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1 Focused Issue of This Month Interstitial Lung Diseases in Collagen Vascular Diseases Sung Hwan Jeong, MD Department of Internal medicine, Gachon University of Medicine and Science E - mail : jsw@gilhospital.com J Korean Med Assoc 2009; 52(1): Abstract Different types of interstitial lung diseases (ILDs) develop in collagen vascular diseases (CVDs) such as scleroderma, rheumatoid arthritis, systemic lupus erythematosus, dermatopolymyositis, Sjogren s syndrome, and mixed connective tissue disease. These CVDs represent various histological patterns, including usual interstitial pneumonia, desquamative interstitial pneumonia, nonspecific interstitial pneumonia, bronchiolitis obliterance organizing pneumonia, diffuse alveolar damage, and bronchiolitis. The clinical presentations, prognosis, and response to treatment vary depending on the underlying CVDs, as well as histological patterns of ILDs. In general, the prognosis and survival rate of ILDs in CVDs are better than idiopathic ILDs. Optimal treatment also varies depending on the type of CVDs and the presence of interstitial lung disease, although in many cases, a combination of corticosteroids and cytotoxic drugs are given. Keywords: Collagen vascular disease; Interstitial lung disease; Fibrosis 30

2 ILD in CVD Figure 1. Pulmonary hypertension in systemic sclerosis in a 46- year-old woman. Figure 2. Fibrosing alveolitis in systemic sclerosis, in a 46 -yearold woman. 31

3 Jeong SH 32

areas of both lungs. Figure 4. RA with NSIP in a 48-year-woman.

4 ILD in CVD Figure 3. RA with fibrosing alveolitis in a 47-year-old woman. CT scan shows honeycombing, irregular linear hyperattenuating areas in the basal areas of both lungs. Figure 4. RA with NSIP in a 48-year-woman. CT scan shows patchy distribution of irregular linear hyperattenuating areas and ground glass attenuation in both lungs. 33

5 Jeong SH Figure 5. RA with necrobiotic nodule in a 47-year-old woman. High-resolution computed tomography shows a rheumatoid nodules located in the both lungs. 34

6 ILD in CVD A B Figure 6. Systemic lupus erythematosus and acute lupus pneumonitis CT scans (3-mm collimation) obtained with lung window at the levels of the aortic arch (A) and lingular segmental bronchus (B) show airspace consolidation in the right upper lobe and groundglass attenuation in the left upper lobe. Bronchial dilatation is seen in the consolidation in the right upper lobe (RadioGraphics 2002; 22: S151-S165). Images by courtesy of Kyung Soo Lee, MD; Samsung Medical Center, Sungkyunkwan University School of Medicine. 35

7 Jeong SH Figure 7. SLE with NSIP in a 42-year-old woman. CT scan shows patchy distribution of irregular linear hyperattenuating areas and ground glass attenuation with traction bronchiectasis in both lungs. 36

8 ILD in CVD Figure 8. Dermatopolymyositis. High-resolution computed tomography at the level of the hila shows a bronchiolitis obliterans with organizing pneumonia pattern (ERJ 2001; 18: S32, 69s-80s). 37

areas of ground-glass attenuation and irregular linear hyperattenuating areas with random distribution in both lungs.

5; H-E stain) shows irregular interstitial fibrosis (arrows) and mononuclear cell infiltration with subpleural predominance.

Images by courtesy of Kyung Soo Lee, MD; Samsung Medical Center, Sungkyunkwan University School of Medicine. A Figure 10.

9 Jeong SH A B C Figure 9. Dermatomyositis and usual interstitial pneumonia (A, B) CT scans obtained at the levels of the bronchus intermedius (A) and liver dome (B) show patchy areas of ground-glass attenuation and irregular linear hyperattenuating areas with random distribution in both lungs. (C) Photomicrograph (original magnification, x 12.5; H-E stain) shows irregular interstitial fibrosis (arrows) and mononuclear cell infiltration with subpleural predominance. Germinal center formation is also seen (arrowheads) (RadioGraphics 2002; 22: S151-S165). Images by courtesy of Kyung Soo Lee, MD; Samsung Medical Center, Sungkyunkwan University School of Medicine. A Figure 10. Sjögren s syndrome and lymphoid interstitial pneumonia (A) CT scan shows centrilobular nodules and branching linear structures (straight arrow) in the right lung. Many thin-walled cysts (curved arrows) were seen in both lungs. (B) Photomicrograph (original magnification, x 20; H-E stain) shows diffuse lymphocyte infiltration in the peribronchovascular interstitium and surrounding alveolar septa (arrows) (RadioGraphics 2002; 22: S151-S165). Images by courtesy of Kyung Soo Lee, MD; Samsung Medical Center, Sungkyunkwan University School of Medicine. B 38

