Acute Exacerbations of Interstitial Pneumonias in Amyopathic Dermatomyositis: Different Pathogenesis in Ordinary Dermatomyositis/Polymyositis When Compared to Amyopathic Dermatomyositis
Osamu Matsubara, Kosuke Miyai, Ryoko Kikuchi, Kiichi Iwaya, Yukio Nakatani, Eugene J Mark. National Defense Medical College, Tokorozawa, Saitama, Japan; Chiba University, Chiba, Japan; Massachusetts General Hospital and Harvard Medical School, Boston, MA
Background: Interstitial pneumonias (IPs) are frequently identified in patients with dermatomyositis (DM) and polymyositis (PM). Amyopathic dermatomyositis (ADM) is a variant of DM that is characterized by the typical skin rash but without the muscle abnormalities. Some patients with ADM develop rapidly progressive IP, which may prompt aggressive therapy. This study compares the cell kinetics of the lung lesions in DM/PM with ADM.
Design: We studied 19 autopsy cases with IP of DM/PM (10 women, mean age 56 yrs., follow-up 2.3 yrs.), including 8 with ADM (4 women, mean age 57 yrs., follow-up 0.8 yrs.) emphasizing pulmonary disease. We compared the clinical features and lung pathology between 8 patients with ADM and 11 patients with ordinary DM/PM. We performed immunohistochmical examination for cell cycle markers, cell proliferation, cell injury, apoptosis, and the tissue reconstruction process using a standard indirect avidin-biotin horseradish peroxidase method with various antigen retrievals.
Results: Of the 11 patients with DM/PM, three had a UIP pattern, three showed a NSIP pattern, and four had widespread organizing pneumonia. All eight patients with ADM demonstrated acute and organizing diffuse alveolar damage (DAD) of whom seven had chronic IP including subpleural or paraseptal distribution of dense fibrosis and tissue remodeling of lung architecture. Immunohistochemically, increased expression of cyclin A2, Ki-67, surfactant proteins, MMP1, MMP7, TIMP-1, TIMP-2 and TGF beta-1 was observed in regenerating pneumocytes, bronchiolar epithelial cells and macrophages and not in fibroblasts in ADM but rarely in ordinary DM/PM. There was widespread positive epithelial apoptotic DNA strand break by nick end-labeling technique (TUNEL) staining in the lungs of ADM, but TUNEL signals were seldom seen in those of ordinary DM/PM.
Conclusions: Acute exacerbation of IPs occurs both in patients with ordinary DM/PM and in ADM. However, the acute exacerbation in the former group is generally an organizing pneumonia, while the acute exacerbation in the latter group is DAD superimposed on chronic IP. Upregulation of cell cycle markers were generally expressed only in the latter group. These results suggest an intrinsic difference in the progression of pulmonary disease between DM/PM and ADM.
Tuesday, March 20, 2012 1:15 PM
Platform Session: Section D, Tuesday Afternoon