What is the best management for a 32-year-old white female patient with newly diagnosed retinal vasculitis of bilateral eyes, positive C-ANCA (Cytoplasmic Anti-Neutrophil Cytoplasmic Antibodies) and anti-PR3 (Proteinase 3), with improving symptoms on steroid medication, such as prednisone (prednisone)?

Management of Retinal Vasculitis with Positive C-ANCA and Anti-PR3

For a 32-year-old white female with bilateral retinal vasculitis, positive C-ANCA and anti-PR3, who is showing improvement on steroids, the recommended management is combination therapy with rituximab and glucocorticoids for induction of remission, followed by maintenance therapy with either rituximab or azathioprine plus low-dose glucocorticoids. 1

Induction Therapy

Initial Assessment

• Confirm diagnosis through clinical presentation and positive C-ANCA/anti-PR3 serology
• Evaluate for other organ involvement (kidney, lung, nervous system)
• Assess disease severity to guide treatment intensity

Recommended Induction Regimen

1. Glucocorticoids:

   • Continue current steroid therapy that has shown improvement
   • Follow standardized tapering schedule based on weight 1:
     • For 50-75 kg patient: Start at 60 mg/day prednisone
     • Taper to 30 mg by week 2,25 mg by weeks 3-4
     • Continue tapering to reach 5 mg/day by weeks 15-16
     • Maintain at 5 mg/day through month 12

2. Immunosuppressive Therapy:

   • Rituximab: 375 mg/m² weekly for 4 weeks 1, 2
   • Pre-medicate with antihistamine and acetaminophen prior to infusion 2

Important: PR3-ANCA positive patients (like this patient) respond better to rituximab than cyclophosphamide, with higher complete remission rates (65% vs 48%) 3

Maintenance Therapy

After achieving remission (typically 3-6 months):

Recommended Maintenance Options

1. Rituximab-based maintenance:

   • 500 mg every 6 months for 18 months (MAINRITSAN protocol) 1
   • OR 1000 mg at month 4,8,12, and 16 after first infusion (RITAZAREM protocol) 1

2. Azathioprine-based maintenance:

   • 1.5-2 mg/kg/day for 18-24 months
   • Then decrease to 1 mg/kg/day until 4 years after diagnosis
   • Then taper by 25 mg every 3 months 1
   • Continue low-dose glucocorticoids (5-7.5 mg/day) for 2 years, then taper gradually 1

Key consideration: Rituximab maintenance has shown superior outcomes with lower relapse rates (5%) compared to azathioprine (29%) at 28 months 2

Monitoring and Follow-up

1. Regular ANCA monitoring:

   • Patients who become and remain ANCA-negative have lower relapse risk 4
   • Positive C-ANCA at 3,12,18, and 24 months significantly increases relapse risk 4
   • PR3-ANCA levels >10 U/ml at 18 and 24 months predict relapse 4

2. Ophthalmologic evaluation:

   • Regular eye examinations to monitor retinal vasculitis activity
   • Visual acuity and visual field testing

3. Laboratory monitoring:

   • Complete blood count, renal function, liver function
   • Urinalysis to detect potential kidney involvement
   • C-reactive protein and erythrocyte sedimentation rate

Infection Prophylaxis

• Pneumocystis jirovecii prophylaxis:
  • Trimethoprim/sulfamethoxazole (800/160 mg on alternate days or 400/80 mg daily) 1
  • Especially important during induction therapy

Potential Pitfalls and Considerations

1. Treatment at experienced centers:

   • Patients with ANCA-associated vasculitis should be treated at centers with experience in AAV management 1

2. Relapse risk factors:

   • PR3-ANCA positivity (as in this patient) carries higher relapse risk
   • Persistent ANCA positivity during follow-up increases relapse risk 4

3. Fertility considerations:

   • Important for this 32-year-old female patient
   • Rituximab is preferred over cyclophosphamide for preserving fertility

4. Bone protection:

   • Osteoporosis prophylaxis should be provided due to glucocorticoid therapy

By following this management approach, the patient's retinal vasculitis can be effectively controlled while minimizing long-term complications and reducing relapse risk. The positive response to steroids already observed is encouraging, and adding rituximab will provide more targeted immunosuppression with better outcomes for this PR3-ANCA positive patient.