Sarcoidosis 

  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: Jul 29, 2011
 

Background

Sarcoidosis is a multisystem inflammatory disease of unknown etiology that predominantly affects the lungs and intrathoracic lymph nodes. Sarcoidosis is manifested by the presence of noncaseating granulomas (NCGs) in affected organ tissues.

Related Medscape Reference articles include Sarcoidosis (emergency medicine focus), Sarcoidosis (dermatology focus), and Sarcoidosis (ophthalmology focus).

Next

Pathophysiology

The cause of sarcoidosis is unknown. Efforts to identify a possible infectious etiology have been unsuccessful. Clinical sequelae result from the impact of NCGs on various organ tissues.

T cells play a central role in the development of sarcoidosis, as they likely propagate an excessive cellular immune reaction. For example, there is an accumulation of CD4 cells accompanied by the release of interleukin (IL)-2 at sites of disease activity. This may be manifest clinically by an inverted CD4/CD8 ratio. There also is an increased production of TH 1 cytokines, such as interferon. Moreover, both tumor necrosis factor (TNF) and TNF receptors are increased in this disease.

The importance of TNF in propagating inflammation in sarcoidosis has been demonstrated by the efficacy of anti-TNF agents, such as pentoxifylline[1] and infliximab,[2, 3] in treating this disease. In addition to T cells, B cells also play a role. There is evidence of B cell hyperreactivity with immunoglobulin production. Antigen-presenting cells also accumulate at sites of involvement in sarcoidosis. Finally, levels of fibrinogenic cytokines (eg, transforming growth factor [TGF]–beta) are increased.

A study by Facco et al suggests that Th17 cells may play a role in the pathogenesis and progression of sarcoidosis; these cells were noted to be present in the blood, bronchoalveolar lavage (BAL) samples, and lung tissue from patients with sarcoidosis, particularly in those with the active form of the disease.[4]

Previous
Next

Epidemiology

Frequency

United States

Incidence ranges from 5-40 cases per 100,000 population. The age-adjusted incidence for whites is 11 cases per 100,000 population. The incidence is considerably higher for African Americans, at 34 cases per 100,000 population. The prevalence is 10 times greater for African Americans than for whites. Approximately 20% of patients who are African American reported an affected family member, while only 5% of whites in the United States who have sarcoidosis state they have family members also diagnosed with sarcoidosis.

International

Incidence is 20 cases per 100,000 population in Sweden and 1.3 cases per 100,000 population in Japan. Sarcoidosis occurs in China, Africa, India, and other developing countries. Although its incidence may be low, the disease remains hidden and often is misdiagnosed as tuberculosis.

Mortality/Morbidity

Data regarding mortality are lacking. Cardiac sarcoid is a major cause for mortality. However, in the US patients with sarcoidosis tend to die from the sarcoidosis because of the complications of end-stage lung disease (eg, respiratory failure, right heart failure).

Functional impairment occurs in only 15-20% of patients and often resolves spontaneously. The overall mortality rate is less than 5% for untreated patients.

The likelihood of regression for pulmonary disease correlates with the extent of parenchymal disease, as noted by chest radiography (CXR) stage.

Cardiac disease is the most commonly reported cause of death in Europe and Japan, while pulmonary involvement most often accounts for mortality in the United States.

According to a study by Swigris et al, the rate of sarcoidosis-related mortality in the United States appears to have increased significantly from 1988-2007, particularly in black females aged 55 years or older. This study also confirmed findings from prior reports, indicating that the underlying cause of death in most patients with sarcoidosis was the disease itself.[5]

Race

See Frequency, United States and Mortality/Morbidity.

Sex

Male-to-female ratio is approximately 2:1.

Age

Incidence peaks in persons aged 25-35 years. A second peak occurs for women aged 45-65 years.

