumatology International Trials Organization
(PRINTO) and the Pediatric Rheumatology Collaborative Study Group
(PRCSG). The Pediatric Rheumatology International Trials Organi-
zation/American College of Rheumatology provisional criteria for
the evaluation of response to therapy in juvenile systemic lupus
erythematosus: prospective validation of the definition of improve-
ment. Arthritis Rheum 2006;55:355– 63.
12. Liang MH, Socher SA, Larson MG, Schur PH. Reliability and validity of
six systems for the clinical assessment of disease activity in systemic
lupus erythematosus. Arthritis Rheum 1989;32:1107–18.
13. Schned ES, Glickstein SL, Doyle MA. Derivation of the SLEDAI [letter].
Arthritis Rheum 1993;36:877.
14. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus
disease activity index 2000. J Rheumatol 2002;29:288 –91.
15. Guzman J, Cardiel MH, Arce-Salinas A, Sanchez-Guerrero J, Alarcon-
Segovia D. Measurement of disease activity in systemic lupus
S117
erythematosus: prospective validation of 3 clinical indices. J Rheuma-
tol 1992;19:1551– 8.
16. Filocamo G, Davi S, Pistorio A, Bertamino M, Ruperto N, Lattanzi B,
et al. Evaluation of 21-numbered circle and 10-centimeter horizontal
line visual analog scales for physician and parent subjective ratings in
juvenile idiopathic arthritis. J Rheumatol 2010;37:1534 – 41.
17. Brunner HI, Silverman ED, To T, Bombardier C, Feldman BM. Risk
factors for damage in childhood-onset systemic lupus erythematosus:
cumulative disease activity and medication use predict disease dam-
age. Arthritis Rheum 2002;46:436 – 44.
18. Ravelli A, Duarte-Salazar C, Buratti S, Reiff A, Bernstein B, Maldonado-
Velazquez MR, et al. Assessment of damage in juvenile-onset systemic
lupus erythematosus: a multicenter cohort study. Arthritis Rheum
2003;49:501–7.
19. Miettunen PM, Ortiz-Alvarez O, Petty RE, Cimaz R, Malleson PN,
Cabral DA, et al. Gender and ethnic origin have no effect on longterm
outcome of childhood-onset systemic lupus erythematosus. J Rheuma-
tol 2004;31:1650 – 4.
20. Lilleby V, Flato B, Forre O. Disease duration, hypertension and medi-
cation requirements are associated with organ damage in childhood-
onset systemic lupus erythematosus. Clin Exp Rheumatol 2005;23:
261–9.
21. Bandeira M, Buratti S, Bartoli M, Gasparini C, Breda L, Pistorio A, et al.
Relationship between damage accrual, disease flares and cumulative
drug therapies in juvenile-onset systemic lupus erythematosus. Lupus
2006;15:515–20.
22. Brunner HI, Feldman BM, Urowitz MB, Gladman DD. Item weightings
for the Systemic Lupus International Collaborating Clinics/American
College of Rheumatology Disease Damage Index using Rasch analysis
do not lead to an important improvement. J Rheumatol 2003;30:292–7.
23. Rasch G. An item analysis which takes individual differences into
account. Br J Math Stat Psychol 1966;19:49 –57.
24. Ruperto N, Buratti S, Duarte-Salazar, Pistorio A, Reiff A, Bernstein B,
et al. Health-related quality of life in juvenile-onset systemic lupus
erythematosus and its relationship to disease activity and damage.
Arthritis Rheum 2004;51:458 – 64.
25. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M,
et al. The development and initial validation of the Systemic Lupus
International Collaborating Clinics/American College of Rheumatology
damage index for systemic lupus erythematosus. Arthritis Rheum
1996;39:363–9.
26. Gladman DD, Urowitz MB, Goldsmith CH, Fortin P, Ginzler E, Gordon
C, et al. The reliability of the Systemic Lupus International Collaborat-
ing Clinics/American College of Rheumatology damage index in pa-
tients with systemic lupus erythematosus. Arthritis Rheum 1997;40:
809 –13.
27. Gutierrez-Suarez R, Ruperto N, Gastaldi R, Pistorio A, Felici E, Burgos-
Vargas R, et al. A proposal for a pediatric version of the Systemic
Lupus International Collaborating Clinics/American College of Rheu-
matology Damage Index based on the analysis of 1,015 patients with
juvenile-onset systemic lupus erythematosus. Arthritis Rheum 2006;
54:2989 –96.
28. Dayal NA, Gordon C, Tucker L, Isenberg DA. The SLICC damage index:
past, present and future. Lupus 2002;11:261–5.
29. Hiraki LT, Hamilton J, Silverman ED. Measuring permanent damage in
pediatric systemic lupus erythematosus. Lupus 2007;16:657– 62.
30. Ravelli A, Ruperto N, Martini A. Outcome in juvenile onset systemic
lupus erythematosus. Curr Opin Rheumatol 2005;17:568 –73.