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Diagnosis of Sarcoidosis

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Abstract

The diagnosis of sarcoidosis, a systemic granulomatous disease, is based on a compatible clinical–radiological picture and the histological evidence of noncaseating granulomas. Other diseases mimicking sarcoidosis, mostly infections and other granulomatoses, have to be excluded. There is no single test for sarcoidosis, and the presence of granulomas alone does not establish the diagnosis. Symptoms of sarcoidosis are not specific and can be markedly different according to organ involvement and disease course. Respiratory symptoms and fatigue are the most common symptoms at any stage of disease. Histological confirmation is not needed for Löfgren’s or Heerfordt’s syndrome and asymptomatic bihilar lymphadenopathy. The radiological staging system is still based on chest radiography, and computed tomography is not mandatory for routine follow-up. 18F-fluorodeoxyglucose positron emission tomography may be of value in special cases. For assessment of lung involvement and follow-up, pulmonary function tests are necessary with vital capacity being the most important single parameter and diffusion capacity the most sensitive. Bronchoscopy with biopsy is the most common procedure for detection of granulomas, when there is no easier biopsy site like skin or peripheral lymph nodes. Endobronchial ultrasonography-guided transbronchial needle aspiration has replaced mediastinoscopy for evaluation of mediastinal and hilar lymph nodes with a high diagnostic yield. Despite numerous studies, no single biomarker can be reliably used for correct diagnosis or exclusion of sarcoidosis. Genetic testing, despite promising advances, has still not been included in routine care for sarcoidosis patients. The long-term prognosis of sarcoidosis depends on the different organ manifestations: Cardiac or central nervous involvement, together with respiratory complications, is critical. A multidisciplinary approach is necessary for comprehensive care of the sarcoidosis patient.

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References

  1. Hunninghake GW, Costabel U, Ando M et al (1999) ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis 16:149–173

    CAS  PubMed  Google Scholar 

  2. Pietinalho A, Ohmichi M, Lofroos AB, Hiraga Y, Selroos O (2000) The prognosis of pulmonary sarcoidosis in Finland and Hokkaido, Japan. A comparative five-year study of biopsy-proven cases. Sarcoidosis Vasc Diffuse Lung Dis 17:158–166

    CAS  PubMed  Google Scholar 

  3. Reich JM, Brouns MC, O'Connor EA, Edwards MJ (1998) Mediastinoscopy in patients with presumptive stage I sarcoidosis: a risk/benefit, cost/benefit analysis. Chest 113:147–153

    Article  CAS  PubMed  Google Scholar 

  4. Patel AS, Siegert RJ, Creamer D et al (2013) The development and validation of the King's Sarcoidosis Questionnaire for the assessment of health status. Thorax 68:57–65

    Article  PubMed  Google Scholar 

  5. De Vries J, Michielsen H, Van Heck GL, Drent M (2004) Measuring fatigue in sarcoidosis: the Fatigue Assessment Scale (FAS). Br J Health Psychol 9:279–291

    Article  PubMed  Google Scholar 

  6. de Kleijn WP, De Vries J, Wijnen PA, Drent M (2011) Minimal (clinically) important differences for the Fatigue Assessment Scale in sarcoidosis. Respir Med 105:1388–1395

    Article  PubMed  Google Scholar 

  7. Wurm K (1960) Die Bedeutung der Stadieneinteilung der Sarkoidose (Morbus Boeck). Dtsch Med Wochenschr 85:1541–1548

    Article  CAS  PubMed  Google Scholar 

  8. Scadding JG (1961) Prognosis of intrathoracic sarcoidosis in England. A review of 136 cases after five years' observation. Br Med J 2:1165–1172

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Walsh SL, Wells AU, Sverzellati N et al (2014) An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study. Lancet Respir Med 2:123–130

    Article  PubMed  Google Scholar 

  10. Mostard RL, van Kroonenburgh MJ, Drent M (2013) The role of the PET scan in the management of sarcoidosis. Curr Opin Pulm Med 19:538–544

    Article  PubMed  Google Scholar 

  11. Mostard RL, Voo S, van Kroonenburgh MJ et al (2011) Inflammatory activity assessment by F18 FDG-PET/CT in persistent symptomatic sarcoidosis. Respir Med 105:1917–1924

