What is the recommended diagnostic workup and treatment for a patient with suspected sarcoidosis?

Diagnostic Workup and Treatment for Suspected Sarcoidosis

For patients with suspected sarcoidosis, obtain tissue confirmation showing noncaseating granulomas from the most accessible site, perform baseline serum calcium testing (the only strong recommendation), and initiate corticosteroids at 20-40 mg prednisone daily if symptomatic with parenchymal infiltrates and abnormal pulmonary function tests. 1, 2, 3

Initial Diagnostic Approach

Clinical Presentation Assessment

• Look for bilateral hilar adenopathy on chest imaging, which is highly characteristic 4
• Identify classic syndromes that may not require biopsy: Löfgren's syndrome (bilateral hilar adenopathy, erythema nodosum, arthritis), lupus pernio (chronic violaceous skin lesions), or Heerfordt's syndrome (fever, parotid enlargement, uveitis, facial nerve palsy) 1
• If these highly specific syndromes are present, you may skip tissue sampling but must maintain close clinical follow-up 1

Imaging Studies

• Order high-resolution CT chest without IV contrast as the preferred initial imaging modality 5
• HRCT detects bilateral hilar adenopathy, perilymphatic nodules, and parenchymal infiltrates more accurately than chest X-ray for early disease 4, 5
• Use CT findings to guide biopsy site selection and assess disease extent 5

Tissue Diagnosis

• Obtain tissue confirmation from the most accessible involved lymph node or organ 6, 4
• Bronchoscopy with transbronchial biopsy is often the first-line approach for pulmonary disease 4
• Look for noncaseating (non-necrotizing) epithelioid granulomas on histopathology 6
• Critical pitfall: You must exclude alternative diagnoses including infections (tuberculosis, fungal), berylliosis, hypersensitivity pneumonitis, vasculitis, and drug-induced reactions 4

Mandatory Baseline Laboratory Testing

Strong Recommendation

• Serum calcium measurement is the only strong recommendation—check this in all patients to screen for abnormal calcium metabolism 1

Conditional Recommendations (Still Important)

• Serum creatinine to screen for renal sarcoidosis 1
• Serum alkaline phosphatase to screen for hepatic involvement 1
• Both 25-OH and 1,25-OH vitamin D levels if vitamin D assessment is needed (sarcoid granulomas produce excess 1α-hydroxylase, converting 25-OH to active 1,25-OH vitamin D, causing hypercalcemia) 1, 6
• Complete blood count for cytopenias from bone marrow or splenic involvement 6

Important caveat: Do NOT rely on serum ACE levels for diagnosis—they lack sensitivity and specificity despite being commonly ordered 4

Cardiac Screening Protocol

All Patients Without Cardiac Symptoms

• Perform baseline ECG on all patients with extracardiac sarcoidosis 1
• Do NOT perform routine echocardiography or 24-hour Holter monitoring unless ECG is abnormal or symptoms develop 1

If Cardiac Involvement Suspected

• Cardiac MRI is the preferred first-line imaging modality 1
• If cardiac MRI unavailable, use dedicated PET scan rather than echocardiography 1
• Cardiac involvement can be fatal and requires specific advanced imaging beyond routine echocardiography 4

Pulmonary Hypertension Screening

When to Suspect PH

Look for: exertional chest pain, syncope, prominent P2 or S4 on exam, reduced 6-minute walk distance, desaturation with exercise, reduced DLCO, increased pulmonary artery diameter on CT, elevated BNP, or fibrotic lung disease 1

Testing Algorithm

• Initial test: transthoracic echocardiography 1
• If TTE suggests PH: perform right heart catheterization to definitively confirm 1
• If TTE does NOT suggest PH but clinical suspicion remains high: determine need for right heart catheterization case-by-case 1

Critical point: Up to 70% of patients with stage IV fibrocystic disease develop precapillary pulmonary hypertension, which dramatically increases mortality risk 3

Treatment Initiation

Indications for Treatment

• Symptomatic patients (cough, dyspnea) with parenchymal infiltrates AND abnormal pulmonary function tests 3
• Hypercalcemia (urgent indication) 6
• Serious extrapulmonary organ involvement (cardiac, neurologic, ocular, renal) 2, 3

First-Line Therapy

• Prednisone 20-40 mg daily for 2 weeks to 2 months 2, 3
• Taper over 6-18 months if symptoms, spirometry, PFTs, and radiographs improve 3
• Prolonged prednisone may be required to stabilize disease 3

Second and Third-Line Therapy

• If requiring prolonged prednisone ≥10 mg/day or experiencing adverse glucocorticoid effects: add methotrexate or azathioprine (second-line) 3
• Anti-TNF agents (third-line) for refractory disease 3

Critical caveat for hypercalcemia: Avoid vitamin D supplementation as this will worsen hypercalcemia due to excess 1α-hydroxylase activity in granulomas 6

Advanced Imaging for Complex Cases

FDG-PET/CT Indications

• Suspected multiorgan involvement requiring extent assessment 4, 5
• Guiding biopsy site selection for difficult-to-access lesions 4
• Monitoring treatment response in select cases 5
• Do NOT use routinely for follow-up due to cost and radiation exposure 5

Gallium-68 Citrate PET/CT

• May be useful for disease activity assessment and detecting extrapulmonary involvement inaccessible to biopsy 7
• Can identify clinically occult malignancies when performed simultaneously with FDG-PET/CT 7

Specialist Referrals

Mandatory Referrals

• Cardiologist if ECG abnormalities, cardiac symptoms, or cardiac imaging findings 4
• Ophthalmologist for baseline eye exam (uveitis screening in all patients) 6, 4
• Nephrologist if creatinine elevated or worsening despite treatment 6, 4

Conditional Referrals Based on Involvement

• Neurologist for cranial nerve palsies (especially facial nerve) or other neurologic symptoms 4
• Dermatologist for lupus pernio, erythema nodosum, or other skin manifestations 4
• Hepatologist for alkaline phosphatase >3x normal 4

Prognosis and Monitoring

Disease Staging and Outcomes

• Scadding stages I-II: 30-80% radiographic remission 3
• Stage III: only 10-40% resolution 3
• Stage IV: no chance of resolution, highest mortality risk (>40% at 5 years) 3
• Overall 5-year mortality approximately 7%, with 60% of deaths due to sarcoidosis itself (80% from cardiopulmonary failure) 3

Follow-Up Strategy

• Serial serum calcium and creatinine to assess treatment response 6
• Follow-up CT should be clinically driven based on symptoms, PFT changes, or treatment decisions—not on a predetermined schedule 5
• Relapse rates range 13-75% depending on stage, organs involved, and socioeconomic factors 3