Skip to main content

Advertisement

SpringerLink
Log in

Nonpulmonary manifestations of sarcoidosis

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Sarcoidosis is one in a heterogeneous family of granulomatous disorders. The clinical manifestations of sarcoidosis can vary widely, depending on the patient and the tissues involved. Recent advances in our understanding of the immunologic steps leading to granuloma formation and persistence have yet to translate into more effective care for patients with this disease. This review discusses the immunology of granuloma formation and systemic disease, the various nonpulmonary expressions of the clinical disease, and the treatment options available to the practicing physician.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Agostini C, Adami F, Semenzato G: New pathogenetic insights into the sarcoid granuloma. Curr Opin Rheumatol 2000, 12:71–76. A detailed review of the immunology of granuloma formation.

    Article  PubMed  CAS  Google Scholar 

  2. 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, 160:736-755. A comprehensive report on the status of sarcoidosis, including pathogenesis, clinical presentation, and treatment.

  3. Mosmann TR, Cherwinski H, Bond MW, et al.: Two types of murine helper T cell clone, I: definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986, 136:2348–2357.

    PubMed  CAS  Google Scholar 

  4. Jankovic D, Liu Z, Gause WC: Th1- and Th2-cell commitment during infectious disease: asymmetry in divergent pathways. Trends Immunol 2001, 22:450–457.

    Article  PubMed  CAS  Google Scholar 

  5. Agostini C, Semenzato G:Biology and immunology of the granuloma. In The Granulomatous Disorders. Edited by James DG, Zumla A. Cambridge: Cambridge University Press; 1999:3–16.

    Google Scholar 

  6. Ina Y, Takada K, Sato T, et al.: Soluble interleukin 2 receptors in patients with sarcoidosis: possible origin. Chest 1992, 102:1128–1133.

    PubMed  CAS  Google Scholar 

  7. Kim DS, Paik SH, Lim CM, et al.: Value of ICAM-1 expression and soluble ICAM-1 level as a marker of activity in sarcoidosis. Chest 1999, 115:1059–1065.

    Article  PubMed  CAS  Google Scholar 

  8. Bianco A, Spiteri MA: Peripheral anergy and local immune hyperactivation in sarcoidosis: a paradox or birds of a feather. Clin Exp Immunol 1997, 110:1–3.

    Article  PubMed  CAS  Google Scholar 

  9. Bansal AS, Bruce J, Hogan PG, et al.: An assessment of peripheral immunity in patients with sarcoidosis using measurements of serum vitamin D3, cytokines and soluble CD23. Clin Exp Immunol 1997, 110:92–97.

    Article  PubMed  CAS  Google Scholar 

  10. Karim M, Ellner JJ: Mechanisms of anergy. In Tuberculosis. Edited by Rom WN, Garay S. New York: Little, Brown and Company; 1999:343–351.

    Google Scholar 

  11. Boussiotis VA, Tsai EY, Yunis EJ, et al.: IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J Clin Invest 2000, 105:1317–1325. An interesting report of work in progress deciphering the anergy and aberrant Th2 responses seen in mycobacterial disease. This has potential crossover interest to those studying anergy in sarcoidosis.

    PubMed  CAS  Google Scholar 

  12. Weinberg I, Vasiliev L, Gotsman I: Anti-dsDNA antibodies in sarcoidosis. Semin Arthritis Rheum 2000, 29:328–331.

    Article  PubMed  CAS  Google Scholar 

  13. Ina Y, Takada K, Yamamoto M, et al.: Antiphospholipid antibodies: a prognostic factor in sarcoidosis? Chest 1994, 105:1179–1183.

    PubMed  CAS  Google Scholar 

  14. Forman JD, Klein JT, Silver RF, et al.: Selective activation and accumulation of oligoclonal V beta-specific T cells in active pulmonary sarcoidosis. J Clin Invest 1994, 94:1533–1542.

    Article  PubMed  CAS  Google Scholar 

  15. Johns CJ, Michele TM: The clinical management of sarcoidosis: a 50-year experience at the Johns Hopkins Hospital. Medicine (Baltimore) 1999, 78:65–111. An exhaustive retrospective report of the clinical management of sarcoidosis at Johns Hopkins Hospital, based on long-term observations of patients at a sarcoidosis clinic. The report includes many examples of granuloma histopathology and an appendix of case studies.

    Article  CAS  Google Scholar 

  16. Chopra S, Vega-Lopez F: Skin granulomas in clinical practice. In The Granulomatous Disorders. Edited by James DG, Zumla A. Cambridge: Cambridge University Press; 1999:485–527.

    Google Scholar 

  17. English JC III, Patel PJ, Greer KE: Sarcoidosis. J Am Acad Dermatol 2001, 44:725–743. A clinical review of the cutaneous manifestations of sarcoidosis, including many photographs depicting the different types of skin lesion.

    Article  PubMed  Google Scholar 

  18. Neville E, Carstairs LS, James DG: Sarcoidosis of bone. Q J Med 1977, 46:215–227.

    PubMed  CAS  Google Scholar 

  19. Shorr AF, Murphy FT, Gilliland WR, et al.: Osseous disease in patients with pulmonary sarcoidosis and musculoskeletal symptoms. Respir Med 2000, 94:228–232.