    Article  CAS  PubMed  Google Scholar 

  12. Mostard RL, Van Kuijk SM, Verschakelen JA et al (2012) A predictive tool for an effective use of (18)F-FDG PET in assessing activity of sarcoidosis. BMC Pulm Med 12:57

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Teirstein AS, Machac J, Almeida O, Lu P, Padilla ML, Iannuzzi MC (2007) Results of 188 whole-body fluorodeoxyglucose positron emission tomography scans in 137 patients with sarcoidosis. Chest 132:1949–1953

    Article  PubMed  Google Scholar 

  14. Boros PW, Enright PL, Quanjer PH, Borsboom GJ, Wesolowski SP, Hyatt RE (2010) Impaired lung compliance and DL, CO but no restrictive ventilatory defect in sarcoidosis. Eur Respir J 36:1315–1322

    Article  CAS  PubMed  Google Scholar 

  15. Martusewicz-Boros MM, Boros WP, Wiatr E, Wesolowski S, Roszkowski-Sliz K (2012) Bronchial hyperreactivity in sarcoidosis patients: correlation with airflow limitation indices. Sarcoidosis Vasc Diffuse Lung Dis 29:99–106

    CAS  PubMed  Google Scholar 

  16. Young LM, Good N, Milne D, Zeng I, Kolbe J, Wilsher ML (2012) The prevalence and predictors of airway hyperresponsiveness in sarcoidosis. Respirology 17:653–659

    Article  PubMed  Google Scholar 

  17. Bonella F, Ohshimo S, Bauer PC, Guzman J, Costabel U Bronchoalveolar lavage. Eur Respir Soc Monogr 48 (Interventional Pulmonology): 59–72

  18. Zaiss AW, Costabel U, Wagner DJ, Baur R, Ruhle KH, Matthys H (1988) T4/T8 ratio in bronchoalveolar lavage fluid: sensitivity and specificity for the diagnosis of sarcoidosis. Prax Klin Pneumol 42(Suppl 1):233–234

    PubMed  Google Scholar 

  19. Winterbauer RH, Lammert J, Selland M, Wu R, Corley D, Springmeyer SC (1993) Bronchoalveolar lavage cell populations in the diagnosis of sarcoidosis. Chest 104:352–361

    Article  CAS  PubMed  Google Scholar 

  20. Costabel U, Ohshimo S, Guzman J (2008) Diagnosis of sarcoidosis. Curr Opin Pulm Med 14:455–461

    Article  CAS  PubMed  Google Scholar 

  21. Selroos O (1976) Fine-needle aspiration biopsy of the spleen in diagnosis of sarcoidosis. Ann N Y Acad Sci 278:517–521

    Article  CAS  PubMed  Google Scholar 

  22. Crick R, Hoyle C, Mather G (1955) Conjunctival biopsy in sarcoidosis. Br Med J 2:1180–1181

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Gilman MJ, Wang KP (1980) Transbronchial lung biopsy in sarcoidosis. An approach to determine the optimal number of biopsies. Am Rev Respir Dis 122:721–724

    CAS  PubMed  Google Scholar 

  24. Koonitz CH, Joyner LR, Nelson RA (1976) Transbronchial lung biopsy via the fiberoptic bronchoscope in sarcoidosis. Ann Intern Med 85:64–66

    Article  CAS  PubMed  Google Scholar 

  25. von Bartheld MB, Dekkers OM, Szlubowski A et al (2013) Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial. JAMA 309:2457–2464

    Article  Google Scholar 

  26. Goyal A, Gupta D, Agarwal R, Bal A, Nijhawan R, Aggarwal AN (2014) Value of different bronchoscopic sampling techniques in diagnosis of sarcoidosis: a prospective study of 151 patients. J Bronchology Interv Pulmonol 21:220–226

    Article  PubMed  Google Scholar 

  27. Wong M, Yasufuku K, Nakajima T et al (2007) Endobronchial ultrasound: new insight for the diagnosis of sarcoidosis. Eur Respir J 29:1182–1186

    Article  CAS  PubMed  Google Scholar 

  28. Costabel U, Bonella F, Ohshimo S, Guzman J (2010) Diagnostic modalities in sarcoidosis: BAL, EBUS, and PET. Semin Respir Crit Care Med 31:404–408

