Sarcoidosis – current view on pathogenesis, diagnosis and treatment

Czech version

Authors: Kolek V.; Žurková M.; Lošťáková V.
Authors‘ workplace: Klinika plicních nemocí a tuberkulózy LF OU a FN Olomouc
Published in: Kardiol Rev Int Med 2019, 21(3): 145-150

Overview

The papers deals with the current opinions on etiopathogenesis of sarcoidosis, presents modern diagnostic procedures and recommended treatment. The etiology of the disease is still unclear, characterized by the formation of non-caseating granulomas, consisting mainly of T lymphocytes and variously modified macrophages. The importance of Th17+ cells that accumulate at the site of inflammation is emphasized. Involvement of an unknown noxa in a predisposed individual is expected. The incidence of the disease is increasing, as well as the reported mortality. Clinical manifestations may vary greatly; however, about a third of cases are asymptomatic. The initiation process begins in the lungs where alveolitis occurs; the lungs are affected in 95% of cases. The disease is systemic in nature and may affect almost all organs and tissues. Manifestations in the eyes, central nervous system and heart are usually severe. Diagnosis is based on a set of clinical manifestations, radiological changes (high-resolution computed tomography), functional examination, and identification of granuloma. Biopsy is usually performed bronchoscopically. Bronchoalveolar lavage and serum biomarker testing may contribute to the diagnosis. Spontaneous remission occurs in up to half of cases. Administration of corticosteroids usually leads to symptom resolution; however, there are persistent and progressive forms of the disease that threaten patients’ lives. In cases of refractory disease, immunosuppressive agents (methotrexate, azathioprine, leflunomide, and mycophenolate mofetil) may be administred in second line therapy. Furthermore, TNFα inhibitors (infliximab, adalimumab) may be administered in third line therapy, if needed. Improvement of organ function and quality of life should be weighed against the possible side effects when considering the therapy indication.

Keywords:

etiopathogenesis – diagnostics – Sarcoidosis

Sources

1. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WA SOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 1999; 160(2): 736– 755. doi: 10.1164/ ajrccm.160.2.ats4-99.

2. Bradley B, Branley HM, Egan JJ et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 (Suppl 5): 1– 58. doi: 10.1136/ thx.2008.101691.

3. Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med 2011; 183(5): 573– 581. doi: 10.1164/ rccm.201006-0865CI.

4. Pastorová B, Kolek V, Žurková M et al. Věkové aspekty sarkoidózy. Stud Pneumol Phthiseol 2018; 78(3): 102– 106.

5. Kolek V et al. Sarkoidóza. Známé a neznámé. Grada: Praha1998.

6. Arkema EV, Grunewald J, Kullberg S et al. Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden. Eur Respir J 2016; 48(6): 1690– 1699. doi: 10.1183/ 13993003.00477-2016.

7. Baughman RP, Field S, Costabel U et al. Sarcoidosis in America. Analysis Based on Health Care Use. Ann Am Thor Soc 2016; 13(8): 1244– 1255. doi: 10.1513/ Annals ATS.201511-760OC.

8. Morimoto T, Azuma A, Abe S et al. Epidemiology of sarcoidosis in Japan. Eur Respir J 2008; 31(2): 372– 379. doi: 10.1183/ 09031936.00075307.

9. Swigris JJ, Olson AL, Huie TJ et al. Sarcoidosis-related mortality in the United States from 1988– 2007. Am J Respir Crit Care Med 2011; 183(11): 1524– 1530. doi: 10.1164/ rccm.201010-1679OC.

10. Baughman RP, Lower EE. Who dies from sarcoidosis and why? Am J Respir Crit Care Med 2011; 183(11): 1446– 1447. doi: 10.1164/ rccm.201103-0409ED.

11. Hunninghake GW, Crystal RG. Pulmonary sarcoidosis. A disorder mediated by excess helper T-lymphocyte activity at sites of disease. N Engl J Med 1981; 305(8): 429– 434. doi: 10.1056/ NEJM198108203050804.

12. Facco M, Cabrelle A, Teramo A. Sarcoidosis is a Th1/ Th17 multisystem disorder. Thorax 2011; 66(2): 144– 150. doi: 10.1136/ thx.2010.140319.