Previous
 
 
Contributor Information and Disclosures
Author

Nader Kamangar, MD, FACP, FCCP, FCCM  Associate Professor of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Los Angeles, David Geffen School of Medicine, Olive View-UCLA Medical Center; Associate Program Director, Pulmonary and Critical Care Multi-Campus Fellowship Program, Cedars-Sinai/West Los Angeles Veterans Affairs/Los Angeles Kaiser Permanente/Olive View-UCLA Medical Center; Site Director, Pulmonary/Critical Care Fellowship Program, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: American Academy of Sleep Medicine, American Association of Bronchology, American College of Chest Physicians, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, California Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Andrew F Shorr, MD, MPH  Assistant Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, Uniformed Services University of the Health Sciences

Andrew F Shorr, MD, MPH is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP  Professor of Genomics and Personalized Medicine Research, Internal Medicine, and Pediatrics, Associate Director, Center for Genomics and Personalized Medicine Research, Director of Research, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi

Disclosure: See below for list of all activities None None

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H  Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD  Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

References
  1. Zabel P, Entzian P, Dalhoff K, Schlaak M. Pentoxifylline in treatment of sarcoidosis. Am J Respir Crit Care Med. May 1997;155(5):1665-9. [Medline].

  2. Doty JD, Mazur JE, Judson MA. Treatment of sarcoidosis with infliximab. Chest. Mar 2005;127(3):1064-71. [Medline].

  3. Yee AM, Pochapin MB. Treatment of complicated sarcoidosis with infliximab anti-tumor necrosis factor-alpha therapy. Ann Intern Med. Jul 3 2001;135(1):27-31. [Medline].

  4. Facco M, Cabrelle A, Teramo A, Olivieri V, Gnoato M, Teolato S, et al. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax. Feb 2011;66(2):144-50. [Medline].

  5. Swigris JJ, Olson AL, Huie TJ, et al. Sarcoidosis-related mortality in the United States from 1988 to 2007. Am J Respir Crit Care Med. Jun 1 2011;183(11):1524-30. [Medline]. [Full Text].

  6. Okada S, Konishi N, Tsumura M, et al. Cardiac infiltration in early-onset sarcoidosis associated with a novel heterozygous mutation, G481D, in CARD15. Rheumatology (Oxford). Apr 9 2009;[Medline].

  7. [Best Evidence] Sverrild A, Backer V, Kyvik KO, et al. Heredity in sarcoidosis: a registry-based twin study. Thorax. Oct 2008;63(10):894-6. [Medline].

  8. Arai Y, Saul JP, Albrecht P, Hartley LH, Lilly LS, Cohen RJ. Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol. Jan 1989;256(1 Pt 2):H132-41. [Medline].

  9. Ardic I, Kaya MG, Yarlioglues M, et al. Impaired heart rate recovery index in patients with sarcoidosis. Chest. Jan 2011;139(1):60-8. [Medline].

  10. Shetler K, Marcus R, Froelicher VF, et al. Heart rate recovery: validation and methodologic issues. J Am Coll Cardiol. Dec 2001;38(7):1980-7. [Medline].

  11. Lower EE, Baughman RP. Prolonged use of methotrexate for sarcoidosis. Arch Intern Med. 1995;155:846-851. [Medline].

  12. Baltzan M, Mehta S, Kirkham TH, Cosio MG. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med. Jul 1999;160(1):192-7. [Medline].

  13. Zic JA, Horowitz DH, Arzubiaga C, King LE Jr. Treatment of cutaneous sarcoidosis with chloroquine. Review of the literature. Arch Dermatol. Jul 1991;127(7):1034-40. [Medline].

  14. Demeter SL. Myocardial sarcoidosis unresponsive to steroids. Treatment with cyclophosphamide. Chest. July 1988;94:202-3. [Medline].

  15. Doty JD, Mazur JE, Judson MA. Treatment of corticosteroid-resistant neurosarcoidosis with a short-course cyclophosphamide regimen. Chest. Nov 2003;124(5):2023-6. [Medline].

  16. Müller-Quernheim J, Kienast K, Held M, Pfeifer S, Costabel U. Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen. Eur Respir J. Nov 1999;14(5):1117-22. [Medline].

  17. Kataria YP. Chlorambucil in sarcoidosis. Chest. Jul 1980;78(1):36-43. [Medline].

  18. York EL, Kovithavongs T, Man SF, Rebuck AS, Sproule BJ. Cyclosporine and chronic sarcoidosis. Chest. Oct 1990;98(4):1026-9. [Medline].

  19. Baughman RP, Judson MA, Teirstein AS, Moller DR, Lower EE. Thalidomide for chronic sarcoidosis. Chest. Jul 2002;122(1):227-32. [Medline].

  20. Callejas-Rubio JL, Lopez-Perez L, Ortego-Centeno N. Tumor necrosis factor-alpha inhibitor treatment for sarcoidosis. Ther Clin Risk Manag. Dec 2008;4(6):1305-13. [Medline].

