Is Propionibacterium acnes a probable causative infectous agent in the pathogenesis of sarcoidosis?
Abstract
More than 120 years have passed since sarcoidosis was recognized for the first time, the exact cause of this systemic granulomatous disease is still unknown. Sarcoidosis is generally considered to be caused by exposure to specific environmental substances to genetically susceptible hosts. Propionibacterium acnes (P. acnes) has been regarded as one of the most probable causative agents of sarcoidosis, since this ubiquitous bacteria is isolated in culture from biopsy samples of lymph nodes from patients with sarcoidosis. Evidences suggesting that P. acnes is involved in the pathogenesis of sarcoidosis are accumulating. These days, intracellular persistence of P. acnes is thought to be implicated in not only sarcoidosis but also diseases of the prostate gland and possibly Parkinson’s disease. The importance of P. acnes as a pathogenic substance is increasing. In this review we would like to summarize researches about P. acnes and sarcoidosis.
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Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet. 2014; 383:1155-67.
Hunninghake, GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, Eklund A, Kitaichi M, Lynch J, Rizzato G, Rose C, Selroos O, Semenzato G, Sharma OP. ATS/ERS/WASOG statement on sarcoidosis. Sarcoidosis Vasculitis Diffuse Lung Disease. 1999; 16: 149-73.
du Bois RM, Goh N, McGrath D, Cullinan P. Is there a role for microorganisms in the pathogenesis of sarcoidosis? J Internal Medicine. 2003; 253(1): 4-17.
Newman LS, Rose CS, Bresnitz EA, Rossman MD, Barnard J, Frederick M, Terrin ML, Weinberger SE, Moller DR, McLennan G, Hunninghake G, DePalo L, Baughman RP, Iannuzzi MC, Judson MA, Knatterud GL, Thompson BW, Teirstein AS, Yeager H Jr, Johns CJ, Rabin DL, Rybicki BA, Cherniack R; ACCESS Research Group. A case controle study of sarcoidosis-envimental and occupational risk factors. American J Respiratory Critical Care Medicine. 2004; 170: 1324-30.
Deubelbeiss U, Gemperli A, Schindler C, Baty F, Brutsche MH.. Prevalence of sarcoidosis in Switzerland is associated with environmental factors. European Respiratory J 2010; 35: 1088-97.
ES Chen, DR Moller. Etiology of Sarcoidosis. Clinical Review Allergy Immunology. 2015: 49: 6-18.
Baughman RP, Lower EE, du Bois RM. Sarcoidosis. Lancet 2003; 361: 1111-18.
Celada LJ, Hawkins C, Drake WP. The Etiologic Role of Infectious Antigens in Sarcoidosis Pathogenesis. Clin Chest Med. 2015; 36(4): 561-8.
Esteves T, Aparicio G, Garcia-Patos V. Is there any association between Sarcoidosis and infectious agents? : a systematic review and meta-analysis. BMC Pulm Med. 2016 Nov 28; 16(1): 165.
Homma JY, Abe C, Chosa H, Ueda K, Saegusa J, Nakayama M, Homma H, Washizaki M, Okano H: Bacteriological investigation on biopsy specimens from patients with sarcoidosis. Japanese J Experimental Medicine. 1978; 48: 251-5.
Abe C, Iwai K, Mikami R, Hosoda Y: Frequent isolation of Propionibacterium acnes from sarcoidosis lymph nodes. Zentralbl Bakteriol Mikrobiol Hyg 1984; 256: 541-7.
Eishi, Y. Etiologic link between sarcoidosis and Propionibacterium acnes. Respiratory Investigation. 2013; 51, 56-68.
Leheste JR, Ruvolo KE, Chros towski JE, Rivera K, Husko C, Miceli A, Selig MK, Brüggemann H, Torres G. P. acnes-Driven Disease Pathology: Current Knowledge and Future Directions. Front Cell Infectious Microbiology. 2017 Mar 14; 7: 81. doi: 10.3389/fcimb.2017.00081.
