eMedicine Specialties > Pulmonology > Interstitial Lung Diseases

Sarcoidosis

Author: Nader Kamangar, MD, FACP, FCCP, FAASM, Assistant Professor of Medicine, Director of Hospitalist/Intensivist Program, Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine at University of California Los Angeles; Associate Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA/West Los Angeles Veterans Affairs Medical Center
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
Contributor Information and Disclosures

Updated: Apr 17, 2009

Introduction

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.

R elated eMedicine articles include Sarcoidosis (emergency medicine focus), Sarcoidosis (dermatology focus), and Sarcoidosis (ophthalmology focus).

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 pentoxifylline1 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.

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.

Race

See Frequency, United States.

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.

Clinical

History

  • Presentation depends on the extent and severity of the organ involved.
    • Approximately 5% of cases are asymptomatic and incidentally detected by CXR.
    • Systemic complaints, fever, anorexia, and arthralgias occur in 45% of cases.
    • Pulmonary, dyspnea on exertion, cough, chest pain, and hemoptysis (rare) occur in 50% of cases.
    • Löfgren syndrome
      • Symptoms consist of fever, bilateral hilar lymphadenopathy (BHL), and polyarthralgias.
      • This presentation is associated with an excellent prognosis.
      • While common in Scandinavian patients, it is uncommon in African American and Japanese patients.

Physical

  • Pulmonary findings
    • They usually are normal but may be significant for crackles.
    • Exertional oxygen desaturation also may be found.
  • CXR staging system
    • Stage 0 is normal CXR findings.
    • Stage I is BHL.
Stage I sarcoidosis.

Stage I sarcoidosis.

[ CLOSE WINDOW ]
Stage I sarcoidosis.

Stage I sarcoidosis.


    • Stage II is BHL and infiltrates.


Stage II sarcoidosis.

Stage II sarcoidosis.

[ CLOSE WINDOW ]
Stage II sarcoidosis.

Stage II sarcoidosis.


    • Stage III is infiltrates alone.


Stage III sarcoidosis.

Stage III sarcoidosis.

[ CLOSE WINDOW ]
Stage III sarcoidosis.

Stage III sarcoidosis.


    • Stage IV is fibrosis.
  • Dermatological manifestations
    • Erythema nodosum may occur.
      • A lower extremity panniculitis with painful, erythematous nodules
      • Associated with Löfgren syndrome but may be seen in other conditions
    • Lupus pernio is the most specific associated cutaneous lesion.
    • Violaceous rash is often seen on the cheeks or nose.
    • Osseous involvement may be present.
    • Maculopapular plaques are possible.
  • Ocular manifestations
    • Anterior or posterior granulomatous uveitis is most frequent.
    • Conjunctival lesions and scleral plaques may also be noted.
    • Ocular involvement may lead to blindness if untreated.
  • Cardiac manifestations
    • Heart failure from cardiomyopathy rarely occurs.
    • Heart block and sudden death may occur.
    • Approximately 25% of patients may have NCGs at autopsy, but fewer than 5% have clinical cardiac disease.
    • Okada et al reported on cardiac infiltration associated with a novel heterogenous mutation (G481D in CARD15) in early-onset sarcoidosis.4
  • Neurologic manifestations (rare)
    • Cranial nerve palsies and hypothalamic/pituitary dysfunction may occur.
    • Lymphocytic meningitis is the most common neurologic manifestation.

Causes

  • The cause of the disease is not known; however, both genetic and environmental factors seem to play a role. As yet, no bacterial, fungal, or viral antigen has been consistently isolated from the sarcoidosis lesions. Sarcoidosis is neither a malignant nor an autoimmune disease. An ongoing National Institutes of Health (NIH)–supported study is investigating genetic and acquired causes of sarcoidosis. Additionally, Sverrild et al reported from a twin study that genetic factors play an important role in an individual’s susceptibility to sarcoidosis.5
  • The following have been suggested as possible candidates that might play a role in causing sarcoidosis.
    • Mycobacteria, such as Mycobacterium tuberculosis, and atypical pathogens have been suggested.
    • Fungi and viruses, particularly Mycoplasma, Chlamydia, and Epstein-Barr virus, have been unconvincingly implicated.

More on Sarcoidosis

Overview: Sarcoidosis
Differential Diagnoses & Workup: Sarcoidosis
Treatment & Medication: Sarcoidosis
Follow-up: Sarcoidosis
Multimedia: Sarcoidosis
References
[ CLOSE WINDOW ]

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. 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].

  5. [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].

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

  7. 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].

  8. 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].

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

  10. 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].

  11. 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].

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

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

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

  15. 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].

  16. 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].

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

  18. 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].

  19. 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].

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

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

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

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

  28. 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].

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

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

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

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

sarcoidosis, sarcoid, noncaseating granulomas, NCGs, non-caseating granulomas, lung disease, pulmonary disease, cardiac sarcoid, sarcoid lesion

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Nader Kamangar, MD, FACP, FCCP, FAASM, Assistant Professor of Medicine, Director of Hospitalist/Intensivist Program, Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine at University of California Los Angeles; Associate Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA/West Los Angeles Veterans Affairs Medical Center
Nader Kamangar, MD, FACP, FCCP, FAASM 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.

Medical Editor

Stephen P Peters, MD, PhD, Professor, Department of Medicine, Wake Forest University
Stephen P Peters, MD, PhD 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

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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: Keck School of Medicine, USC None None

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint 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, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
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.