Internal and Emergency Medicine

, Volume 13, Issue 3, pp 325–331 | Cite as

Sarcoidosis: a review for the internist

  • Elena BargagliEmail author
  • Antje Prasse


Sarcoidosis is a systemic granulomatous lung disease of unknown origin affecting people of any age, mainly young adults. The disease is extremely heterogeneous with an unpredictable clinical course. Different phenotypes have been identified: an acute syndrome can be distinguished from subacute and chronic variants. About 20% of patients are chronically progressive and may develop lung fibrosis. Sarcoidosis usually involves the lungs and thoracic lymph nodes, although the skin, eyes, bones, liver, spleen, heart, upper respiratory tract and nervous system can also be affected. No reliable indicators of clinical outcome are available, and there is no single serological biomarker with demonstrated unequivocal diagnostic and prognostic value. Diagnosis requires histological confirmation although a presumptive diagnosis may be acceptable in special conditions. This review examines the diagnostic approach to sarcoidosis involving a multidisciplinary team of specialists in which the internist has the task of identifying all pulmonary and extrapulmonary localizations of the disease and of managing complications and comorbidities.


Sarcoidosis Diagnosis Clinical manifestations Internal medicine 



High-resolution computed tomography


Interstitial lung diseases


Lung function tests


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human and animal rights

This research does not involve humans or animals. It is a revision of the literature. The ethical standards have been respected.

Informed consent

For this type of study formal consent was not required therefore no informed consent was needed.