Colina M, LoMonaco A, Khodeir M, Trotta F. “Propionibacterium acnes and SAPHO syndrome: a case report and literature review,” Clinical and Experimental Rheumatology. 2007; 25(3): 457-60.
Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TS. “Association between sciatica and Propionibacterium acnes,” Lancet 2001; 357: 2024-25.
Moore WEC, Holdeman LV. Propionibacterium. In Bergey’s Manual of Determinating Bacteriology. 8th Edition, The Williams and Wilkins Company Ltd. Baltimore, p633-41, 1974
Funke G, Von Graevenitz A, Clarridge JE III, Bernard KA. “Clinical microbiology of Coryneformbacteria” Clinical Microbiology Reviews. 1997; 10(1): 125-59
Grice EA and Segre JA. “The skin microbiome,” Nature Reviews Microbiology. 2011; 9(4): 244-53.
Delgado S, Su´arez A, Mayo B. “Identification, typing and characterisation of Propionibacterium strains from healthy mucosa of the human stomach,” International Journal of Food Microbiology. 2011; 149(1); 65-72.
Dessinioti C, Katsambas AD. The role of Propionibacterium acnes in acne pathogenesis: facts and controversies. Clinical Dermatology. 2010; 28(1): 2–7.
Jugeau S, Tenaud I, Knol AC, Jarrousse V, Quereux G, Khammari A, Dreno B.
Induction of Toll-like receptors by Propionibacterium acnes. Br. J. Dermatol. 2005; 153(6), 1105-13.
Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL. Activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses. J. Immunology. 2002; 169(3), 1535-41.
Vowels BR, Yang S, Leyden JJ. Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes Propionibacterium acnes: implications for chronic inflammatory
acne. Infectious Immunology. 1995; 63(8), 3158-65.
Perry A., and Lambert P. Propionibacterium acnes: infection beyond the skin. Expert Review. Anti Infective Therapy. 2011; 9(12): 1149-56.
Portillo ME, Corvec S, Borens O, Trampuz A. Propionibacterium acnes: an underestimated pathogen in implant-associated infections. Biomedical Research International. 2013:804391. doi: 10.1155/2013/804391.
Deramo VA and Ting TD, “Treatment of Propionibacterium acnes endophthalmitis,” CurrentOpinion inOphthalmology. 2001; 12(3): 225-9.
Conen A, Walti LN, Merlo A, et al. “Characteristics and treatment outcome of cerebrospinal fluid shunt-associated infections in adults: a retrospective analysis over an 11-year period,” Clinical Infectious Disease. 2008; 47(1): 73-82.
Delahaye F1, Fol S, Célard M, Vandenesch F, Beaune J, Bozio A, de Gevigney G.
“Propionibacterium acnes infective endocarditis. Study of 11 cases and review of literature,” Arch des Maladies du Coeur et des Vaisseaux. 2005; 98(12): 1212-18.
Del Pozo JL, Tran NV, Petty PM, Johnson CH, Walsh MF, Bite U, Clay RP, Mandrekar JN, Piper KE, Steckelberg JM, Patel R. “Pilot study of association of bacteria on breast implants with capsular contracture,” Journal of Clinical Microbiology. 2009; 47(5): 1333-7.
Rieger UM, Pierer G, L¨uscher NJ, and Trampuz A, “Sonication of removed breastimplants for improved detection of subclinical infection,” Aesthetic Plastic Surgery. 2009; 33(3): 404-8.
Piper KE, Jacobson MJ, Cofield RH, Sperling JW, Sanchez-Sotelo J, Osmon DR, McDowell A, Patrick S, Steckelberg JM, Mandrekar JN, Fernandez Sampedro M, Patel R. “Microbiologic diagnosis of prosthetic shoulder infection by use of implant sonication,” Journal of Clinical Microbiology. 2009; 47(6): 1878-84.
Scott MT, Milas L. The distribution and persistence in vivo of Corynebacterium parvum in relation to its antitumor activity. Cancer Res. 1977; 37: 1673-9.
de Brouwer B, Veltkamp M, Wauters CA, Grutters JC, Janssen R. Propionibacterium acnes isolated from lymph nodes of patients with sarcoidosis. Sarcoidosis Vasculitis Diffuse Lung Dis. 2015; 32(3): 271-4.
