Semin Respir Crit Care Med 2020; 41(05): 733-740
DOI: 10.1055/s-0040-1710371
Review Article

Nonlife-Threatening Sarcoidosis

Marina Dornfeld Cunha Castro
1   Department of Medicine, Division of Respiratory Diseases, Interstitial Lung Diseases Center, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
,
Carlos Alberto de Castro Pereira
1   Department of Medicine, Division of Respiratory Diseases, Interstitial Lung Diseases Center, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
› Author Affiliations

Abstract

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The outcome is quite variable and is mainly related to persistent inflammatory processes and the development of fibrosis. Many prognostic factors have been described, but the disease evolution is not yet entirely known. The nonthreatening course is characterized by spontaneous involution or stability after treatment withdrawal. Löfgren's syndrome is a subset within the spectrum of sarcoidosis phenotypes, composed of acute onset of fever, bilateral hilar lymphadenopathy, erythema nodosum and/or bilateral ankle periarticular inflammation/arthritis, specifically characterized by a self-limiting disease course. In contrast, advanced fibrotic sarcoidosis with pulmonary hypertension phenotype is correlated with a poor prognosis. Further studies are necessary to detail phenotypes to better understand the mechanisms of the disease and plan future clinical therapeutic studies.



Publication History

Article published online:
10 August 2020

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  • References

  • 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 (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med 1999; 160 (02) 736-755
  • 2 Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med 2011; 183 (05) 573-581
  • 3 Govender P, Berman JS. The diagnosis of sarcoidosis. Clin Chest Med 2015; 36 (04) 585-602
  • 4 Cox CE, Davis-Allen A, Judson MA. Sarcoidosis. Med Clin North Am 2005; 89 (04) 817-828
  • 5 Sharma O. Definition and history of sarcoidosis. Eur Respir Mon. 2005; 32: 1-12
  • 6 Valeyre D, Bernaudin JF, Uzunhan Y. , et al. Clinical presentation of sarcoidosis and diagnostic work-up. Semin Respir Crit Care Med 2014; 35 (03) 336-351
  • 7 Pereira CA, Dornfeld MC, Baughman R, Judson MA. Clinical phenotypes in sarcoidosis. Curr Opin Pulm Med 2014; 20 (05) 496-502
  • 8 Neville E, Walker AN, James DG. Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients. Q J Med 1983; 52 (208) 525-533
  • 9 Marjolein D, Celine H, Marjon E, Jolanda DV. Sarcoidosis-associated disability. In: Baughman RP, Valeyre D. , eds. Sarcoidosis—A Clinician's Guide. St. Louis, Missouri, EUA: Elsevier; 2019: 257-264
  • 10 Baughman RP, Drent M, Culver DA. , et al. Endpoints for clinical trials of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2012; 29 (02) 90-98
  • 11 Culver DA, Baughman RP. It's time to evolve from Scadding: phenotyping sarcoidosis. Eur Respir J 2018; 51 (01) 1800050
  • 12 Mañá J, Salazar A, Manresa F. Clinical factors predicting persistence of activity in sarcoidosis: a multivariate analysis of 193 cases. Respiration 1994; 61 (04) 219-225
  • 13 Mañá J, Badrinas F. Prognosis of sarcoidosis. An unresolved issue. Sarcoidosis 1992; 9 (01) 15-20
