49_58특집_박무석

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1 Focused Issue of This Month Diagnosis and Treatment of Hypersensitivity Pneumonitis Moo Suk Park, MD Department of Internal Medicine, Yonsei University College of Medicine E - mail : pms70@yuhs.ac J Korean Med Assoc 2009; 52(1): Abstract Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is an immunologically mediated granulomatous, inflammatory disease of the lungs caused by repeated inhalation of various antigens. HP may occur in acute, subacute, or chronic forms. Chronic HP may be progressive, irreversible, and evolve to fibrotic interstitial lung disease. The diagnosis of HP can be made from a combination of clinical, laboratory, radiologic, and pathologic findings. A careful environmental and occupational history and establishment of exposure to a known inciting antigen are key factors in making the diagnosis of HP. Serum precipitating antibodies, bronchoalveolar lavage, and lung biopsy may be helpful in making the diagnosis. The pathology of HP is characterized by interstitial lymphocytic infiltration, poorlyformed noncaseating granulomas, cellular bronchiolitis, and fibrosis. In the pathogenesis of HP, recent studies showed that both type III and type IV hypersensitivity reactions are involved and are mediated by immune complexes and Th1 T cells, respectively. IFN- is essential for the development of HP, and IL-10 appears to modulate the severity of the disease. TNF- and TGF- have been implicated in development of the pulmonary fibrosis that is seen in chronic HP. Avoidance of organic antigen exposure is the most important factor for the management of HP. There is often an apparent beneficial response to corticosteroids in the cases of severe acute and subacute HP, and for chronic HP that is severe or progressive. Keywords: Hypersensitivity pneumonitis; Extrinsic allergic alveolitis; Interstitial lung disease; Diagnosis; Treatment 49

2 Park MS Table 1. Common antigens and diseases for development of hypersensitivity pneumonitis Antigen Source Disease Microorganisms Saccharopolyspora rectivirgula Moldy hay and compost Farmer s lung Thermoactinomyces sacchari Sugar cane residue (bagass) Bagassosis Bacillus subtlis proteins Contaminated wood dust Woodworker s lung Penicillium casei Cheese mold Cheese washer s lung Aspergillus clavatus Contaminated barley Malt worker s lung Mycobacterium avium Hot tubs Hot tub lung intracellulare Trichosporon cutaneum Mold in Japanese homes Japanese summer-type pneumonitis Animal proteins Avian proteins Bird droppings and feathers Bird fancier s disease and pigeon breeder s disease Rodent proteins Rodent dander, urine, serum Animal handler s lung and laboratory worker s lung Animal fur dust Animal pelts Furrier s lung Chemicals Isocyanates Paint hardeners, polyurethan foams Chemical walker s lung Anhydrides Plastic components Chemical walker s lung Pyrethrum Insecticides Insecticide user s lung 50

3 Diagnosis and Treatment of HP Figure 1. Chest X-ray of acute hypersensitivity pneumonitis. Chest X-ray showed some reticulonodular densities in both upper lobes. 51

glass attenuation and tiny, ill-defined centrilobular nodules on upper and lower lung field. Figure 3.

4 Park MS Figure 2. High-resolution computed tomography scans of acute hypersensitivity pneumonitis showed discrete ground glass attenuation and tiny, ill-defined centrilobular nodules on upper and lower lung field. Figure 3. After recurrent exposure to antigen, chest X-ray showed diffuse poorly-defined small nodular densities and diffuse ground glass opacities in subacute patient with hypersensitivity pneumonitis. 52

glass attenuatiuon and tiny, ill-defined centrilobular nodules, predominant on upper lung field. Figure 5.