Minami J, Eishi Y, Ishige Y, Kobayashi I, Ishige I, Kobayashi D, Ando N, Uchida K, Ikeda S, Sorimachi N, Karasuyama H, Takemura T, Takizawa T, Koike M. Pulmonary granulomas caused experimentally in mice by a recombinant trigger factor protein of Propionibacterium acnes. J Med Dent Sci. 2003; 50(4): 265-74.
Ishige I, Eishi Y, Takemura T, Kobayashi I, Nakata K, Tanaka I, Nagaoka S, Iwai K, Watanabe K, Takizawa T, Koike M. Propionibacterium acnes is the most common bacterium commensal in peripheral lung tissue and mediastinal lymph nodes from subjects without sarcoidosis. Sarcoidosis Vasculitis Diffuse Lung Dis Off J WASOG/World Assoc Sarcoidosis Other Granulomatous Dis. 2005; 22: 33-42.
Ishige I, Usui Y, Takemura T, Eishi Y. Quantitative PCR of mycobacterial and propionibacterial DNA in lymph nodes of Japanese patients with sarcoidosis. Lancet 1999; 354: 120-3
Eishi Y, Suga M, Ishige I, Kobayashi D, Yamada T, Takemura T, Takizawa T, Koike M, Kudoh S, Costabel U, Guzman J, Rizzato G, Gambacorta M, du Bois R, Nicholson AG, Sharma OP, Ando M. Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis. J Clinical Microbiology. 2002; 40(1): 198-204
Zhou Y, Wei YR, Zhang Y, Du SS, Baughman RP, Li HP. Real-time quantitative reverse transcription-polymerase chain reaction to detect propionibacterial ribosomal RNA in the lymph nodes of Chinese patients with sarcoidosis. Clin Experimental Immunology. 2015 ; 181(3): 511-7.
Zhao MM, Du SS, Li QH, Chen T, Qiu H, Wu Q, Chen SS, Zhou Y, Zhang Y, Hu Y, Su YL, Shen L, Zhang F, Weng D, Li HP. High throughput 16SrRNA gene sequencing reveals the correlation between Propionibacterium acnes and sarcoidosis. . Respiratory Research (2017) 18:28 DOI 10.1186/s12931-017-0515-z
Iwai K, Takemura T, Kitaichi M, Kawabata Y, Matsui Y. Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern. Acta Pathol Jpn 1993;43 :377-85.
James DG, Neville E, Siltzbach LE. A worldwide review of sarcoidosis. In seventh International Conference on Sarcoidosis. Ann N Y Acad Sci. 1976; 278: 321-34.
Hiramatsu J, Kataoka M, Nakata Y, Okazaki K, Tada S, Tanimoto M, Eishi Y: Propionibacterium acnes DNA detected in bronchoalveolar lavage cells from patients with sarcoidosis. Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2003; 20: 197-203
Ichikawa H, Kataoka M, Hiramatsu J, Ohmori M, Tanimoto Y, Kanehiro A, Nakata Y, Tanimoto Y. “Quantitative analysis of propionibacterial DNA in bronchoalveolar lavage cells from patients with sarcoidosis,” Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2008; 25: 15-20.
Yamada T, Eishi Y, Ikeda S, Ishige I, Suzuki T, Takemura T, Takizawa T, Koike M.
In situ localization of Propionibacterium acnes DNA in lymph nodes from sarcoidosis patients by signal amplification with catalysed reporter deposition. J Pathol. 2002; 198(4): 541-7.
Nakata Y, Ejiri T, Kishi T, Mori Y, Hioka T, Kataoka M, Ohnoshi Y, Kimura I. Alveolar lymphocyte proliferation induced by Propionibacterium acnes in sarcoidosis
patients. Acta Medica Okayama 1986; 40(5): 257-64
Ebe Y, Ikushima S, Yamaguchi T, Kohno K, Azuma A, Sato K, Ishige I, Usui Y, Takemura T, Eishi Y. Proliferative response of peripheral blood mononuclear cells and levels of antibody to recombinant protein from Propionibacterium acnes DNA expression library in Japanese patients with sarcoidosis. Sarcoidosis Vasculitis Diffuse Lung Dis Off J WASOG/World Assoc Sarcoidosis Other Granulomatous Dis 2000; 17: 256-65.