  • 14 Mañá J, Salazar A, Pujol R, Manresa F. Are the pulmonary function tests and the markers of activity helpful to establish the prognosis of sarcoidosis?. Respiration 1996; 63 (05) 298-303
  • 15 Mañá J, Rubio-Rivas M, Villalba N. , et al. Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis: cohort study of a 40-year clinical experience at a tertiary referral center in Barcelona, Spain. Medicine (Baltimore) 2017; 96 (29) e7595
  • 16 Pérez-Alvarez R, Brito-Zerón P, Kostov B. , et al; SarcoGEAS-SEMI Registry. Systemic phenotype of sarcoidosis associated with radiological stages. Analysis of 1230 patients. Eur J Intern Med 2019; 69: 77-85
  • 17 Baughman RP, Lower EE. Features of sarcoidosis associated with chronic disease. Sarcoidosis Vasc Diffuse Lung Dis 2015; 31 (04) 275-281
  • 18 Schupp JC, Freitag-Wolf S, Bargagli E. , et al. Phenotypes of organ involvement in sarcoidosis. Eur Respir J 2018; 51 (01) 1700991
  • 19 Rubio-Rivas M, Franco J, Corbella X. Sarcoidosis presenting with and without Löfgren' s syndrome: clinical, radiological and behavioral differences observed in a group of 691 patients. Joint Bone Spine 2019; 87 (02) 141-147
  • 20 Sauer WH, Stern BJ, Baughman RP, Culver DA, Royal W. High-risk sarcoidosis. Current concepts and research imperatives. Ann Am Thorac Soc 2017; 14 (Suppl. 06) S437-S444
  • 21 Wojciech J. Piotrowski. Prognostic Factors in Sarcoidosis, Sarcoidosis Diagnosis and Management, Prof. Mohammad Hosein Kalantar Motamedi (Ed.), ISBN: 978-953-307-414-6, InTech; 2011: Available from: http://www.intechopen.com/books/sarcoidosis-diagnosis-and-management/prognostic-factors-in-sarcoidosis Rijeka, Croatia
  • 22 Baughman RP, Costabel U, du Bois RM. Treatment of sarcoidosis. Clin Chest Med 2008; 29 (03) 533-548
  • 23 Grunewald J. Review: role of genetics in susceptibility and outcome of sarcoidosis. Semin Respir Crit Care Med 2010; 31 (04) 380-389
  • 24 Judson MA. Strategies for identifying pulmonary sarcoidosis patients at risk for severe or chronic disease. Expert Rev Respir Med 2017; 11 (02) 111-118
  • 25 Siltzbach LE, James DG, Neville E. , et al. Course and prognosis of sarcoidosis around the world. Am J Med 1974; 57 (06) 847-852
  • 26 Walsh SL, Wells AU, Sverzellati N. , et al. An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study. Lancet Respir Med 2014; 2 (02) 123-130
  • 27 Judson MA, Boan AD, Lackland DT. The clinical course of sarcoidosis: presentation, diagnosis, and treatment in a large white and black cohort in the United States. Sarcoidosis Vasc Diffuse Lung Dis 2012; 29 (02) 119-127
  • 28 Le V, Crouser ED. Sarcoidosis models: past, present, and future. In: Baughman RP, Valeyre D. , eds. Sarcoidosis—A Clinician's Guide. St. Louis, Missouri, EUA: Elsevier; 2019: 67-73
  • 29 Grunewald J, Eklund A. Sex-specific manifestations of Löfgren's syndrome. Am J Respir Crit Care Med 2007; 175 (01) 40-44
  • 30 Baughman RP, Teirstein AS, Judson MA. , et al; Case Control Etiologic Study of Sarcoidosis (ACCESS) research group. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164 (10 Pt 1): 1885-1889
  • 31 Judson MA, Baughman RP, Thompson BW. , et al; ACCESS Research Group. Two year prognosis of sarcoidosis: the ACCESS experience. Sarcoidosis Vasc Diffuse Lung Dis 2003; 20 (03) 204-211
