ORIGINAL
ARTICLE
Initial Predictors
of Survival in Patients
with Systemic Sclerosis
(Scleroderma) Junichi Kaburaki, Chang Chur Lee1), Masataka Kuwana2), Takeshi Tojo3), Yasuo Ikeda2), Makoto Takano and Yuzo Funatsu Department of Internal Medicine, Tokyo Electric Power Company Hospital, Imazato Clinic1), Department of Internal Medicine, School of Medicine, Keio University2) and Department of Internal Medicine, National Tokyo Daini Hospital3), Tokyo, Japan (Received
for publication
on June 17, 1992)
Abstract. We conducted a retrospective study of 86 patients with systemic sclerosis (SSc) to clarify the initial predictors of survival at the first visit to the hospital. A life-table analysis of survival was performed concerning 137 items from their histories, physical examinations, and laboratory data. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years. Ten items were found to be the initial predictors of survival in patients with SSc. Of these 10 items, 9 items showed significant differences within 5 years of the first visit to the hospital. Patients with resting electrocardiographic abnor malities, such as atrial or ventricular arrhythmias, or conduction disturbances, pulmonary fibrosis on the chest x-ray films, or decreased vital capacity had significantly lower survival rates. However, patients with anti-centromere antibody had a significantly better survival rate. In addition, males, aged patients over 65 years old, and survival rates. lower survival ened survival Key words:
patients with proteinuria, leucopenia, or hypergammaglobulinemia had significantly lower Only patients with proximal scleroderma at the first visit to the hospital had a significantly rate after 8 years. These results are useful in predicting individual patients at risk of short and in managing these patients. (Keio j Med 41 (3): 141-145, 1992)
initial
symptoms,
survival
rates,
prognosis
the hospital are not clear. In this study, clinical and laboratory data at the first visit to the hospital were analyzed to clarify the initial predictors of survival in Japanese patients with SSc.
Introduction
Systemic sclerosis (SSc: scleroderma) is a systemic con nective tissue disease characterized by fibrotic and de generative changes in the skin and vascular changes, and is accompanied by serious internal organ involvement.1,2 Clinical severity and progression vary among subsets ranging from limited scleroderma to diffuse scleroderma, according to the extent of skin involvement. However, patients often have different degrees of visceral involve ment and different prognoses even when classified in the same subset.3 Many retrospective studies on survival in SSc patients have been performed. is Clinical manifestations and laboratory data during the entire observation period were analyzed in these studies. Although it is generally accepted that cardiopulmonary and renal involvements have been the main causes of decreased survival, the initial predictors in patients with SSc at the first visit to 鏑 木 淳 一,李
彰 哲,桑
名 正 隆,東
條
毅,池
田 康 夫,高
野
Patients and Methods Patients Eighty-six patients with SSc at Keio University Hospi tal, Department of Internal Medicine, were studied. These patients were diagnosed with SSc according to the preliminary criteria for the classification of SSc of the American Rheumatism Association (American College of Rheumatology).16 Five patients with complete CREST syndrome were included. However, they were not defi nitely diagnosed as overlap syndrome with systemic lupus erythematosus, polymyositis or dermatomyositis .
慎,船
津雄 三
Reprint requests to: Dr Junichi Kaburaki, Department of Internal Medicine, Tokyo Electric Power Company Hospital , 9-2 Shinanomachi, Shi njuku, Tokyo 160, Japan 141
Kaburaki
142
Methods
of Survival in Systemic
Sclerosis
percent at 5 years and 68.2 percent at 10 years (Fig 1).
The
medical
One
records
hundred
physical
of
of
of
Internal
the
72
items
of
were
regarded
The
most
base
for
and
first
visit
to
items
of
the
them
were
rheumatic
histories,
data
within
Nine
initial
clinical
selected
clinical
of
items
were
56
in
items
manifestations.
from
diseases
and These
the
proposed
uniform
by
the
The
Sera Serum
data Arthritis
life-table of
method
SSc
with
the
from
was
all
Patients
was
escence
method, anti-U1
for
determining
the
patients
were
stored
antibodies
RNP
immunodiffusion
at
were method.18
examined
by
while
had
the
-20•Ž
until
screened
were
the
Anti-centromere
indirect
immunofluor
anti-Topoisomerase
antibody
use.
by
I
identified
by
findings
was
be
SSc
the
(Table
on present
initial
whether or
predictors
1).
differences
who
had
such
as
resting atrial
Out
of
within
each
absent.
