eMedicine Specialties > Pulmonology > Interstitial Lung Diseases

Sarcoidosis: Differential Diagnoses & Workup

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

Differential Diagnoses

Catscratch Disease
Lymphoma, Mediastinal
Eosinophilic Granuloma (Histiocytosis X)
Lymphoma, Non-Hodgkin
Lung Cancer, Non-Small Cell
Lymphomatoid Granulomatosis
Lung Cancer, Oat Cell (Small Cell)
Tuberculosis
Lymphoma, Diffuse Large Cell
Lymphoma, Follicular
Lymphoma, Lymphoblastic

Other Problems to Be Considered

Hilar infiltrates

Eosinophilic granuloma
Fungal infection
Lung cancer
Lymphoma
Tuberculosis

NCG on a biopsy

Berylliosis
Catscratch disease
Fungal infection
Hypersensitivity pneumonitis
Leprosy
Primary biliary cirrhosis
Tuberculosis

Workup

Laboratory Studies

  • Routine lab evaluation often is unrevealing.
  • Hypercalcemia or hypercalciuria may occur (NCGs secrete 1,25 vitamin D). Hypercalcemia is seen in about 10-13% of patients, whereas hypercalciuria is 3 times more common.
  • An elevated alkaline phosphatase level suggests hepatic involvement. Although liver involvement is common, it rarely is clinically relevant.
  • Angiotensin converting enzyme (ACE) levels may be elevated.
    • NCGs secrete ACE, which may function as a cytokine.
    • Serum ACE levels are elevated in 60% of patients at the time of diagnosis.
    • Serum ACE levels may correlate with total body granuloma load.
    • Levels may be increased in fluid from bronchoalveolar lavage or in cerebrospinal fluid.
    • Sensitivity and specificity as a diagnostic test is limited (60 and 70%, respectively).
    • There is no clear prognostic value.
    • Serum ACE levels may decline in response to therapy.
    • Decisions on treatment should not be based on the ACE level alone.

Imaging Studies

  • A chest radiograph is central to evaluation.
  • Routine chest CT scan adds little.
  • High-resolution CT (HRCT) scanning of the chest may be helpful.
    • It identifies active alveolitis versus fibrosis.
    • It correlates with yield of biopsy.
  • Gallium scans may be performed.
    • There is little correlation with clinical status.
    • The scan has low sensitivity and specificity as a diagnostic test.
    • It is used infrequently. Prior to the ease and availability of bronchoscopy, gallium scanning was occasionally employed as a diagnostic test. It may still be helpful in a subset of patients in whom the clinical picture remains confusing despite histologic evidence of NCGs (eg, differentiating chronic hypersensitivity pneumonitis from sarcoidosis).
  • The optimal imaging study for assessment of cardiac involvement is unclear. Some authors recommend the combined use of gallium and thallium scanning. However, the studies relying on this technique were small and were subject to significant bias. Moreover, even the criterion standard test for cardiac involvement, which is endomyocardial biopsy, is prone to sampling error, because sarcoidosis tends to be a patchy disease in cardiac tissue.

Other Tests

  • Pulmonary function tests (PFTs) and a carbon monoxide diffusion capacity test of the lungs for carbon monoxide (DLCO) may be performed.
    • They are used routinely in evaluation and follow-up.
    • The most common abnormality is an isolated decrease in DLCO.
    • A restrictive pattern is seen in patients with more advanced pulmonary disease.
    • Approximately 15-20% of patients have obstruction.
  • Cardiopulmonary exercise testing is a sensitive test for identifying and quantifying the extent of pulmonary involvement. Cardiopulmonary exercise testing also may suggest cardiac involvement that otherwise is not evident.
  • In accordance with the position statement of the American Thoracic Society, all patients should have an annual ECG. If patients report palpitations, this should prompt a through evaluation with at least a Holter monitor.

Procedures

  • Diagnosis requires biopsy in most cases.
  • Some asymptomatic patients who do not require treatment and only have BHL may be monitored without a biopsy.
  • Transbronchial biopsy (TBB) via fiberoptic bronchoscope is often done.
    • The yield is high.
    • Results may be positive, even in the setting of normal CXR findings.
  • Endobronchial biopsy is done during bronchoscopy and increases the yield of the procedure.
  • If therapy is to be given for sarcoidosis, tissue confirmation is essential. Watchful waiting is indicated only for patients who exhibit a classic presentation, are asymptomatic, and can ensure close follow-up.

Histologic Findings

The central histologic finding is the presence of NCGs with special stains negative for fungus and mycobacteria.

Noncaseating granuloma.

Noncaseating granuloma.

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Noncaseating granuloma.

Noncaseating granuloma.


More on Sarcoidosis

Overview: Sarcoidosis
Differential Diagnoses & Workup: Sarcoidosis
Treatment & Medication: Sarcoidosis
Follow-up: Sarcoidosis
Multimedia: Sarcoidosis
References
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References

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Further Reading

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Keywords

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

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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.

 
 
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