Ziegenhagen MW1, Schrum S, Zissel G, Zipfel PF, Schlaak M, Müller-Quernheim J.J. Increased expression of proinflammatory chemokines in bronchoalveolar lavage cells of patients with progressing idiopathic pulmonary fibrosis and sarcoidosis. Investig Med. 1998; 46(5): 223-31.
Mori Y, Nakata Y, Kataoka M, Ejiri T, Hioka T, Maeda T, Hosoya S, Ohnoi Y, Kimura I. Interleukin-2 production and receptor expression of alveolar lymphocytes stimulated by Propionibacterium acnes in sarcoidosis. Nihon Kyobu Shikkan Gakkai Zasshi (in Japanese with English abstract). 1989; 27: 42–50.
Furusawa H, Suzuki Y, Miyazaki Y, Inasea N, Eishi Y. Th1 and Th17 immune responses to viable Propionibacterium acnes in patients with sarcoidosis. Respiratory
Investigation 2012; 50:104-9
Schupp JC, Tchaptchet S, Lützen N, Engelhard P, Müller-Quernheim J, Freudenberg MA, Prasse A. Immune response to Propionibacterium acnes in patients with
sarcoidosis-in vivo and in vitro. BMC Pulm Med. 2015; 24; 15:75. doi: 10.1186/s12890
-015-0070-7.
Yorozu P, Furukawa A, Uchida K, Akashi T, Kakegawa T, Ogawa T, Minami J, Suzuki Y, Awano N, Furusawa H, Miyazaki Y, Inase N, Eishi Y. Propionibacterium acnes catalase induces increased Th1 immune response in sarcoidosis patients. Respir Investig. 2015; 53(4): 161-9.
Igarashi R and Inatomi K. Propionibacterium acnes in the biopsied lymph nodes of sarcoidosis patients demonstrated by an immunofluorescence and immunoperoxydase staining techniques. Nippon Kyobu Sikkan Gakkai Zasshi ( in Japanese with English abstract). 1988; 26: 507-11.
Negi M, Takemura T, Guzman J, Uchida K, Furukawa A, Suzuki Y, Iida T, Ishige I, Minami J, Yamada T, Kawachi H, Costabel U, Eishi Y. Localization of Propionibacterium acnes in granulomas supports a possible etiologic link between sarcoidosis and the bacterium. Mod Pathol. 2012; 25(9): 1284-97.
Akimoto J, Nagai K, Ogasawara D, Tanaka Y, Izawa H, Kohno M, Uchida K, Eishi Y. Solitary tentorial sarcoid granuloma associated with Propionibacterium acnes infection: case report. J Neurosurg. 2017 ; 127(3): 687-90.
Yang G, Eishi Y, Raza A, Rojas H, Achiriloaie A, De Los Reyes K, Raghavan R. Propionibacterium acnes -associated neurosarcoidosis: A case report with review of the literature. Neuropathology. 2017 Aug 30. doi: 10.1111/neup.12411.
Goto H, Usui Y, Umazume A, Uchida K, Eishi Y. Propionibacterium acnes as a possible pathogen of granuloma in patients with ocular sarcoidosis. Br J Ophthalmol. 2017 Mar 7. pii: bjophthalmol-2016-309248. doi: 10.1136/bjophthalmol-2016-309248.
Asakawa N, Uchida K, Sakakibara M, Omote K, Noguchi K, Tokuda Y, Kamiya K, Hatanaka KC, Matsuno Y, Yamada S, Asakawa K, Fukasawa Y, Nagai T, Anzai T, Ikeda Y, Ishibashi-Ueda H, Hirota M, Orii M, Akasaka T, Uto K, Shingu Y, Matsui Y, Morimoto SI, Tsutsui H, Eishi Y. Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients. PLoS One. 2017 Jul 7; 12(7): e0179980. doi: 10.1371/journal.pone.0179980. eCollection 2017.
