Sarcoidosis
BASICS
- Definition: Noninfectious, multisystem, granulomatous disease of unknown cause.
- Classic features: Bilateral hilar adenopathy, pulmonary infiltrates, ocular or skin lesions.
- Common presentation: ~50% diagnosed asymptomatic (abnormal chest x-ray).
- Systems affected: Primarily pulmonary, but also cardiovascular, GI, hematologic, endocrine, renal, neuro, derm, ophthalmologic, musculoskeletal.
- Synonyms: Löfgren syndrome (EN, hilar adenopathy, fever, arthralgias), Heerfordt syndrome (uveitis, parotid enlargement, facial palsy, fever), lupus pernio, Besnier-Boeck disease.
EPIDEMIOLOGY
- Incidence: ~6/100 person-years.
- Prevalence: 10–20 per 100,000 (higher in Black Americans, women, Scandinavians, Japanese).
- Peak age: Women 50–69 yr; men 40–59 yr.
- Rare in children.
ETIOLOGY & PATHOPHYSIOLOGY
- Etiology: Unknown; likely exaggerated cell-mediated immune response to unknown antigen(s).
- Genetics: Familial clustering; MHC region on chr6; higher prevalence in specific populations (Scandinavians, Japanese, Black Americans).
- Risk factors: Not fully defined.
DIAGNOSIS
Diagnosis requires: 1. Clinical presentation 2. Noncaseating granulomatous inflammation on biopsy (not always required) 3. Exclusion of other diseases
History
- May be asymptomatic.
- Nonspecific complaints:
- Nonproductive cough, SOB, fever, night sweats, weight loss, fatigue, eye pain, chest pain, palpitations, arrhythmias, skin lesions, polyarthritis.
- Systemic symptoms more likely in age >70.
Physical Exam
- May be normal.
- Lungs: wheezing, fine crackles.
- Extrapulmonary (30%):
- Eye: uveitis, retinitis, conjunctival nodules, lacrimal gland enlargement
- CN VII palsy, salivary swelling, arrhythmia, hepatosplenomegaly
- Rashes: maculopapular, waxy nodular, plaques (lupus pernio), erythema nodosum (Löfgren)
- Polyarthritis
Differential Diagnosis
- Infectious: TB, atypical mycobacteria, fungal, Brucella, T. whipplei, tularemia, Bartonella, Coxiella, herpes zoster, Toxoplasma, schistosomiasis, leishmaniasis
- Lymphoma
- Autoimmune: vasculitis, Langerhans cell histiocytosis, IBD
- Hypersensitivity pneumonitis
Diagnostic Tests
- Labs:
- CBC, HIV, creatinine, alk phos, transaminases, calcium, vitamin D (25- and 1,25-OH), baseline eye exam, ECG
- Serum ACE: elevated in >75%, NOT diagnostic
- Imaging:
- Chest x-ray (Scadding classification)
- 0: Normal
- 1: Bilateral hilar adenopathy
- 2: Hilar adenopathy + parenchymal infiltrates
- 3: Parenchymal infiltrates with shrinking hilar nodes
- 4: Parenchymal infiltrates with volume loss, bronchiectasis, calcification/cyst
- HRCT: peribronchial disease
- PET scan: areas of disease activity
- Cardiac MRI or PET (extracardiac disease/cardiac involvement)
- Echocardiogram for suspected pulmonary hypertension
- PFTs: Restrictive pattern, ↓ DLCO
- Biopsy: Noncaseating granulomas (not always required if classic syndrome present)
- Preferred: EBUS-guided lymph node sampling
- Bronchoscopy with biopsy for lung involvement
- ALERT: Löfgren syndrome (acute sarcoid with bilateral hilar adenopathy, EN, arthritis): no biopsy required, observation only.
TREATMENT
- Spontaneous remission common.
- No treatment for asymptomatic individuals or those with stages I–III and mild/normal lung function (monitor closely).
- Treat if: Cardiac, CNS, renal, ocular involvement, hypercalcemia, worsening lung function/symptoms/radiology.
Medications
- First Line:
- Systemic corticosteroids:
- Prednisone 0.3–0.6 mg/kg (20–40 mg/day) for 4–6 wk
- Taper if stable, continue 10–20 mg/day for 8–12 mo
- High-dose (80–100 mg/day) for severe organ involvement
- Exclude TB before starting
- Topical/inhaled steroids for mild skin/lung involvement
- Second Line:
- Immunosuppressants: Methotrexate, azathioprine, leflunomide, mycophenolate (regular CBC/LFT monitoring)
- Antimalarials: Hydroxychloroquine/chloroquine (less clear benefit)
- TNF antagonists (infliximab): Refractory cases
Surgery
- Lung transplant: For severe, refractory cases
Referral
- Pulmonology for most
- Specialist referral based on organ involvement
ONGOING CARE
Monitoring
- ~23% develop new manifestations in 3 years.
- Monitor serum calcium, creatinine, alk phos annually.
- On prednisone: see every 1–2 months.
- Not on therapy: q3 months for 2 years (Hx, PE, PFT, labs as indicated).
- On hydroxychloroquine: eye exam q6–12 months.
Patient Education
PROGNOSIS
- 50%: spontaneous resolution within 2 years.
- 25%: significant fibrosis, stable after 2 years.
- 25%: chronic disease (higher in Black Americans).
- Death rate <5% (higher in Black American women).
- Prolonged steroid use (>6 mo) = higher chronic disease risk.
COMPLICATIONS
- Significant respiratory involvement (cor pulmonale)
- Pulmonary hemorrhage (aspergillosis in damaged lung)
- Heart: CHF, arrhythmias
- Eye: rare blindness
- CNS: serious consequences
ICD-10 CODES
- D86.89 Sarcoidosis of other sites
- D86.81 Sarcoid meningitis
- D86.2 Sarcoidosis of lung with lymph nodes
CLINICAL PEARLS
- Sarcoidosis = noninfectious, multisystem granulomatous disease of unknown cause, usually young/mid-aged adults.
- Diagnosis: clinical findings, exclusion of other diseases, noncaseating granulomas on biopsy (not always required).