eMedicine Specialties > Ophthalmology > Unclassified Disorders

Sarcoidosis: Differential Diagnoses & Workup

Author: Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Coauthor(s): L Raymond DeBarge, MD, Assistant Professor, Department of Ophthalmology, University of Tennessee College of Medicine at Chattanooga
Contributor Information and Disclosures

Updated: Dec 5, 2008

Differential Diagnoses

Acute Retinal Necrosis
Leiomyoma, Iris
Amblyopia
Lyme Disease
Ankylosing Spondylitis
Macular Edema, Irvine-Gass
Behcet Disease
Melanoma, Choroidal
Bell Palsy
Multifocal Choroidopathy Syndromes
Branch Retinal Artery Occlusion
Neovascular Membranes, Subretinal
Branch Retinal Vein Occlusion
Neovascularization, Choroidal
Central Retinal Vein Occlusion
Nonpseudophakic Cystoid Macular Edema
Chalazion
Ocular Hypertension
Coccidioidomycosis
Ocular Hypotony
Conjunctivitis, Allergic
Ocular Manifestations of Syphilis
Dacryoadenitis
Oculomotor Nerve Palsy
Dacryocystitis
Optic Neuritis, Adult
Diplopia
Papilledema
Dry Eye Syndrome
Pigmented Lesions of the Eyelid
Eales Disease
Pseudopapilledema
Epimacular Membrane
Ptosis, Adult
Episcleritis
Retinal Detachment, Exudative
Exophthalmos
Scleritis
Giant Cell Arteritis
Sjogren Syndrome
Glaucoma, Angle Closure, Acute
Sudden Visual Loss
Glaucoma, Angle Closure, Chronic
Synechia, Peripheral Anterior
Glaucoma, Low Tension
Toxoplasmosis
Glaucoma, Primary Open Angle
Trochlear Nerve Palsy
Glaucoma, Uveitic
Tuberculosis
Gout
Tumors, Orbital
HLA-B27 Syndromes
Uveitis, Anterior, Childhood
Idiopathic Intracranial Hypertension
Uveitis, Anterior, Granulomatous
Inflammatory Bowel Disease
Uveitis, Anterior, Nongranulomatous
Keratitis, Interstitial
Uveitis, Fuchs Heterochromic
Keratoconjunctivitis, Sicca
Uveitis, Intermediate
Keratopathy, Band
Vogt-Koyanagi-Harada Disease
Lacrimal Gland Tumors

Other Problems to Be Considered

Neurosarcoid

Giant cell arteritis, epidemic parotitis, Hodgkin disease, leprosy, syphilis, tuberculosis (TB), multiple sclerosis (MS), Lyme disease (facial nerve palsies and nerve root syndromes), Wegener granulomatosis, Behçet disease, and meningeal carcinomatosis

Ocular sarcoid

Eyelid granulomatous processes include chalazia, dermal tuberculosis, fungal infections, juvenile xanthogranuloma, and foreign bodies.

Orbital granulomatous pathologies comprise lipogranulomas, Wegener granulomatosis, TB, syphilis, fungal infections, parasites (eg, microfilariae, nematode larvae), and panophthalmitis.

Uveitic entities in the differential diagnosis of granulomatous uveitis: Infectious entities include nonpyogenic systemic infections associated with TB, cat-scratch disease, syphilis, brucellosis, leprosy, and leptospirosis. Protozoan infections include amebiasis, toxoplasmosis, and trypanosomiasis. Fungal infections include actinomycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, nocardiosis, and sporotrichosis. Helminth infestations include Ascaris, cysticercosis, taeniasis, Diptera larvae, and nematode infestations (onchocerciasis and Toxocara, Ancylostoma, and Necator species). Viral uveitis includes herpes simplex, herpes zoster, vaccinia, and cytomegalovirus.

Other entities in the differential diagnosis are lens-induced uveitis, lymphoma, histiocytosis X, and neoplastic and posttreatment of ocular melanoma with proton beam irradiation.

Differential diagnosis of posterior uveitis that may clinically mimic sarcoidosis includes the following: birdshot chorioretinopathy; Vogt-Koyanagi-Harada syndrome; sympathetic ophthalmia; toxoplasmosis; Behçet disease; acute multifocal choroiditis; MS; TB; syphilis; vasculitides due to Wegener granulomatosis, systemic lupus erythematosus (SLE), Whipple disease, ankylosing spondylitis, Crohn disease, and relapsing polychondritis; acute multifocal placoid pigment epitheliopathy (AMPPE); and CNS lymphoma.