Ten
of these
survival 10
5 years
of
electrocardiographic or
disturbances,
a significantly
with
immunofluorescence
antibody
used
depending
items, the
first
hospital.
malities,
patients.8,9
to
significant
conduction
anti-nuclear
indirect
patients
to
examined manifestation
found
9 showed visit
Foundation.17
survival
was
initial
items
examinations, included.
Survival
one
Department
encoded.
were
Initial clinical manifestations and subsequent survival
reviewed.
their
University,
physical
data as
were
from
laboratory Keio
were
laboratory
of
patients
items
Medicine,
histories,
all
thirty-seven
examinations,
year
and
J. et al. Initial Predictors
other
at
(P•ƒ0.01)
patients (Fig
fibrosis
on
creased
vital
survival
rates
Similarly, chest
capacity (Fig
x-ray had
3,
the
visit
survival
normal
significantly
to
the
rate,
or hospital
compared
electrocardiographic
patients films
abnor arrhythmias,
first
lower
with
2). their
ventricular
with or
pulmonary
patients (P•ƒ0.01)
with
de lower
4).
antibody
the
double
method.18
Results
Patient profiles Of the 86 patients with SSc studied, 75 were women and 11 were men. All patients were Japanese. The mean age of the patients at the first visit to the hospital was 47.5 years (range, 19 to 76). Six patients over 65 years old were regarded as the aged. The mean observation period was 5.1 years (range, 0 to 15). During the obser vation period, 46 patients survived, while 25 patients died and 15 patients were lost to follow-up. Overall The
survivorship observed
Table
cumulative
1
survival
Initial Predictors
rates
of Survival
were
in Patients
78.0
Fig 1 Observed cumulative survival rate (CSR) for Japanese patients with systemic sclerosis at Kcio University Hospital. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years.
with Systemic Sclerosis
Keio J Med 41 (3): 141-145,
Fig
2
Observed
abnormal
cumulative
resting
normal
resting
lower
or
survival
graphic
survival
rate
electrocardiographic
findings,
conduction
rate,
findings
(CSR)
such
disturbances
compared
for
findings.
electrocardiographic
arrhythmias,
143
1992
with
patients
as
or ventricular
atrial had
with
with
who
(•œ-•œ),
patients
SSc
Patients
a
normal
had
Fig
ab
4
Observed
decreased values
significantly
(•œ-•œ)
electrocardio
with
vital less had
normal
than
cumulative capacity. 80
percent.
a significantly vital
capacity
survival
rate
Decreased Patients lower
vital who
survival
(CSR) capacity
for
patients was
with
defined
had
decreased
vital
capacity
rate,
compared
with
patients
as
(•›•c•›).
(•›•c•›)).
Discussion
Various kinds of internal organ involvement as well as fibrotic and degenerative changes in the skin have been found in patients with SSc.2,19 These involvements were related to the prognoses and the subsets of these
Fig
3
Observed
pulmonary fibrosis
on
survival
rate,
on
their
of
the
chest
with
with
better
anti-nuclear Males,
x-ray films
patients
(CSR)
for
Patients had
without
pulmonary
a
had
with
pulmonary
significantly
lower
fibrosis
antibody rate,
patients
who
(•œ-•œ)
survival
had
from
the
(•›•c•›).
a signifi viewpoint
antibodies. aged
patients,
(white
blood
patients cell
hypergammaglobulinemia than
rate films.
