영남의대학술지제27권제1호 Yeungnam Univ. J. of Med. Vol.27 No.1 p57-62, June. 2010 증례 폐포단백증 1 예 우대형 박정은 류영하 김현정 신경철 정진홍 이관호 영남대학교의과대학내과학교실 A Case of Pulmonary Alveolar Proteinosis Dae-Hyung Woo, Jung-Eun Park, Yung-Ha Ryu, Hyun-Jung Kim, Kyeong-Cheol Shin, Jin Hong Chung, Kwan Ho Lee 1) -Abstract- Department of Internal Medicine, College of Medicine, Yeungnam University, Daegu, Korea Pulmonary alveolar proteinosis (PAP) is a rare disorder that s characterized by accumulation of surfactant components in the alveolar space. Idiopathic PAP is recognized as an autoimmune disease that s due to impaired alveolar macrophage function and this caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We report here a case of pulmonary alveolar proteinosis that was deemed interstitial lung disease at the initial diagnosis. A 61-year-old man presented with intermittent blood tinged sputum and dyspnea on exertion. The man was a painter for 30 years and he had a 10 pack-years smoking history. Chest computerized tomography (CT) revealed multifocal ground-glass opacity with interstitial thickening at both lungs. His pulmonary function tests and methacholine test revealed non specific results. He was diagnosed with interstitial lung disease on the basis of the chest CT finding and occupational history. However, seven months later, his symptoms progressed. Follow-up chest CT was performed. Wedge resection via videoassisted thoracoscopic surgery (the anterior basal segment of the left lower lobe) was done. Microscopic examination showed large groups of alveoli with excessive amounts of surfactant and a complex mixture of protein and lipid (fat) molecules. Finally, he was diagnosed as having pulmonary alveolar proteinosis. 책임저자 : 신경철, 대구광역시남구대명5동 317-1, 영남대학교의과대학내과학교실 Tel: (053) 620-3850, Fax: (053) 654-8386, E-mail: shin@med.yu.ac.kr 57
- 우대형 박정은 류영하 김현정 신경철 정진홍 이관호 - Key Words: Pulmonary alveolar proteinosis, ChestCT 서론폐포단백증은폐포내에 PAS(Periodic acid- Schiff) 염색양성인불용성의인지질이풍부한단백질과같은물질이폐포와기관지에침착하여가스교환의장애를일으키는것을특징으로하는질환으로 1958년 Rosen 등 1) 에의해 27예가처음보고되었고, 국내에서는 1986 년유등 2) 에의해 1예가보고된후몇차례보고된적이있는질환이다. 저자들은 30년동안페인트공으로일해왔던환자로, 약 2개월간의운동시호흡곤란을주소로내원하여간질성폐질환으로진단하고, 치료하였던환자가증상의호전이없고영상학적으로병변이진행되어비디오흉강경하폐생검검사로폐포단백증으로진단된1예를경험하였기에문헌고찰과함께보고하는바이다. 61세남자가내원 2달전부터간헐적인혈담과운동시에심해지는호흡곤란이있어본원외래를방문하였다. 내원당시의식은명료하였고, 객담과기침은없었으며, 호흡곤란도없 This result does not indicate an asthma component Fig. 2. Methacholine challenge results of the subject. 증 례 The FVC and FEV1 are normal. The FEV1/FVC ratio is relatively normal Fig. 1. PFT results of the subject. Ground glass opacities and fine reticular infiltration are noted at both lower lung fields. Fig. 3. Initial chest X-ray of the subject. 58
- 폐포단백증 1 예 - Fig. 4. Initial chest CT (09.05.12)of the subject. Multifocal ground glass opacities with interstitial thickening are predominately seen at both lower lungs. 었다. 직업력상페인트공으로 30년간일을하였으며, 10갑년의흡연력이있었다. 일반혈액검사에서백혈구 6,140 /mm 3, 혈색소 15 g/dl, 혈소판 227,000 /mm 3 이었으며, 총 IgE 3013 KU/L 및간기능검사를포함한혈액검사와소변검 사에서특이소견은없었다. 시행한폐기능검사상특이소견은없었고 (Fig. 1), Methacholine 검사에서도특이소견없었다 (Fig. 2). 흉부엑스선검사에서양측폐의간유리성음영과미세한망상의침윤이관찰되었고 (Fig. 3), 흉부전 Fig. 5. Follow-up chest CT of the subject. The progression of multifocal ground glass opacities with interstitial thickening in both lungs is noted. 59