10 ILD in CVD Figure 11. Mixed connective tissue disease and usual interstitial pneumonia. CT scan shows subpleural areas of groundglass attenuation, irregular linear hyperattenuating areas, and traction bronchiectasis and bronchiolectasis (arrows) (RadioGraphics 2002; 22: S151-S165). Images by courtesy of Kyung Soo Lee, MD; Samsung Medical Center, Sungkyunkwan University School of Medicine. 11. Marten K, Dicken V, Kneitz C, Hohmann M, Kenn W, Hahn D, Engelke C, Intrstitial lung disease associated with collagen vascular disorders:disease quantification using a computeraided diagnosis tool. Eur Radiol 2008; 11: Kim DS, Yoo B, Lee JS, Kim EK, Lim CM, Lee SD, Koh Y, Kim WS, Kim WD, Colby TV, Kitiaichi M. The major histopathologic pattern of pulmonary fibrosis in scleroderma is nonspecific interstitial pneumonia, Sarcoidosis Vasc Diffuse Lung Dis 2002; 19: Kim EA, Lee KS, Johkoh T, Kim TS, Suh GY, Kuon OJ, Han J. Interstitial Lung Diseases Associated with Collagen Vascular Diseases: Radiologic and Histopathologic Findings. Radio Graphics 2002; 22: S151-S Oguz Uzun, Tekin Akpolat, Levent Erkan, Pulmonary Vasculitis in Behcet disease: A Cumulative Analysis 2005; 127: Parambil JG, Myers JL, Ryu JH. Diffuse Alveolar Damage: Uncommon Manifestation of Pulmonary Involvement in Patients With Connective Tissue Diseases. 2006; 130: Kang EH, Lee EB, Shin KC, Im CH, Chung DH, Han SK, Song YW. Interstitial lung disease in patients with plymyositis, dermatomyositis and amyopathic dermatomyositis, Rheumatology 2005; 44: F.Figen Ayhan-Ardie, Oznur Oken, Z.Rezan Yorgancioglu, Nilgun Ustun, F.Dilek Gokharman, Pulmonary involvement in lifelong non-somking patients with rheumatoid arthritis and ankylosing spondylitis without respiratory symtoms, Clin Rheumatol 2006; 25: Lamblin C, Bergoin C, Saelens T, Wallaert B. Interstitial lung diseases in collagen vascular diseases, Eur Respir J 2001; 18: S32, 69s-80s. 19. Suda T, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Naito T, Hashimoto D, Sato J, Toyoshima M, Hashizume H, Chida K. Interstitial lung diseases associated with amyopathic dermatomyositis, Eur Respir J 2006; 28: Bodolay E, Szekanecz Z, Dévényi K, Galuska L, Csípo I, Vègh J, Garai I, Szegedi G. Rheumatology. Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD), Rheutology 2005; 44: Wells AU, Hansell DM, Rubens MB, King AD, Cramer D, Black CM, du Bois RM. Fibrosing alveolitis in systemic sclerosis: indices of lung function in relation to extent of disease on computed tomography. Arthritis Rheum 1997; 40: Harrison NK, Glanville AR, Strickland B, Haslam PL, Corrin B, Addis BJ, Lawrence R, Millar AB, Black CM, Turner-Warwick M. Pulmonary involvement in systemic sclerosis: the detection of early changes by thin section CT scan, bronchoalveolar 39