  1. 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 16:149–173PubMedGoogle Scholar
  2. 2.
    Moller DR, Chen ES (2002) Genetic basis of remitting sarcoidosis: triumph of the trimolecular complex? Am J Respir Cell Mol Biol 27:391–395CrossRefPubMedGoogle Scholar
  3. 3.
    Prior C, Knight RA, Herold M (1996) Pulmonary sarcoidosis: patterns of cytokine release in vitro. Eur Respir J 9:47–53CrossRefPubMedGoogle Scholar
  4. 4.
    Kouranos V, Jacob J, Wells AU (2015) Severe sarcoidosis. Clin Chest Med 36:715–726CrossRefPubMedGoogle Scholar
  5. 5.
    Duchemann B, Annesi-Maesano I, Jacobe de Naurois C, Sanyal S, Brillet PY, Brauner M, Kambouchner M, Huynh S, Naccache JM, Borie R, Piquet J, Mekinian A, Virally J, Uzunhan Y, Cadranel J, Crestani B, Fain O, Lhote F, Dhote R, Saidenberg-Kermanac’h N, Rosental PA, Valeyre D, Nunes H (2017) Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris. Eur Respir J 50(2):1602419. CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Chen ES, Song Z, Willett MH, Heine S, Yung RC, Liu MC, Groshong SD, Zhang Y, Tuder RM, Moller DR (2010) Serum amyloid A regulates granulomatous inflammation in sarcoidosis through Toll-like receptor-2. Am J Respir Crit Care Med 181:360–373CrossRefPubMedGoogle Scholar
  7. 7.
    Lieberman J, Schleissner LA, Nosal A, Sastre A, Mishkin FS (1983) Clinical correlations of serum angiotensin-converting enzyme (ACE) in sarcoidosis. A longitudinal study of serum ACE, 67gallium scans, chest roentgenograms, and pulmonary function. Chest 84:522–528CrossRefPubMedGoogle Scholar
  8. 8.
    Bargagli E, Mazzi A, Rottoli P (2008) Markers of inflammation in sarcoidosis: blood, urine, BAL, sputum, and exhaled gas. Clin Chest Med 29:445–458CrossRefPubMedGoogle Scholar
  9. 9.
    Landi C, Bargagli E, Carleo A et al (2015) A functional proteomics approach to the comprehension of sarcoidosis. J Proteom 128:375–387CrossRefGoogle Scholar
  10. 10.
    Bargagli E, Magi B, Olivieri C et al (2011) Analysis of serum amyloid A in sarcoidosis patients. Respir Med 105:775–778CrossRefPubMedGoogle Scholar
  11. 11.
    Ivanišević J, Kotur-Stevuljević J, Stefanović A et al (2016) Association of serum amyloid A and oxidative stress with paraoxonase 1 in sarcoidosis patients. Eur J Clin Investig 46:418–424CrossRefGoogle Scholar
  12. 12.
    Prasse A, Katic C, Germann M, Buchwald A, Zissel G, Müller-Quernheim J (2008) Phenotyping sarcoidosis from a pulmonary perspective. Am J Respir Crit Care Med 177(3):330–336CrossRefPubMedGoogle Scholar
  13. 13.
    Scadding JG (1961) Prognosis of intrathoracic sarcoidosis in England. BMJ 4:1165–1172CrossRefGoogle Scholar
  14. 14.
    Chaigne B, Guillevin L (2017) Vasculitis for the internist: focus on ANCA-associated vasculitis. Intern Emerg Med 12(5):577–585CrossRefPubMedGoogle Scholar
  15. 15.
    Elia F, Aprà F, Crupi V (2017) Understanding and improving decisions in clinical medicine (II): making sense of reasoning in practice. Intern Emerg Med (in press) Google Scholar
  16. 16.
    Grunewald J, Eklund A (2009) Lofgren’s syndrome: human leukocyte antigen strongly influences the disease course. Am J Respir Crit Care Med 179:307–312CrossRefPubMedGoogle Scholar
  17. 17.
    Govender P, Berman JS (2015) The diagnosis of sarcoidosis. Clin Chest Med 36(4):585–602CrossRefPubMedGoogle Scholar
  18. 18.
    Descamps V, Bouscarat F (2016) Cutaneous manifestations of sarcoidosis. Ann Dermatol Venereol 143(1):39–50CrossRefPubMedGoogle Scholar
  19. 19.
    Kingah P, Alam M, Chugh K, Kamholz J, Samavati L (2016) Role of pulmonary evaluation in diagnosis of neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 33(3):209–215PubMedGoogle Scholar
  20. 20.
    McDonnell MJ, Saleem MI, Wall D, Gilmartin JJ, Rutherford RM, O’Regan A (2016) Predictive value of C-reactive protein and clinically relevant baseline variables in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 33(4):331–340PubMedGoogle Scholar
  21. 21.
    Judson MA (2008) The diagnosis of sarcoidosis. Clin Chest Med 29:415–427CrossRefPubMedGoogle Scholar
  22. 22.
    Baughman RP, Papanikolaou I (2017) Current concepts regarding calcium metabolism and bone health in sarcoidosis. Curr Opin Pulm Med 23(5):476–481CrossRefPubMedGoogle Scholar
  23. 23.
    Minisola S, Cipriani C, Occhiuto M, Pepe J (2017) New anabolic therapies for osteoporosis. Intern Emerg Med 12(7):915–921CrossRefPubMedGoogle Scholar
  24. 24.
    Kefella H, Luther D, Hainline C (2017) Ophthalmic and neuro-ophthalmic manifestations of sarcoidosis. Curr Opin Pulm Med 28(6):587–594Google Scholar
  25. 25.
    Yang SJ, Salek S, Rosenbaum JT (2017) Ocular sarcoidosis: new diagnostic modalities and treatment. Curr Opin Pulm Med 23(5):458–467CrossRefPubMedGoogle Scholar
  26. 26.
    Velter C, Lipsker D (2016) Cutaneous panniculitis. Rev Med Intern 37(11):743–750CrossRefGoogle Scholar
  27. 27.
    Kluger N (2017) Cutaneous complications related to tattoos: 31 cases from Finland. Dermatology 233(1):100–109CrossRefPubMedGoogle Scholar
  28. 28.
    Tugal-Tutkun I (2017) Systemic vasculitis and the eye. Curr Opin Rheumatol 29(1):24–32CrossRefPubMedGoogle Scholar
  29. 29.
