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BRIEF REPORT
Year : 2023 | Volume
: 41
| Issue : 1 | Page : 31-35
Myositis-specific antibodies in dermatomyositis: A single-center experience of 33 cases in Taiwan
Wei-Ting Liu1, Chao-Chun Yang2
1 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2 International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan
Correspondence Address:
Prof. Chao-Chun Yang
Department of Dermatology, National Cheng Kung University Hospital, No. 138, Sheng-Li Rd., Tainan 704
Taiwan
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ds.DS-D-22-00122
Dermatomyositis (DM) is a systemic autoimmune disease characterized by unique cutaneous manifestations and inflammatory myopathies. With the discovery of myositis-specific antibodies (MSAs), patients with DM, especially those with a higher risk of life-threatening complications, can be classified according to the MSA type. This retrospective study aimed to investigate the clinical significance of MSAs in patients with DM in Taiwan. A total of 33 patients with DM who underwent the MSA test, including 26 with classic DM and 7 with amyopathic DM, were included. There were 13 men and 20 women, with a mean age at diagnosis of 49.6 years. MSA was detected in 26 (78.8%) of 33 patients with DM. The most frequently detected MSA was anti-melanoma differentiation-associated protein 5 (MDA5) (10/33, 30.3%) followed by anti-transcription intermediary factor-1γ (TIF-1γ) (8/33, 24.2%). Dysphagia was present in 6 (18.2%) of the 33 patients and more frequently developed in patients with anti-TIF-1γ (+) (5/8, 62.5%) than those with anti-TIF-1γ (−) (1/25, 4.0%). Interstitial lung disease was noted in 15 patients (45.5%) and developed more frequently in patients with anti-MDA5 (+) (7/10, 70.0%) than those with anti-MDA5 (−) (8/23, 34.8%). Malignancies were detected in 4 (12.1%) patients, with one each of anti-Mi-2 (+), anti-TIF-1γ (+), anti-ARS (+), and MSA (−). Mortality occurred in 6 (18.2%) patients, of whom 4 were anti-MDA5 (+). Anti-MDA5 and anti-TIF-1γ were the two most commonly detected MSAs. The presence of specific MSAs is associated with a certain phenotype, and integrating MSAs while evaluating DM aids in accurate patient management.
Keywords: Anti-melanoma differentiation-associated protein 5 dermatomyositis, anti-transcription intermediary factor-1γ dermatomyositis, dysphagia, interstitial lung disease, myositis-specific antibodies
Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by distinct cutaneous lesions, varying degrees of muscle involvement, and heterogeneous systemic manifestations.[1] Upon diagnosis of DM, a thorough evaluation of possible systemic involvement, especially occult malignancies or interstitial lung disease (ILD), is of utmost importance. Therefore, there is a high demand for markers that facilitate the identification of these potentially fatal complications.
Myositis-specific antibodies (MSAs) are exclusively associated with IIM. Ever since the first MSA, anti-Mi2 antibody, was discovered in 1976, more MSAs and their clinical significance have been subsequently identified.[2] The advent of commercially available kits to detect MSAs potentiates the classification of DM according to the presence of specific antibodies and provides information for treatment plans and prognosis. DM-associated MSAs include anti-Mi2, anti-transcription intermediary factor-1γ (anti-TIF-1γ), anti-melanoma differentiation-associated protein 5 (anti-MDA5), anti-nuclear matrix protein 2 (anti-NXP2), and anti-small ubiquitin-like modifier activating enzyme 1 (anti-SAE1). Anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies are non-DM-associated MSAs associated with antisynthetase syndrome, which carries the risk of developing myositis with ILD.[1] The presence of MSAs in patients with DM is associated with the development of specific symptoms. For example, the presence of anti-MDA5 antibodies is associated with distinct mucocutaneous features, such as ulcerations and painful palmar papules. Patients with anti-MDA5 and anti-ARS antibodies have an increased risk of ILD, whereas anti-TIF-1γ and anti-NXP2 DM are more likely to be malignancy related.[1],[3]
In this study, we aimed to define the prevalence and clinical significance of MSAs, particularly their association with malignancies or ILD, in Taiwanese patients with DM. A literature review and a comparison with other studies were also performed.
Materials and MethodsThis study was approved by the Institutional Review Board of National Cheng Kung University Hospital (approval number: B-ER-111-180; approval date: July 1, 2022). Patient consent was waived by the IRB.
This hospital-based retrospective study enrolled patients who were diagnosed with DM, including classic DM and clinically amyopathic DM (CADM), and had been tested on MSAs from July 2018 to April 2021 in our hospital. The diagnosis of classic DM was based on Bohan and Peter's criteria;[4] and “definite” and “probable” cases were included. For CADM, the patient must fulfill the criteria defined by Euwer and Sontheimer.[5] CADM was diagnosed if the patient had typical cutaneous manifestations of DM and remained negative for muscle weakness or muscle enzyme elevation for more than 6 months.[6] The clinical information, including photography records, was reviewed from the chart. The presence of cutaneous signs and systemic symptoms was documented when reported by the patients during follow-up. Patients were diagnosed with ILD according to chest computed tomography results. Malignancies that were detected 3 years prior to or after the diagnosis of DM were considered DM associated.
