Sarcoidosis - Angiotensin Converting Enzyme

Sarcoidosis is a multisystemic disorder of unknown etiology, characterized by granuloma formation.

Epidemiology

• Incidence – 10-15/100,000 in U.S.; 40/100,000 in some North European countries and among African Americans
• Age – peak incidence 20-39 years
• Sex – F>M
• Ethnicity – most prevalent in Swedish, Danish and African Americans

Risk Factors

• Family member with sarcoidosis (5-fold increased risk)

Pathophysiology

• Result of chronic immunological response associated with a genetic susceptibility and specific infections or environmental factors
• Accumulation of activated T-cells and macrophages at site of disease activity
• Lymphocytes are CD4 type
• Macrophages release cytokines that drive inflammation, granuloma formation and eventual fibrosis

Disease Stages

• Stage I – isolated thoracic lymphadenopathy
• Stage II – lymphadenopathy plus lung infiltration
• Stage III – lung infiltration
• Stage IV – overt pulmonary fibrosis

Clinical Presentation

• Asymptomatic (30-50%) diagnosed by routine chest X-ray with abnormalities of hilar adenopathy
• Nonspecific (30%) – fever, weight loss, fatigue
• Pulmonary (30%)
  • Löfgren syndrome – bilateral hilar adenopathy, ankle arthritis, fever, myalgia, weight loss and erythema nodosum
  • Dyspnea, wheezing
• Dermatologic – maculopapular rashes, plaques and nodules (lupus pernio), erythema nodosum and lupus pernio
• Cardiac – rhythm disorders, infiltrative cardiomyopathy and pericarditis
• Ophthalmic – anterior uveitis
• Hepatic/Splenic – granulomas, but dysfunction is rare
• Endocrine – hypercalcemia with nephrolithiasis
• Central nervous system (CNS) – neurosarcoidosis is an uncommon, but serious manifestation of sarcoidosis, affecting about 5-10% of patients
  • The most common manifestations include myelopathy, cranial neuropathy and encephalopathy
  • Untreated patients may develop acute neurologic emergencies, including seizures, cord compression and increased intracranial pressure
  • Heerfordt’s syndrome – uveitis, parotid gland enlargement, fever and cranial neuropathy (usually 7th nerve)

Diagnosis

• Indications for testing – lymphadenopathy on chest x-ray or other appropriate clinical signs and symptoms consistent with diagnosis of sarcoidosis
• Laboratory testing
  • Rule out other granulomatous diseases – consider stains and cultures for fungi and tuberculosis (TB test)
  • Chemistry panel – may demonstrate hypercalcemia (~10%), hypercalcuria (~30%) or liver transaminase elevations (~20%)
  • Angiotensin converting enzyme (ACE) – may have elevated level (2x normal) but this is not diagnostic for disease
    • Reflects disease activity and may be useful to follow disease activity
    • Cerebrospinal fluid (CSF) ACE – elevated level supports diagnosis of neurologic sarcoidosis but is not diagnostic
• Histology – presence of noncaseating granulomas
• Fiber optic bronchoscopy with bronchoalveolar lavage, transbronchial biopsy or endobronchial biopsy
  • CD4/CD8 ratio higher than 3.5 is suggestive of sarcoidosis and is further supported if ACE levels are abnormal
  • If criteria above are met and clinical presentation is consistent with sarcoidosis, absence of granulomas on biopsy does not negate the diagnosis of sarcoidosis
• Pulmonary function testing – full function testing with diffusing capacity of the lung for carbon monoxide (DLCO) demonstrates decreased volumes and diffusion capacity
• Imaging studies
  • Pulmonary disease – high resolution CT produces better diagnostic yield than a chest X-ray; classically shows widespread micronodules with perilymphangitic distribution in middle and upper lobes (unnecessary test for most patients)
    • Justified when there are atypical chest X-ray findings or normal chest X-rays but suspicion of disease
    • For detection of complications of lung disease
  • Central nervous system disease
    • Gadolinium-enhanced MRI

Differential Diagnosis

• Chronic beryllium disease
• Fungal infection
• Hypersensitivity pneumonitis
• Malignancy – lymphoma
• Tuberculosis
• Wegener’s granulomatosis

Indications for Ordering

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

General References

References from the ARUP Institute for Clinical and Experimental Pathology®