Sarcoidosis

 

Clinical Background

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 in 20s-30s
  • Sex – M<F
  • 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
    • 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 syndrome – uveitis, parotid gland enlargement, fever and cranial neuropathy (usually 7th nerve)