  • 32 Silva AL, Melo N, Caetano Mota P. , et al. Pulmonary sarcoidosis: prognostic factors at diagnosis in patients from North of Portugal. Reumatol Clin 2018; (e-pub ahead of print) DOI: 10.1016/j.reuma.2018.10.004.
  • 33 Takada K, Ina Y, Noda M, Sato T, Yamamoto M, Morishita M. The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis. J Clin Epidemiol 1993; 46 (04) 359-366
  • 34 Loddenkemper R, Kloppenborg A, Schoenfeld N, Grosser H, Costabel U. Clinical findings in 715 patients with newly detected pulmonary sarcoidosis—results of a cooperative study in former West Germany and Switzerland. WATL Study Group. Wissenschaftliche Arbeitsgemeinschaft für die Therapie von Lungenkrankheitan. Sarcoidosis Vasc Diffuse Lung Dis 1998; 15 (02) 178-182
  • 35 Lofgren S, Lundback H. The bilateral hilar lymphoma syndrome; a study of the relation to age and sex in 212 cases. Acta Med Scand 1952; 142 (04) 259-264
  • 36 Karakaya B, Kaiser Y, van Moorsel CHM, Grunewald J. Löfgren's syndrome: diagnosis, management, and disease pathogenesis. Semin Respir Crit Care Med 2017; 38 (04) 463-476
  • 37 Brown F, Tanner LS. Lofgren syndrome. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing: NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health; 2019
  • 38 Mañá J, Gómez-Vaquero C, Montero A. , et al. Löfgren's syndrome revisited: a study of 186 patients. Am J Med 1999; 107 (03) 240-245
  • 39 Löfgren S. Primary pulmonary sarcoidosis. II. Clinical course and prognosis. Acta Med Scand 1953; 145 (06) 465-474
  • 40 Löfgren S. Primary pulmonary sarcoidosis. I. Early signs and symptoms. Acta Med Scand 1953; 145 (06) 424-431
  • 41 Grunewald J. HLA associations and Löfgren's syndrome. Expert Rev Clin Immunol 2012; 8 (01) 55-62
  • 42 Scadding JG. Prognosis of intrathoracic sarcoidosis in England. A review of 136 cases after five years' observation. BMJ 1961; 2 (5261): 1165-1172
  • 43 Spagnolo P. Genetics of sarcoidosis. In: Baughman RP, Valeyre D. , eds. Sarcoidosis—A Clinician's Guide. St. Louis, Missouri, EUA: Elsevier; 2019: 55-66
  • 44 Sato H, Grutters JC, Pantelidis P. , et al. HLA-DQB1*0201: a marker for good prognosis in British and Dutch patients with sarcoidosis. Am J Respir Cell Mol Biol 2002; 27 (04) 406-412
  • 45 Grunewald J, Eklund A. Löfgren's syndrome: human leukocyte antigen strongly influences the disease course. Am J Respir Crit Care Med 2009; 179 (04) 307-312
  • 46 Spagnolo P, Renzoni EA, Wells AU. , et al. C-C chemokine receptor 2 and sarcoidosis: association with Lofgren's syndrome. Am J Respir Crit Care Med 2003; 168 (10) 1162-1166
  • 47 Grunewald J, Idali F, Kockum I. , et al. Major histocompatibility complex class II transactivator gene polymorphism: associations with Löfgren's syndrome. Tissue Antigens 2010; 76 (02) 96-101
  • 48 Judson MA, Costabel U, Drent M. , et al. The WASOG sarcoidosis organ assessment instrument: an update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis 2014; 31 (01) 19-27
  • 49 Judson MA, Thompson BW, Rabin DL. , et al; ACCESS Research Group. The diagnostic pathway to sarcoidosis. Chest 2003; 123 (02) 406-412
  • 50 Müller NL, Mawson JB, Mathieson JR, Abboud R, Ostrow DN, Champion P. Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings. Radiology 1989; 171 (03) 613-618
  • 51 Nunes H, Brillet PY, Valeyre D, Brauner MW, Wells AU. Imaging in sarcoidosis. Semin Respir Crit Care Med 2007; 28 (01) 102-120