    Birnbaum AD, French DD, Mirsaeidi M, Wehrli S (2015) Sarcoidosis in the national veteran population: association of ocular inflammation and mortality. Ophthalmology 122(5):934–938CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Bargagli E, Olivieri C, Penza F, Bertelli P, Gonnelli S, Volterrani L, Rottoli P (2011) Rare localizations of bone sarcoidosis: two case reports and review of the literature. Rheumatol Int 31(11):1503–1506CrossRefPubMedGoogle Scholar
  31. 31.
    Carter JM, Howe BM, Inwards CY (2017) Conditions simulating primary bone neoplasms. Surg Pathol Clin 10(3):731–748CrossRefPubMedGoogle Scholar
  32. 32.
    Rottoli P, Bargagli E, Chidichimo C, Nuti D, Cintorino M, Ginanneschi C, Caruso G (2006) Sarcoidosis with upper respiratory tract involvement. Respir Med 100(2):253–257CrossRefPubMedGoogle Scholar
  33. 33.
    Morgenthau AS, Teirstein AS (2011) Sarcoidosis of the upper and lower airways. Expert Rev Respir Med 5(6):823–833CrossRefPubMedGoogle Scholar
  34. 34.
    Agrawal A, Sahni S, Iftikhar A, Talwar A (2015) Pulmonary manifestations of renal cell carcinoma. Respir Med 109(12):1505–1508CrossRefPubMedGoogle Scholar
  35. 35.
    Mehta D, Lubitz SA, Frankel Z, Wisnivesky JP, Einstein AJ, Goldman M, Machac J, Teirstein A (2008) Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value of outpatient testing. Chest 133:1426–1435CrossRefPubMedGoogle Scholar
  36. 36.
    Smedema JP, Snoep G, van Kroonenburgh MP, van Geuns RJ, Dassen WR, Gorgels AP, Crijns HJ (2005) Cardiac involvement in patients with pulmonary sarcoidosis assessed at two university medical centers in the Netherlands. Chest 128:30–35CrossRefPubMedGoogle Scholar
  37. 37.
    Culver DA, Ribeiro Neto ML, Moss BP, Willis MA (2017) Neurosarcoidosis. Semin Respir Crit Care Med 38(4):499–513CrossRefPubMedGoogle Scholar
  38. 38.
    Ogawa Y, Saraya T, Fujiwara M, Takizawa H (2017) Massive neurosarcoidosis. Intern Med 56(18):2537–2538CrossRefPubMedCentralPubMedGoogle Scholar
  39. 39.
    Hebel R, Dubaniewicz-Wybieralska M, Dubaniewicz A (2015) Overview of neurosarcoidosis: recent advances. J Neurol 262(2):258–267CrossRefPubMedGoogle Scholar
  40. 40.
    Said G (2013) Sarcoidosis of the peripheral nervous system. Handb Clin Neurol 013(115):485–495CrossRefGoogle Scholar
  41. 41.
    Levitt DG, Levitt MD (2017) Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states. Clin Exp Gastroenterol 10:147–168CrossRefPubMedCentralPubMedGoogle Scholar
  42. 42.
    Cunha BA, Sivarajah T, Jimada I (2017) Sarcoidosis with fever and a splenic infarct due to CMV or lymphoma? Heart Lung 46(5):394–396CrossRefPubMedGoogle Scholar
  43. 43.
    Baratto L, Park SY, Hatami N, Davidzon G, Srinivas S, Gambhir SS, Iagaru A (2017) 18F-FDG silicon photomultiplier PET/CT: a pilot study comparing semi-quantitative measurements with standard PET/CT. PLoS One 12(6):e0178936CrossRefPubMedCentralPubMedGoogle Scholar
  44. 44.
    Silva M, Nunes H, Valeyre D, Sverzellati N (2015) Imaging of sarcoidosis. Clin Rev Allergy Immunol 49(1):45–53CrossRefPubMedGoogle Scholar
  45. 45.
    Al-Kofahi K, Korsten P, Ascoli C, Virupannavar S, Mirsaeidi M, Chang I, Qaqish N, Saketkoo LA, Baughman RP, Sweiss NJ (2016) Management of extrapulmonary sarcoidosis: challenges and solutions. Ther Clin Risk Manag 12:1623–1634CrossRefPubMedCentralPubMedGoogle Scholar
  46. 46.
    Fang C, Huang H, Xu Z (2016) Immunological evidence for the role of mycobacteria in sarcoidosis: a meta-analysis. PLoS One 11(8):e0154716CrossRefPubMedCentralPubMedGoogle Scholar
  47. 47.
    Tyan CC, Machuca T, Czarnecka K, Ko HM, da Cunha Santos G, Boerner SL, Pierre A, Cypel M, Waddell T, Darling G, de Perrot M, Keshavjee S, Geddie W, Yasufuku K (2017) Performance of endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of isolated mediastinal and hilar lymphadenopathy. Respiration 94(5):457–464CrossRefPubMedGoogle Scholar
  48. 48.
    Ramachandraiah V, Aronow W, Chandy D (2017) Pulmonary sarcoidosis: an update. Postgrad Med 129(1):149–158CrossRefPubMedGoogle Scholar
  49. 49.
    Presotto L, Busnardo E, Gianolli L, Bettinardi V (2016) An update on technical and methodological aspects for cardiac PET applications. Q J Nucl Med Mol Imaging 60(4):285–307PubMedGoogle Scholar
  50. 50.
    Mortaz E, Rezayat F, Amani D, Kiani A, Garssen J, Adcock IM, Velayati A (2016) The roles of T helper 1, T helper 17 and regulatory T cells in the pathogenesis of sarcoidosis. Iran J Allergy Asthma Immunol 15(4):334–339PubMedGoogle Scholar
  51. 51.
    Mortaz E, Gudarzi H, Tabarsi P, Adcock IM, Masjedi MR, Jamaati HR, Garssen J, Velayati AA, Redegeld FA (2015) Flow cytometry applications in the study of immunological lung disorders. Iran J Allergy Asthma Immunol 14(1):12–18PubMedGoogle Scholar
  52. 52.
    Bargagli E, Bennett D, Maggiorelli C et al (2013) Human chitotriosidase: a sensitive biomarker of sarcoidosis. J Clin Immunol 33:264–270CrossRefPubMedGoogle Scholar

Copyright information

© SIMI 2018

Authors and Affiliations

  1. 1.Respiratory Medicine, Department of Clinical and Experimental Medicine, Department of Clinical and Experimental Biomedical SciencesUniversity Hospital Careggi (AOUC)FlorenceItaly
  2. 2.Medizinische Hochschule HannoverHannoverGermany

Personalised recommendations