What is the initial workup and treatment for a patient suspected of having sarcoidosis?

Sarcoidosis Workup

The workup for suspected sarcoidosis requires establishing three diagnostic criteria: compatible clinical presentation, nonnecrotizing granulomatous inflammation on tissue biopsy (unless classic syndromes are present), and exclusion of alternative diagnoses, followed by systematic organ screening with mandatory baseline serum calcium testing. 1

Diagnostic Criteria

The diagnosis rests on three pillars that must all be satisfied 1:

• Compatible clinical presentation with symptoms such as unexplained cough, dyspnea, constitutional symptoms, or classic syndromes 1, 2
• Histopathologic evidence of nonnecrotizing (noncaseating) granulomas on tissue sampling 1
• Exclusion of alternative causes of granulomatous disease including infections (especially tuberculosis), malignancy, and other granulomatous conditions 1

When Tissue Biopsy Can Be Avoided

For patients with high clinical suspicion presenting with Löfgren's syndrome (bilateral hilar adenopathy, erythema nodosum, arthralgia), lupus pernio, or Heerfordt's syndrome, lymph node sampling is NOT recommended 1, 3. These patients require close clinical follow-up instead of immediate biopsy 1, 4.

When Tissue Biopsy Is Required

For all other presentations without these classic syndromes, obtain tissue confirmation from the most accessible involved site 3:

• EBUS-guided lymph node sampling has 87% diagnostic yield with <0.1% complication rate 4
• Mediastinoscopy has 98% diagnostic yield but is more invasive 4
• Core needle biopsy is preferred over fine-needle aspiration to enable proper histological examination 4

Mandatory Baseline Laboratory Testing

Strong Recommendation (Must Perform)

• Serum calcium - This is the ONLY strong recommendation from the American Thoracic Society for baseline screening, as abnormal calcium metabolism can cause serious complications including renal insufficiency in 42% of untreated patients 1, 3

Conditional Recommendations (Should Perform)

• Serum creatinine to screen for renal sarcoidosis 1, 3
• Serum alkaline phosphatase to screen for hepatic sarcoidosis 1, 3
• Both 25-OH and 1,25-OH vitamin D levels if vitamin D assessment is needed, as sarcoidosis granulomas produce excess 1α-hydroxylase 1, 3
• Complete blood count to evaluate for cytopenias from bone marrow or splenic involvement 3
• Serum ACE level may correlate with disease activity but lacks sensitivity/specificity for diagnosis 3

Additional Testing Based on Clinical Context

• Tuberculosis testing (interferon-gamma release assay or tuberculin skin test) to exclude TB 4
• IgG4 levels if IgG4-related disease is in the differential 4

Imaging Studies

• High-resolution chest CT to characterize lymphadenopathy, assess parenchymal involvement, and determine Scadding stage 4, 5
• Pulmonary function tests (spirometry and diffusion capacity) to assess for restrictive physiology and impaired gas exchange 4

Cardiac Screening Protocol

All patients with suspected or confirmed sarcoidosis must undergo baseline ECG screening, even without cardiac symptoms 1, 3, 6. This is critical because cardiac sarcoidosis causes >70% of sarcoidosis deaths in Japan and contributes significantly to mortality worldwide 5.

Screening Algorithm

1. Baseline ECG for all patients (conditional recommendation) 1, 6

2. Do NOT perform routine echocardiography or 24-hour Holter monitoring in asymptomatic patients with normal ECG 1, 6

3. If ECG is abnormal OR cardiac symptoms are present:

   • First-line: Cardiac MRI (preferred imaging modality) 1, 6
   • If cardiac MRI unavailable: Dedicated PET scan (NOT echocardiography) 1, 6

Common Pitfall

The American Thoracic Society explicitly recommends AGAINST routine echocardiography for screening, though it acknowledges these tests may be considered case-by-case given their low risk 1. The key is that ECG abnormalities or symptoms must trigger advanced imaging (MRI or PET), not just echocardiography.

Pulmonary Hypertension Screening

For patients with suspected pulmonary hypertension (exertional chest pain/syncope, prominent P2 or S4, reduced 6-minute walk distance, desaturation with exercise, reduced DLCO, increased PA diameter on CT, elevated BNP, or fibrotic lung disease) 1:

1. Initial screening: Transthoracic echocardiography 1
2. If TTE suggests PH: Right heart catheterization to definitively confirm and distinguish precapillary from postcapillary PH 1
3. If TTE does NOT suggest PH: Determine need for right heart catheterization case-by-case 1

This is critical because sarcoidosis-associated pulmonary hypertension occurs in 5-20% of patients and is an independent risk factor for mortality 1.

Treatment Considerations

While treatment is beyond the scope of "workup," understanding treatment implications guides the urgency of diagnosis:

• Hypercalcemia requires urgent corticosteroid therapy 3
• Avoid vitamin D supplementation as it worsens hypercalcemia 3
• Prednisone is first-line treatment for symptomatic disease causing significant organ dysfunction or QOL impairment 7, 5, 8
• Typical starting dose: 20-40 mg daily for symptomatic pulmonary disease with parenchymal infiltrates and abnormal PFTs 5

Follow-Up Requirements

• Close clinical follow-up is mandatory for patients who do not undergo biopsy due to classic presentations 1, 4
• Serial serum calcium and creatinine to monitor for complications and treatment response 3
• Ophthalmology referral for baseline uveitis screening 3
• Cardiology referral if ECG abnormalities or cardiac symptoms develop 3
• Nephrology referral if creatinine remains elevated despite treatment 3