Acute Pulmonary Exacerbation of Sarcoidosis

  • Efstratios PanselinasEmail author
  • Marc A. Judson
Part of the Respiratory Medicine book series (RM, volume 17)


Sarcoidosis patients frequently experience an acute exacerbation of pulmonary sarcoidosis (APES). Despite the frequent occurrence of APES, there is a paucity of information regarding its definition, diagnostic criteria, diagnosis, and treatment. APES is a significant clinical problem that adversely affects the quality of life of sarcoidosis patients. We propose the following clinical criteria for the diagnosis of APES: the development or worsening of pulmonary symptoms over at least a 1-month period in patients with known sarcoidosis that cannot be not explained by an alternative cause, combined with a decline in spirometry (≥10 % from previous baseline FVC and/or FEV1). Risk factors for APES include previous treatment with corticosteroids, Black race, and fibrocystic sarcoidosis. The pathogenesis of APES may involve direct or indirect effects of pulmonary granulomatous inflammation. Although relatively low-dose corticosteroid (20 mg of daily prednisone equivalent) for a relatively short time (3 weeks duration) is usually adequate to resolve APES, the corticosteroid tapering schedule and the prognosis of APES are unknown. We believe that further attention to APES will improve the quality of life of sarcoidosis patients.


Sarcoidosis Pulmonary exacerbation Definition Risk factors Diagnosis Differential diagnosis Treatment Corticosteroids 