A commercial kit (EUROLINE Autoimmune Inflammatory Myopathies 16 Ag [IgG] [Lübeck, Germany]) was used to detect MSAs, including anti-MDA5, anti-TIF-1γ, anti-ARS, anti-Mi2, anti-NXP2, and anti-SAE1. The results were graded according to the signal intensity determined by the EUROLineScan system, with strong (++) or very strong signal intensity (+++) for the six MSAs, regarded as a positive result in our study. A borderline or weakly positive (+) result was not regarded as a positive result.[7]
The association between MSAs and clinical or laboratory characteristics was evaluated using the Wilcoxon rank-sum test for continuous variables and the Fisher's exact test for categorical variables. Statistical significance was set at P < 0.05.
ResultsThirty-three patients with DM with available MSA data were identified, and consisted of 20 women and 13 men [Table 1]. The mean age at DM diagnosis was 49.6 ± 18.8 years. The mean follow-up time was 61.6 months (range: 1 − 245 months).
Table 1: Characteristics of dermatomyositis patients and their association to myositis-specific antibodiesPositive MSAs were detected in 26 (78.8%) patients: 10 (30.3%), 8 (24.2%), 3 (9.1%), 3 (9.1%), 1 (3%), and 1 (3%) of anti-MDA5, anti-TIF-1γ, anti-ARS, anti-Mi2, anti-NXP2, and anti-SAE1, respectively [Table 2]. Seven patients (21.2%) tested negative for MSAs.
Table 2: Prevalence of myositis-specific antibodies in different cohortsAmong the three pathognomonic cutaneous signs of DM, Gottron papules were the most common cutaneous presentation (20/29, 69%), followed by the heliotrope sign (18/30, 60%) and Gottron sign (11/25, 44%). Other cutaneous features included the V sign (16/27, 59.3%), shawl sign (13/26, 50%), mechanic's hands (11/27, 40.7%), periungual erythema (22/28, 78.6%), ulceration (8/26, 30.8%), calcinosis cutis (6.1%), and alopecia (15.2%) [Table 1]. Anti-MDA5 (+) patients developed V signs less frequently (25% vs. 73.7%, P < 0.05), whereas cutaneous ulceration more frequently (83.3% vs. 15%, P < 0.05). Other cutaneous signs were not associated with specific MSA.
Regarding systemic symptoms, 5 (15.2%) patients experienced body weight loss and 10 (30.3%) patients developed arthralgia. Dysphagia was identified in 6 (18.2%) patients with DM and more frequently developed in patients with anti-TIF-1γ (+) (62.5%) than those with anti-TIF-1γ (−) (4.0%) (P < 0.05). ILD was identified in 15 (45.5%) patients with DM and less frequently developed in patients with anti-TIF-1γ (+) (12.5%) than those with TIF-1γ (−) (56.0%) (P < 0.05). ILD developed more frequently in patients with anti-MDA5 (+) (70.0%) than those with anti-MDA5 (−) (34.8%), although the difference was not statistically significant.
Malignancies were detected in 4 (12.1%) patients with DM, including one anti-TIF-1γ (+) and one anti-ARS (+) each with lung adenocarcinoma, one anti-Mi2 (+) with colorectal cancer, and one MSA (−) with invasive breast ductal carcinoma. Mortality occurred in 6 (18.2%) patients, and all four anti-MDA5 (+) mortality cases occurred within 2 months after diagnosis due to rapidly progressive ILD (RP-ILD), one anti-TIF-1γ (+) patient died of lung adenocarcinoma within 2 years, and one anti-ARS (+) (anti-EJ) patient died of decompensated heart failure 5 years after DM diagnosis.
DiscussionThe prevalence of MSA in patients with DM varies across studies [Table 2].[7],[8],[9],[10] The most commonly detected MSA in this study was the anti-MDA5 antibody (30.3%), similar to the finding in the Chinese (36.6%) population.[9] However, in two studies conducted in the United States and The Netherlands, anti-TIF-1γ (34.4%) and anti-ARS (18.2%) antibodies were most commonly detected.[7],[8]
Anti-MDA5 (+) DM shows distinct mucocutaneous manifestations, such as cutaneous ulceration, and an increased risk of ILD in 42%−100% of reported cases, including RP-ILD.[3] Consistently, in the present study, 70% of anti-MDA5 (+) patients with DM had ILD, and among them, four patients with RP-ILD had mortality. In the present study, dysphagia developed more frequently in patients with anti-TIF1γ (+), which is in concordance with the Japanese study by Mugii et al.[11]
In the present case series, 12.1% of the DM cases had associated malignancies. Recently, Hsu et al. reported 1100 DM cases in Taiwan from 2001 to 2019, of which 61 (5.55%) had malignancies. The three most common cancer types were nasopharyngeal cancer, followed by lung and breast cancer.[12] Among the different MSA subtypes, anti-TIF-1γ (+) or anti-NXP2 (+) DM is known to increase cancer risk.[2] However, this tendency was not detected in our case series. This discrepancy could be explained by the shorter follow-up time or the smaller sample size in our study. Our study was limited by its nonregistry-based and retrospective nature, and further large-scale studies are warranted.
ConclusionThe two most commonly detected MSAs, in this study, were anti-MDA5 and anti-TIF-1γ. Patients with DM having anti-TIF-1γ antibodies are more likely to present with dysphagia, and early recognition of anti-MDA5 (+) DM is important because of the high frequency of potentially fatal ILD. Further, specific MSAs are associated with certain phenotypes, and integrating MSAs during the DM evaluation aids in accurate patient management.
Financial support and sponsorship
Nil.
Conflicts of interest
Prof. Chao-Chun Yang, an Associate Editor at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other author declared no conflict of interest in writing this paper.
References
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