anti-centromere
(P•ƒ0.01)
copenia
survival chest
x-ray
compared
Patients cantly
cumulative
fibrosis
patients. Tuffanelli and Winkelmann reported that the 5-year survival rate in patients with SSc was only 70.3% in 1961.5 However, the 5-year survival rate in patients with SSc was recently estimated to be 75 or 77%.14,20 In this study, the 5-year survival rate was 78.0%. Therefore, this study confirmed recent advances in the management of SSc patients, including the development of new drugs such as vasodilators and angiotensin-converting enzyme inhibitor,1 and the current concept of better quality of life.21 Many retrospective studies on survival among patients with SSc have been published.3-15,20,22 All of the authors have agreed that the development of serious visceral involvement, such as heart or lung, portends early mor tality in patients with SSc.4,7-9.11.12.14.15.22 We have already shown that the incidence of cardiac failure and respiratory failure as causes of death were high in SSc
2 g/dl)
with
count
less
(serum
had
significantly
proteinuria, than
leu
4000/ƒÊl),
gammaglobulin (P•ƒ0.05)
lower
or more
survival
rates. In
addition,
significantly with first
patients
patients visit
with
(P•ƒ0.05)
to
with the
lower only
hospital.
proximal
scleroderma
survival
sclerodactyly
rate, 8
years
had
a
compared after
the
patients who died within 5 years of their first visit to the hospital.23 In this study, resting electrocardiographic abnor malities, pulmonary fibrosis on the chest x-ray films , and reduced vital capacity were able to serve as initial predictors of survival at the first visit to the hospital. Although ambulatory electrocardiography was rec ommended in the managment of patients with SSc ,22 this study emphasized the clinical usefulness of resting electrocardiography at the first visit to the hospital . Arrhythmias and conduction disturbances may be caused
Kaburaki
144
by myocardial fibrosis, leading to cardiac failure.24 In addition, pulmonary fibrosis can cause cardiac failure as a result of pulmonary hypertension and respiratory infec tion. Moreover, non-invasive studies, such as echocardio graphy and myocardial perfusion scanning, are necessary to evaluate these points. Patients with anti-centromere antibody had better survival rates. This finding was compatible with the report by Steen et al,20 and confirmed the clinical import ance of anti-nuclear antibodies. It was recently reported that other anti-nuclear antibodies, such as anti-7-2 RNP (Th) antibody and anti-RNA polymerase complex anti bodies, are capable of serving as predictors of the prog nosis in patients with SSc.18Various kinds of anti-nuclear antibodies should be identified to predict the survival of these patients. Males and aged Japanese patients had lower survival rates. This finding confirmed the results of previously reported foreign studies.3,6-10,12,15,22 Proteinuuuria may be a sign of scleroderma renal crisis. Otherwise, proteinuria, leucopenia, and hypergammaglobulinemia suggested overlapping featuuuuuuuu of systemic lupus erythematosus. Careful clinical assessment is necessary to treat these patients. In the literature, the extent of skin involvement has been unclear in terms of prognosis. Barnett et al, re ported the association between the prognosis and the early extent of clinical skin involvement.13 However, Cunningham et al, found that mortality was unrelated to the extent of skin involvement.11 Although patients with proximal scleroderma at the first visit to the hospital had a lower survival rate, the difference was only found to be significant after 8 years. Therefore, our results suggest that the degree of visceral involvement has a more important role than skin involvement. In this study, initial predictors of survival in patients with SSc were found. These findings are useful in pre dicting individual patients at risk of shortened survival and in managing these patients. Further studies are necessary to analyze other factors and various kinds of therapy.
3. 4.
5. 6.
7. 8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18. Acknowledgements: The authors arc deeply indebted to Dr Mitsuo Homma, Honorary Professor of Internal Medicine, School of Medicine, Keio University, for his encouragement during this study. A part of this study was supported by the Sclcroderma Research Grant for Intractable Diseases from the Japanese Ministry of Health and Welfare.
References
19.
20.
