From the Guidelines
Elevated cytokines and ACE levels are a significant indicator of active inflammatory processes, particularly suggestive of sarcoidosis, and require prompt evaluation and management to prevent morbidity and mortality. The combination of elevated cytokines and ACE levels is a critical biomarker for various inflammatory conditions, including sarcoidosis, tuberculosis, fungal infections, and autoimmune disorders. Cytokines, such as interleukin-2 (IL-2) and tumor necrosis factor (TNF)-α, play a crucial role in regulating immune responses, and their elevation typically indicates active inflammation or immune system activation 1. ACE levels, on the other hand, are particularly significant as markers for sarcoidosis, a multisystem inflammatory disorder characterized by granuloma formation.
Key Considerations
- Elevated serum levels of ACE, IL-2R, and lysozyme are usually associated with more aggressive disease and multiple-organ involvement 1.
- The immune system's response to SARS-CoV-2, the virus responsible for COVID-19, can also lead to elevated cytokine levels and cardiac risk, particularly in patients with underlying cardiovascular disease 1.
- Management of elevated cytokines and ACE levels typically involves treating the underlying cause, which may include corticosteroids, antimicrobials, or immunomodulatory medications.
Treatment Options
- Corticosteroids like prednisone (starting at 20-40mg daily with gradual tapering) for sarcoidosis.
- Specific antimicrobials for infections.
- Additional immunomodulatory medications such as methotrexate (10-25mg weekly) or hydroxychloroquine (200mg twice daily) for refractory cases. Regular monitoring of these biomarkers can help track disease activity and treatment response, with decreasing levels generally indicating improvement. It is essential to prioritize the management of elevated cytokines and ACE levels to prevent long-term morbidity and mortality, particularly in patients with underlying conditions such as cardiovascular disease 1.
From the Research
Significance of Elevated Cytokines and ACE Levels
- Elevated Angiotensin-Converting Enzyme (ACE) levels are considered a serological marker of sarcoidosis, but they can also be encountered in other medical conditions, such as non-Hodgkin's lymphoma, cirrhosis, and interstitial lung disease 2.
- The clinical correlation between ACE levels and disease activity in sarcoidosis is disputable, with studies showing that ACE levels do not always correlate with disease activity 2, 3.
- Extremely elevated ACE activity can be suggestive of familial hyperactivity of ACE, a benign condition that can be confirmed by genetic testing 4.
- Some ACE mutations can increase ACE shedding, leading to elevated serum ACE levels and potentially incorrect diagnosis of sarcoidosis 5.
- The measurement of serum ACE activity can be helpful in the diagnosis and disease monitoring of sarcoidosis, but it is not a specific test and can be elevated in other conditions 6.
- Elevated cytokines can be associated with various conditions, including sarcoidosis, but the significance of elevated cytokines and ACE levels together is not clearly defined in the provided studies.
ACE Levels and Disease Activity
- ACE levels around the time of diagnosis were higher than ACE levels in remission, but a paired analysis did not find a statistically significant difference in ACE levels between the two timepoints 2.
- A positive correlation between lack of cardiac involvement and elevated ACE levels was found on multivariate analysis 2.
- Changes in steroid dose were negatively correlated with serum ACE level, with an increase in steroid dose leading to a fall in ACE level 3.
Diagnostic Considerations
- Elevated ACE levels had a positive predictive value of 12.76% and a negative predictive value of 94.6% for the diagnosis of sarcoidosis in one study 2.
- ACE phenotyping, together with whole exome sequencing, can be a diagnostic approach to identify ACE mutations and prevent misdiagnosis of sarcoidosis based on elevated blood ACE levels 5.