Clinical significance of HScore and MS score comparison in the prognostic evaluation of anti-MDA5-positive patients with dermatomyositis and ...
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Modern Rheumatology, 00, 2021, 1–7
DOI: https://doi.org/10.1093/mr/roab017
Original Article
Clinical significance of HScore and MS score comparison in
the prognostic evaluation of anti-MDA5-positive patients
with dermatomyositis and interstitial lung disease
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab017/6348539 by guest on 27 November 2021
Shengnan Zhaoa , Xiaolei Maa , Xin Zhanga , Ziyi Jina , Wei Hub , Bingzhu Huaa , Hong Wanga ,
Xuebing Fenga , Lingyun Suna and Zhiyong Chena,*
a
Department of Rheumatology and Immunology, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China
b
Department of Clinical Laboratory, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
*Correspondence: Zhiyong Chen; chainzhiyong@163.com; Department of Rheumatology and Immunology, Drum Tower Clinical Medical College of Nanjing
Medical University, 321 Zhongshan Road, Nanjing Jiangsu 210008, China.
ABSTRACT
Objectives: To evaluate the clinical significance of the HScore and MS score in the prognosis of anti-melanoma differentiation-associated gene
5 (MDA5) positive patients with dermatomyositis (DM) and interstitial lung disease (ILD).
Methods: The clinical features as well as HScore and MS score were compared between the survivors (n = 61) and nonsurvivors (n = 36) among
97 anti-MDA5-positive DM-ILD patients. Potential prognostic factors were analysed.
Results: Compared with survivors, nonsurvivors had significantly older age, tended to be male, and had a significantly higher frequency of
fever at disease onset, higher levels of aspartate transaminase, lactate dehydrogenase, and serum ferritin, as well as higher values of HScore
and MS score but had a significantly lower frequency of arthritis at disease onset. Multivariate analysis revealed that age ≥50 years [hazard
ratio (HR) = 2.70, p = .040, 95% confidence interval (CI) 1.05–6.97)], male gender (HR = 3.20, p = .017, 95% CI 1.23–8.28), and higher HScore
(HR = 3.72, p = .003, 95% CI 1.56–8.86) were independent risk factors for mortality. Patients with more risk factors had significantly poorer
survival (p < .001).
Conclusions: Older age, high HScore, and male gender are risk factors for poor survival among anti-MDA5-positive DM-ILD patients, suggesting
the potential role of macrophage activation in the pathogenesis.
KEYWORDS: Anti-melanoma differentiation-associated gene 5 (anti-MDA5); dermatomyositis; interstitial lung disease; HScore; MS score
Introduction markers, such as IL-18, ferritin [3], sCD163 [4], and CD206
Interstitial lung disease (ILD) is a common manifestation [5], are elevated and associated with the prognosis of
and a major prognostic factor in patients with polymyosi- anti-MDA5-positive DM-ILD, suggesting that an MAS-like
tis/dermatomyositis (PM/DM). The clinical course and the immunopathologic process occurs in these patients.
severity of ILD in patients with PM/DM are largely clas- Recently, the HScore and MS score have been developed
sified according to myositis-specific antibodies (MSAs). for the classification of patients with reactive haemophago-
Generally, ILD progresses slowly in patients with anti- cytic syndrome and sJIA-associated MAS, respectively [6, 7].
aminoacyl-tRNA synthetase antibodies (e.g. anti-Jo1) but Given that patients with DM-ILD with anti-MDA5 antibod-
deteriorates rapidly in some patients, especially those with ies share several serological features with those with MAS,
anti-melanoma differentiation-associated gene 5 (MDA5) we hypothesised that the HScore and/or MS score maybe use-
antibodies; this is known as rapidly progressive ILD ful for predicting the prognosis of patients with DM-ILD and
(RP-ILD) [1]. anti-MDA5 antibodies. We tested this hypothesis by a retro-
Macrophage activation syndrome (MAS) is a life- spective review of patients with DM hospitalised in a tertiary
threatening condition that tends to occur in various rheumatic medical centre.
diseases, such as systemic juvenile idiopathic arthritis (sJIA),
adult-onset Still’s disease (AOSD), and systemic lupus erythe-
matosus [2]. It is generally accepted that MAS is caused by a Materials and methods
‘cytokine storm’ characterised as the striking elevation of the Participants and data collection
levels of a number of macrophage activation-related factors, Among hospitalised patients diagnosed with PM/DM between
such as ferritin, IL-18, soluble CD25 (sCD25), and sCD163, August 2010 and December 2013 in the Department of
a condition similar to the primary and secondary forms Rheumatology and Immunology, the Affiliated Drum Tower
of haemophagocytic lymphohistiocytosis [2]. Previous stud- Hospital of Nanjing University Medical School, Nanjing,
ies have demonstrated that macrophage activation-related China, 97 positive for anti-MDA5 antibodies with available
Received 21 January 2021; Accepted 29 May 2021
© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved.