    Article  PubMed  CAS  Google Scholar 

  20. Wilcox A, Bharadwaj P, Sharma OP: Bone sarcoidosis. Curr Opin Rheumatol 2000, 12:321–330. This article provides a detailed review of the title topic and many examples of the different radiologic images seen in osseous sarcoidosis.

    Article  PubMed  CAS  Google Scholar 

  21. Hamada K, Nagai S, Tsutsumi T, et al.: Ionized calcium and 1,25-dihydroxyvitamin D concentration in serum of patients with sarcoidosis. Eur Respir J 1998, 11:1015–1020.

    Article  PubMed  CAS  Google Scholar 

  22. Milman N, Lund JO, Graudal N, et al.: Diagnostic value of routine radioisotope bone scanning in a series of 63 patients with pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2000, 17:67–70.

    PubMed  CAS  Google Scholar 

  23. Barnard J, Newman LS: Sarcoidosis: immunology, rheumatic involvement, and therapeutics. Curr Opin Rheumatol 2001, 13:84–91.

    Article  PubMed  CAS  Google Scholar 

  24. Otake S, Ishigaki T: Muscular sarcoidosis. Semin Musculoskelet Radiol 2001, 5:167–170.

    Article  PubMed  CAS  Google Scholar 

  25. Ferriby D, de Seze J, Stojkovic T, et al.: Long-term follow-up of neurosarcoidosis. Neurology 2001, 57:927–929.

    PubMed  CAS  Google Scholar 

  26. Rothova A: Ocular involvement in sarcoidosis. Br J Ophthalmol 2000, 84:110–116. This article discusses in detail the diagnosis and treatment of ocular sarcoidosis.

    Article  PubMed  CAS  Google Scholar 

  27. Edelsten C, Pearson A, Joynes E, et al.: The ocular and systemic prognosis of patients presenting with sarcoid uveitis. Eye 1999, 13:748–753.

    PubMed  Google Scholar 

  28. Papadopoulos KI, Hornblad Y, Liljebladh H, et al.: High frequency of endocrine autoimmunity in patients with sarcoidosis. Eur J Endocrinol 1996, 134:331–336.

    Article  PubMed  CAS  Google Scholar 

  29. Fernandes SR, Singsen BH, Hoffman GS: Sarcoidosis and systemic vasculitis. Semin Arthritis Rheum 2000, 30:33–46. Necrotizing sarcoid granulomatosis is a rare variant of sarcoidosis. This article provides a 10-year retrospective review of cases treated at the Cleveland Clinic, along with additional examples culled from the literature.

    Article  PubMed  CAS  Google Scholar 

  30. Marie I, Lecomte F, Levesque H, et al.: Lofgren’s syndrome as the first manifestation of acute infection due to Chlamydia pneumoniae: a prospective study. Clin Infect Dis 1999, 28:691–692.

    PubMed  CAS  Google Scholar 

  31. Judson MA: An approach to the treatment of pulmonary sarcoidosis with corticosteroids: the six phases of treatment. Chest 1999, 115:1158–1165. The author provides a standardized approach to using corticosteroids in sarcoidosis. In this article, he discusses the pros and cons of corticosteroid use, and some of the controversy concerning their efficacy in providing long-term benefits.

    Article  PubMed  CAS  Google Scholar 

  32. Eule H, Weinecke A, Roth I, 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.

    Article  PubMed  CAS  Google Scholar 

  33. Nagai S, Izumi T: [Corticosteroid treatment to patients with sarcoidosis]. Nippon Rinsho 1994, 52:1633–1642.

    PubMed  CAS  Google Scholar 

  34. Gottlieb JE, Israel HL, Steiner RM, et al.: Outcome in sarcoidosis: the relationship of relapse to corticosteroid therapy. Chest 1997, 111:623–631.

    PubMed  CAS  Google Scholar 

  35. Pietinalho A, Tukiainen P, Haahtela T, et al.: Oral prednisolone followed by inhaled budesonide in newly diagnosed pulmonary sarcoidosis: a double-blind, placebo-controlled multicenter study. Finnish Pulmonary Sarcoidosis Study Group. Chest 1999, 116:424–431.

    Article  PubMed  CAS  Google Scholar 

  36. Baughman RP, Lower EE: A clinical approach to the use of methotrexate for sarcoidosis. Thorax 1999, 54:742–746. An algorithm is provided for methotrexate use as a steroid-sparing agent in the treatment of sarcoidosis.

    Article  PubMed  CAS  Google Scholar 

  37. Muller-Quernheim J, Kienast K, Held M, et al.: Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen. Eur Respir J 1999, 14:1117–1122.

    Article  PubMed  CAS  Google Scholar 

  38. Lower EE, Broderick JP, Brott TG, et al.: Diagnosis and management of neurological sarcoidosis. Arch Intern Med 1997, 157:1864–1868.