Workup

Laboratory Studies

  • The serum level of ACE is frequently elevated in sarcoidosis and is of value in supporting the diagnosis of sarcoidosis. The ACE level may be useful in the monitoring of disease activity. This is particularly true in extrathoracic disease when typical chest radiologic findings are absent. Serum levels tend to be higher in clinically active disease but may be low at the onset of acute disease. Combined use of ACE levels with gallium scans increased the diagnostic specificity in cases of clinically active systemic sarcoidosis from 83% to 99% when compared to ACE levels alone, without sacrificing sensitivity. CSF ACE levels may be elevated in up to 50% of patients with neurosarcoid.
  • The serum calcium level may be elevated in 5-18% of patients with sarcoidosis, reflecting the remote effects of 1,25-dihydroxyvitamin D metabolism.

Imaging Studies

  • Chest x-rays have been used to stage disease activity. A good quality chest x-ray is sufficient when typical changes are observed. Requesting an evaluation for sarcoidosis is imperative when ordering a chest x-ray since the radiologist will be far more likely to make subtle observations supporting the diagnosis of sarcoidosis.
  • Neuroimaging: In suspected neurosarcoidosis, MRI may be invaluable. MRI is generally more useful than CT scan, especially with posterior fossa disease. The most common lesions on MRI include multiple white matter lesions, meningeal enhancement, optic nerve enhancement and mass lesions in the brain parenchyma. The distinction from demyelinating disease can often be difficult.
  • Nuclear studies: To highlight potential biopsy sites and to aid in tissue diagnosis, gallium scans are often obtained in cases of suspected neurosarcoidosis when both chest x-ray findings and serum ACE levels are normal. Gallium 67 citrate scans often are supportive when typical findings are lacking. This is especially true in neurosarcoidosis or uveitis when a biopsy may not be feasible.

Procedures

  • Diagnosis requires a biopsy in most cases. As a rule, the most accessible site with the lowest morbidity should be considered. A biopsy should be performed on palpable lymph nodes or elevated superficial skin lesions, if present.
    • Conjunctival biopsy: Conjunctival tissue is readily available with low morbidity. A biopsy should be considered even in the absence of lesions. A blind or random conjunctival biopsy yields positive histologic evidence of sarcoidosis in 10-28% cases of suspected sarcoidosis.
    • Lacrimal gland biopsy: In cases of lacrimal gland enlargement or when the lacrimal glands are involved on gallium scan, a biopsy may be useful. A transconjunctival approach has been recommended to minimize the risk of secondary keratoconjunctivitis sicca.
  • Bronchoscopy, particularly fiberoptic bronchoscopy, yields positive biopsy results in 60% of stage I disease and greater than 80% of stage II or III pulmonary sarcoidosis. Transbronchial or airway mucosal sampling is useful in the initial histologic confirmation of sarcoidosis.
  • Pulmonary function tests (PFTs) primarily reflect interstitial lung disease with decreased lung volumes. PFT results may be abnormal before chest x-ray findings and are useful in determining the extent of pulmonary involvement.

Histologic Findings

The typical histologic findings obtained from biopsy specimens include diffuse noncaseating epithelioid granulomas. Infectious etiologies need to be excluded by culture and/or staining.

The epithelioid granulomas are well-formed compact aggregates, of varying age, ranging from highly cellular to relatively acellular collections.

More on Sarcoidosis

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

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Keywords

sarcoidosis, ocular sarcoidosis, sarcoid, ocular sarcoid, neurosarcoid, neurosarcoidosis, granulomatous disease, noncaseating epithelioid granuloma, granulomata, Boeck disease, Boeck’s disease, Boeck's sarcoid, Hutchinson disease, Hutchinson’s disease

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Contributor Information and Disclosures

Author

Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Andrew A Dahl, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

L Raymond DeBarge, MD, Assistant Professor, Department of Ophthalmology, University of Tennessee College of Medicine at Chattanooga
L Raymond DeBarge, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Physicians, American Medical Association, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Medical Editor

John D Sheppard Jr, MD, MMSc, Professor of Ophthalmology, Microbiology and Molecular Biology, Clinical Director, Thomas R Lee Center for Ocular Pharmacology, Program Director, Ophthalmology Residency Training, Eastern Virginia Medical School; President, Virginia Eye Consultants
John D Sheppard Jr, MD, MMSc is a member of the following medical societies: American Academy of Ophthalmology, American Society for Microbiology, American Society of Cataract and Refractive Surgery, American Uveitis Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

R Christopher Walton, MD, Professor, Director of Uveitis and Ocular Inflammatory Disease Service, Department of Ophthalmology, Assistant Dean for Graduate Medical Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital
R Christopher Walton, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Healthcare Executives, American Uveitis Society, Association for Research in Vision and Ophthalmology, and Retina Society
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
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