eMedicine Specialties > Emergency Medicine > Rheumatology

Sarcoidosis: Differential Diagnoses & Workup

Author: Ramy Yakobi, MD, MBA, Medical Director of Emergency Department, Beth Israel/Kings Highway Division; Lecturer, Physician Assistant School, Cornell School of Medicine; Lecturer, Pre-hospital Management of Patient, Cornell/New York Presbyterian Hospital; Director of Emergency Department, New York Community Hospital
Contributor Information and Disclosures

Updated: Jul 28, 2009

Differential Diagnoses

Arthritis, Rheumatoid
Systemic Lupus Erythematosus
Multiple Sclerosis
Tuberculosis
Pericarditis and Cardiac Tamponade
Pneumothorax, Iatrogenic, Spontaneous and Pneumomediastinum
Pulmonary Embolism

Other Problems to Be Considered

Angina
Bronchitis
Fungal pneumonia
Histiocytosis X
Leprosy
Lymphoma
Lung cancer
Pulmonary alveolar proteinosis (PAP)
Pneumoconiosis (eg, silicosis, berylliosis)

Workup

Laboratory Studies

  • Complete blood count
  • Leukocytosis

    • With or without eosinophilia
    • Elevated erythrocyte sedimentation rate (ESR)
  • Hypercalcemia is observed in 10-15% of cases. (It may be helpful to remember the mnemonic "Pam P. Schmidt," in which P represents parathyroid hormone [PTH], A represents Addison, M represents multiple myeloma, P represents Paget, S represents sarcoidosis [or other granulomatous disease], C represents cancer [lungs, multiple myeloma, breast], M represents milk-alkali syndrome, I represents immobilization, D represents vitamin D, and T represents thiazides.) Although hypercalcemia is present by definition, it is rarely clinically significant. If other organs are involved, such as the liver, kidney, or endocrine organs, laboratory results pertinent to these organs are abnormal.
  • Serum angiotensin-converting enzyme (ACE) level is elevated in 75% of cases. The value of monitoring ACE levels remains unclear.
  • The serum PO4 and alkaline phosphatase levels can be increased.
  • A 24-hour urinalysis assessment indicates that calcium levels are increased.
  • A slit lamp examination generally is obtained periodically, even if the patient is asymptomatic.
  • Immunologic studies can show falsely elevated antinuclear antibodies (ANA) and rheumatoid factor (RF) levels and hypergammaglobulinemia.
  • Patients with sarcoidosis may have myocardial involvement and elevated creatine kinase (CK) and CK-MB levels.

Imaging Studies

  • Chest radiography is an integral part of the diagnosis and staging. In addition, the radiograph may demonstrate pleural involvement, such as a pneumothorax or pleural effusion.
    • Stage O - No findings
    • Stage I - Bilateral hilar adenopathy
    • Stage II - Bilateral hilar adenopathy and parenchymal involvement (reticular opacities)
    • Stage III - Parenchymal involvement (reticular opacities) with shrinking adenopathy
    • Stage IV - Parenchymal involvement turns into volume loss (pulmonary fibrosis); cavitations and calcifications may also be seen


Stage II sarcoidosis. Courtesy of Anthony Notino,...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.

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Stage II sarcoidosis. Courtesy of Anthony Notino,...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.



Stage II sarcoidosis. Courtesy of Anthony Notino...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.

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Stage II sarcoidosis. Courtesy of Anthony Notino...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.

  • Gallium 67 scanning is used for staging of disease and for detecting extrapulmonary sarcoidosis. Gallium bound by inflammatory tissue and not by fibrotic tissue can distinguish areas of fibrosis from inflammation.
  • Other types of radiotracer scanning may be available. Technetium-labeled depreotide that binds somatostatin receptors was used with good results in some cases.


Stage II sarcoidosis. Courtesy of Anthony Notino,...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.

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Stage II sarcoidosis. Courtesy of Anthony Notino,...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.



Stage II sarcoidosis. Courtesy of Anthony Notino,...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.

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Stage II sarcoidosis. Courtesy of Anthony Notino,...

Stage II sarcoidosis. Courtesy of Anthony Notino, MD, New York Hospital, Department of Radiology, Cornell Medical Center.

Other Tests

  • Skin anergy with purified protein derivative (PPD) is common in patients with sarcoidosis but obviously not specific.
  • Kveim-Stilzbach test
    • A suspension from the spleen or a lymph node of a patient with a confirmed diagnosis of sarcoidosis is injected intradermally into a patient suspected to be affected by the disease.
    • Test results are considered positive if a nodule appears within 2-7 weeks.
    • A biopsy sample is then taken from the nodule to find similarities to sarcoid granuloma.
    • The time required for this test, the incidence of false-negative and false-positive results, and the availability of more timely diagnostic tests make this procedure unpopular in the United States. 
  • Electrocardiography
    • Signs of hypercalcemia (eg, decreased QT interval)
    • Ventricular tachycardia
    • Bundle-branch block or complete heart blocks
    • ST elevation, PR depression caused by pericarditis, or ST elevation caused by ventricular aneurysm 
  • A Holter monitor may be indicated to detect arrhythmias.
  • Bronchoalveolar lavage (BAL) is useful as an adjunct in demonstrating CD4/CD8 ratio.