Senaldi G, Yin S, Shaklee CL, Piguet PF, Mak TW, Ulich TR. Corynebacterium parvum- and Mycobacterium bovis Bacillus Calmette-Guerin-induced granuloma formation is inhibited in TNF receptor I (TNF-RI)knockout mice and by treatment with soluble TNF-RI. J Immunol 1996; 157: 5022-6.
Tsuji H, Harada A, Mukaida N, Nakanuma Y, Bluethmann H, Kaneko S, Yamakawa K, Nakamura SI, Kobayashi KI, Matsushima K. Tumor necrosis factor receptor p55 is essential for intrahepatic granuloma formation and hepatocellularapoptosis in a murine model of bacterium-induced fulminant hepatitis. Infect Immun1997;65 : 1892-8.
Yoneyama H, Matsuno K, Zhang Y, Murai M, Itakura M, Ishikawa S, Hasegawa G, Naito M, Asakura H, Matsushima K. Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease. J Exp Med 2001; 193: 35-49.
Nishiwaki T, Yoneyama H, Eishi Y, Matsuo N, Tatsumi K, Kimura H, Kuriyama T, Matsushima K. Indigenous pulmonary Propionibacterium acnes primes the host in the development of sarcoid-like pulmonary granulomatosis in mice. Am J Pathol 2004; 165: 631-9.
Itakura M, Tokuda A, Kimura H, Nagai S, Yoneyama H, Onai N, Ishikawa S, Kuriyama T, Matsushima K. Blockade of secondary lymphoid tissue chemokine exacerbates Propionibacterium acnes -induced acute lung inflammation. J Immunology 2001 ; 166(3): 2071-9.
Werner JL, Escolero SG, Hewlett JT, Mak TN, Williams BP, Eishi Y, Núñez G. Induction of Pulmonary Granuloma Formation by Propionibacterium acnes Is Regulated by MyD88 and Nox2. Am J Respir Cell Mol Biol. 2017 Jan;56(1):121-130. doi: 10.1165/rcmb.2016-0035OC.
McCaskill JG1, Chason KD, Hua X, Neuringer IP, Ghio AJ, Funkhouser WK, Tilley SL. Pulmonary immune responses to Propionibacterium acnes in C57BL/6 and BALB/c mice. Am J Respir Cell Mol Biol. 2006; 35(3): 347-56.
Jiang D, Huang X, Geng J, Dong R, Li S, Liu Z, Wang C, Dai H. Pulmonary fibrosis in a mouse model of sarcoid granulomatosis induced by booster challenge with Propionibacterium acnes. Oncotarget. 2016; 7(23): 33703-14. doi: 10.18632/oncotarget.
Iio K1, Iio TU, Okui Y, Ichikawa H, Tanimoto Y, Miyahara N, Kanehiro A, Tanimoto M, Nakata Y, Kataoka M. Experimental pulmonary granuloma mimicking sarcoidosis induced by Propionibacterium acnes in mice. Acta Med Okayama. 2010; 64(2): 75-83.
Kamata M, Tada Y, Mitsui A, Shibata S, Miyagaki T, Asano Y, Sugaya M, Kadono T, Sato S. ICAM-1 deficiency exacerbates sarcoid-like granulomatosis induced by Propionibacterium acnes through impaired IL-10 production by regulatory T cells. Am J Pathol. 2013; 83(6): 731-9.
Yi ES, Lee H, Suh YK, Tang W, Qi M, Yin S, Remick DG, Ulich TR. Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats. Am J Pathol. 1996; 149(4): 1303-12.
Ichiyasu H, Suga M, Iyonaga K, Ando M. Role of monocyte chemoattractant protein-1 in Propionibacterium acnes -induced pulmonary granulomatosis. Microsc Res Tech. 2001; 53(4): 288-97.
Zissel G, Müller-Quernheim J. Cellular Players in the Immunopathogenesis of Sarcoidosis. Clinical Chest Med. 2015 ; 36(4): 549-60.