Acute pulmonary exacerbation of sarcoidosis


Antiretroviral therapy


Computed tomography


Human immunodeficiency virus


Human leukocyte antigen




Sarcoidosis-associated pulmonary hypertension


Tumor necrosis factor


  1. 1.
    Hunninghake GW, et al. 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. 1999;16(2):149–73.PubMedGoogle Scholar
  2. 2.
    Mana J, et al. Recurrent sarcoidosis: a study of 17 patients with 24 episodes of recurrence. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20(3):212–21.PubMedGoogle Scholar
  3. 3.
    Gottlieb JE, et al. Outcome in sarcoidosis. The relationship of relapse to corticosteroid therapy. Chest. 1997;111(3):623–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Hunninghake GW, et al. Outcome of the treatment for sarcoidosis. Am J Respir Crit Care Med. 1994;149(4 Pt 1):893–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Judson MA, et al. The utility of the chest radiograph in diagnosing exacerbations of pulmonary sarcoidosis. Respirology. 2008;13(1):97–102.PubMedCrossRefGoogle Scholar
  6. 6.
    McKinzie BP, et al. Efficacy of short-course, low-dose corticosteroid therapy for acute pulmonary sarcoidosis exacerbations. Am J Med Sci. 2010;339(1):1–4.PubMedCrossRefGoogle Scholar
  7. 7.
    Rizzato G, Montemurro L, Colombo P. The late follow-up of chronic sarcoid patients previously treated with corticosteroids. Sarcoidosis Vasc Diffuse Lung Dis. 1998;15(1):52–8.PubMedGoogle Scholar
  8. 8.
    Johns CJ, et al. Longitudinal study of chronic sarcoidosis with low-dose maintenance corticosteroid therapy. Outcome and complications. Ann N Y Acad Sci. 1986;465:702–12.PubMedCrossRefGoogle Scholar
  9. 9.
    Israel HL, et al. Factors affecting outcome of sarcoidosis. Influence of race, extrathoracic involvement, and initial radiologic lung lesions. Ann N Y Acad Sci. 1986;465:609–18.PubMedCrossRefGoogle Scholar
  10. 10.
    Rodrigues SC, et al. Factor analysis of sarcoidosis phenotypes at two referral centers in Brazil. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28(1):34–43.PubMedGoogle Scholar
  11. 11.
    Eule H, et al. The possible influence of corticosteroid therapy on the natural course of pulmonary sarcoidosis. Late results of a continuing clinical study. Ann N Y Acad Sci. 1986;465:695–701.PubMedCrossRefGoogle Scholar
  12. 12.
    Alazemi S, Campos MA. Interferon-induced sarcoidosis. Int J Clin Pract. 2006;60(2):201–11.PubMedCrossRefGoogle Scholar
  13. 13.
    Li SD, et al. Reactivation of sarcoidosis during interferon therapy. J Gastroenterol. 2002;37(1):50–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Hurst EA, Mauro T. Sarcoidosis associated with pegylated interferon alfa and ribavirin treatment for chronic hepatitis C: a case report and review of the literature. Arch Dermatol. 2005;141(7):865–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Lenner R, et al. Recurrent pulmonary sarcoidosis in HIV-infected patients receiving highly active antiretroviral therapy. Chest. 2001;119(3):978–81.PubMedCrossRefGoogle Scholar
  16. 16.
    Mirmirani P, et al. Sarcoidosis in a patient with AIDS: a manifestation of immune restoration syndrome. J Am Acad Dermatol. 1999;41(2 Pt 2):285–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Morris DG, et al. Sarcoidosis following HIV infection: evidence for CD4+ lymphocyte dependence. Chest. 2003;124(3):929–35.PubMedCrossRefGoogle Scholar
  18. 18.
    Martinez FJ, et al. Recurrence of sarcoidosis following bilateral allogeneic lung transplantation. Chest. 1994;106(5):1597–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Barbers RG. Role of transplantation (lung, liver, and heart) in sarcoidosis. Clin Chest Med. 1997;18(4):865–74.PubMedCrossRefGoogle Scholar
  20. 20.
    Walker S, et al. Medium term results of lung transplantation for end stage pulmonary sarcoidosis. Thorax. 1998;53(4):281–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Nunley DR, et al. Lung transplantation for end-stage pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16(1):93–100.PubMedGoogle Scholar
  22. 22.
    Burns AM, Green PJ, Pasternak S. Etanercept-induced cutaneous and pulmonary sarcoid-like granulomas resolving with adalimumab. J Cutan Pathol. 2012;39(2):289–93.PubMedCrossRefGoogle Scholar
  23. 23.
    Louie GH, Chitkara P, Ward MM. Relapse of sarcoidosis upon treatment with etanercept. Ann Rheum Dis. 2008;67(6):896–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Verschueren K, et al. Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients. Clin Rheumatol. 2007;26(11):1969–71.PubMedCrossRefGoogle Scholar
