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Objective: An important barrier in the study of systemic sclerosis (SSc) is the difficulty in measuring disease activity. We reviewed the literature on currently available global measures of disease
activity in SSc.
Methods: The PubMed database (1950-2006) was searched for the key words scleroderma in
conjunction with disease activity and then disease severity. All relevant original and review
articles in English and French were reviewed. Textbooks in rheumatology and pertinent secondary
references were also reviewed.
Results: There are currently 3 tools that are used to measure disease activity globally in SSc.
Physician global assessments have been commonly used but have not been formally evaluated. The
Valentini Disease Activity Index is a new measure that consists of 10 variables and a resulting score
ranging from 0 to 10. It appears easy to use but lacks some face and content validity and responsiveness to change has yet to be demonstrated. The Medsger Disease Severity Scale measures
disease severity in 9 organ systems. However, it assesses mostly damage and is difficult to score.
Conclusions: There is currently no gold standard measure of disease activity in SSc. Given the need
to measure disease activity in SSc and the limitations of the currently available instruments, efforts
are ongoing to develop new ones. This represents a major challenge but one that remains particularly important to undertake.
2007 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 37:93-98
Keywords: disease activity, scleroderma, outcome measures, review
*Assistant Professor, Division of Rheumatology, McGill University, Montreal, Canada; and SMBD-Jewish General Hospital, Montreal, Canada.
Assistant Professor, Department of Mathematics and Statistics, McGill University, Montreal, Canada; and SMBD-Jewish General Hospital, Montreal, Canada.
Associate Professor, Division of Rheumatology, McGill University, Montreal,
Canada; and SMBD-Jewish General Hospital, Montreal, Canada.
This study was funded in part by the Canadian Institutes of Health Research, the
Scleroderma Society of Canada, and educational grants from Actelion Pharmaceuticals and Pfizer Inc. The study sponsors had no role in the design of the study, in the
collection, analysis, and interpretation of the data, in the writing of the article, and in
the decision to submit the article for publication.
Address reprint requests to: Marie Hudson, MD, MPH, SMBD-Jewish General
Hospital, Room A-216, 3755 Cote Ste. Catherine Road, Montreal, Quebec, H3T 1E2,
Canada. E-mail: marie.hudson@mcgill.ca.
ical subsets are recognized in terms of skin involvement, either limited (skin involvement distal to the
elbows and knees) or diffuse (skin involvement proximal to the elbows and knees in addition to the trunk)
(11). SSc is thought to affect over 16,000 Canadians
and up to 100,000 Americans (12-16). There is currently no known cure (17).
An important barrier in the study of SSc has been and
continues to be the difficulty in measuring disease activity
(18-20). Disease activity (20-23) usually measures the aspect of disease that varies over time and is potentially
reversible spontaneously or under drug treatment. This
is in contradistinction to disease damage and severity.
Damage measures irreversible tissue injury that results
from disease (20-23). Disease severity lacks an accepted
definition (21). Some (24,25) use it as a modifier of activity and incorporate it into ratings of activity (does the
disease manifestation require treatment, does it impose
functional limitations). Some (21) equate it to a measure
of prognosis. Others (22) take it to represent the total
effect of disease on organ function at a given point in time,
including both reversible (activity) and irreversible components (damage).
93
94
95
Score
96
0 (normal)
General
Peripheral
vascular
No
Raynauds;
Raynauds
not
requiring
vasoldialtors
Skin
TSS 0
Joint/tendon
FTP 00.9 cm
Muscle
Normal
proximal
muscle
strength
Gastrointestinal Normal
tract
esophagram;
normal
small bowel
series
Lung
DLCO 80%;
FVC 80%;
No fibrosis
on
radiograph;
sPAP 35
mmHg
Heart
EKG normal;
LVEF 50%
Kidney
No history of
SRC with
serum
creatinine
1.3 mg/dl
1 (mild)
2 (moderate)
3 (severe)
4 (end stage)
Digital gangrene
TSS 114
FTP 1.01.9 cm
Proximal weakness,
mild
TSS 3039
FTP 4.04.9 cm
Proximal weakness,
severe
TSS 40
FTP 5.0 cm
Ambulation aids
required
TSS 1529
FTP 2.03.9 cm
Proximal weakness,
moderate
Antibiotics required
Distal esophageal
for bacterial
hypoperistalsis;
overgrowth
small bowel series
abnormal
Hyperalimentation
Malabsorption
required
syndrome; episodes
of pseudoobstruction
DLCO 7079%;
FVC 7079%;
Basilar rales;
fibrosis on
radiograph; sPAP
3549 mmHg
Oxygen required
EKG conduction
defect; LVEF
4549%
History of SRC with
serum creatinine
1.5 mg/dl
EKG arrhythmia
requiring Rx; LVEF
3040%
History of SRC with
serum creatinine
2.55.0 mg/dl
History of SRC
with serum
creatinine 5.0
mg/dl or dialysis
required
Wt, weight; PCV, packed cell volume (hematocrit); Hb, hemoglobin; TSS, total skin score; FTP, fingertip to palm distance in flexion; DLCO,
diffusing capacity for carbon monoxide, % predicted; FVC, forced vital capacity, % predicted; sPAP, estimated pulmonary artery pressure
by Doppler echo; EKG, electrocardiogram; LVEF, left ventricular ejection fraction; Rx, treatment; CHF, congestive heart failure; SRC,
scleroderma renal crisis.
