ACE Inhibitors in Scleroderma
ACE inhibitors must be started immediately at high doses when scleroderma renal crisis (SRC) develops, as they dramatically improve survival from 15% to 76% at 1 year, and should be continued long-term even if dialysis is required. 1
Treatment of Scleroderma Renal Crisis
Immediate Management
- Start ACE inhibitors immediately upon diagnosis of SRC with aggressive dose escalation to control blood pressure, as this is the cornerstone of therapy that transformed SRC from a uniformly fatal condition to one with 76% 1-year survival. 1, 2
- Captopril and enalapril are the most extensively studied agents in this context. 1
- Add calcium channel blockers if blood pressure remains inadequately controlled despite maximal ACE inhibitor dosing. 3
Long-term Outcomes with ACE Inhibitors
- Continue ACE inhibitors indefinitely, even after initiating dialysis, as 55% of patients who remain on ACE inhibitors can discontinue dialysis after 3-18 months, compared to 0% without ACE inhibitor therapy. 4, 2
- Survival rates with ACE inhibitor treatment: 76% at 1 year, 66% at 5 years, compared to 15% at 1 year and 10% at 5 years without ACE inhibitors. 1
- More recent data shows survival of 71-82% at 1 year, 59-60% at 5 years, and 42-47% at 10 years when ACE inhibitors/ARBs are used. 1
Poor Prognostic Factors Despite ACE Inhibitors
Patients with the following features have worse outcomes even with ACE inhibitor therapy: 2
- Older age
- Male sex
- Initial serum creatinine >270 μmol/L (>3 mg/dL)
- Inadequately controlled blood pressure
- Congestive heart failure at presentation
Critical Caveat: No Role for Prophylactic Use
Do NOT use ACE inhibitors prophylactically in high-risk scleroderma patients to prevent SRC, as published evidence does not support preventive use to decrease risk of development or improve outcome of SRC. 1, 5
Monitoring Requirements
In Patients on Glucocorticoids
- Monitor blood pressure and renal function closely in all scleroderma patients receiving glucocorticoids, particularly those on ≥15 mg/day prednisone, as this increases SRC risk 4.4-fold (OR 4.4; 95% CI 2.1-9.4). 1
- High-dose steroids (≥30 mg/day) are particularly associated with normotensive SRC. 1
High-Risk Populations Requiring Vigilance
Monitor closely for SRC development in patients with: 3
- Diffuse cutaneous systemic sclerosis in first 4-5 years of disease
- Rapidly progressive skin thickening
- Anti-RNA polymerase III antibodies (present in one-third of SRC cases)
- Recent corticosteroid exposure
Strength of Evidence
The recommendation for ACE inhibitors in SRC carries a strength of recommendation C from EULAR guidelines, reflecting the absence of randomized controlled trials (which are considered unethical given the dramatic mortality benefit observed in cohort studies). 1 The evidence base consists of prospective cohort studies and case series demonstrating consistent, substantial survival benefits that have been replicated across multiple centers over decades. 1, 4, 2