11 Jeong SH lavage and 99mTc-DTPA clearance. Respir Med 1989; 83: Bouros DE, Polychronopoulos V, Conron M, Black CM, Nicholson A, dubois RM. Histopathologic subgroups in patients with fibrosing alveolitis associated with systemic sclerosis. Eur Respir J 1999; 14: 30(s), 272S. 14. Wallaert B, Aerts C, Bart F, Hatron PY, Dracon M, Tonnel AB, Voisin C. Alveolar macrophage dysfunction in systemic lupus erythematosus. Am Rev Respir Dis 1987; 136: Wallaert B, Hatron PY, Grosbois JM, Tonnel AB, Devulder B, Voisin C. Subclinical pulmonary involvement in collagen vascular diseases assessed by bronchoalveolar lavage. Relationship between alveolitis and subsequent changes in lung function. Am Rev Respir Dis 1986; 133: White B, Wigley F, Wise R, Bleecker E. Expression of chemokines interleukin-8 (IL-8), RANTES, and macrophage inhibitory factor-1 (MIP-1) in bronchoalveolar lavage fluid of patients with systemic sclerosis (SSc). Arthritis Rheum 1994; 37: S Rennard SI, Bitterman PB, Ozaki T, Rom WN, Crystal RG. Colchicine suppresses the release of fibroblast growth factors from alveolar macrophages in vitro. Am Rev Respir Dis 1988; 137: DeClerck LS, Dequeker J, Francx L, Demedts M. D-Penicillamine therapy and interstitial lung disease in scleroderma. Arthritis Rheum 1987; 30: Silver RM, Warrick JH, Kinsella MB, Staudt LS, Baumann MH, Strange C. Cyclophosphamide and lowdose prednisone therapy in patients with systemic sclerosis (scleroderma) with interstitial lung disease. J Rheumatol 1993; 20: Clements PJ, Lachenbruch PA, Sterz M, Danovitch G, Hawkins R, Ippoliti A, Paulus HE. Cyclosporine in systemic sclerosis. Results of a fortyeight-week open safety study in ten patients. Arthritis Rheum 1993; 36: Yousem SA, Colby TV, Carrington CB. Lung biopsy in rheumatoid arthritis. Am Rev Respir Dis 1985; 131: McDonagh J, Greaves M, Wright AR, Heycock C, Owen JP, Kelly C. High resolution computed tomography of the lungs in patients with RA and interstitial lung disease. Br J Rheumatol 1994; 33: Yousem SA, Colby TV, Carrington CB. Follicular bronchitis/ bronchiolitis. Human Pathol 1985; 16: Gosset P, Perez T, Lassalle P, Duquesnoy B, Farre JM, Tonnel AB, Capron A. Increased TNF-a secretion by alveolar macrophages from patients with rheumatoid arthritis. Am Rev Respir Dis 1991; 143: Epler GR, Colby TV, McLoud TC, Carrington CB, Gaensler EA. Bronchiolitis obliterans organizing pneumonia. N Engl J Med 1985; 312: Rolla G, Brussino L, Bertero MT, Colagrande P, Converso M, Bucca C, Polizzi S, Caligaris-Cappio F. Increased nitric oxide in exhaled air of patients with systemic lupus erythematosus. J Rheumatol 1997; 24: Holgate ST, Glass DN, Haslam P, Maini RN, Turner-Warwick M. Respiratory involve-ment in systemic lupus erythematosus: A clinical and immunological study. Clin Exp Immunol 1976; 24: Mino M, Noma S, Taguchi Y, Tomii K, Kohri Y, Oida K. Pulmonary involvement in polymyositis and dermato-myositis: sequential evaluation with CT. AJR 1997; 169: Deheinzelin D, Capelozzi VL, Kairala RA, Barbas JV, Saldiva PHN, de Carvalho CRR. Intertstitial lung disease in primary Sjögren9s syndrome: clinical pathological evaluation and response to treatment. Am J Respir Crit Care Med 1996; 15: Lahdensuo A, Korpela M. Pulmonary findings in patients with primary Sjögren9s syndrome. Chest 1995;108: Peer Reviewers Commentary 40

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9.Æ¯Áýb61Ç¿ÀÁ¤806~816’ J KMA Special Issue Won Jung Koh, MD O Jung Kwon, MD Division of Pulmonary and Critical Care Medicine, Department of Medicine, Sungkyunkwan University School of Medicine E mail : wjkoh@smc.samsung.co.kr