13. Huang H, Lu Z, Jiang C. Imbalance between Th17 and regulatory T-Cells in sarcoidosis. Int J Mol Sci 2013; 14(11): 21463– 21473. doi: 10.3390/ ijms141121463.

14. Facco M. Cabrelle A, Teramo A et al. Sarcoidosis is a Th1/ Th17 multisystem disorder. Thorax 2011; 66(2): 144– 150. doi: 10.1136/ thx.2010.140319.

15. Martinetti M, Tinelli C, Kolek V et al. “The Sarcoidosis Map”: a joint survey of clinical and immunogenetic findings in two European countries. Am J Respir Crit Care Med 1995; 152(2): 557– 564. doi: 10.1164/ ajrccm.152.2.7633707.

16. Wahlström J, Dengjel J, Winqvist O et al. Autoimmune T cell responses to antigenic peptides presented by bronchoalveolar lavage cell HLA-DR molecules in sarcoidosis. Clin Immunol 2009; 133(3): 353– 363. doi: 10.1016/ j.clim.2009.08.008.

17. Baughman RP, Teirstein A, Judson M et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164 (10 Pt 1): 1885– 1889. doi: 10.1164/ ajrccm.164.10.2104046.

18. Kolek V, Hutyrová B, Lošťáková V. MORSA-multicentrická moravská studie epidemiologických trendů sarkoidózy 1991– 2000. Stud Pneumol Phthiseol 2005; 65(1): 17– 20.

19. Žurková M, Kriegová E, Zapletalová J et al. Srovnání klinických parametrů u pacientů s nitrohrudní a generalizovanou formou sarkoidózy. Stud Pneumol Phthiseol 2013; 73(6): 237– 242.

20. Baughman RP, Judson MA, Wells A. The indications for the treatment of sarcoidosis: Wells Law. Sarcoid Vasc Dif Lung Dis 2017; 34(4): 280– 282.

21. Amin EN, Closser DR, Crouser ED. Current best practice in the management of pulmonary and systemic sarcoidosis. Ther Adv Respir Dis 2014; 8(4): 111– 132. doi: 10.1177/ 1753465814537367 .

22. Korsten P, Strohmayer K, Baughman RP et al. Refractory pulmonary sarcoidosis: proposal of a definition and recommendation for the diagnostic and therapeutic approach. Clin Pulm Med 2016; 23(2): 67– 75. doi: 10.1097/ CPM.0000000000000136.

23. Panselinas E, Judson MA. Acute pulmonary exacerbations of sarcoidosis. Chest 2012; 142(4): 827– 836. doi: 10.1378/ chest.12-1060.

24. Schutt AC, Bullington WM, Judson MA. Pharmacotherapy for pulmonary sarcoidosis: a Delphi consensus study. Respir Med 2010; 104(5): 717– 723. doi: 10.1016/ j.rmed.2009.12.009.

25. Baughman RB, Grutters JC. New treatment strategies for pulmonary sarcoidosis: antimetabolites, biological drugs, and other treatment approaches. Lancet Respir Med 2015; 3(10): 813– 822. doi: 10.1016/ S2213-2600(15)00199-X.

26. Korsten P, Mirsaeidi M, Sweiss NJ. Nonsteroidal therapy of sarcoidosis. Curr Opin Pulm Med 2013; 19(5): 516– 523. doi: 10.1097/ MCP.0b01 3e3283642ad0.

27. Baughman RP, Nunes H, Sweiss N et al. Established and experimental medical therapy of pulmonary sarcoidosis. Eur Respir J 2013; 41(6): 1424– 1438. doi: 10.1183/ 09031936.00060612.

28. Saketkoo LA, Baughman RP. Biologic therapies in the treatment of sarcoidosis. Expert Rev Clin Immunol 2016; 12(8): 817– 825. doi: 10.1080/ 1744666X.2016.1175301.

29. Sweiss NJ, Lower EE, Mirsaeidi M et al. Rituximab in the treatment of refractory pulmonary sarcoidosis. Eur Respir J 2014; 43(5): 1525– 1528. doi: 10.1183/ 09031936.00224513.

30. Sweiss, NJ, Curran J, Baughman RP. Sarcoidosis, role of tumor necrosis factor inhibitors and other biologic agents, past, present, and future concepts. Clin Dermatol 2007; 25(3): 341– 346. doi: 10.1016/ j.clindermatol.2007.03.012.