    Article  PubMed  Google Scholar 

  29. Plit ML, Havryk AP, Hodgson A et al (2013) Rapid cytological analysis of endobronchial ultrasound-guided aspirates in sarcoidosis. Eur Respir J 42:1302–1308

    Article  PubMed  Google Scholar 

  30. Studdy PR, Lapworth R, Bird R (1983) Angiotensin-converting enzyme and its clinical significance—a review. J Clin Pathol 36:938–947

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Kruit A, Grutters JC, Gerritsen WB et al (2007) ACE I/D-corrected Z-scores to identify normal and elevated ACE activity in sarcoidosis. Respir Med 101:510–515

    Article  PubMed  Google Scholar 

  32. Grutters JC, Fellrath JM, Mulder L, Janssen R, van den Bosch JM, van Velzen-Blad H (2003) Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation. Chest 124:186–195

    Article  CAS  PubMed  Google Scholar 

  33. Bargagli E, Bennett D, Maggiorelli C et al (2013) Human chitotriosidase: a sensitive biomarker of sarcoidosis. J Clin Immunol 33:264–270

    Article  CAS  PubMed  Google Scholar 

  34. Su R, Nguyen ML, Agarwal MR et al (2013) Interferon-inducible chemokines reflect severity and progression in sarcoidosis. Respir Res 14:121

    Article  PubMed Central  PubMed  Google Scholar 

  35. Baba Y, Kubo T, Kitaoka H et al (2012) Usefulness of high-sensitive cardiac troponin T for evaluating the activity of cardiac sarcoidosis. Int Heart J 53:287–292

    Article  CAS  PubMed  Google Scholar 

  36. Miyoshi S, Hamada H, Kadowaki T et al (2010) Comparative evaluation of serum markers in pulmonary sarcoidosis. Chest 137:1391–1397

    Article  CAS  PubMed  Google Scholar 

  37. Honda K, Okada F, Ando Y et al (2011) Comparison of pulmonary thin section CT findings and serum KL-6 levels in patients with sarcoidosis. Br J Radiol 84:229–235

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Janssen R, Sato H, Grutters JC et al (2003) Study of Clara cell 16, KL-6, and surfactant protein-D in serum as disease markers in pulmonary sarcoidosis. Chest 124:2119–2125

    Article  CAS  PubMed  Google Scholar 

  39. Grunewald J, Eklund A, Olerup O (2004) Human leukocyte antigen class I alleles and the disease course in sarcoidosis patients. Am J Respir Crit Care Med 169:696–702

    Article  PubMed  Google Scholar 

  40. Grunewald J, Brynedal B, Darlington P et al (2010) Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients. Respir Res 11:25

    Article  PubMed Central  PubMed  Google Scholar 

  41. Valentonyte R, Hampe J, Huse K et al (2005) Sarcoidosis is associated with a truncating splice site mutation in BTNL2. Nat Genet 37:357–364

    Article  CAS  PubMed  Google Scholar 

  42. Zhou T, Zhang W, Sweiss NJ et al (2012) Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis. PLoS One 7:e44818

    Article  PubMed Central  PubMed  Google Scholar 

  43. Hiraga H, Yuwai K, Hiroe M (1993) Guideline for diagnosis of cardiac sarcoidosis: study report on diffuse pulmonary diseases. The Japanese Ministry of Health and Welfare. pp 23–24

  44. Judson MA, Costabel U, Drent M et al (2014) The WASOG Sarcoidosis Organ Assessment Instrument: an update of a previous clinical tool. Sarcoidosis Vasc Diffuse Lung Dis 31:19–27

    PubMed  Google Scholar 

  45. Birnie DH, Sauer WH, Bogun F et al (2014) HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 11:1305–1323

    Article  PubMed  Google Scholar 

  46. Ohira H, Tsujino I, Ishimaru S et al (2008) Myocardial imaging with 18 F-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis. Eur J Nucl Med Mol Imaging 35:933–941

    Article  PubMed  Google Scholar 

  47. Youssef G, Leung E, Mylonas I et al (2012) The use of 18 F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaanalysis including the Ontario experience. J Nucl Med 53:241–248

    Article  CAS  PubMed  Google Scholar 

  48. Watanabe E, Kimura F, Nakajima T et al (2013) Late gadolinium enhancement in cardiac sarcoidosis: characteristic magnetic resonance findings and relationship with left ventricular function. J Thorac Imaging 28:60–66

