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Sarcoidosis: a review for the internist

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Abstract

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.

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Abbreviations

HRCT:

High-resolution computed tomography

ILD:

Interstitial lung diseases

LFT:

Lung function tests

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. Moller DR, Chen ES (2002) Genetic basis of remitting sarcoidosis: triumph of the trimolecular complex? Am J Respir Cell Mol Biol 27:391–395

    Article  CAS  PubMed  Google Scholar 

  3. Prior C, Knight RA, Herold M (1996) Pulmonary sarcoidosis: patterns of cytokine release in vitro. Eur Respir J 9:47–53

    Article  CAS  PubMed  Google Scholar 

  4. Kouranos V, Jacob J, Wells AU (2015) Severe sarcoidosis. Clin Chest Med 36:715–726

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1183/13993003.02419-2016

    Article  PubMed Central  PubMed  Google Scholar 

  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 181:360–373

    Article  CAS  PubMed  Google Scholar 

  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 84:522–528

    Article  CAS  PubMed  Google Scholar 

  8. Bargagli E, Mazzi A, Rottoli P (2008) Markers of inflammation in sarcoidosis: blood, urine, BAL, sputum, and exhaled gas. Clin Chest Med 29:445–458

    Article  CAS  PubMed  Google Scholar 

  9. Landi C, Bargagli E, Carleo A et al (2015) A functional proteomics approach to the comprehension of sarcoidosis. J Proteom 128:375–387

    Article  CAS  Google Scholar 

  10. Bargagli E, Magi B, Olivieri C et al (2011) Analysis of serum amyloid A in sarcoidosis patients. Respir Med 105:775–778

    Article  CAS  PubMed  Google Scholar 

  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 46:418–424

    Article  Google Scholar 

  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):330–336

    Article  CAS  PubMed  Google Scholar 

  13. Scadding JG (1961) Prognosis of intrathoracic sarcoidosis in England. BMJ 4:1165–1172

    Article  Google Scholar 

  14. Chaigne B, Guillevin L (2017) Vasculitis for the internist: focus on ANCA-associated vasculitis. Intern Emerg Med 12(5):577–585

    Article  PubMed  Google Scholar 

  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)

  16. Grunewald J, Eklund A (2009) Lofgren’s syndrome: human leukocyte antigen strongly influences the disease course. Am J Respir Crit Care Med 179:307–312

    Article  PubMed  Google Scholar 

  17. Govender P, Berman JS (2015) The diagnosis of sarcoidosis. Clin Chest Med 36(4):585–602

    Article  PubMed  Google Scholar 

  18. Descamps V, Bouscarat F (2016) Cutaneous manifestations of sarcoidosis. Ann Dermatol Venereol 143(1):39–50

    Article  CAS  PubMed  Google Scholar 

  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):209–215

    PubMed  Google Scholar 

  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):331–340

    PubMed  Google Scholar 

  21. Judson MA (2008) The diagnosis of sarcoidosis. Clin Chest Med 29:415–427

    Article  PubMed  Google Scholar 

  22. Baughman RP, Papanikolaou I (2017) Current concepts regarding calcium metabolism and bone health in sarcoidosis. Curr Opin Pulm Med 23(5):476–481

    Article  CAS  PubMed  Google Scholar 

  23. Minisola S, Cipriani C, Occhiuto M, Pepe J (2017) New anabolic therapies for osteoporosis. Intern Emerg Med 12(7):915–921

    Article  PubMed  Google Scholar 

  24. Kefella H, Luther D, Hainline C (2017) Ophthalmic and neuro-ophthalmic manifestations of sarcoidosis. Curr Opin Pulm Med 28(6):587–594

    Google Scholar 

  25. Yang SJ, Salek S, Rosenbaum JT (2017) Ocular sarcoidosis: new diagnostic modalities and treatment. Curr Opin Pulm Med 23(5):458–467