J. et al. Initial Predictors
of Survival
in Systemic
Rowell NR: The prognosis of systemic sclerosis. Br J Dermatol 1976, 95: 57-60 Farmer RG, Gifford RW, Hines EA: Prognostic significance of Raynaud's phenomenon and other clinical characteristics of systemic scleroderma: a study of 271 cases. Circulation 1960, 21: 1088-1095 Tuffanelli DL, Winkelmann RK: Systemic scleroderma: a clinical study of 727 cases. Arch Dermatol 1961, 84: 359-371 Masi AT, D'Angelo WA: Epidemiology of fatal systemic sclerosis (diffuse scleroderma): a 15-year survey in Baltimore. Ann Intern Mcd 1967, 66: 870-883 Bennett R, Bluestone R, Holt PJL, Bywaters EGL: Survival in scleroderma. Ann Rheum Dis 1971, 30: 581-588 Medsger TA Jr, Masi AT, Rodnan GP, Benedek TG, Robinson H: Survival with systemic sclerosis (scleroderma): a life-table analysis of clinical and demographic factors in 309 patients. Ann Intern Med 1971, 75: 369-376 Medsger TA Jr, Masi AT: Survival with scleroderma-II: a life table analysis of clinical and demographic factors in 358 male U. S. veteran patients. J Chron Dis 1973, 26: 647-660 Barnett AJ: Scleroderma (progressive systemic sclerosis): pro gress and course based on a personal series of 118 cases. Med J Aust 1978, 2: 129-134 Cunningham PH, Andrews BS, Davis JS IV: Scleroderma: devel opments from Osler to the present. Southern Med J 1980, 6: 770-774 Wynn J, Fineberg N, Matzer L, Cortada X, Armstrong W, Dillon JC, Kinney EL: Prediction of survival in progressive systemic sclerosis by multivariate analysis of clinical features. Am Heart J 1985, 110: 123-127 Barnett AJ, Miller MH, Littlejohn GO: A survival study of patients with scleroderma diagnosed over 30 years (1953-1983): the value of a simple cutaneous classification in the early stages of the disease. J Rheumatol 1988, 15: 276-283 Lally EV, Jimenez SA, Kaplan SR: Progressive systemic sclerosis: mode of presentation, rapidly progressive disease course, and mortality based on an analysis of 91 patients. Semin Arthritis Rheum 1988, 18: 1-13 Altman RD, Medsger TA Jr, Bloch DA, Michel BA: Predictors of survival in systemic sclerosis (scleroderma). Arthritis Rheum 1991, 34: 403-413 Subcommittee for Scleroderma Criteria of the American Rheu matism Association Diagnostic and Therapeutic Criteria Com mittee: Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980, 23: 581-590 Arthritis Foundation: Uniform database for the rheumatic disease. In: Rodnan GP, Schumacher HR, ed, Primer on the Rheumatic Diseases, Atlanta, Arthritis Foundation, 1983, 215-217 Kuwana M, Mimori T, Hama N, Kaburaki J, Okano T, Tojo T: Clinical significance of anti-nucleolar antibodies detected by immunoprecipitation method in patients with systemic sclerosis. Ryumachi (J Jpn Rheum Assoc) 1992, 32: 39-46 (in Japanese) D'Angelo WA, Fries JF, Masi AT, Shulman LE: Pathologic observations in systemic sclerosis (scleroderma): a study of fifty eight autopsy cases and fifty-eight matched controls. Am J Med 1969, 46: 428-440 Steen VD, Powell DL, Medsger
TA Jr: Clinical correlations
prognosis based on serum autoantibodies in patients sclerosis. Arthritis Rheum 1988, 31: 196-203 1. 2.
Medsger TA Jr: Progressive systemic sclerosis. Clin Rheum Dis 1983, 9: 655-670 Mcdsgcr TA Jr: Systemic sclerosis (scleroderma), localized sclero derma, cosinophilic fasciitis, and calcinosis. In: MaCarty DJ, ed, Arthritis and Allied Conditions: A Textbook of Rheumatology, Philadelphia,
Lea and Febiger,
1989, 1118-1165
Sclerosis
and
with systemic
21.
Kaburaki J, Kawai S, Kuwana M, Tojo T, Takano M, Funatsu Y: Quality of life (QOL) in patients with systemic sclerosis. Nippon Rinshoumeneki Gakkai Kaishi (Jpn J Clin Immunol) 1991, 14: 626-632 (in Japanese)
22.