    Article  PubMed  CAS  Google Scholar 

  39. Martinet Y, Pinkston P, Saltini C, et al.: Evaluation of the in vitro and in vivo effects of cyclosporine on the lung Tlymphocyte alveolitis of active pulmonary sarcoidosis. Am Rev Respir Dis 1988, 138:1242–1248.

    PubMed  CAS  Google Scholar 

  40. Morse SI, Cohn ZA, Hirsch JG, et al.: The treatment of sarcoidosis with chloroquine. Am J Pathol 1961, 30:779–784.

    CAS  Google Scholar 

  41. Baltzan M, Mehta S, Kirkham TH, et al.: Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med 1999, 160:192–197.

    PubMed  CAS  Google Scholar 

  42. Bachelez H, Senet P, Cadranel J, et al.: The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol 2001, 137:69–73.

    PubMed  CAS  Google Scholar 

  43. Georgiou S, Monastirli A, Pasmatzi E, et al.: Cutaneous sarcoidosis: complete remission after oral isotretinoin therapy. Acta Derm Venereol 1998, 78:457–459.

    Article  PubMed  CAS  Google Scholar 

  44. Spiteri MA, Taylor SJ: Retinoids in the treatment of cutaneous sarcoidosis. Arch Dermatol 1985, 121:1486.

    Article  PubMed  CAS  Google Scholar 

  45. Waldinger TP, Ellis CN, Quint K, et al.: Treatment of cutaneous sarcoidosis with isotretinoin. Arch Dermatol 1983, 119:1003–1005.

    Article  PubMed  CAS  Google Scholar 

  46. Badot V, Servais G, Peretz A: Induction of anti-nuclear and antiDNA antibodies in rheumatoid arthritis patients treated with infliximab. Arthritis Rheum 2001, 44:S205.

    Google Scholar 

  47. De Bandt M, Descamps V, Meyer O: Two cases of etanerceptinduced lupus-like syndrome in RA patients. Arthritis Rheum 2001, 44:S372.

    Google Scholar 

  48. Morris AJ, Morris CR, Hernandez CR: Anticardiolipin antibodies developing during infliximab therapy. Arthritis Rheum 2001, 44:S373.

    Google Scholar 

  49. Baker DG, Clark J, Keenan GF, et al.: Tuberculosis occurring in patients receiving the anti-TNF agent infliximab. Arthritis Rheum 2001, 44:S105.

    Article  Google Scholar 

  50. Yee AM, Pochapin MB: Treatment of complicated sarcoidosis with infliximab anti-tumor necrosis factor-alpha therapy. Ann Intern Med 2001, 135:27–31.

    PubMed  CAS  Google Scholar 

  51. Sweiss NJ, Ellman MH, Curran JJ, et al.: TNF-inhibition as novel treatment for refractory sarcoidosis. Arthritis Rheum 2001, 44:S121.

    Google Scholar 

  52. Estines O, Revuz J, Wolkenstein P, et al.: [Sarcoidosis: thalidomide treatment in ten patients]. Ann Dermatol Venereol 2001, 128:611–613.

    PubMed  CAS  Google Scholar 

  53. Carlesimo M, Giustini S, Rossi A, et al.: Treatment of cutaneous and pulmonary sarcoidosis with thalidomide. J Am Acad Dermatol 1995, 32:866–869.

    Article  PubMed  CAS  Google Scholar 

  54. Oliver SJ, Kikuchi T, Krueger JG, et al.: Thalidomide induces granuloma differentiation in sarcoid skin lesions associated with disease improvement. Clin Immunol 2002, In press. This article provides a detailed immunologic analysis of thalidomide’s effects on the sarcoidosis disease process.

  55. Haslett PA, Klausner JD, Makonkawkeyoon S, et al.: Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. AIDS Res Hum Retroviruses 1999, 15:1169–1179.

    Article  PubMed  CAS  Google Scholar 

  56. Oliver SJ, Moreira A, Kaplan G: Immune stimulation in scleroderma patients treated with thalidomide. Clin Immunol 2000, 97:109–120.

    Article  PubMed  CAS  Google Scholar 

  57. Bekker LG, Haslett P, Maartens G, et al.: Thalidomide-induced antigen-specific immune stimulation in patients with human immunodeficiency virus type 1 and tuberculosis. J Infect Dis 2000, 181:954–965.

    Article  PubMed  CAS  Google Scholar 

  58. Corral LG, Haslett PAJ, Muller GW, et al.: Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNFalpha. J Immunol 1999, 163:380–386.

    PubMed  CAS  Google Scholar 

  59. Haslett PA, Corral LG, Albert M, et al.: Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998, 187:1885–1892.

    Article  PubMed  CAS  Google Scholar 

  60. Davies FE, Raje N, Hideshima T, et al.: Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001, 98:210–216.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cellular Physiology & Immunology, Rockefeller University, 1230 York Avenue, 10021, New York, NY, USA

    Stephen J. Oliver MD

Authors
  1. Stephen J. Oliver MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oliver, S.J. Nonpulmonary manifestations of sarcoidosis. Curr Rheumatol Rep 4, 170–178 (2002). https://doi.org/10.1007/s11926-002-0013-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-002-0013-1

Keywords

Search

Navigation