Procedures

  • Bronchoalveolar lavage
    • BAL shows increases in the CD4/CD8 ratio, lymphocytes, and cytokines.
    • Studies performed to correlate the presence of these markers with prognosis were not conclusive. However, a study by Bacha et al has shown that a high CD4/CD8 ratio seems to be predictive of a poor prognosis in those with multiple extrathoracic organ involvement. Their study of 40 patients with clinically and histologically evident sarcoidosis showed that, before corticosteroid treatment, total cell count was increased with a T lymphocytosis and an increase in the CD4/CD8 ratio, as shown in BAL fluid. After corticosteroid treatment, a significant decrease in CD4/CD8 ratio and lymphocyte proportion was noted in BAL fluid. Patients with multiple extrathoracic lesions had significantly higher CD4/CD8 ratios compared with those with only intrathoracic involvement.2
  • Biopsy is an integral part of the diagnosis and is of very high yield.
    • The site of biopsy is dictated by clinical presentation of the organ involved.
    • The sensitivity is highest from lung parenchyma and 5-10 biopsy specimens generally are needed.
  • Pulmonary function tests (PFTs) are not required for diagnosis, but results may range from reference range to findings consistent with restrictive lung disease.

More on Sarcoidosis

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

  1. Peros-Golubicic T, Ljubic S. Cigarette smoking and sarcoidosis. Acta Med Croatica. 1995;49(4-5):187-93. [Medline].

  2. Bacha D, Ayadi-Kaddour A, Ismail O, El Mezni F. Bronchoalveolar lavage impact in sarcoidosis: study of 40 cases. Tunis Med. Jan 2009;87(1):38-42. [Medline].

  3. Drent M. Association of heterozygote glucose-6-phosphate-dehydrogenase deficiency with more advanced disease in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. Mar 1999;16(1):108-9. [Medline].

  4. Belfer MH, Stevens RW. Sarcoidosis: a primary care review. Am Fam Physician. Dec 1998;58(9):2041-50, 2055-6. [Medline].

  5. Chapelon-Abric C, de Zuttere D, Duhaut P, Veyssier P, et al. Cardiac sarcoidosis: a retrospective study of 41 cases. Medicine (Baltimore). Nov 2004;83(6):315-34. [Medline].

  6. du Bois RM. Corticosteroids in sarcoidosis: friend or foe?. Eur Respir J. Jul 1994;7(7):1203-9. [Medline].

  7. Erb N, Cushley MJ, Kassimos DG, Shave RM, Kitas GD. An assessment of back pain and the prevalence of sacroiliitis in sarcoidosis. Chest. Jan 2005;127(1):192-6. [Medline].

  8. Khan AH, Ghani F, Khan A, Khan MA, Khurshid M. Role of serum angiotensin converting enzyme in sarcoidosis. J Pak Med Assoc. May 1998;48(5):131-3. [Medline].

  9. Lewis SJ, Ainslie GM, Bateman ED. Efficacy of azathioprine as second-line treatment in pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. Mar 1999;16(1):87-92. [Medline].

  10. Soliman DM, Twigg HL III. Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages. Am J Physiol. Oct 1992;263(4 Pt 1):L471-8. [Medline].

  11. Tanoue LT, Elias JA. Systemic sarcoidosis. In: Textbook of Pulmonary Disease. 6th ed. Lippincott-Raven; 1998:407-28.

  12. Wahlstrom J, Berlin M, Skold CM, Wigzell H, Eklund A, Grunewald J. Phenotypic analysis of lymphocytes and monocytes/macrophages in peripheral blood and bronchoalveolar lavage fluid from patients with pulmonary sarcoidosis. Thorax. Apr 1999;54(4):339-46. [Medline].

  13. Young C, Burrows R, Katz J, Beynon H. Hypercalcaemia in sarcoidosis. Lancet. Jan 30 1999;353(9150):374. [Medline].

  14. Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, et al. Central nervous system sarcoidosis--diagnosis and management. QJM. Feb 1999;92(2):103-17. [Medline].

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Further Reading

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Keywords

sarcoidosis, multiorgan disease, granulomatous disease, granulomas, noncaseating granulomas, lung disease, erythema nodosum, Kveim-Stilzbach test, bronchoalveolar lavage, pulmonary function test, PFT, tuberculosis, pneumonia, hypercalcemia, immunoglobulin M, IgM, hyperglobulinemia

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Contributor Information and Disclosures

Author

Ramy Yakobi, MD, MBA, Medical Director of Emergency Department, Beth Israel/Kings Highway Division; Lecturer, Physician Assistant School, Cornell School of Medicine; Lecturer, Pre-hospital Management of Patient, Cornell/New York Presbyterian Hospital; Director of Emergency Department, New York Community Hospital
Ramy Yakobi, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians
Disclosure: Nothing to disclose.

Medical Editor

Joseph A Salomone III, MD, EMS Medical Director, Kansas City, Missouri; Associate Professor and Staff Physician, Truman Medical Centers/UMKC School of Medicine
Joseph A Salomone III, MD is a member of the following medical societies: American Academy of Emergency Medicine, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine
Gino A Farina, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
Robert E O'Connor, MD, MPH is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physician Executives, American Heart Association, American Medical Association, Medical Society of Delaware, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

 
 
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