5 Diagnosis and Treatment of HP Figure 4. High-resolution computed tomography scans of subacute hypersensitivity pneumonitis showed discrete ground glass attenuatiuon and tiny, ill-defined centrilobular nodules, predominant on upper lung field. Figure 5. Chest X-ray of chronic hypersensitivity pneumonitis. Chest X-ray showed coarse rericular opacities with diffusely scattered patchy ground glass opacities in both lung fields. 53

patchy areas of lung fibrosis, mainly peribronchiolar regions, and traction bronchiectasis or

6 Park MS Figure 6. (A) High-resolution computed tomography scans of chronic hypersensitivity pneumonitis showed patchy areas of lung fibrosis, mainly peribronchiolar regions, and traction bronchiectasis or bronchiolectasis, slightly dominant on the upper lung field. Lobular air trappings were also seen in multifocal areas. (B) End-stage chronic hypersensitivity pneumonitis. A B 54

7 Diagnosis and Treatment of HP Table 2. Comparison of three types of hypersensitivity pneumonitis Characteristics Acute Subacute Chronic Onset time 4~48 hours Weeks to 4months 4months to years Fever, chill Dyspnea Cough Non-productive Productive Productive Weight loss Crackles Bibasilar Diffuse Diffuse Chest radiograph Reticulo-nodular infiltration Reticulo-nodular infiltration Reticular, fibrosis (patchy or diffuse) (patchy or diffuse) diffuse HRCT* Nodules and GGO Nodules, GGO, air-trapping Nodules, GGO, fibrosis, air-trapping, emphysema PFT Restrictive Restrictive or mixed Restrictive or mixed Diffusing capacity Decreased Decreased Decreased Pathology Diffuse alveolar damage, Poorlyformed noncaseating Centrilobular and subpleural fibrosis alveolitis granulomas, peribronchiolar bridging fibrosis, emphysema, lymphocytic infiltration lung cysts Prognosis Good Good Poor *HRCT: high-resolution computed tomography, GGO: ground glass opacities, PFT: pulmonary function test Table 3. Proposed diagnostic evaluations and findings for hypersensitivity pneumonitis Diagnostic evaluations Preferred findings Medical history Recurrent episodes of respiratory symptoms, flu-like symptoms, symptoms 4~8hours after exposure of antigen, weight loss Occupational, hobby, and Identify duration, frequency, concentration, particle size of antigen environmental histories Physical examination Bilateral basilar inspiratory crackles Chest radiograph Normal, patch or diffuse infiltrates HRCT* Acute and subacute-small poorly-defined centirobular nodules, ground glass opacities, bilateral peribronchial airspace consolidations, mosaic perfusion. Chronicreticular and linear opacities, fibrosis, traction bronchiectasis, honeycombing, lung cysts, air trapping, peribronchial and subpleural lesions. Pulmonary function tests Normal, restrictive or mixed pattern, decreased diffusing capacity Serum precipitins Elevated titers indicate exposure to antigen, negative results don t rule out HP Antigen inhalation Natural or laboratory-based challenges if possible provocation tests Bronchoalveolar lavage CD8+ lymphocyte predominance, neutrophil within 48hours Lung biopsy if diagnosis Transbronchial or surgical biopsy. Peribronchiolar lymphocytic infiltration, poorlyformed is in doubt noncaseating granulomas, fibrosis if chronic cases *HRCT: high-resolution computed tomography 55

granuloma (H & E X 100). Figure 8. Pathologic findings of chronic hypersensitivity pneumonitis.

8 Park MS Figure 7. Pathologic findings of subacute hypersensitivity pneumonitis. Lymphocyte infiltration of the respiratory bronchioles and alveolar walls with ill-defined granuloma (H & E X 100). Figure 8. Pathologic findings of chronic hypersensitivity pneumonitis. Chronic interstitial pneumonia pattern with illdefined granuloma and focal fibroblastic proliferation (H & E X 100). 56

