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).

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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]

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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.

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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.

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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 S†P
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



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