What are the guidelines for screening and treating sarcoidosis in individuals with symptoms or a family history of the disease, particularly in high-risk ethnic groups such as African Americans or Europeans?

Screening for Sarcoidosis

There is no population-based screening program for sarcoidosis, even in high-risk ethnic groups, because the disease requires clinical suspicion based on symptoms or incidental radiographic findings before diagnostic evaluation is initiated. 1, 2

Who Should Be Evaluated for Sarcoidosis

Sarcoidosis evaluation should be triggered by clinical presentation, not by screening asymptomatic individuals—even those with family history or high-risk ethnicity (African Americans, Scandinavians). 3, 4 The disease commonly presents with:

• Persistent dry cough and dyspnea in young to middle-aged adults 5
• Constitutional symptoms: fever, unintentional weight loss, fatigue, night sweats 3, 5
• Incidental bilateral hilar adenopathy on chest imaging 6
• Skin manifestations: erythema nodosum, lupus pernio, maculopapular lesions 3, 6
• Ocular symptoms: uveitis, vision changes 3

Approximately 50% of patients are asymptomatic at diagnosis, discovered incidentally on chest radiography. 6

Diagnostic Workup When Sarcoidosis Is Suspected

Initial Imaging and Laboratory Tests

When clinical suspicion exists, begin with:

• Chest X-ray and high-resolution CT scan to detect bilateral hilar adenopathy and perilymphatic nodules 2
• Serum calcium (strong recommendation)—screen for abnormal calcium metabolism even without symptoms of hypercalcemia 1
• Serum creatinine—screen for renal involvement 1, 2
• Serum alkaline phosphatase—screen for hepatic involvement 1, 2
• Both 25-OH and 1,25-OH vitamin D levels if vitamin D assessment is needed, as granulomas produce excess 1α-hydroxylase 1, 2
• Baseline ECG for all patients to screen for cardiac involvement, even without cardiac symptoms 1, 2, 7

Cardiac Screening Protocol

Do NOT perform routine transthoracic echocardiography or 24-hour Holter monitoring in asymptomatic patients with normal ECG. 1, 2, 7 However:

• If ECG shows abnormalities or cardiac symptoms are present, proceed immediately to cardiac MRI with late gadolinium enhancement as first-line imaging 2, 7
• Cardiac MRI abnormalities predict a 9-fold increase in cardiac mortality 2, 7
• If MRI is unavailable or contraindicated, use dedicated cardiac PET scan rather than echocardiography 2, 7

Tissue Diagnosis Requirements

Three diagnostic criteria must be satisfied: compatible clinical presentation, histopathologic evidence of noncaseating granulomas, and exclusion of alternative causes. 1, 4

Exception—biopsy NOT required for:

• Löfgren's syndrome (bilateral hilar adenopathy, erythema nodosum, arthritis, fever) 1, 2
• Lupus pernio 1, 2
• Heerfordt's syndrome (parotid enlargement, uveitis, facial nerve palsy, fever) 1, 2

These syndromes have sufficiently high diagnostic specificity to establish diagnosis without tissue sampling, though close clinical follow-up is mandatory. 1, 2

For all other presentations, obtain tissue from the most accessible involved site:

• EBUS-guided lymph node sampling has 87% diagnostic yield with <0.1% complication rate 2
• Look for noncaseating epithelioid granulomas with multinucleated giant cells 2

Common Pitfalls to Avoid

• Do not rely on ACE levels alone—they lack sensitivity and specificity for diagnosis 2, 3
• Do not assume normal ECG excludes cardiac sarcoidosis—ECG has low sensitivity (only 32% when combined with echocardiography) 7
• Always exclude alternative granulomatous diseases: tuberculosis, fungal infections, berylliosis, hypersensitivity pneumonitis, lymphoma, drug-induced reactions 2, 4
• Do not supplement vitamin D in patients with hypercalcemia—this will worsen the condition 8
• Recognize that hepatotoxic treatments should be avoided in patients with elevated alkaline phosphatase 1

Specialist Referrals Based on Findings

• Cardiologist: if ECG abnormalities, cardiac symptoms, or abnormal cardiac imaging 2
• Ophthalmologist: for baseline eye exam and if ocular symptoms develop 2, 8
• Nephrologist: if creatinine elevated or hypercalciuria present 2, 8
• Hepatologist: if alkaline phosphatase >3× normal 2
• Neurologist: if cranial nerve palsies or neurological symptoms 2
• Dermatologist: for skin manifestations requiring biopsy or treatment 2

Key Point on Family History and Ethnicity

While genetic predisposition and ethnicity (African American, Scandinavian) affect disease risk and course, these factors alone do not warrant screening in asymptomatic individuals. 3, 9 Evaluation should only be initiated when symptoms, physical findings, or incidental imaging abnormalities raise clinical suspicion. 4, 5