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

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Last updated: May 10, 2025View editorial policy

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From the Guidelines

Angiotensin-converting enzyme (ACE) inhibitors are not typically used as a primary treatment for sarcoidosis. The standard first-line treatment for symptomatic sarcoidosis is corticosteroids, usually prednisone starting at 20-40 mg daily for 1-3 months, followed by a gradual taper over 6-12 months depending on clinical response, as suggested by the european position paper on rhinosinusitis and nasal polyps 2020 1. For patients who cannot tolerate steroids or who have steroid-resistant disease, second-line options include methotrexate (10-25 mg weekly), hydroxychloroquine (200-400 mg daily), or TNF-alpha inhibitors like infliximab (3-5 mg/kg IV at weeks 0,2, and 6, then every 4-8 weeks).

Key Points to Consider

  • While ACE levels may be elevated in sarcoidosis patients and are sometimes used as a biomarker for disease activity, ACE inhibitors themselves do not treat the underlying inflammatory process of sarcoidosis, as noted in the european position paper on rhinosinusitis and nasal polyps 2020 1.
  • The confusion may arise because ACE is often measured as a diagnostic marker in sarcoidosis, but inhibiting ACE does not address the granulomatous inflammation that characterizes the disease.
  • Treatment decisions should be based on organ involvement, symptom severity, and disease progression rather than ACE levels alone, with a focus on improving morbidity, mortality, and quality of life outcomes.

Additional Considerations

  • In many cases, particularly Stage 1 disease, the disease undergoes spontaneous remission within two years without specific treatment, and around 75% can be managed symptomatically with NSAIDS 1.
  • Those with more advanced disease as evidenced by raised SACE or extrapulmonary involvement will usually require treatment, and about 50% may experience a relapse, with 1 in 10 developing serious disability 1.

From the Research

Ace for Sarcoidosis

  • Angiotensin-Converting Enzyme (ACE) is a biomarker used in the diagnosis and follow-up of sarcoidosis patients, although its sensitivity and specificity are low 2, 3, 4.
  • ACE levels are higher in sarcoidosis patients not treated with ACE inhibitors (ACEIs) compared to those treated with ACEIs 2.
  • The use of ACEIs, such as zofenopril, perindopril, enalapril, and ramipril, can affect ACE levels in sarcoidosis patients, with zofenopril resulting in higher ACE levels 2.
  • ACE can be measured in serum, bronchoalveolar lavage fluid (BAL), and cerebrospinal fluid (CSF) to aid in the diagnosis of sarcoidosis, particularly in patients with extra-pulmonary locations 3.
  • The diagnostic utility of ACE for sarcoidosis has been investigated in several studies, with results showing a poor sensitivity and insufficient specificity of high ACE for diagnosis of sarcoidosis 4.

Treatment and Outcomes

  • The use of ACEIs and angiotensin receptor blockers (ARBs) can have divergent effects on outcomes in patients with sarcoidosis, with ACEIs associated with increased mortality risk and worse cardiac and respiratory outcomes 5.
  • An optimized fluorescent kinetic assay for ACE activity has been developed, which can aid in the accurate diagnosis of sarcoidosis, particularly when combined with ACE I/D genotype determination 6.

Measurement and Interpretation

  • Serum ACE activity determination can be affected by endogenous ACE inhibitors and interfering factors, such as albumin, triglycerides, hemoglobin, and bilirubin 6.
  • Genotype-dependent and genotype-independent reference values of ACE activity can be established to improve the diagnostic accuracy of sarcoidosis 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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