For permissions, please e-mail: journals.permissions@oup.com2 Zhao et al.
data were enrolled in the current study. Immunoblot testing continuous values were expressed as mean ± standard devi-
(EUROIMMUN, Beijing, China) was used to detect the pres- ation (SD) and were compared by the Student t test. The
ence of MSAs. In some of the patients, anti-MDA5 antibod- chi-squared test was performed to evaluate categorical data.
ies were measured by enzyme-linked immunosorbent assay Kaplan–Meier analysis and log-rank tests were used for the
using recombinant MDA5 antigen as described previously initial survival analysis. Cox regression analysis was used to
[8]. ILD was detected by high-resolution computed tomog- estimate the hazard ratio (HR) and 95% confidence inter-
raphy (HRCT). Clinical and laboratory data were extracted vals (95% CIs) and to identify baseline factors associated
from medical records. The HScore and MS score were cal- with survival. The optimal cut-off value was determined by
culated as described previously [6, 7]. The HScore is an receiver operating characteristic (ROC) curve analysis and,
aggregate of the scores for nine variables: known underlying subsequently, the HScore and MS score were classified into
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immunosuppression, temperature, organomegaly, number of two categories according to the optimal Youden index-based
cytopenias, ferritin, triglyceride, fibrinogen, serum glutamic cut-off point value, respectively. Multivariate analysis was
oxaloacetic transaminase, and features of haemophagocyto- performed using a multivariate Cox regression model. A p-
sis on bone marrow aspirate. The MS score was calculated valueHScore and MS score for anti-MDA5-positive DM-ILD 3 erythrocyte sedimentation rate (ESR), and C-reactive protein age cut-off point for the survival of patients with anti-MDA5 (CRP) between the surviving and nonsurviving patients pos- antibodies was 50 years. A poorer survival rate was also itive for anti-MDA5 antibodies. Compared with survivors, observed in patients with age of onset ≥50 years than in those nonsurvivors were older (53.0 ± 11.1 vs 46.8 ± 13.3 years, with age
4 Zhao et al. Table 2. Baseline characteristics of 97 anti-MDA5-positive DM-ILD patients with HS score ≥95.5 and HS score
HScore and MS score for anti-MDA5-positive DM-ILD 5
Table 3. Prediction of mortality in anti-MDA5-positive DM-ILD patients by univariate and multivariate Cox regression analyses.
Univariate analysis Multivariate analysis (model 1) Multivariate analysis (model 2)
p-value Hazard ratio 95% CI p-value Hazard ratio 95% CI p-value Hazard ratio 95% CI
Age, ≥50 years .074 2.16 0.93–5.02 .040 2.70 1.05–6.97 .017 3.07 1.22–7.71
Male gender .069 2.10 0.94–4.68 .017 3.20 1.23–8.28 .040 2.56 1.04–6.29
Presence of fever at the .034 2.71 1.08–6.78
disease onset
Absence of arthritis at the .046 2.36 1.02–5.48 .600 1.28 0.51–3.25 .891 1.10 0.27–4.48
disease onset
White cell .465 0.69 0.26–1.85
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count,6 Zhao et al.
AOSD-associated MAS compared with the MS score [26]. Z.C.) and the National Natural Science Foundation of China
A recent prospective cohort study found that the HScore is (NO.81871282 to S.Z.).
an independent predictor of 30-day survival in patients with
systemic inflammatory response syndrome [27]. Collectively,
these reports indicate that the HScore is a useful tool for Conflict of interest
detecting MAS secondary to autoimmune and autoinflamma- None declared.
tory diseases, and its power may be greater than that of the
MS score.
In univariate analysis, serum ferritin had an HR of 6.5 [area Funding
under the curve (AUC) = 0.74], which was higher than that of None declared.
Downloaded from https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roab017/6348539 by guest on 27 November 2021
the HScore (HR = 4.1, AUC = 0.64), suggesting that serum
ferritin may be superior to the HScore in predicting the mor-
tality of patients with DM-ILD and anti-MDA5 antibodies. References
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