eMedicine Specialties > Dermatology > Reactive & Inflammatory Dermatoses

Sarcoidosis: Differential Diagnoses & Workup

Author: Karen Podlipsky Gould, MD, Physician, Private Practice
Coauthor(s): Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Sep 8, 2009

Differential Diagnoses

Cutaneous Tuberculosis
Lupus Erythematosus, Subacute Cutaneous
Drug Eruptions
Lymphocytoma Cutis
Granuloma Annulare
Necrobiosis Lipoidica
Granuloma Faciale
Psoriasis, Plaque
Ichthyosis, Lamellar
Syphilis
Leprosy
Tinea Corporis
Lichen Planus
Lupus Erythematosus, Discoid

Other Problems to Be Considered

B-cell lymphoma
Foreign body reaction
Lichen planopilaris

Workup

Laboratory Studies

  • CBC count with differential and platelets
    • Leukopenia and/or thrombocytopenia are frequent findings.
    • Eosinophilia occurs in 24% of patients, and anemia occurs in 5% of patients.
  • Serum calcium and 24-hour urine calcium levels
    • Hypercalciuria has been found in 49% of patients in some studies, whereas 13% of patients had hypercalcemia.
    • Hypercalcemia occurs in sarcoidosis due to increased intestinal absorption of calcium that results from overproduction of a metabolite of vitamin D by pulmonary macrophages.
  • Serum angiotensin-converting enzyme (ACE) level11
    • Serum ACE level is elevated in 60% of patients; therefore, this test is not sensitive in diagnosing sarcoidosis.
    • Serum ACE levels are helpful in monitoring disease activity and treatment response. ACE is derived from epithelioid cells of the granulomas, therefore, it reflects granuloma load in the patient.
  • Serum chemistries, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, BUN, and creatinine levels: These levels may be elevated with hepatic and renal involvement.
  • Other: Elevated liver function tests suggestive of hepatic dysfunction, elevated erythrocyte sedimentation rate, elevated anti-nuclear antibodies (30%), diabetes insipidus, and renal failure may be noted.

Imaging Studies

  • Chest radiography
    • Radiographic involvement is seen in almost 90% of patients. Chest radiography is used in staging the disease.
    • Stage I disease shows bilateral hilar lymphadenopathy (BHL). Stage II disease shows BHL plus pulmonary infiltrates. Stage III disease shows pulmonary infiltrates without BHL (see Media Files 2-3). Stage IV disease shows pulmonary fibrosis.


Bilateral hilar lymphadenopathy.

Bilateral hilar lymphadenopathy.

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Bilateral hilar lymphadenopathy.

Bilateral hilar lymphadenopathy.



Stage III pulmonary disease with pulmonary infilt...

Stage III pulmonary disease with pulmonary infiltrates.

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Stage III pulmonary disease with pulmonary infilt...

Stage III pulmonary disease with pulmonary infiltrates.

  • CT of the thorax
    • CT of the thorax may demonstrate lymphadenopathy or granulomatous infiltration.
    • Other findings may include small nodules with a bronchovascular and subpleural distribution, thickened interlobular septae, honeycombing, bronchiectasis, and alveolar consolidation.
  • Whole body gallium Ga 67 scanning
    • Two common findings seen in sarcoidosis are the lambda and panda patterns.
    • The lambda pattern is produced by uptake of the right paratracheal and bilateral hilar lymph nodes. The panda image is produced by symmetric uptake by the lacrimal and parotid glands.
    • Also see the Society of Nuclear Medicine clinical guideline summary, Procedure guideline for gallium scintigraphy in inflammation.12

Other Tests

  • Kveim test
    • This test is the most specific test for sarcoidosis. It is not commonly available because of difficulty in obtaining a validated antigen source as well as a fear of transmitting infection.
    • The Kveim test involves intradermal injection of tissue from the spleen or the lymph node of a patient with sarcoidosis. A biopsy sample is obtained from the area 4-6 weeks after injection, and it is histologically examined for noncaseating granuloma formation, which, if found, indicates a positive result.
  • Tuberculin skin test
    • Patients with sarcoidosis have impaired delayed-type immune reactions.
    • Two thirds of patients have cutaneous anergy to the tuberculin skin test.
  • Pulmonary function test
    • The most common abnormalities found are defects in diffusing capacity and vital capacity.
    • Evidence of both restrictive abnormalities and obstructive abnormalities may be found.
  • Bronchoalveolar lavage with a CD4/CD8 ratio: A CD4/CD8 ratio of more than 3.5 has a specificity of 94% for sarcoidosis.
  • Electrocardiogram
    • An ECG should be performed to rule out unsuspected or asymptomatic arrhythmias or heart block.
    • Unsuspected ECG abnormalities may be seen in 10% or more of patients with systemic sarcoidosis, including Löfgren syndrome (see Physical).

Procedures

  • Biopsy of tissue
    • The skin is the most easily accessible tissue for biopsy. Biopsy of all cutaneous lesions of sarcoidosis, except EN, is helpful because, histologically, EN is not specific for sarcoidosis.
    • Obtaining a biopsy specimen is extremely important in confirming the diagnosis of sarcoidosis.
    • Biopsy specimens need to be sent for histologic examination, and staining may need to be performed to rule out infectious causes of granuloma formation, including mycobacterial and deep fungal infections.
    • Tissue culture may be appropriate in some clinical settings, especially if fungal or atypical mycobacterial infections are suspected.
    • A biopsy sample of bronchial mucosa demonstrates the presence of noncaseating granulomas.

Histologic Findings

Typical sarcoid lesions are characterized by the presence of circumscribed granulomas of epithelioid cells with little or no necrosis (see Media File 10).

Histopathologic features of sarcoidosis showing t...

Histopathologic features of sarcoidosis showing the hallmark noncaseating granulomas.

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Histopathologic features of sarcoidosis showing t...

Histopathologic features of sarcoidosis showing the hallmark noncaseating granulomas.


Granulomas are usually in the superficial dermis, but they may involve the thickness of the dermis and extend to the subcutaneous tissue. Islands of epithelioid cells may contain a few Langhans giant cells. Giant cells may contain asteroid or Schaumann bodies. Asteroid bodies are star-shaped eosinophilic structures. Schaumann bodies are round or oval, laminated structures, which are usually calcified at the periphery. Granulomas are referred to as naked because they only have a sparse lymphocytic infiltrate at the margins or granulomas. Fibrosis, if present, usually starts at the periphery and advances toward the center.

More on Sarcoidosis

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

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Keywords

sarcoidosis, angiolupoid sarcoid, Besnier-Boeck-Schaumann disease, Boeck's sarcoid, Darier-Roussy disease, lupus pernio, multiple benign sarcoid of Boeck, Schaumann benign lymphogranulomatosis, subcutaneous sarcoid, uveoparotid fever

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Contributor Information and Disclosures

Author

Karen Podlipsky Gould, MD, Physician, Private Practice
Karen Podlipsky Gould, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey P Callen, MD, Professor of Medicine, Chief, Division of Dermatology, University of Louisville School of Medicine
Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and American College of Rheumatology
Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Electrical Optical Sciences Honoraria Consulting; Centocor Honoraria Consulting; Medicis Honoraria Consulting; Celgene Honoraria Consulting

Medical Editor

Ponciano D Cruz Jr, MD, Vice-Chair, JB Shelmire Professor, Department of Dermatology, University of Texas Southwestern Medical Center
Ponciano D Cruz Jr, MD is a member of the following medical societies: Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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