to measure disease activity exist in other rheumatic diseases, namely rheumatoid arthritis and ankylosing spondylitis (50-55), and are useful complements to traditional
biomedical assessments of disease activity based on clinical and laboratory measures (56). In addition, in the absence of a gold standard to define disease activity, both
physician and patient assessments of disease activity can
be used together (57,58). For example, in a study of
Raynauds phenomenon in patients with SSc, both
physician and patient assessments of Raynauds phenomenon activity were found to be valid and reliable
and the authors recommended that both be included in
the core set of measures for use in future clinical trials
in this area (59). Nevertheless, although SSc patients
are able to self-report symptoms and function accurately (60-62), it remains to be shown whether they can
97
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
98
29. Fiocco U, Rosada M, Cozzi L, Ortolani C, De Silvestro G, Ruffatti A, et al. Early phenotypic activation of circulating helper
memory T cells in scleroderma: correlation with disease activity.
Ann Rheum Dis 1993;52(4):272-7.
30. Steen VD, Engel EE, Charley MR, Medsger TA Jr. Soluble serum
interleukin 2 receptors in patients with systemic sclerosis. J Rheumatol 1996;23(4):646-9.
31. Valentini G, Bencivelli W, Bombardieri S, DAngelo S, Della
Rossa A, Silman AJ, et al. European Scleroderma Study Group to
define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria.
Ann Rheum Dis 2003;62(9):901-3.
32. Ward MM, Marx AS, Barry NN. Comparison of the validity and
sensitivity to change of 5 activity indices in systemic lupus erythematosus. J Rheumatol 2000;27(3):664-70.
33. van der Heijde DM, van t Hof M, van Riel PL, van de Putte LB.
Development of a disease activity score based on judgment in
clinical practice by rheumatologists. J Rheumatol 1993;20(3):
579-81.
34. Della Rossa A, Valentini G, Bombardieri S, Bencivelli W, Silman
AJ, DAngelo S, et al. European multicentre study to define disease activity criteria for systemic sclerosis. I. Clinical and epidemiological features of 290 patients from 19 centres. Ann Rheum Dis
2001;60(6):585-91.
35. Valentini G, Della Rossa A, Bombardieri S, Bencivelli W, Silman
AJ, DAngelo S, et al. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of
disease activity variables and development of preliminary activity
indexes. Ann Rheum Dis 2001;60(6):592-8.
36. Cohen J. Statistical Power Analysis for the Behavioral Sciences,
2nd ed. Hillsdale, NJ, Lawrence Erlbaum, 1988.
37. Bombardieri S, Medsger TA Jr, Silman AJ, Valentini G. The
assessment of the patient with systemic sclerosis. Introduction.
Clin Exp Rheumatol 2003;21(3 Suppl 29):S2-4.
38. La Montagna G, Meli R, Criscuolo T, DAngelo S, Valentini G.
Bioactivity of prolactin in systemic sclerosis. Clin Exp Rheumatol
2004;22(2):145-50.
39. Sfrent-Cornateanu R, Mihai C, Balan S, Ionescu R, Moldoveanu
E. The IL-6 promoter polymorphism is associated with disease
activity and disability in systemic sclerosis. J Cell Mol Med 2006;
10(4):955-9.
40. Volpe A, Biasi D, Caramaschi P, Mantovani W, Bambara LM,
Canestrini S, et al. Levels of F2-isoprostanes in systemic sclerosis:
correlation with clinical features. Rheumatology (Oxford) 2006;
45(3):314-20.
41. Steen VD, Medsger TA Jr. Long-term outcomes of scleroderma
renal crisis. Ann Intern Med 2000;133(8):600-3.
42. Geirsson AJ, Wollheim FA, Akesson A. Disease severity of 100
patients with systemic sclerosis over a period of 14 years: using a
modified Medsger scale. Ann Rheum Dis 2001;60(12):1117-22.
43. Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst
DE, et al. Cyclophosphamide versus placebo in scleroderma lung
disease. N Engl J Med 2006;354(25):2655-66.
44. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002;29(2):
288-91.
45. Hughes P, Holt S, Rowell NR, Dodd J. Thymus-dependent (T)
lymphocyte deficiency in progressive systemic sclerosis. Br J Dermatol 1976;95(5):469-73.
46. Furst DE, Clements PJ, Hillis S, Lachenbruch PA, Miller BL,
Sterz MG, et al. Immunosuppression with chlorambucil, versus
placebo, for scleroderma. Results of a three-year, parallel, randomized, double-blind study. Arthritis Rheum 1989;32(5):584-93.
47. Medsger TA Jr, Bombardieri S, Czirjak L, Scorza R, Della Rossa
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.