  25. 25.
    Parronchi P, et al. Effects of interferon-alpha on cytokine profile, T cell receptor repertoire and peptide reactivity of human allergen-specific T cells. Eur J Immunol. 1996;26(3):697–703.PubMedCrossRefGoogle Scholar
  26. 26.
    Lopez V, et al. Cutaneous sarcoidosis developing after treatment with pegylated interferon and ribavirin: a new case and review of the literature. Int J Dermatol. 2011;50(3):287–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Foulon G, et al. Sarcoidosis in HIV-infected patients in the era of highly active antiretroviral therapy. Clin Infect Dis. 2004;38(3):418–25.PubMedCrossRefGoogle Scholar
  28. 28.
    Haramati LB, et al. Newly diagnosed pulmonary sarcoidosis in HIV-infected patients. Radiology. 2001;218(1):242–6.PubMedGoogle Scholar
  29. 29.
    Naccache JM, et al. Sarcoid-like pulmonary disorder in human immunodeficiency virus-infected patients receiving antiretroviral therapy. Am J Respir Crit Care Med. 1999;159(6): 2009–13.PubMedCrossRefGoogle Scholar
  30. 30.
    Wittram C, Fogg J, Farber H. Immune restoration syndrome manifested by pulmonary sarcoidosis. AJR Am J Roentgenol. 2001;177(6):1427.PubMedCrossRefGoogle Scholar
  31. 31.
    Johnson BA, et al. Recurrence of sarcoidosis in pulmonary allograft recipients. Am Rev Respir Dis. 1993;148(5):1373–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Bjortuft O, et al. Single lung transplantation as treatment for end-stage pulmonary sarcoidosis: recurrence of sarcoidosis in two different lung allografts in one patient. J Heart Lung Transplant. 1994;13(1 Pt 1):24–9.PubMedGoogle Scholar
  33. 33.
    Kazerooni EA, Jackson C, Cascade PN. Sarcoidosis: recurrence of primary disease in transplanted lungs. Radiology. 1994;192(2):461–4.PubMedGoogle Scholar
  34. 34.
    Carre P, et al. Recurrence of sarcoidosis in a human lung allograft. Transplant Proc. 1995;27(2):1686.PubMedGoogle Scholar
  35. 35.
    Kazerooni EA, Cascade PN. Recurrent miliary sarcoidosis after lung transplantation. Radiology. 1995;194(3):913.PubMedGoogle Scholar
  36. 36.
    Muller C, et al. Sarcoidosis recurrence following lung transplantation. Transplantation. 1996;61(7):1117–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Padilla ML, Schilero GJ, Teirstein AS. Sarcoidosis and transplantation. Sarcoidosis Vasc Diffuse Lung Dis. 1997;14(1):16–22.PubMedGoogle Scholar
  38. 38.
    Collins J, et al. Frequency and CT findings of recurrent disease after lung transplantation. Radiology. 2001;219(2):503–9.PubMedGoogle Scholar
  39. 39.
    van der Stoep D, et al. Sarcoidosis during anti-tumor necrosis factor-alpha therapy: no relapse after rechallenge. J Rheumatol. 2009;36(12):2847–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Utz JP, et al. Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis. Chest. 2003;124(1):177–85.PubMedCrossRefGoogle Scholar
  41. 41.
    Clementine RR, et al. Tumor necrosis factor-alpha antagonist-induced sarcoidosis. J Clin Rheumatol. 2010;16(6):274–9.PubMedCrossRefGoogle Scholar
  42. 42.
    O'Shea FD, Marras TK, Inman RD. Pulmonary sarcoidosis developing during infliximab therapy. Arthritis Rheum. 2006;55(6):978–81.PubMedCrossRefGoogle Scholar
  43. 43.
    Toussirot E, et al. Sarcoidosis occurring during anti-TNF-alpha treatment for inflammatory rheumatic diseases: report of two cases. Clin Exp Rheumatol. 2008;26(3):471–5.PubMedGoogle Scholar
  44. 44.
    Maurice MM, et al. Treatment with monoclonal anti-tumor necrosis factor alpha antibody results in an accumulation of Th1 CD4+ T cells in the peripheral blood of patients with rheumatoid arthritis. Arthritis Rheum. 1999;42(10):2166–73.PubMedCrossRefGoogle Scholar
  45. 45.
    Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573–81.PubMedCrossRefGoogle Scholar
  46. 46.
    Chen ES, et al. Serum amyloid A regulates granulomatous inflammation in sarcoidosis through Toll-like receptor-2. Am J Respir Crit Care Med. 2010;181(4):360–73.PubMedCrossRefGoogle Scholar
  47. 47.
    Panselinas E, Judson MA. Acute pulmonary exacerbations of sarcoidosis. Chest. 2012;142(4):827–36.PubMedCrossRefGoogle Scholar
  48. 48.
    Israel HL, Fouts DW, Beggs RA. A controlled trial of prednisone treatment of sarcoidosis. Am Rev Respir Dis. 1973;107(4):609–14.PubMedGoogle Scholar
  49. 49.
    Lower EE, Baughman RP. Prolonged use of methotrexate for sarcoidosis. Arch Intern Med. 1995;155(8):846–51.PubMedCrossRefGoogle Scholar
  50. 50.