    Article  PubMed  Google Scholar 

  49. Blankstein R, Osborne M, Naya M et al (2014) Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 63:329–336

    Article  PubMed Central  PubMed  Google Scholar 

  50. Hoitsma E, Faber CG, Drent M, Sharma OP (2004) Neurosarcoidosis: a clinical dilemma. Lancet Neurol 3:397–407

    Article  PubMed  Google Scholar 

  51. Hebel R, Dubaniewicz-Wybieralska M, Dubaniewicz A (2015) Overview of neurosarcoidosis: recent advances. J Neurol 262: 258-267

  52. Iwai K, Tachibana T, Takemura T, Matsui Y, Kitaichi M, Kawabata Y (1993) Pathological studies on sarcoidosis autopsy. I. Epidemiological features of 320 cases in Japan. Acta Pathol Jpn 43:372–376

    CAS  PubMed  Google Scholar 

  53. Agnihotri SP, Singhal T, Stern BJ, Cho TA (2014) Neurosarcoidosis. Semin Neurol 34:386–394

    Article  PubMed  Google Scholar 

  54. Heij L, Dahan A, Hoitsma E (2012) Sarcoidosis and pain caused by small-fiber neuropathy. Pain Res Treat 2012:256024

    PubMed Central  PubMed  Google Scholar 

  55. Hoitsma E, Drent M, Sharma OP (2010) A pragmatic approach to diagnosing and treating neurosarcoidosis in the 21st century. Curr Opin Pulm Med 16:472–479

    Article  PubMed  Google Scholar 

  56. Hoitsma E, Marziniak M, Faber CG et al (2002) Small fibre neuropathy in sarcoidosis. Lancet 359:2085–2086

    Article  CAS  PubMed  Google Scholar 

  57. Hoitsma E, Reulen JP, de Baets M, Drent M, Spaans F, Faber CG (2004) Small fiber neuropathy: a common and important clinical disorder. J Neurol Sci 227:119–130

    Article  CAS  PubMed  Google Scholar 

  58. Segal BM (2013) Neurosarcoidosis: diagnostic approaches and therapeutic strategies. Curr Opin Neurol 26:307–313

    Article  CAS  PubMed  Google Scholar 

  59. Wengert O, Rothenfusser-Korber E, Vollrath B et al (2013) Neurosarcoidosis: correlation of cerebrospinal fluid findings with diffuse leptomeningeal gadolinium enhancement on MRI and clinical disease activity. J Neurol Sci 335:124–130

    Article  PubMed  Google Scholar 

  60. Wasfi YS, Rose CS, Murphy JR et al (2006) A new tool to assess sarcoidosis severity. Chest 129:1234–1245

    Article  PubMed  Google Scholar 

  61. Oki M, Saka H, Kitagawa C et al (2007) Real-time endobronchial ultrasound-guided transbronchial needle aspiration is useful for diagnosing sarcoidosis. Respirology 12:863–868

    Article  PubMed  Google Scholar 

  62. Garwood S, Judson MA, Silvestri G, Hoda R, Fraig M, Doelken P (2007) Endobronchial ultrasound for the diagnosis of pulmonary sarcoidosis. Chest 132:1298–1304

    Article  PubMed  Google Scholar 

  63. Tremblay A, Stather DR, Maceachern P, Khalil M, Field SK (2009) A randomized controlled trial of standard vs endobronchial ultrasonography-guided transbronchial needle aspiration in patients with suspected sarcoidosis. Chest 136:340–346

    Article  PubMed  Google Scholar 

  64. Baughman RP, Culver DA, Judson MA (2011) A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med 183:573–581

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Conflict of Interest

T.E. Wessendorf, F. Bonella, and U. Costabel declare that they have no conflict of interest.

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Authors and Affiliations

  1. Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University Duisburg-Essen, Tüschener Weg 40, 45239, Essen, Germany

    Thomas E. Wessendorf, Francesco Bonella & Ulrich Costabel

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  1. Thomas E. Wessendorf
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  2. Francesco Bonella
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  3. Ulrich Costabel
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Correspondence to Thomas E. Wessendorf.

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Wessendorf, T.E., Bonella, F. & Costabel, U. Diagnosis of Sarcoidosis. Clinic Rev Allerg Immunol 49, 54–62 (2015). https://doi.org/10.1007/s12016-015-8475-x

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