Sarcoidosis

Snapshot

• A previously healthy 30-year-old African American woman has fatigue, arthralgia, and a nodular rash over the trunk and upper extremities for three weeks. There are twelve 3-8 mm, pale, indurated plaques over the chest, back, and upper extremities. The liver is palpable 2 cm below the right costal margin with a percussion span of 14 cm, and the spleen tip is palpable 3 cm below the left costal margin. There is no pain or limitation of any of the joints. A chest radiograph shows bilateral lymphadenopathy.

Introduction

• Idiopathic condition characterized by granulmomatous inflammation of multiple organs
  • lungs most commonly involved organ
  • commonly causes restrictive lung disease 
    • may also cause obstructive or mixed pattern
  • mediated by CD4 T_H cells
    • ↑ IFN-gamma 
  • granulomas can affect all organ systems
    • liver/spleen
    • bone
    • heart
• Epidemiology
  • most common in black females
  • smoking does not ↑ risk
  • presents most commonly in 3rd or 4th decade
• Associated conditions
• diabetes insipidus (granulomatous infiltration of posterior pituitary)

Presentation

• Symptoms
  • may be asymptomatic
    • 50% as incidental chest radiograph findings
  • cough
  • fever, malaise
  • arthritis
    • symptoms mainly in the ankle and legs
  • can be GRUELING
    • Granulomas
    • Rheumatoid arthritis
    • Uveitis
    • Erythema nodosum
    • Lymphadenopahy
    • Interstitial fibrosis
    • Negative TB
    • Gammaglobulinemia
• Physical exam
  • skin lesions
    • nodular granulomatous lesions
    • facial rash
    • erthyma nodosum 
      • painful nodules
      • also seen in rheumatic fever
  • eye lesions
    • uveitis 
      • ↓ vision and glaucoma
• enlarged salivary and lacrimal glands

Evaluation

• Diagnosis is clinical and often one of exclusion
• Chest radiograph
  • bilateral hilar lymphadenopathy
  • lungs involved in 90% of the cases
• Labs
  • ↑ serum ACE (not uniformly) 
  • hypercalcemia 
    • ↑ 1-α-hydroxylase → hypervitaminosis D
      • can cause hypercalemia and renal failure chronically
    • commonly tested, less commonly seen (only about 11%)
  • serum protein electrophoresis (SPE) shows polyclonal gammopathy
  • lack of response to CD4 T_H skin tests (like PPD) due to ↑ lung activity and ↓ systemic activity
• Pulmonary function tests
  • restrictive pattern is common (normal FEV1/FVC with normal TLC)
    • however, obstructive or mixed pattern may also be seen
• Bronchoalveolar lavage
  • high CD4:CD8 T-cell ratio 
    • due to CD4 infiltrate into the interstitium as well as intralveolar space
    • contrasted to the low ratio in hypersensitivity pneumonitis and HIV
• Biopsy 
  • noncaseating granulomas with multinucleated giant cells   
    • very suggestive of sarcoidosis 
• laminated calcium concretions present (cause of density on CXR)

Treatment

• Conservative
  • observationfine in most cases 
    • majority experience remission within two years without treatment
• Pharmacologic
  • topical preferred when possible (skin, eyes, nasal, airway, etc)
  • corticosteroids
  • indications
    • extra-pulmonary manifestations: cardiac, neurologic, or uveitis
    • symptomatic hepatosplenomegaly
    • significant hypercalcemia
• only if refractory to observations

Prognosis

• Relapsing/remitting course with 50% resolving spontaneously
• Progression
  • Stage I – bilateral hilar lymphadenopathy
  • Stage II – bilateral hilar lymphadenopathy + upper lobe infiltrates
  • Stage III – lung infiltrates only
  • Stage IV – lung fibrosis