Beijer E, Veltkamp M, Meek B, Moller DR. Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights. Semin Respir Crit Care Med. 2017; 38(4): 404-416.
Gabrilovich MI1, Walrath J, van Lunteren J, Nethery D, Seifu M, Kern JA, Harding CV, Tuscano L, Lee H, Williams SD, Mackay W, Tomashefski JF Jr, Silver RF. Disordered Toll-like receptor 2 responses in the pathogenesis of pulmonary sarcoidosis. Clin Exp Immunol. 2013; 173: 512-22.
Kalis C, Gumenscheimer M, Freudenberg N, Tchaptchet S, Fejer G, Heit A, Akira S,
Galanos C, Freudenberg MA. Requirement for TLR9 in the Immunomodulatory Activity of Propionibacterium acnes. The Journal of Immunology, 2005; 174: 4295-4300.
Rastogi R, Du W, Ju D, Pirockinaite G, Liu Y, Nunez G, Samavati L. Dysregulation of p38 and MKP-1 in response to NOD1/TLR4 stimulation in sarcoid bronchoalveolar cells. Am J Respir Crit Care Med. 2011; 183(4): 500-10.
Tanabe T, Ishige I, Suzuki Y, Aita Y, Furukawa A, Ishige Y, Uchida K, Suzuki T, Takemura T, Ikushima S, Oritsu M, Yokoyama T, Fujimoto Y, Fukase K, Inohara N, Nunez G, Eishi Y. Sarcoidosis and NOD1 variation with impaired recognition of intracellular Propionibacterium acnes. Biochim Biophys Acta. 2006 Sep; 1762(9): 794-801. Epub 2006 Jul 25.
Qian M, Fang X, Wang X. Autophagy and inflammation. Clin Transl Med. 2017 Dec; 6(1): 24. doi: 10.1186/s40169-017-0154-5..
Fischer N, Mak TN, Shinohara DB, Sfanos KS, Meyer TF, Brüggemann H. Deciphering the intracellular fate of Propionibacterium acnes in macrophages. Biomed Res Int. 2013; 2013: 603046. doi: 10.1155/2013/603046.
Nakamura T, Furukawa A, Uchida K, Ogawa T, Tamura T, Sakonishi D, Wada Y, Suzuki Y, Ishige Y, Minami J, Akashi T, Eishi Y. Autophagy Induced by Intracellular Infection of Propionibacterium acnes. PLoS One. 2016 May 24; 11(5): e0156298. doi: 10.1371/journal.pone.0156298. eCollection 2016.
Bachelez H, Senet P, Cadranel J, Kaoukhov A, Dubertret L. The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol. 2001; 137(1): 69-73.
Park DJ, Woog JJ, Pulido JS, Cameron JD. Minocycline for the treatment of ocular and ocular adnexal sarcoidosis. Arch Ophthalmol. 2007; 125(5): 705-9.
Miyazaki E, Ando M, Fukami T, Nureki S, Eishi Y, Kumamoto T. Minocycline for the treatment of sarcoidosis: is the mechanism of action immunomodulating or antimicrobial effect? Clin Rheumatol. 2008; 27(9): 1195-7.
Takemori N, Nakamura M, Kojima M, Eishi Y. Successful treatment in a case of Propionibacterium acnes -associated sarcoidosis with clarithromycin administration: a case report. J Med Case Rep. 2014 Jan 15; 8: 15. doi: 10.1186/1752-1947-8-15.
Baba K, Yamaguchi E, Matsui S, Niwa S, Onoe K, Yagi T, Hattori T, Ozawa H, Hara K. A case of sarcoidosis with multiple endobronchial mass lesions that disappeared with antibiotics. Sarcoidosis Vasc Diffuse Lung Dis. 2006; 23(1) : 78-9.
Yamaguchi T. Antibiotic treatment for sarcoidosis. Nihon Kyoubu Rinshou (in Japanese). 2008; 67(4): 309-318.
DOI: http://dx.doi.org/10.18103/imr.v3i11.614
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