title: Interstitial lung disease in clinically amyopathic dermatomyositis with and without anti-MDA-5 antibody: to lump or split?
abstract: BACKGROUND
  Interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM-ILD) is often refractory and rapidly progressive. Although the anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibody is associated with rapidly progressive ILD (RP-ILD), differences in clinical features and prognosis of anti-MDA-5 antibody-positive and -negative CADM-ILD remain unclear.
  
  
  METHODS
  To clarify the differences in the clinical features and prognosis between anti-MDA-5 antibody-positive and -negative cases, we retrospectively reviewed the medical records of patients diagnosed with CADM-ILD with and without anti-MDA-5 antibody at Kurashiki Central Hospital from January 2005 to September 2014.
  
  
  RESULTS
  Anti-MDA-5 antibody was found in 10 of 16 patients (63%). The levels of Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) at the first visit were significantly lower in positive patients than in negative patients, whereas the levels of aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP), and the CD4(+)/CD8(+) ratio in the bronchoalveolar lavage (BAL) fluid were significantly higher in positive patients than negative patients. Subpleural ground-glass opacity (GGO) or irregular linear opacity was predominant in positive patients. Peribronchovascular consolidation was predominant in negative patients. Positive patients had significantly lower survival rates than negative patients, with all six fatal cases occurring in positive patients who died of refractory ILD within 92 days from the first visit despite intensive treatment.
  
  
  CONCLUSIONS
  There are clear differences in the clinical features and prognosis of anti-MDA-5 antibody-positive and -negative CADM-ILD. Low serum KL-6 and SP-D levels, high serum AST and γ-GTP levels, high CD4(+)/CD8(+) ratio in BAL fluid, and predominance of subpleural GGO or irregular linear opacity in HRCT may help to discriminate anti-MDA-5 antibody-positive CADM-ILD with poor prognosis.
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. isatoshi0112@gmail.com.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. ma6390@kchnet.or.jp.
authors.forename: Machiko
authors.initials: M
authors.lastname: Arita
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. mm13127@kchnet.or.jp.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Morita
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. si14011@kchnet.or.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeo
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. ai12306@kchnet.or.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. ft13419@kchnet.or.jp.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tokioka
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. mn13134@kchnet.or.jp.
authors.forename: Maki
authors.initials: M
authors.lastname: Noyama
authors.affiliation: Department of Rheumatology, Kurashiki Central Hospital, Okayama, Japan. km13483@kchnet.or.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Misaki
authors.affiliation: Department of Pathology, Kurashiki Central Hospital, Okayama, Japan. notohara@kchnet.or.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Notohara
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Miwa 1-1-1, Kurashiki-city, Okayama, 710-8602, Japan. ishidat@kchnet.or.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D003520:Cyclophosphamide / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D003882:Dermatomyositis / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D017563:Lung Diseases, Interstitial / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000906:Antibodies; D015415:Biomarkers; D016572:Cyclosporine; D003520:Cyclophosphamide; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1