Kostis JB, Seibold JR, Turkevich D, Masi TA, Grau RG, Medsger TA Jr, Steen VD, Clements PJ, Szydlo L, D'Angelo WA: Pro-
145
Keio J Med 41 (3): 141-145, 1992
23.
gnostic importance of cardiac arrhythmias in systemic sclerosis. Am J Med 1988, 84: 1007-1015 Kaburaki J, Kuwana M, Tojo T, Takano M, Funatsu Y: Clinical manifestations of the early dead cases in patients with systemic sclerosis (SS). Connect Tissue 1991, 22: 151-152
24.
Follansbee WP, Curtiss EI, Rahko PS, Medsger TA Jr, Lavine SJ, Owens GR, Steen VD: The electrocardiogram in systemic sclerosis (scleroderma): study of 102 consecutive cases with func tional correlations and review of the literature. Am J Med 1985, 79: 183-192
ARTICLE
Initial Predictors
of Survival in Patients
with Systemic Sclerosis
(Scleroderma) Junichi Kaburaki, Chang Chur Lee1), Masataka Kuwana2), Takeshi Tojo3), Yasuo Ikeda2), Makoto Takano and Yuzo Funatsu Department of Internal Medicine, Tokyo Electric Power Company Hospital, Imazato Clinic1), Department of Internal Medicine, School of Medicine, Keio University2) and Department of Internal Medicine, National Tokyo Daini Hospital3), Tokyo, Japan (Received
for publication
on June 17, 1992)
Abstract. We conducted a retrospective study of 86 patients with systemic sclerosis (SSc) to clarify the initial predictors of survival at the first visit to the hospital. A life-table analysis of survival was performed concerning 137 items from their histories, physical examinations, and laboratory data. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years. Ten items were found to be the initial predictors of survival in patients with SSc. Of these 10 items, 9 items showed significant differences within 5 years of the first visit to the hospital. Patients with resting electrocardiographic abnor malities, such as atrial or ventricular arrhythmias, or conduction disturbances, pulmonary fibrosis on the chest x-ray films, or decreased vital capacity had significantly lower survival rates. However, patients with anti-centromere antibody had a significantly better survival rate. In addition, males, aged patients over 65 years old, and survival rates. lower survival ened survival Key words:
patients with proteinuria, leucopenia, or hypergammaglobulinemia had significantly lower Only patients with proximal scleroderma at the first visit to the hospital had a significantly rate after 8 years. These results are useful in predicting individual patients at risk of short and in managing these patients. (Keio j Med 41 (3): 141-145, 1992)
initial
symptoms,
survival
rates,
prognosis
the hospital are not clear. In this study, clinical and laboratory data at the first visit to the hospital were analyzed to clarify the initial predictors of survival in Japanese patients with SSc.
Introduction
Systemic sclerosis (SSc: scleroderma) is a systemic con nective tissue disease characterized by fibrotic and de generative changes in the skin and vascular changes, and is accompanied by serious internal organ involvement.1,2 Clinical severity and progression vary among subsets ranging from limited scleroderma to diffuse scleroderma, according to the extent of skin involvement. However, patients often have different degrees of visceral involve ment and different prognoses even when classified in the same subset.3 Many retrospective studies on survival in SSc patients have been performed. is Clinical manifestations and laboratory data during the entire observation period were analyzed in these studies. Although it is generally accepted that cardiopulmonary and renal involvements have been the main causes of decreased survival, the initial predictors in patients with SSc at the first visit to 鏑 木 淳 一,李
彰 哲,桑
名 正 隆,東
條
毅,池
田 康 夫,高
野
Patients and Methods Patients Eighty-six patients with SSc at Keio University Hospi tal, Department of Internal Medicine, were studied. These patients were diagnosed with SSc according to the preliminary criteria for the classification of SSc of the American Rheumatism Association (American College of Rheumatology).16 Five patients with complete CREST syndrome were included. However, they were not defi nitely diagnosed as overlap syndrome with systemic lupus erythematosus, polymyositis or dermatomyositis .
慎,船
津雄 三
Reprint requests to: Dr Junichi Kaburaki, Department of Internal Medicine, Tokyo Electric Power Company Hospital , 9-2 Shinanomachi, Shi njuku, Tokyo 160, Japan 141
Kaburaki
142
Methods
of Survival in Systemic
Sclerosis
percent at 5 years and 68.2 percent at 10 years (Fig 1).