- 우대형 박정은 류영하 김현정 신경철 정진홍 이관호 - 산화단층촬영 (Fig. 4) 에서는양측폐하에서다수의폐실질이두꺼워지는양상으로보여간질성폐질환으로진단되었다. 7개월뒤환자는호흡곤란증상지속되어외래를방문하였고, 외래에서시행한흉부전산화단층촬영 (Fig. 5) 에서병변이진행하였으며, 조직학적확인을위해비디오흉강경하조직검사를시행하였다. 검체의육안적모습은지방질이침착되어보였으며 (Fig. 6), 조직학적검사에서는폐포내에지방조직과단백질이침착된전형적인폐포단백증의소견을보였고 (Fig. 7), PAS 염색에양성, GMS(Grocott's Methenamine Silver) 염색에음성소견있어 폐포단백증으로진단되었다. 현재외래로정기적 Fig. 6. Gross findings of the wedge resection biopsy specimen of the left lower lobe of the subject. Protein deposition is noted in it. A B C D Fig. 7. The pathology findings were large groups of alveoli with excessive amounts of surfactant and a complex mixture of protein and lipid(fat) molecules (A), positive PAS staining (B) and negative GMS staining (C), (D). 60
- 폐포단백증 1 예 - 진료를받고있으며임상증상의호전을보이고, 호흡곤란의정도가심하지않아전폐세척술과 GM-CSF(Granulocyte/macrophage colony stimulating factor) 사용은하지않고있다. 고 폐포단백증은비정형적이고불용성인인지질이풍부한단백질과같은물질이폐포와기관지세지에침착함으로서산소교환의장애가일어나는질환이다. 3) 이질환은 Rosen 등 1) 에의해 1958년처음기술되었는데병리조직소견이워낙독특하였기때문에과거부터존재하였던질환을발견한것이아니라새로이생겨난질환이라고생각하였다. 1) 그동안이질병의원인에대해수많은논란이있어왔으나, 1994년 GM-CSF 가결핍된유전자결손쥐 (knockout mice) 에서인간의폐포단백증과비슷한조직양상을보이는것이알려지면서부터폐포단백증의발병기전및치료에있어중요한진전이있어왔다. 3, 4) 폐포단백증은 100만명당 3.7명의유병률을보이는드문질환으로 5) 국내에서는 1986년부터 30여 6, 7) 편의증례보고가있어왔다. 이학적검사소견은특징적이지는않으나약 50% 에서흡기시수포음이, 25% 에서청색증이, 그외적은빈도로곤봉형수지가나타나기도한다. 말초혈액검사, 생화학검사, 소변검사는일반적으로정상범위로나타나며 LDH 수치는종종상승되는결과를보여질병의중증도를나타내는지표가되기도한다. 3) 폐기능검사에서는주로제한성장애의양상으로나타나고, 단순흉부방사선에서양측폐를비교적비슷한정도로침범하고폐문주위에서주변부 찰 로침윤해들어가는박쥐또는나비모양의소견을보이며, 고해상도컴퓨터단층촬영시때때로간유리모양의침윤과소엽간중격의비후로인한보도블록모양의양상을보인다. 방사선소견이심함에도불구하고증상이경미할수도있어그소견이일치하지는않는다. 4) 진단은기관지경하또는개흉폐생검을시행하여확진할수있는데, 전형적인광학현미경소견은폐포벽과간질조직이잘유지되며폐포내에 PAS 염색양성으로호산성과립상물질이관찰된다. 폐포안에변형된포말상의폐포대식세포가발견되고면역조직화학염색에서표면활성단백질양성의소견을보인다. 때때로이차감염이동반되는경우림프구침윤에의한폐포벽비후나드물게폐포벽섬유화소견을보이기도한다. 4) 최근에는임상증상, 검사소견, 방사선소견등에서폐포단백증이의심되어지는경우, 기관지폐포세척술을시행하여육안적으로탁한우유빛또는회색빛세척액이다량으로보이고, 세포학적검사에서과립상의비세포성호산성단백질이포말상대식세포및전자현미경검사로층판상소체를나타내는표면활성단백질을증명함으로써확진한다. 8) 최신치료인 GM-CSF 를피하투여또는흡입시키는방법은적어도절반이상에서는효과가있다고보지만, 치료전후의 GM-CSF 자가항체의정량적인변화와 GM-CSF 투여량과자가항체의정량적관계등이명료하게밝혀져야할필요성이제기되고있다. 장기간의 GM- CSF 사용이골수에미치는영향, 폐섬유화의가능성등부작용에대해좀더연구되어져야 8, 9) 할필요성이있다. 본증례는환자의직업력과흉부전산화단층 61
- 우대형 박정은 류영하 김현정 신경철 정진홍 이관호 - 촬영으로판단했을때간질성폐질환으로오인되었던환자로, 증상의지속적인악화와영상학적으로병변이진행하여, 흉강경하조직검사시행후폐포단백증으로진단하였다. 흔한질병이아니고, 문진과흉부전산화단층촬영만으로진단을하기힘든경우로조직학적검사가확진에필요함을보여주는증례이다. 참고문헌 1. Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med 1958 Jun5; 258(23): 1123-42. 2. 유덕종, 최정윤, 이원식, 정태훈, 곽정석, 손태중. Pulmonary alveolar proteinosis 1예. 제63차추계결핵학술대회초록집 1986. 3. Stanley E, Lieschke GJ, Grail D, Metcalf D, Hodgson G, Gall JA, et al. Granulocyte/ macrophage colony stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci USA 1994 Jun7;91(12):5592-6. 4. Trapnell BC, Whitsett JA, Nakata K. Pulmonary alveolar proteinosis. N Engl J Med 2003 Dec25;349(26):2527-39. 5. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med 2002 Jul;166(2):215-35. 6. Kim G, Lee SJ, Lee HP, Yoo CG, Han SK, Shim YS, et al. The clinical characteristics of pulmonary alveolar proteinosis. experience at Seoul National University Hospital, and review of the literature. J Korean Med Sci 1999;14: 159-64. 7. Seo JH, Bahk JH. Whole Lung Lavage and Extracorporeal Membrane Oxygenation in a Patient with Pulmonary Alveolar Proteinosis and Lung cancer. Korean J Anesthesiol 2005; 48:549-52. 8. Wang BM, Stern EJ, Schmidt RA, Pierson DJ. Diagnosing pulmonary alveolar proteinosis. A review and an update. Chest 1997 Feb;111 (2):460-6. 9. Ioachimescu OC, Kavuru MS. Pulmonary alveolar proteinosis. Chron Respir Dis 2006;3 (3):149-59. 62