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DOI 10.1007/s10067-015-3139-z
ORIGINAL ARTICLE
Received: 12 August 2015 / Revised: 29 October 2015 / Accepted: 28 November 2015 / Published online: 10 December 2015
# International League of Associations for Rheumatology (ILAR) 2015
Introduction
Clinically amyopathic dermatomyositis (CADM) is a distinct
subtype of dermatomyositis (DM) that causes the same cutaneous symptoms as classic DM with little or no evidence of
muscular manifestations [13]. It has been reported that
CADM represents an estimated 20 % of all DM patients.
CADM is also characterized by an increased risk of lung disease, such as interstitial lung disease (ILD) [4, 5]. The lung
involvement becomes the most common cause of respiratory
failure and death in CADM. In particular, rapidly progressiveinterstitial lung disease (RP-ILD) in patients with DM is frequently fatal within months [6]. Therefore, predictive factors
for RP-ILD are very important in the management of patients
with CADM.
In 2005, Sato et al. identified a novel autoantibody
rec ognizin g a 14 0-kDa a utoantige n, m elan oma
differentiation-associated protein (MDA)-5, in patients
with DM, particularly in those with CADM [7].
Accumulating evidences have demonstrated that MDA5 is associated with ILD and severe cutaneous vasculopathy in CADM [710]. However, the main barrier is
that the determination of MDA-5 is limited in research
laboratories. On the other hand, we have realized that
there may be some other clinical manifestations associating with the poor outcome in CADM.
In this study, we summarized the clinical data to explore the
risk factors which are related to developing RP-ILD in patients
with CADM. We also evaluated the predicting value of serum
anti-MDA5 antibody and other clinical manifestations to
114
P valueb
53.69.7
5:6
2.93.1
1 (10 %)a
1 (10 %)
1 (10 %)
6 (55 %)
7 (64 %)
6 (55 %)
7 (64 %)
6 (55 %)
7 (64 %)
6 (55 %)
9 (82 %)
0 (0 %)
8 (73 %)
48.813.1
13:16
29.015.9
5 (17 %)
5 (11 %)
3 (10 %)
5 (17 %)
7 (24 %)
4 (14 %)
3 (10 %)
3 (10 %)
4 (14 %)
5 (17 %)
19 (66 %)
3 (10 %)
4 (14 %)
0.28
0.62
0.00
0.46
0.46
0.70
0.04
0.03
0.01
0.00
0.01
0.00
0.03
0.28
0.37
0.00
Obtained with Fishers exact test for the comparison of frequencies, Mann-Whitney U test for the comparison of
age and disease duration, and the t test for the comparisons of mean values
115
Wald
OR
95 % CI for OR
P value
Skin ulcerations
1.75
5.04
5.76
1.2526.57
0.03
1.71
5.00
5.50
1.2324.51
0.03
2.39
2.72
8.38
9.67
10.94
15.17
2.1755.25
2.7384.18
0.00
0.00
Lymphocytes <500/L
2.34
7.43
10.40
1.9356.04
0.01
CD4 <200/L
CD8 <200/L
2.39
1.75
8.38
5.04
10.94
5.76
2.1755.25
1.2526.57
0.00
0.03
2.81
10.58
16.67
3.0690.82
0.00
Results
Forty adult CADM patients were enrolled in the study. The
patients were divided into two groups: CADM + RP-ILD (n=
11) and CADM (n=29), according to having RP-ILD or not.
Six patients had already shown RP-ILD at the initial diagnosis
of CADM. The clinical characteristics of the patients are summarized in Table 1. It should be noted that the disease duration, estimated from the onset of subjective symptoms to the
Wald
OR
95 % CI or OR
P value
2.53
2.31
2.34
5.63
4.38
3.95
12.54
10.09
10.40
1.56101.36
1.1687.93
1.03104.79
0.02
0.04
0.05
2.55
3.78
2.86
3.90
7.12
4.35
12.75
43.97
17.37
1.02159.65
2.73708.80
1.19254.09
0.05
0.01
0.04
116
Discussion
CADM is a unique subset of DM, showing a high incidence of
fatal ILD. It has been established that anti-MDA5 Ab was an
important predictive factor for the poor outcome of ILD
[710]. However, the present problem is that there is no commercial method available for detecting MDA-5 Ab in clinic.
In the present study, we found that except for anti-MDA5 Ab,
routine clinical indexes, including skin ulcerations, serum ferritin level, and lymphocyte counts, may also help predict RPILD in patients with CADM.
Several previous studies have revealed an association between skin ulcer and RP-ILD in the patients with DM [4, 14,
15]. They reported that skin ulcers were observed in 7 of 12
(58 %), 7 of 9 (78 %), and 5 of 15 (33 %) DM patients with
RP-ILD, respectively. In our study, skin ulcer was found in 6
of 11 (55 %) patients with CADM concomitant with RP-ILD,
which is comparable to the previous results. The association
between skin ulcer and ILD may indicate that vasculitis is the
common pathological cause of skin changes and ILD.
Previously, Gono et al. have reported that elevated levels of
serum ferritin were related to the severity of ILD in patients
with DM [16]. They found that the cumulative survival rate
was lower in the subset with ferritin >1500 ng/mL than that in
the subset with ferritin <1500 ng/mL in DM patients. Here, we
found that the presence of serum ferritin >2000 g/L was
statistically more frequent in the CADM patients with RPILD than in those without it (64 versus 10 %). Ferritin is the
major molecule for iron storage, which is mainly secreted by
the activating macrophages and plays a crucial role in sequestration of potentially harmful molecules of reactive iron. High
levels of serum ferritin may reflect aberrant production of
ferritin by activating macrophages in patients with RP-ILD.
In addition, though lymphocytopenia has been reported in
DM patients, our results, for the first time, revealed that
lymphocytopenia is related to RP-ILD.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Acknowledgments The work is supported by National Nature Science
Foundation of China of under Grant (No. 81271324) and Liaoning Province Nature Science Funds (201202250) to PT Yang.
Compliance with ethical standards The whole research was approved
by the local ethic commission of the First Affiliated Hospital of China
Medical University.
13.
14.
Disclosures None.
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