Clinical and laboratory features of fatal rapidly progressive interstitial lung disease associated with juvenile dermatomyositis

Kobayashi, N.; Takezaki, Shunichiro; Kobayashi, Ichiro; Iwata, Nakao; Mori, Masaaki; Nagai, Koutatsu; Nakano, Naoko; Miyoshi, Mari; Kinjo, Noriko; Murata, Takuji; Masunaga, Kenji; Umebayashi, Hiroaki; Imagawa, Tomoyuki; Agematsu, Kazunaga; Sato, Shinji; Kuwana, Masataka; Yamada, Masafumi; Takei, Shuji; Yokota, Shumpei; Koike, Kenichi; Ariga, Tadashi

doi:10.1093/rheumatology/keu385

Cited by 127 publications

(113 citation statements)

References 40 publications

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“…Interstitial lung disease was more common in both cohorts with this autoantibody, compared to patients without these antibodies. In the UK patients, other common features included oral and cutaneous ulceration, arthritis and milder muscle disease, which was similar to findings in US and European adult cohorts with MDA 5 autoantibodies .…”

Section: Serologic Classification Of Jiimssupporting

confidence: 84%

The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes

2016

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The aim of this review is to summarize recent advances in the understanding of the clinical and autoantibody phenotypes, their associated outcomes, and the pathogenesis of the juvenile idiopathic inflammatory myopathies (JIIMs). The major clinical and autoantibody phenotypes in children have many features similar to those in adults, and each has distinct demographic and clinical features and associated outcomes. The most common myositis autoantibodies in JIIM patients are anti-p155/140, anti-MJ, and anti-MDA5. Higher mortality has been associated with overlap myositis as well as with the presence of anti-synthetase and anti-MDA5 autoantibodies; a chronic illness course and lipodystrophy have been associated with anti-p155/140 autoantibodies; and calcinosis has been associated with anti-MJ autoantibodies. Histologic abnormalities of JIIMs detectable on muscle biopsy have also been correlated with myositis-specific autoantibodies; for example, patients with anti-MDA5 show low levels of inflammatory infiltrate and muscle damage on biopsy. The first genome-wide association study of adult and juvenile dermatomyositis revealed three novel genetic associations, BLK, PLCL1, and CCL21, and confirmed that the human leukocyte antigen region is the primary risk region for juvenile dermatomyositis. Here we review the well-established pathogenic processes in JIIMs, including the type 1 interferon and endoplasmic reticulum stress pathways. Several novel JIIM-associated inflammatory mediators, such as the innate immune system proteins, myeloid-related peptide 8/14, galectin 9, and eotaxin, have emerged as promising biomarkers of disease. Advances in our understanding of the phenotypes and pathophysiology of the JIIMs are leading to better tools to help clinicians stratify and treat these heterogeneous disorders.

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Section: Serologic Classification Of Jiimssupporting

confidence: 84%

The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes

2016

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“…Fulminant presentations with ILD, CADM and anti-MDA-5 autoantibodies may be especially frequent in Japanese patients compared with other east Asian or non-Asian patients [35,64], although a publication bias cannot be excluded. In a Japanese retrospective series of 54 patients with JDM [66], 10 had rapidly progressive ILD and 19 had chronic ILD, illustrating the particularly frequent pulmonary involvement in the Asian population.…”

Section: Rapidly Progressive Ildmentioning

confidence: 99%

Idiopathic inflammatory myopathies and the lung

et al. 2015

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Idiopathic inflammatory myositis (IIM) is a group of rare connective tissue diseases (CTDs) characterised by muscular and extramuscular signs, in which lung involvement is a challenging issue. Interstitial lung disease (ILD) is the hallmark of pulmonary involvement in IIM, and causes morbidity and mortality, resulting in an estimated excess mortality of 50% in some series. Except for inclusion body myositis, these extrapulmonary disorders are associated with the general and visceral involvement frequently found in other CTDs including fever, Raynaud's phenomenon, arthralgia, nonspecific cutaneous modifications and ILD, for which the prevalence is estimated to be up to 65%. Substantial heterogeneity exists within the spectrum of IIMs, and each condition is associated with various frequencies and subtypes of pulmonary involvement. This heterogeneity is partly related to the presence of various autoantibodies encompassing anti-synthetase, anti-MDA5 and anti-PM/Scl. ILD is present in all subsets of IIM including juvenile myositis, but is more frequent in dermatomyositis and overlap myositis. IIM can also be associated with other presentations of respiratory involvement, namely pulmonary arterial hypertension, pleural disease, infections, drug-induced toxicity, malignancy and respiratory muscle weakness. Here, we critically review the current knowledge about adult and juvenile myositis-associated lung disease with a detailed description of therapeutics for chronic and rapidly progressive ILD. @ERSpublications Interstitial lung disease is a leading cause of morbidity in dermatomyositis/polymyositis

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“…Specificity for anti–NXP‐2 or anti‐MDA5 autoantibodies, visualized as a 140‐kd band, was determined by enzyme‐linked immunosorbent assay, as described previously . Since recent studies in the literature have identified important associations between the clinical features of juvenile DM and the presence of MSAs , and relatively fewer patients with myositis‐associated autoantibodies (MAAs) were present in the biopsy cohort (with low numbers in individual groups), we elected to focus on the patient groups in whom the frequencies of MSAs, i.e., anti–TIF‐1γ, anti–NXP‐2, anti‐MDA5, and anti–Mi‐2, were sufficient for these analyses. Patients with MAAs or unidentified bands were excluded during the statistical analyses of associations with muscle biopsy scores and associations between muscle biopsy scores, MSA subtypes, and long‐term outcomes.…”

Section: Methodsmentioning

confidence: 99%

Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis

Deakin

Yasin

Simou

et al. 2016

Arthritis & Rheumatology

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ObjectiveJuvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis‐specific autoantibodies (MSAs) have prognostic significance in juvenile DM.MethodsMuscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow‐up 4.9 years). Long‐term treatment status (on or off medication over time) was modeled using generalized estimating equations.ResultsMuscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48‐fold higher odds (95% confidence interval [95% CI] 1.12–1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10‐fold higher odds (95% CI 1.01–1.21; P = 0.038). A protective effect was identified in patients with anti–Mi‐2 autoantibodies, in whom the odds of remaining on treatment were 7.06‐fold lower (95% CI 1.41–35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti–nuclear matrix protein 2 autoantibodies, anti–transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61‐fold higher odds (95% CI 1.16–2.22; P = 0.004), and for the total biopsy score, 1.13‐fold higher odds (95% CI 1.03–1.24; P = 0.013).ConclusionHistopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease.

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Clinical and laboratory features of fatal rapidly progressive interstitial lung disease associated with juvenile dermatomyositis

Cited by 127 publications

References 40 publications

The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes

The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes

Idiopathic inflammatory myopathies and the lung

Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis

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