From the Guidelines
Angiotensin-converting enzyme (ACE) has a sensitivity of 24-45% for diagnosing sarcoidosis, as indicated by the table in the 2020 European position paper on rhinosinusitis and nasal polyps 1. This means that while elevated ACE levels can support a diagnosis of sarcoidosis, a normal ACE level does not rule out the disease. ACE levels can be elevated in active sarcoidosis because epithelioid cells within sarcoid granulomas produce ACE, leading to increased serum levels. However, ACE levels can also be elevated in other conditions such as tuberculosis, fungal infections, hyperthyroidism, and liver diseases, making it a non-specific marker. Additionally, ACE levels can be normal in patients with sarcoidosis who are taking ACE inhibitors or who have less active disease. For these reasons, ACE testing should be used as part of a comprehensive diagnostic approach that includes clinical presentation, radiographic findings, and histopathological confirmation when possible. Other biomarkers like soluble interleukin-2 receptor may offer better sensitivity in some cases, but tissue biopsy showing non-caseating granulomas remains the gold standard for diagnosis.
Some studies, such as the 2016 American Heart Association scientific statement on dilated cardiomyopathies 1, and the 2020 American Thoracic Society clinical practice guideline on diagnosis and detection of sarcoidosis 1, provide information on the diagnosis and treatment of sarcoidosis, but they do not specifically address the sensitivity of ACE for diagnosing sarcoidosis. Therefore, the most relevant and recent evidence for this question is the 2020 European position paper on rhinosinusitis and nasal polyps 1.
Key points to consider when interpreting ACE levels in the context of sarcoidosis diagnosis include:
- ACE levels can be elevated in active sarcoidosis, but also in other conditions
- ACE levels can be normal in patients with sarcoidosis who are taking ACE inhibitors or who have less active disease
- ACE testing should be used as part of a comprehensive diagnostic approach
- Tissue biopsy showing non-caseating granulomas remains the gold standard for diagnosis.
From the Research
Sensitivity of Angiotensin-Converting Enzyme (ACE) for Diagnosing Sarcoidosis
- The sensitivity of ACE for diagnosing sarcoidosis has been reported to be 58.1% in one study 2, with a specificity of 83.8%.
- However, the sensitivity rose to 85.9% if only those samples taken from patients in whom sarcoidosis was suspected on initial presentation were included, and 92.1% if only those with clinically active sarcoidosis were included 2.
- Another study reported a sensitivity of 41.4% and a specificity of 89.9% for high ACE levels in diagnosing sarcoidosis 3.
- A review of 327 sarcoidosis patients and 1,274 patients with various disorders reported a sensitivity of 0.55 and a specificity of 0.99 for elevated SACE 4.
- The sensitivity of ACE can be influenced by the relative frequency of active and inactive sarcoidosis, as well as the prevalence of other diseases such as military tuberculosis and silicosis 2.
- Combining ACE with other biomarkers, such as chitotriosidase, may improve the diagnostic accuracy of sarcoidosis, with a reported sensitivity of 90.5% and specificity of 79.3% 5.
Factors Affecting Sensitivity
- The sensitivity of ACE can be affected by the clinical status of the patient, with higher sensitivity in patients with active disease 2, 6.
- The presence of other diseases, such as liver disorders, diabetes mellitus, hyperthyroidism, asbestosis, or silicosis, can also affect the sensitivity of ACE 4.
- The use of ACE as a diagnostic tool may be limited by its poor sensitivity and insufficient specificity in some populations 3.