  • 52 de Kleijn WP, Elfferich MD, De Vries J. , et al. Fatigue in sarcoidosis: American versus Dutch patients. Sarcoidosis Vasc Diffuse Lung Dis 2009; 26 (02) 92-97
  • 53 Drent M, Strookappe B, Hoitsma E, De Vries J. Consequences of sarcoidosis. Clin Chest Med 2015; 36 (04) 727-737
  • 54 Judson MA. Parasarcoidosis syndromes. In: Baughman RP, Valeyre D. , eds. Sarcoidosis—A Clinician's Guide. St. Louis, Missouri, EUA: Elsevier; 2019: 167-177
  • 55 De Vries J, Michielsen H, Van Heck GL, Drent M. Measuring fatigue in sarcoidosis: the fatigue assessment scale (FAS). Br J Health Psychol 2004; 9 (Pt 3): 279-291
  • 56 Bosse-Henck A, Koch R, Wirtz H, Hinz A. Fatigue and excessive daytime sleepiness in sarcoidosis: prevalence, predictors, and relationships between the two symptoms. Respiration 2017; 94 (02) 186-197
  • 57 Drent M, Lower EE, De Vries J. Sarcoidosis-associated fatigue. Eur Respir J 2012; 40 (01) 255-263
  • 58 Sharp M, Brown T, Chen E, Rand CS, Moller DR, Eakin MN. Psychological burden associated with worse clinical outcomes in sarcoidosis. BMJ Open Respir Res 2019; 6 (01) e000467
  • 59 Hinz A, Brähler E, Möde R, Wirtz H, Bosse-Henck A. Anxiety and depression in sarcoidosis: the influence of age, gender, affected organs, concomitant diseases and dyspnea. Sarcoidosis Vasc Diffuse Lung Dis 2012; 29 (02) 139-146
  • 60 Korsten P, Strohmayer K, Baughman RP, Sweiss NJ. Refractory pulmonary sarcoidosis—proposal of a definition and recommendations for the diagnostic and therapeutic approach. Clin Pulm Med 2016; 23 (02) 67-75
  • 61 Judson MA, Preston S, Hu K. , et al. Quantifying the relationship between symptoms at presentation and the prognosis of sarcoidosis. Respir Med 2019; 152: 14-19
  • 62 Baughman RP, Judson MA, Teirstein A. , et al. Presenting characteristics as predictors of duration of treatment in sarcoidosis. QJM 2006; 99 (05) 307-315
  • 63 Doubková M, Pospíšil Z, Skřičková J, Doubek M. Prognostic markers of sarcoidosis: an analysis of patients from everyday pneumological practice. Clin Respir J 2015; 9 (04) 443-449
  • 64 Baughman RP, Lower EE. Who dies from sarcoidosis and why?. Am J Respir Crit Care Med 2011; 183 (11) 1446-1447
  • 65 Prasse A, Katic C, Germann M, Buchwald A, Zissel G, Müller-Quernheim J. Phenotyping sarcoidosis from a pulmonary perspective. Am J Respir Crit Care Med 2008; 177 (03) 330-336
  • 66 Rodrigues SC, Rocha NA, Lima MS. , et al. Factor analysis of sarcoidosis phenotypes at two referral centers in Brazil. Sarcoidosis Vasc Diffuse Lung Dis 2011; 28 (01) 34-43
  • 67 Castro MDC, Pereira CAC, Soares MR. A Simple Multidimensional Score to Predict the Clinical Course of Sarcoidosis in the Initial Evaluation: [Ph.D. Dissertation]. São Paulo: Division of Respiratory Diseases, Department of Medicine, Federal University of São Paulo (UNIFESP); 2017
  • 68 Rodrigues MM, Coletta EN, Ferreira RG, Pereira CA. Delayed diagnosis of sarcoidosis is common in Brazil. J Bras Pneumol 2013; 39 (05) 539-546
  • 69 Guleria R, Mahashur A, Ghoshal AG, Thomas PK, Raghu G, Baughman RP. Challenges in diagnosing sarcoidosis in tuberculosis endemic regions: clinical scenario in India. Sarcoidosis Vasc Diffuse Lung Dis 2016; 33 (04) 381-384
  • 70 Agrawal R, Kee AR, Ang L. , et al. Tuberculosis or sarcoidosis: opposite ends of the same disease spectrum?. Tuberculosis (Edinb) 2016; 98: 21-26