    Panselinas E, Rodgers JK, Judson MA. Clinical outcomes in sarcoidosis after cessation of infliximab treatment. Respirology. 2009;14(4):522–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Paramothayan NS, Lasserson TJ, Jones PW. Corticosteroids for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2005;(2):CD001114.Google Scholar
  52. 52.
    Zaki MH, et al. Corticosteroid therapy in sarcoidosis. A five-year, controlled follow-up study. N Y State J Med. 1987;87(9):496–9.PubMedGoogle Scholar
  53. 53.
    Bechtel JJ, et al. Airway hyperreactivity in patients with sarcoidosis. Am Rev Respir Dis. 1981;124(6):759–61.PubMedGoogle Scholar
  54. 54.
    Shorr AF, Torrington KG, Hnatiuk OW. Endobronchial involvement and airway hyperreactivity in patients with sarcoidosis. Chest. 2001;120(3):881–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Lynch 3rd JP, et al. Pulmonary sarcoidosis. Semin Respir Crit Care Med. 2007;28(1):53–74.PubMedCrossRefGoogle Scholar
  56. 56.
    Nunes H, et al. Imaging in sarcoidosis. Semin Respir Crit Care Med. 2007;28(1):102–20.PubMedCrossRefGoogle Scholar
  57. 57.
    Smith-Bindman R, et al. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med. 2009;169(22):2078–86.PubMedCrossRefGoogle Scholar
  58. 58.
    Swigris JJ, et al. Increased risk of pulmonary embolism among US decedents with sarcoidosis from 1988 to 2007. Chest. 2011;140(5):1261–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Schutt AC, Bullington WM, Judson MA. Pharmacotherapy for pulmonary sarcoidosis: a Delphi consensus study. Respir Med. 2010;104(5):717–23.PubMedCrossRefGoogle Scholar
  60. 60.
    Baughman RP, Winget DB, Lower EE. Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial. Sarcoidosis Vasc Diffuse Lung Dis. 2000;17(1):60–6.PubMedGoogle Scholar
  61. 61.
    Vucinic VM. What is the future of methotrexate in sarcoidosis? A study and review. Curr Opin Pulm Med. 2002;8(5):470–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Baughman RP, Lower EE. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2004;21(1):43–8.PubMedGoogle Scholar
  63. 63.
    Sahoo DH, et al. Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis. Eur Respir J. 2011;38(5):1145–50.PubMedCrossRefGoogle Scholar
  64. 64.
    Lewis SJ, Ainslie GM, Bateman ED. Efficacy of azathioprine as second-line treatment in pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16(1):87–92.PubMedGoogle Scholar
  65. 65.
    Muller-Quernheim J, et al. Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen. Eur Respir J. 1999;14(5):1117–22.PubMedCrossRefGoogle Scholar
  66. 66.
    Kouba DJ, et al. Mycophenolate mofetil may serve as a steroid-sparing agent for sarcoidosis. Br J Dermatol. 2003;148(1):147–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Moudgil A, Przygodzki RM, Kher KK. Successful steroid-sparing treatment of renal limited sarcoidosis with mycophenolate mofetil. Pediatr Nephrol. 2006;21(2):281–5.PubMedCrossRefGoogle Scholar
  68. 68.
    Baughman RP, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006;174(7):795–802.PubMedCrossRefGoogle Scholar
  69. 69.
    Rossman MD, et al. A double-blinded, randomized, placebo-controlled trial of infliximab in subjects with active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23(3):201–8.PubMedGoogle Scholar
  70. 70.
    Callejas-Rubio JL, et al. Treatment of therapy-resistant sarcoidosis with adalimumab. Clin Rheumatol. 2006;25(4):596–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Zabel P, et al. Pentoxifylline in treatment of sarcoidosis. Am J Respir Crit Care Med. 1997;155(5):1665–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Park MK, et al. Steroid-sparing effects of pentoxifylline in pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2009;26(2):121–31.PubMedGoogle Scholar
  73. 73.
    Baltzan M, et al. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med. 1999;160(1):192–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Chloroquine in the treatment of sarcoidosis. A report from the Research Committee of the British Tuberculosis Association. Tubercle. 1967;48(4):257–72.Google Scholar
  75. 75.
    Carlesimo M, et al. Treatment of cutaneous and pulmonary sarcoidosis with thalidomide. J Am Acad Dermatol. 1995;32(5 Pt 2):866–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Judson MA, et al. The effect of thalidomide on corticosteroid-dependent pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23(1):51–7.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Pulmonary Medicine411 General Army HospitalTripoliGreece
  2. 2.Division of Pulmonary and Critical Care Medicine, Department of MedicineAlbany Medical College, Albany Medical CenterAlbanyUSA

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