Sarcoidosis

Pathophysiology

• Thought to be related to abnormal T-cell activation

Differential Diagnosis

• Hilar lymphadenopathy
  • Sarcoidosis
  • Infection: TB, fungal, HIV, mycoplasma
  • Malignancy: lymphoma
  • Others

Scadding Classification

1. Stage I: Bilateral hilar lymphadenopathy (70% resolve)
2. Stage II: Above, with interstitial lung disease (50% resolve)
3. Stage III: Interstitial lung disease alone (15% resolve)
4. Stage IV: Fibrotic, "burnt out" lungs (0% resolve)

Risk Factors

• Women more than men (2:1)
• More common in African-Americans

Clinical Presentation

Extrapulmonary disease

• Skin: Erythema nodosum and lupus pernio, and others
• Cardiac: 40% of patients, though only 5-10% are symptomatic
• CNS: 5-10%, multiple presentations
• Eyes: 10% of all uveitis cases, usually bilateral
• Hypercalcemia
• Nephrocalcinosis

Diagnosis

• Evidence of granulomatous inflammation (often on BAL or EBUS) without infection
• Either lung involvement or multiorgan involvement

Investigations

• Labs
  • CBC, lytes, creatinine, calcium, liver panel
• Imaging
  • High-res CT scan
• Other
  • PFTs: most commonly restrictive with decreased DLCO, but can show combined restriction-obstruction, or rarely any other pattern. Often normal.
  • EKG for cardiac involvement
  • Eye exam for uveitis

Management

• Only treat if symptomatic, as many will resolve spontaneously
  • Spontaneous remission depends on Scadding stage (I 70%, II 50%, III 15%, IV 0%)
• Prednisone 20-40mg daily for 8-12 weeks, then taper
  • Add vitamin D and calcium if serum calcium is low
  • Can still use bisphosphates for bone protection
• Second-line steroid-sparing agents include
  • Methotrexate
  • Azathioprine, leflonamide, MMF, hydroxychloroquine, thalidomide
  • TNG-alpha inhibitors are last line

Management by organ system

Organ	Clinical Features	Treatment
Lungs	Dyspnea w FEV1 or FVC <70%	Prednisone 24-40 mg/day
Lungs	Cough, wheeze	Inhaled corticosteroid
Eyes	Anterior uveitis	Topical corticosteroid
Eyes	Posterior uveitis	Prednisone 20-40 mg/day
Eyes	Optic neuritis	Prednisone 20-40 mg/day
Skin	Lupus pernio	Prednisone 20-40 mg/day Hydroxychloroquine 400 mg/day Thalidomide 100-150 mg/day Methotrexate 10-15 mg/week
Skin	Plaques or nodules	Prednisone 20-40 mg/day Hydroxychloroquine 400 mg/day
Skin	Erythema nodosum	NSAID
CNS	Cranial nerve palsies	Prednisone 20-40 mg/day
CNS	Intracerebral involvement	Prednisone 40 mg/day Azathioprine 150 mg/day Hydroxychloroquine 400 mg/day
Heart	Complete heart block	Pacemaker
Heart	Ventricular fibrillation or tachycardia	AICD
Heart	Decreased LVEF <35%	AICD and prednisone 30-40 mg/day
Liver	Cholestatic hepatitis with constitutional symptoms	Prednisone 20-40 mg/day Ursodiol 15 mg/kg per day
MSK	Arthralgias	NSAID
MSK	Granulomatous arthritis	Prednisone 20-40 mg/day
MSK	Myositis or myopathy	Prednisone 20-40 mg/day
Calcium	Kidney stones, fatigue	Prednisone 20-40 mg/day Hydroxychloroquine 400 mg/day

from the [NEJM sarcoidosis review article][1]

Further Reading

• [1]: Iannuzzi MC, Rubicki BA, and Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65.
• Costabel U and Hunninghake GW. ATS/ERS/WASOG statement on sarcoidosis. Eur Respir J. 1999 Oct;14(4):735-7.