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.

Fig. 1

Chronological changes in serum KL-6 and SP-D. a Serum KL-6 levels at first visit and after 1–4 weeks’ treatment initiation in each patient of the anti-MDA-5 antibody positive (left) and negative groups (right). b Serum SP-D levels at first visit and after 1–4 weeks’ treatment initiation in each patient of the anti-MDA-5 antibody positive (left) and negative groups (right). Abbreviations: KL-6, Krebs von den Lungen-6; SP-D, surfactant protein D; MDA-5, anti-melanoma differentiation-associated gene 5

Fig. 2

High-resolution computed tomography findings. Representative photographs of HRCT scans are presented. a and b initial HRCT scans of fatal cases positive for anti-MDA-5 antibody showing subpleural GGO. (C) HRCT scans of an anti-MDA-5 antibody-positive patient who survived, showing subpleural irregular linear opacity. (D) HRCT scans of an anti-MDA-5 antibody-negative patient showing peribronchovascular consolidation. Abbreviations: GGO, ground-glass opacity; HRCT, high-resolution computed tomography; MDA-5, anti-melanoma differentiation-associated gene 5

Fig. 3

Comparison of survival curves with and without anti-MDA-5 antibody. Cumulative survival probabilities were estimated using the Kaplan–Meier method. The log-rank test was used to compare survival among patient groups. A p value of <0.05 was considered statistically significant. Abbreviation: MDA-5, anti-melanoma differentiation-associated gene 5