  21. Bachelez H, Senet P, Cadranel J, Kaoukhov A, Dubertret L. The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol. Jan 2001;137(1):69-73. [Medline].

  22. Nathan SD. Lung transplantation: disease-specific considerations for referral. Chest. Mar 2005;127(3):1006-16. [Medline].

  23. Alberts C, van der Mark TW, Jansen HM. Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study. Dutch Study Group on Pulmonary Sarcoidosis. Eur Respir J. May 1995;8(5):682-8. [Medline].

  24. Baughman RP, Iannuzzi MC, Lower EE, Moller DR, Balkissoon RC, Winget DB, et al. Use of fluticasone in acute symptomatic pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. Oct 2002;19(3):198-204. [Medline].

  25. Chesnutt AN. Enigmas in sarcoidosis. West J Med. Jun 1995;162(6):519-26. [Medline].

  26. Devaney K, Goodman ZD, Epstein MS, Zimmerman HJ, Ishak KG. Hepatic sarcoidosis. Clinicopathologic features in 100 patients. Am J Surg Pathol. Dec 1993;17(12):1272-80. [Medline].

  27. Gibson GJ, Prescott RJ, Muers MF, Middleton WG, Mitchell DN, Connolly CK, et al. British Thoracic Society Sarcoidosis study: effects of long term corticosteroid treatment. Thorax. Mar 1996;51(3):238-47. [Medline].

  28. Hunninghake GW. Goal of the treatment for sarcoidosis. Minimize harm for the patient. Am J Respir Crit Care Med. Nov 1997;156(5):1369-70. [Medline].

  29. Hunninghake GW, Gilbert S, Pueringer R, Dayton C, Floerchinger C, Helmers R, et al. Outcome of the treatment for sarcoidosis. Am J Respir Crit Care Med. Apr 1994;149(4 Pt 1):893-8. [Medline].

  30. Johns CJ, Zachary JB, MacGregor MI, Curtis JL, Scott PP, Terry PB. The longitudinal study of chronic sarcoidosis. Trans Am Clin Climatol Assoc. 1982;94:173-81. [Medline].

  31. Kataria YP, Holter JF. Immunology of sarcoidosis. Clin Chest Med. 1997;18:719-740. [Medline].

  32. Moller DR. Etiology of sarcoidosis. Clin Chest Med. 1997;14:695-706. [Medline].

  33. Newman LS, Rose CS, Maier LA. Sarcoidosis [published erratum appears in N Engl J Med 1997 Jul 10;337(2):139]. N Engl J Med. Apr 24 1997;336(17):1224-34. [Medline].

  34. Paramothayan S, Jones PW. Corticosteroid therapy in pulmonary sarcoidosis: a systematic review. JAMA. Mar 13 2002;287(10):1301-7. [Medline].

  35. Sharma OP. Cardiac and neurologic dysfunction in sarcoidosis. Clin Chest Med. Dec 1997;18(4):813-25. [Medline].

  36. Winterbauer RH, Kirtland SH, Corley DE. Treatment with corticosteroids. Clin Chest Med. Dec 1997;18(4):843-51. [Medline].

  37. Zissel G, Müller-Quernheim J. Sarcoidosis: historical perspective and immunopathogenesis (Part I). Respir Med. Feb 1998;92(2):126-39. [Medline].

Previous
Next
 
Stage I sarcoidosis.
Stage II sarcoidosis.
Stage III sarcoidosis.
Noncaseating granuloma.
Table 1. Prognosis
StageRemission (%)Asymptomatic at 5 y (%)CXR Clearing (%)Mortality (%)
Stage I60-9095540
Stage II40-70583111
Stage III10-20251018
Stage IV0N/A0N/A
Table 2. Results of Multicenter Trial Sponsored by the British Thoracic Society
CharacteristicsGroup L*Group SP
Dyspnea score (range 1-4)0.240.47NS
Fibrosis score (range 0-16)0.831.47NS
FEV1 (% predicted)95.986.90.05
VC§ (% predicted)99.890.80.02
DLCOII (% predicted)84.377.7NS
Weight gain (kg)+3.26+0.990.02
*Long-term steroids



†Short bursts of steroids



‡Forced expiratory volume in 1 second



§Ventilatory capacity



II Diffusing capacity of lung for carbon monoxide



Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.