Incidence

Peaks at 30 to 50 years of age in men and 50 to 60 years in women. Rare in children

Prevalence

True prevalence unknown due to lack of diagnostic sensitivity and other factors.

Genetics

• Although worldwide in distribution, increased prevalence in Scandinavians, Japanese, Black Americans, and women
• Link to the loci in the HLA Class II region and butyrophilin-like 2 genes (BTNL2)

PHYSICAL EXAM

• Many patients have a normal physical exam.
• Lungs may reveal wheezing/fine interstitial crackles.

• ~30% of patients have extrapulmonary manifestations, including the following:
  • Uveitis, retinitis, or other eye findings: conjunctival nodules, lacrimal gland enlargement, cataracts, glaucoma, papilledema
  • Cranial nerve palsies, especially 7th nerve
  • Salivary gland swelling or lymphadenopathy
  • Arrhythmias
  • Hepatosplenomegaly
  • Polyarthritis
  • Rashes
    • Maculopapular of nares, eyelids, forehead, base of neck at hairline, and previous trauma sites
    • Waxy nodular of face, trunk, and extensor surfaces of extremities
    • Plaques (lupus pernio) of nose, cheeks, chin, and ears
    • EN (component of Löfgren syndrome)

Initial Tests (lab, imaging)

• Screening for extrapulmonary disease:
  • Complete blood cell count, HIV
  • Creatinine (renal sarcoidosis)
  • Alkaline phosphatase (hepatic sarcoidosis) +/− transaminase testing
  • Calcium
  • 25- and 1,25-OH vitamin D levels to determine if replacement needed
• Baseline eye exam
• Baseline ECG
  • If high risk symptoms or ECG changes (such as heart block) concerning for cardiac sarcoidosis, cardiac MRI or cardiac FDG PET-CT
• Biomarkers show evidence of inflammation and are not pathognomonic tests:
  • Serum ACE elevated in 50–60% of patients but lacks diagnostic specificity
  • CRP, serum amyloid A, chitotriosidase, interleukin-2 receptor also show inflammation and disease activity
• FDG PET-CT most effective for tissue-specific inflammatory activity if assessing for biopsy site
• CXR or CT scan may reveal granulomas/hilar adenopathy. CXRs are staged using Scadding classification.
  • Stage 0 = normal
  • Stage 1 = bilateral hilar adenopathy alone
  • Stage 2 = bilateral hilar adenopathy + parenchymal infiltrates (primarily upper lobes)
  • Stage 3 = parenchymal infiltrates with shrinking hilar adenopathy
  • Stage 4 = parenchymal infiltrates with volume loss, bronchiectasis, calcification, or cyst formation
• For patients with suspected pulmonary hypertension, transthoracic echocardiogram is suggested and may lead to right heart catheterization if indicated.

Follow-Up Tests & Special Considerations

Patients with asymptomatic bilateral hilar lymphadenopathy

• If high clinical suspicion for sarcoidosis (i.e., Löfgren syndrome, lupus pernio, Heerford syndrome), biopsy not needed
• If tissue sampling determined to be necessary, endobronchial ultrasound (EBUS)-guided lymph node sampling preferred over mediastinoscopy

Diagnostic Procedures/Other

• Pulmonary function tests (PFTs) may reveal restrictive pattern with decreased carbon monoxide diffusing capacity (DLCO).
• Ophthalmologic examination may reveal uveitis, retinal vasculitis, or conjunctivitis.
• ECG
• Tuberculin skin test
• Biopsy of lesions should reveal noncaseating granulomas.
• If lungs are affected, bronchoscopy with biopsy of central and peripheral airways is helpful. EBUS-guided transbronchial needle aspiration may have a better diagnostic yield.

Test Interpretation

Noncaseating epithelioid granulomas without evidence of fungal/mycobacterial infection

First Line

• No FDA-approved treatment for sarcoidosis
• Systemic corticosteroids in the symptomatic individual or with worsening lung function or radiographic findings
  • Optimal dose of glucocorticoids is not known. Prior to initiating glucocorticoids, must exclude tuberculosis
  • 0.3 to 0.6 mg/kg ideal body weight (20 to 40 mg/day) for 4 to 6 weeks
  • If stable, taper by 5 mg/week to 10 to 20 mg/day over the next 6 weeks.
  • If no relapse, 10 to 20 mg/day for 8 to 12 months; relapse is common.
  • Higher doses (80 to 100 mg/day) may be warranted in patients with acute respiratory failure and cardiac, neurologic, or ocular disease.
• In patients with skin disease, topical steroids may be effective.
• Inhaled steroids (800 to 1,600 μg BID) may be of some clinical benefit in early disease with mild pulmonary symptoms.
  • Contraindications and significant possible interactions: Refer to the manufacturer’s profile of each drug.

Second Line

• All alternative agents to glucocorticoids carry substantial risk for toxicity, including myelosuppression, hepatotoxicity, and opportunistic infection. Prior to utilizing these medications, assess for adherence to steroid therapy, comorbid disease, or other complicating factors contributing to steroid failure. Referral to specialist is recommended.
• Glucocorticoid-sparing agents should be initiated early if patients require long-term suppression of inflammation. Could also be used as first line
  • Methotrexate
  • Other immunosuppressants include azathioprine, leflunomide, or mycophenolate.
  • Antimalarial agent hydroxychloroquine is particularly useful with cutaneous disease, hypercalcemia, and some cases of neurosarcoidosis
  • Use of immunosuppressants require regular monitoring of CBC and LFTs. Vaccinations should be up to date.
• Tumor necrosis factor antagonists, such as infliximab and adalimumab, have been useful in refractory cases.

Patient Monitoring

• Approximately 30% of patients with sarcoidosis will develop a new disease manifestation within 3 years of baseline evaluation.
• Monitor serum calcium, creatinine, alkaline phosphatase annually
• Patients on prednisone for symptoms should be seen every 1 to 2 months while on therapy.
• Patients not requiring therapy should be seen every 3 months for at least the first 2 years after diagnosis, obtaining a history and physical exam, laboratory testing tailored to sites of disease activity, PFTs, and ambulatory pulse oximetry.
• If on hydroxychloroquine, obtain ophthalmologic exam every 6 to 12 months.
• Other testing per individual patient’s symptoms, including HRCT, echocardiogram, Holter monitoring, urinalysis (UA), thyroid-stimulating hormone (TSH), bone density, MRI of brain, ophthalmologic exam