9 Diagnosis and Treatment of HP Table 4. Histologic differential diagnosis of hypersensitivity pneumonitis Histologic features HP Sarcoidosis LIP NSIP UIP Granuloma Poorly formed Well formed Well or poorly Absent Absent Distribution Random, Lymphangitic Random - - peribronchiolar Cell infiltrates Prominent, Minimal Extensive, Moderate, Minimal peribronchiolar diffuse diffuse Interstitial fibrosis Frequent in Advanced cases Unusual Frequent Frequent chronic HP Centrilobular fibrosis Frequent in Occasional Absent Minimal Minimal chronic HP Honeycomb Frequent in Occasional in Absent Occasional in Frequent chronic HP advanced cases fibrotic NSIP Fibroblastic foci Occasional Absent Absent Occasional Frequent HP : hypersensitivity pneumonitis, LIP: lymphoid interstitial pneumonia, NSIP: nonspecific interstitial pneumonia, UIP: usual interstitial pneumonia, Modified from Takemura, et al (17). 57

10 Park MS 11. Selman M. Hypersensitivity pneumonitis. In: Schwarz MI, King TE Jr, ed. Interstitial lung disease. 4th ed. London: BC Decker Inc, 2003: Mohr LC. Hypersensitivity pneumonitis. Curr Opin Pulm Med 2004; 10: Selman M. Hypersensitivity pneumonitis: a multifaceted deceiving disorder. Clin Chest Med 2004; 25: McSharry C, Anderson K, Bourke SJ, Boyd G. Takes your breath away-the immunology of allergic alveolitis. Clin Exp Immunol 2002; 128: Bourke SJ, Dalphin JC, Boyd G, McSharry C, Baldwin CI, Calvert JE. Hypersensitivity pneumonitis: current concepts. Eur Respir J 2001; 18(S): Patel AM, Ryu JH, Reed CE. Hypersensitivity pneumonitis: current concepts and future questions. J Allergy Clin Immunol 2001; 108: Schuyler M, Gott K, Cherne A. Mediators of hypersensitivity pneumonitis. J Lab Clin Med 2000; 136: Yamasaki H, Ando M, Brazer W, Center DM, Cruilshank WW. Polarized type I cytokine profile in bronchoalveolar lavage T cells in patients with hypersensitivity pneumonitis. J Immunol 1999; 163: Suga M, Yamasaki H, Nakagawa K, Kohroqi H, Ando M. Mechanisms accounting for granulomatous responses in hypersensitivity pneumonitis. Sarcoidosis Vasc Diffuse Lung Dis 1997; 14: Yi ES. Hypersensitivity pneumonitis. Crit Rev Clin Lac Sci 2002; 39: Girard M, Israel-Assayag E, Cormier Y. Pathogenesis of hypersensitivity pneumonitis. Curr Opin Allergy Clin Immunol 2004; 4: Camarena A, Juarez A, Mejia M, Estrada A, Carrillo G, Falfán R, Zuñiga J, Navarro C, Granados J, Selman M. Major histocompatibility complex and tumor necrosis factor-a polymorphism in pigeon breeder s disease. Am J Respir Crit Care Med 2001; 163: Glazer CS, Rose CS, Lynch DA. Clinical and radiologic manifestations of hypersensitivity pneumonitis. J Thorac Imaging 2002; 17: Silva CI, Churg A, Muller NL. Hypersensitivity pneumonitis: spectrum of high-resolution CT and pathologic findings. AJR 2007; 188: Churg A, Muller NL, Flint J, Wright JL. Chronic hypersensitivity pneumonitis. Am J Surg Pathol 2006; 30: Lacasse Y, Selman M, Costabel U, Dalphin JC, Ando M, Morell F, Erkinjuntti-Pekkanen R, Muller N, Colby TV, Schuyler M, Cormier Y; HP Study Group. Clinical diagnosis of hypersensitivity pneumonitis. Am J Respir Crit Care Med 2003; 168: Takemura T, Akashi T, Ohtani Y, Inase N, Yoshizawa Y. Pathology of hypersensitivity pneumonitis. Curr Opin Pulm Med 2008; 14: Lacasse Y, Cormier Y. Hypersensitivity pneumonitis. Orphanet J Rare Dis 2006; 1: 25. Peer Reviewers Commentary 58

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