What is the role of serum Angiotensin-Converting Enzyme (ACE) levels in the diagnosis of sarcoidosis?

Role of Serum ACE in Diagnosis of Sarcoidosis

Serum angiotensin-converting enzyme (ACE) has limited diagnostic utility for sarcoidosis due to poor sensitivity and insufficient specificity, and should not be relied upon as a primary diagnostic test.

Diagnostic Value of Serum ACE

Sensitivity and Specificity

• Serum ACE has poor sensitivity (41.4%) and insufficient specificity (89.9%) for diagnosing sarcoidosis 1
• Positive predictive value is only 25.4%, making it an unreliable standalone diagnostic test 1
• False positive rates vary across conditions:
  • 2% in normal controls
  • 9.2% in tuberculosis (higher in military TB)
  • 48% in silicosis
  • 100% in Gaucher's disease 2

Confounding Factors

• ACE inhibitor medications significantly reduce serum ACE levels, potentially leading to:
  • Delayed diagnosis
  • False impression of disease activity
  • Diagnostic errors 3
• In one study, 62 sarcoidosis patients on ACE inhibitors had their ACE levels reduced to normal or below normal range 3
• Only 40% of cases had medication lists recorded in outpatient charts, highlighting a common pitfall 3

Clinical Applications

Disease Monitoring

• Serial measurements of serum ACE can be useful for:
  • Following clinical course of established sarcoidosis
  • Predicting clinical relapse or improvement 4
  • Correlating with disease activity 2

Correlation with Disease Manifestations

• ACE levels are significantly higher in:
  • Radiographic Types II and III compared to Types I and 0
  • Patients with extrathoracic disease involvement
  • Patients with clinically active disease 2
• ACE levels correlate well with disease activity longitudinally, both during spontaneous remission and steroid therapy 2

Current Guideline Recommendations

The American Thoracic Society's 2020 clinical practice guideline on diagnosis and detection of sarcoidosis does not include serum ACE among its primary diagnostic recommendations 5. Instead, the guideline emphasizes:

• Diagnosis based on three criteria:

  • Compatible clinical presentation
  • Non-caseating granulomatous inflammation in tissue samples
  • Exclusion of alternative causes of granulomatous disease 5

• Recommended diagnostic tests include:

  • Baseline serum calcium (strong recommendation)
  • Baseline serum creatinine and alkaline phosphatase (conditional recommendations)
  • Baseline ECG for cardiac screening (conditional recommendation) 5

Practical Considerations

When Measuring ACE

• Always check for concurrent ACE inhibitor use before interpreting results 3
• Consider measuring both 25-OH and 1,25-OH vitamin D levels when assessing vitamin D metabolism in sarcoidosis patients 6

Alternative Diagnostic Approaches

• For cardiac sarcoidosis: Cardiac MRI is preferred over other imaging modalities 5, 6
• For suspected pulmonary hypertension: Initial testing with transthoracic echocardiography is recommended 5
• In cases with high clinical suspicion (Löfgren syndrome, lupus pernio, or Heerfordt syndrome), tissue sampling may not be necessary, but close clinical follow-up is required 5, 6

Conclusion

While serum ACE has been traditionally used in sarcoidosis evaluation, its diagnostic value is limited by poor sensitivity and specificity. It may have more utility in monitoring disease activity in established cases than in initial diagnosis. Clinicians should be aware of the significant confounding effect of ACE inhibitor medications when interpreting results.