The
medical
One
records
hundred
physical
of
of
of
Internal
the
72
items
of
were
regarded
The
most
base
for
and
first
visit
to
items
of
the
them
were
rheumatic
histories,
data
within
Nine
initial
clinical
selected
clinical
of
items
were
56
in
items
manifestations.
from
diseases
and These
the
proposed
uniform
by
the
The
Sera Serum
data Arthritis
life-table of
method
SSc
with
the
from
was
all
Patients
was
escence
method, anti-U1
for
determining
the
patients
were
stored
antibodies
RNP
immunodiffusion
at
were method.18
examined
by
while
had
the
-20•Ž
until
screened
were
the
Anti-centromere
indirect
immunofluor
anti-Topoisomerase
antibody
use.
by
I
identified
by
findings
was
be
SSc
the
(Table
on present
initial
whether or
predictors
1).
differences
who
had
such
as
resting atrial
Out
of
within
each
absent.
Ten
of these
survival 10
5 years
of
electrocardiographic or
disturbances,
a significantly
with
immunofluorescence
antibody
used
depending
items, the
first
hospital.
malities,
patients.8,9
to
significant
conduction
anti-nuclear
indirect
patients
to
examined manifestation
found
9 showed visit
Foundation.17
survival
was
initial
items
examinations, included.
Survival
one
Department
encoded.
were
Initial clinical manifestations and subsequent survival
reviewed.
their
University,
physical
data as
were
from
laboratory Keio
were
laboratory
of
patients
items
Medicine,
histories,
all
thirty-seven
examinations,
year
and
J. et al. Initial Predictors
other
at
(P•ƒ0.01)
patients (Fig
fibrosis
on
creased
vital
survival
rates
Similarly, chest
capacity (Fig
x-ray had
3,
the
visit
survival
normal
significantly
to
the
rate,
or hospital
compared
electrocardiographic
patients films
abnor arrhythmias,
first
lower
with
2). their
ventricular
with or
pulmonary
patients (P•ƒ0.01)
with
de lower
4).
antibody
the
double
method.18
Results
Patient profiles Of the 86 patients with SSc studied, 75 were women and 11 were men. All patients were Japanese. The mean age of the patients at the first visit to the hospital was 47.5 years (range, 19 to 76). Six patients over 65 years old were regarded as the aged. The mean observation period was 5.1 years (range, 0 to 15). During the obser vation period, 46 patients survived, while 25 patients died and 15 patients were lost to follow-up. Overall The
survivorship observed
Table
cumulative
1
survival
Initial Predictors
rates
of Survival
were
in Patients
78.0
Fig 1 Observed cumulative survival rate (CSR) for Japanese patients with systemic sclerosis at Kcio University Hospital. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years.
with Systemic Sclerosis
Keio J Med 41 (3): 141-145,
Fig
2
Observed
abnormal
cumulative
resting
normal
resting
lower
or
survival
graphic
survival
rate
electrocardiographic
findings,
conduction
rate,
findings
(CSR)
such
disturbances
compared
for
findings.
electrocardiographic
arrhythmias,
143
1992
with
patients
as
or ventricular
atrial had
with
with
who
(•œ-•œ),
patients
SSc
Patients
a
normal
had
Fig
ab
4
Observed
decreased values
significantly
(•œ-•œ)
electrocardio
with
vital less had
normal
than
cumulative capacity. 80
percent.
a significantly vital
capacity
survival
rate
Decreased Patients lower
vital who
survival
(CSR) capacity
for
patients was
with
defined
had
decreased
vital
capacity
rate,
compared
with
patients
as
(•›•c•›).
(•›•c•›)).
