How to manage increased Angiotensin-Converting Enzyme (ACE) levels in patients with sarcoidosis who are taking corticosteroids?

From the Guidelines

If ACE levels increase while on steroid treatment for sarcoidosis, the primary approach is to optimize the steroid regimen rather than focusing solely on the ACE levels, as recommended by the European Respiratory Journal in 2021 1.

Key Considerations

• Typically, prednisone at 20-40mg daily for 4-6 weeks is recommended, followed by a slow taper over 6-12 months based on clinical response.
• If ACE levels remain elevated despite adequate steroid treatment, consider adding steroid-sparing agents such as methotrexate (10-25mg weekly), azathioprine (50-200mg daily), or hydroxychloroquine (200-400mg daily) as suggested by the Delphi consensus recommendations in 2020 1.
• It's essential to understand that ACE levels should not be the only parameter guiding treatment decisions, as they don't always correlate perfectly with disease activity.
• Instead, focus on clinical symptoms, pulmonary function tests, and imaging findings when assessing treatment effectiveness, as emphasized by the European Respiratory Review in 2020 1.

Monitoring and Maintenance

• Regular monitoring every 3-6 months is recommended during treatment.
• Some patients may require long-term maintenance therapy if they experience frequent relapses when steroids are tapered.
• The goal is to control inflammation while minimizing steroid-related side effects through appropriate dosing and potentially adding steroid-sparing medications.

Treatment Algorithm

• The treatment algorithm for symptomatic or organ-threatening sarcoidosis derived from the Delphi consensus recommendations suggests adding antimetabolites, such as methotrexate, in cases of disease progression or toxicity 1.
• Biologics, especially monoclonal antibodies to TNFs, such as infliximab, may be considered in cases of insufficient response or severe disease, as recommended by the European Respiratory Review in 2020 1.

From the Research

Managing Increased ACE Levels on Steroids in Sarcoidosis

• Increased ACE levels on steroids in sarcoidosis may not be a reliable indicator of disease activity, as shown in a study from 1983 2.
• The study found a negative correlation between changes in steroid dose and serum ACE level, suggesting that ACE levels may not be useful for following disease activity in patients during a change in medication.
• In cases where ACE levels increase on steroids, consideration may be given to alternative treatments, such as steroid-sparing agents, to minimize the risks associated with long-term steroid use 3.
• Methotrexate and azathioprine are two commonly used steroid-sparing agents in the treatment of sarcoidosis, with similar efficacy in reducing prednisone dose and improving lung function 4.
• Methotrexate is often preferred for the treatment of chronic sarcoidosis when corticosteroids have inadequate efficacy and/or severe adverse effects 5.
• Other cytotoxic agents, such as leflunomide and hydroxychloroquine, may also be considered as second-line treatments, although the evidence supporting their use is limited 6.

Treatment Options

• Steroid-sparing agents, such as methotrexate and azathioprine, may be used to reduce the dose of prednisone and minimize the risks associated with long-term steroid use.
• Alternative treatments, such as biologic therapy, may be considered for patients who are refractory to standard therapy 3.
• The choice of treatment should be individualized based on the patient's specific needs and circumstances, taking into account the potential benefits and risks of each treatment option.