    Article  PubMed  Google Scholar 

  26. Velter C, Lipsker D (2016) Cutaneous panniculitis. Rev Med Intern 37(11):743–750

    Article  CAS  Google Scholar 

  27. Kluger N (2017) Cutaneous complications related to tattoos: 31 cases from Finland. Dermatology 233(1):100–109

    Article  CAS  PubMed  Google Scholar 

  28. Tugal-Tutkun I (2017) Systemic vasculitis and the eye. Curr Opin Rheumatol 29(1):24–32

    Article  CAS  PubMed  Google Scholar 

  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):934–938

    Article  PubMed Central  PubMed  Google Scholar 

  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):1503–1506

    Article  PubMed  Google Scholar 

  31. Carter JM, Howe BM, Inwards CY (2017) Conditions simulating primary bone neoplasms. Surg Pathol Clin 10(3):731–748

    Article  PubMed  Google Scholar 

  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):253–257

    Article  PubMed  Google Scholar 

  33. Morgenthau AS, Teirstein AS (2011) Sarcoidosis of the upper and lower airways. Expert Rev Respir Med 5(6):823–833

    Article  PubMed  Google Scholar 

  34. Agrawal A, Sahni S, Iftikhar A, Talwar A (2015) Pulmonary manifestations of renal cell carcinoma. Respir Med 109(12):1505–1508

    Article  PubMed  Google Scholar 

  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 133:1426–1435

    Article  PubMed  Google Scholar 

  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 128:30–35

    Article  PubMed  Google Scholar 

  37. Culver DA, Ribeiro Neto ML, Moss BP, Willis MA (2017) Neurosarcoidosis. Semin Respir Crit Care Med 38(4):499–513

    Article  PubMed  Google Scholar 

  38. Ogawa Y, Saraya T, Fujiwara M, Takizawa H (2017) Massive neurosarcoidosis. Intern Med 56(18):2537–2538

    Article  PubMed Central  PubMed  Google Scholar 

  39. Hebel R, Dubaniewicz-Wybieralska M, Dubaniewicz A (2015) Overview of neurosarcoidosis: recent advances. J Neurol 262(2):258–267

    Article  CAS  PubMed  Google Scholar 

  40. Said G (2013) Sarcoidosis of the peripheral nervous system. Handb Clin Neurol 013(115):485–495

    Article  Google Scholar 

  41. Levitt DG, Levitt MD (2017) Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states. Clin Exp Gastroenterol 10:147–168

    Article  PubMed Central  PubMed  Google Scholar 

  42. Cunha BA, Sivarajah T, Jimada I (2017) Sarcoidosis with fever and a splenic infarct due to CMV or lymphoma? Heart Lung 46(5):394–396

    Article  PubMed  Google Scholar 

  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):e0178936

    Article  PubMed Central  PubMed  Google Scholar 

  44. Silva M, Nunes H, Valeyre D, Sverzellati N (2015) Imaging of sarcoidosis. Clin Rev Allergy Immunol 49(1):45–53

    Article  CAS  PubMed  Google Scholar 

  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 12:1623–1634

    Article  PubMed Central  PubMed  Google Scholar 

  46. Fang C, Huang H, Xu Z (2016) Immunological evidence for the role of mycobacteria in sarcoidosis: a meta-analysis. PLoS One 11(8):e0154716

    Article  PubMed Central  PubMed  Google Scholar 

  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):457–464

    Article  PubMed  Google Scholar 

  48. Ramachandraiah V, Aronow W, Chandy D (2017) Pulmonary sarcoidosis: an update. Postgrad Med 129(1):149–158

    Article  PubMed  Google Scholar 

  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):285–307

    PubMed  Google Scholar 

  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):334–339

    PubMed  Google Scholar 

  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):12–18

    PubMed  Google Scholar 

  52. 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 

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Correspondence to Elena Bargagli.

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

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Bargagli, E., Prasse, A. Sarcoidosis: a review for the internist. Intern Emerg Med 13, 325–331 (2018). https://doi.org/10.1007/s11739-017-1778-6

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