Discussion
Various kinds of internal organ involvement as well as fibrotic and degenerative changes in the skin have been found in patients with SSc.2,19 These involvements were related to the prognoses and the subsets of these
Fig
3
Observed
pulmonary fibrosis
on
survival
rate,
on
their
of
the
chest
with
with
better
anti-nuclear Males,
x-ray films
patients
(CSR)
for
Patients had
without
pulmonary
a
had
with
pulmonary
significantly
lower
fibrosis
antibody rate,
patients
who
(•œ-•œ)
survival
had
from
the
(•›•c•›).
a signifi viewpoint
antibodies. aged
patients,
(white
blood
patients cell
hypergammaglobulinemia than
rate films.
anti-centromere
(P•ƒ0.01)
copenia
survival chest
x-ray
compared
Patients cantly
cumulative
fibrosis
patients. Tuffanelli and Winkelmann reported that the 5-year survival rate in patients with SSc was only 70.3% in 1961.5 However, the 5-year survival rate in patients with SSc was recently estimated to be 75 or 77%.14,20 In this study, the 5-year survival rate was 78.0%. Therefore, this study confirmed recent advances in the management of SSc patients, including the development of new drugs such as vasodilators and angiotensin-converting enzyme inhibitor,1 and the current concept of better quality of life.21 Many retrospective studies on survival among patients with SSc have been published.3-15,20,22 All of the authors have agreed that the development of serious visceral involvement, such as heart or lung, portends early mor tality in patients with SSc.4,7-9.11.12.14.15.22 We have already shown that the incidence of cardiac failure and respiratory failure as causes of death were high in SSc
2 g/dl)
with
count
less
(serum
had
significantly
proteinuria, than
leu
4000/ƒÊl),
gammaglobulin (P•ƒ0.05)
lower
or more
survival
rates. In
addition,
significantly with first
patients
patients visit
with
(P•ƒ0.05)
to
with the
lower only
hospital.
proximal
scleroderma
survival
sclerodactyly
rate, 8
years
had
a
compared after
the
patients who died within 5 years of their first visit to the hospital.23 In this study, resting electrocardiographic abnor malities, pulmonary fibrosis on the chest x-ray films , and reduced vital capacity were able to serve as initial predictors of survival at the first visit to the hospital. Although ambulatory electrocardiography was rec ommended in the managment of patients with SSc ,22 this study emphasized the clinical usefulness of resting electrocardiography at the first visit to the hospital . Arrhythmias and conduction disturbances may be caused
Kaburaki
144
by myocardial fibrosis, leading to cardiac failure.24 In addition, pulmonary fibrosis can cause cardiac failure as a result of pulmonary hypertension and respiratory infec tion. Moreover, non-invasive studies, such as echocardio graphy and myocardial perfusion scanning, are necessary to evaluate these points. Patients with anti-centromere antibody had better survival rates. This finding was compatible with the report by Steen et al,20 and confirmed the clinical import ance of anti-nuclear antibodies. It was recently reported that other anti-nuclear antibodies, such as anti-7-2 RNP (Th) antibody and anti-RNA polymerase complex anti bodies, are capable of serving as predictors of the prog nosis in patients with SSc.18Various kinds of anti-nuclear antibodies should be identified to predict the survival of these patients. Males and aged Japanese patients had lower survival rates. This finding confirmed the results of previously reported foreign studies.3,6-10,12,15,22 Proteinuuuria may be a sign of scleroderma renal crisis. Otherwise, proteinuria, leucopenia, and hypergammaglobulinemia suggested overlapping featuuuuuuuu of systemic lupus erythematosus. Careful clinical assessment is necessary to treat these patients. In the literature, the extent of skin involvement has been unclear in terms of prognosis. Barnett et al, re ported the association between the prognosis and the early extent of clinical skin involvement.13 However, Cunningham et al, found that mortality was unrelated to the extent of skin involvement.11 Although patients with proximal scleroderma at the first visit to the hospital had a lower survival rate, the difference was only found to be significant after 8 years. Therefore, our results suggest that the degree of visceral involvement has a more important role than skin involvement. In this study, initial predictors of survival in patients with SSc were found. These findings are useful in pre dicting individual patients at risk of shortened survival and in managing these patients. Further studies are necessary to analyze other factors and various kinds of therapy.
3. 4.
5. 6.
7. 8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18. Acknowledgements: The authors arc deeply indebted to Dr Mitsuo Homma, Honorary Professor of Internal Medicine, School of Medicine, Keio University, for his encouragement during this study. A part of this study was supported by the Sclcroderma Research Grant for Intractable Diseases from the Japanese Ministry of Health and Welfare.
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