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

Cutaneous Sarcoidosis Workup

For suspected cutaneous sarcoidosis, perform a punch biopsy of the skin lesion to confirm noncaseating granulomas, then systematically screen for multiorgan involvement with baseline serum calcium (strong recommendation), ECG, chest imaging, serum creatinine, and alkaline phosphatase, even in asymptomatic patients. 1, 2

Diagnostic Confirmation

Tissue Diagnosis

• Punch biopsy of the cutaneous lesion is the primary diagnostic step, with an 81.6% diagnostic yield and only 4% complication rate 3
• Target the most accessible skin lesion showing specific features (papules, plaques, nodules, lupus pernio, or scar infiltration) 2, 4
• Histopathology must demonstrate noncaseating (non-necrotizing) epithelioid granulomas with macrophage aggregates, multinucleated giant cells, and minimal lymphocytic inflammation 2

Exception to Biopsy Requirement

• If the patient presents with lupus pernio, Löfgren's syndrome, or Heerfordt's syndrome, you may skip tissue sampling due to sufficiently high diagnostic specificity 1, 2
• These patients require close clinical follow-up instead 1

Mandatory Baseline Laboratory Screening

Strong Recommendation

• Serum calcium - This is the only strong recommendation from the American Thoracic Society to screen for abnormal calcium metabolism, which occurs even without symptoms 1, 2

Conditional Recommendations

• Serum creatinine to screen for renal sarcoidosis 1, 2
• Serum alkaline phosphatase to 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 converting 25-OH to active 1,25-OH vitamin D, causing hypercalcemia 1, 2

Additional Useful Tests

• Complete blood count to evaluate for cytopenias from bone marrow or splenic involvement 5
• Serum ACE level may correlate with disease activity but lacks sensitivity/specificity for diagnosis 5, 3

Cardiac Screening Protocol

All patients with cutaneous sarcoidosis require baseline cardiac screening because cardiac involvement occurs in 25% of cases and can be fatal. 2

• Baseline ECG for every patient, even without cardiac symptoms 1, 2
• Do NOT perform routine echocardiography or 24-hour Holter monitoring in asymptomatic patients with normal ECG 1, 2
• If ECG is abnormal or cardiac symptoms are present: proceed to cardiac MRI with late gadolinium enhancement as first-line imaging, which predicts 9-fold increased cardiac mortality 2
• If MRI is contraindicated or unavailable, use dedicated cardiac PET scan as second choice 2

Pulmonary Evaluation

• Chest X-ray and high-resolution CT scan to detect bilateral hilar adenopathy, perilymphatic nodules, and parenchymal infiltrates 2
• Consider bronchoscopy with BAL and transbronchial biopsy if pulmonary involvement is suspected but additional tissue confirmation is needed 2
• BAL lymphocytosis and elevated CD4/CD8 ratio are more frequent in patients with specific cutaneous lesions and predict progressive disease 3

Ophthalmologic Screening

• Referral to ophthalmology for baseline eye examination to screen for uveitis, optic neuritis, scleritis, or retinitis 2, 5
• This is essential even in asymptomatic patients as ocular involvement is common 6

Prognostic Considerations

High-Risk Cutaneous Features

• Lupus pernio and plaques are associated with more severe systemic involvement and chronic course 7
• Almost all patients with lupus pernio have stage 0 or 1 pulmonary disease 3
• Specific cutaneous lesions (showing granulomas on biopsy) correlate with BAL lymphocytosis, elevated CD4/CD8 ratio, elevated ACE, and higher frequency of progressive disease 3

Lower-Risk Features

• Erythema nodosum (nonspecific lesion) is the hallmark of acute, benign disease with better prognosis 7

Critical Pitfalls to Avoid

• Do not rely solely on ACE levels - they lack adequate sensitivity and specificity 2
• Do not assume isolated cutaneous disease will remain isolated - 50% of patients with initially isolated cutaneous sarcoidosis develop systemic involvement within 4-9 years, requiring long-term monitoring 8
• Do not miss cardiac involvement - it can be fatal and requires specific screening beyond routine physical examination 2
• Exclude alternative granulomatous diseases including infections (tuberculosis, fungal), berylliosis, hypersensitivity pneumonitis, vasculitis, and drug-induced sarcoid-like reactions (especially immunotherapeutics and anti-TNF agents) 2

Specialist Referrals Based on Findings

• Cardiologist if ECG abnormalities, cardiac symptoms, or abnormal cardiac imaging 2
• Nephrologist if elevated creatinine, hypercalciuria, or nephrolithiasis 2
• Hepatologist if alkaline phosphatase >3x normal 2
• Neurologist if cranial nerve palsies (especially facial nerve) or other neurological symptoms 2
• Dermatologist for ongoing management of skin manifestations 2

Long-Term Monitoring

• Annual clinical assessment is reasonable even after prolonged remission, as recurrence can occur after 25+ years 9
• Serial monitoring of serum calcium, creatinine, and alkaline phosphatase 5
• Repeat chest imaging if new respiratory symptoms develop 9