What is the recommended acute treatment for scleroderma renal crisis, including angiotensin‑converting‑enzyme (ACE) inhibitor dosing and management of malignant hypertension?

Treatment of Scleroderma Renal Crisis

Initiate an ACE inhibitor immediately upon diagnosis of scleroderma renal crisis and escalate the dose aggressively to achieve rapid blood pressure control—this single intervention increases 1-year survival from 15% to 76%. 1

Immediate Pharmacologic Management

Start ACE inhibitor therapy without delay:

• Begin captopril or enalapril immediately at diagnosis, even before obtaining renal biopsy confirmation 1, 2
• These two agents have the most extensive evidence base in scleroderma renal crisis 1, 2
• Escalate the ACE inhibitor dose rapidly and aggressively to achieve maximal blood pressure control 2, 3
• Add additional antihypertensive agents (calcium channel blockers, then diuretics, then alpha-blockers) only if blood pressure remains uncontrolled despite maximum tolerated ACE inhibitor doses 4

Continue ACE inhibitor therapy despite rising creatinine:

• Do not discontinue the ACE inhibitor if serum creatinine rises—this is expected and stopping the drug dramatically worsens outcomes 2, 3
• Maintain ACE inhibitor therapy even after dialysis initiation, as renal recovery can occur over 3-18 months 2
• More than half of patients who require dialysis eventually regain renal function and discontinue dialysis, particularly when blood pressure control is optimal 1, 3

Blood Pressure Targets and Monitoring

Achieve aggressive blood pressure control:

• The goal is rapid normalization of blood pressure using maximally tolerated ACE inhibitor doses 2, 4
• Monitor blood pressure continuously during the acute phase and adjust medications frequently 1
• Perfect blood pressure control is the strongest predictor of dialysis discontinuation and renal recovery 3

Critical Management Pitfalls to Avoid

Do not use ACE inhibitors prophylactically:

• ACE inhibitors should not be started in scleroderma patients without active renal crisis, as prophylactic use may be harmful and worsen renal outcomes 5
• The EULAR guidelines explicitly recommend against prophylactic ACE inhibitor therapy 1

Reduce or discontinue corticosteroids immediately:

• Prednisone ≥15 mg/day increases scleroderma renal crisis risk 4.4-fold (OR 4.4; 95% CI 2.1-9.4) 1, 2
• Recent corticosteroid exposure within 3 months increases risk 6.2-fold (95% CI 2.2-17.6) 2
• High-dose steroids (≥30 mg/day) are particularly associated with normotensive scleroderma renal crisis, which carries worse prognosis 2, 6

Survival Outcomes with ACE Inhibitor Therapy

The evidence for ACE inhibitors is compelling despite lack of randomized trials:

• 1-year survival improves from 15% (without ACE inhibitors) to 76% (with ACE inhibitors) 1, 2
• 5-year survival improves from 10% (without ACE inhibitors) to 66% (with ACE inhibitors) 1, 2
• This represents a EULAR strength of recommendation C, reflecting consistent survival benefits across multiple prospective cohort studies despite absence of randomized controlled trials 2

Special Circumstance: Pregnancy

Use ACE inhibitors in pregnant patients with active scleroderma renal crisis:

• The American College of Rheumatology strongly recommends ACE inhibitor or ARB therapy for active scleroderma renal crisis in pregnancy, despite known teratogenicity in second and third trimesters 1
• The risk of maternal or fetal death from untreated scleroderma renal crisis exceeds the medication risk 1
• Distinguish scleroderma renal crisis from preeclampsia, as management strategies differ critically 1, 2

Renal Replacement Therapy Considerations

Initiate dialysis when indicated but continue ACE inhibitor:

• Dialysis is frequently required during acute scleroderma renal crisis 3, 4
• Continue ACE inhibitor therapy throughout dialysis, as approximately 50% of patients recover sufficient renal function to discontinue dialysis 1, 2, 3
• Patients requiring dialysis for more than 2 years should be evaluated for renal transplantation 3
• Renal transplantation outcomes in systemic sclerosis show 5-year patient survival of approximately 82%, similar to other connective tissue disorders 4

Emerging Therapies for Refractory Cases

Consider alternative agents only in refractory cases:

• C5 complement inhibitors and endothelin receptor antagonists have been reported in case series for refractory scleroderma renal crisis 4
• Plasma exchange may provide benefit in patients with microangiopathy or ACE inhibitor intolerance 4
• These therapies lack robust evidence and should be reserved for cases unresponsive to standard ACE inhibitor-based management 4, 5