What is the recommended treatment for a patient with Granulomatosis with Polyangiitis (GPA) affecting the orbit?

Treatment of Orbital GPA

For patients with GPA presenting with orbital mass lesions (orbital pseudotumor), immunosuppressive therapy is the first-line treatment, with rituximab plus glucocorticoids preferred for remission induction. 1

Initial Treatment Approach

Remission Induction Therapy

Rituximab is conditionally recommended over cyclophosphamide for remission induction in orbital GPA. 1, 2

• Rituximab dosing: 375 mg/m² intravenously once weekly for 4 weeks 1, 3
• Glucocorticoid regimen: Methylprednisolone 1,000 mg IV daily for 1-3 days, followed by oral prednisone (typically 1 mg/kg/day, maximum 80 mg/day) 1
• Glucocorticoids should begin within 14 days prior to or with rituximab initiation 3
• A reduced-dose glucocorticoid regimen is preferred to minimize toxicity while maintaining efficacy 2

When to Consider Surgical Intervention

Debulking surgery should only be considered if there is urgent need for decompression, such as acute visual loss due to optic nerve compression. 1

• Immunosuppressive therapy alone is almost always the initial treatment of choice for orbital mass lesions 1
• Surgery combined with immunosuppressive therapy is reserved for life- or organ-threatening compression 1

Remission Maintenance Therapy

After achieving remission, rituximab is the preferred maintenance agent. 2, 4

• Rituximab maintenance dosing: 500 mg IV every 6 months 1, 3
• Initiate maintenance within 24 weeks after the last induction infusion, but no sooner than 16 weeks 3
• Alternative maintenance options include methotrexate (up to 25 mg/week) or azathioprine (up to 2 mg/kg/day) 1, 4

Essential Prophylaxis and Monitoring

Pneumocystis jirovecii pneumonia prophylaxis is conditionally recommended for all patients receiving rituximab or cyclophosphamide. 1, 2

• Continue prophylaxis for at least 6 months after the last rituximab dose 1
• This reduces the risk of opportunistic infections during immunosuppression 2, 5

Treatment decisions should be based on clinical symptoms and diagnostic studies, not ANCA titers alone. 1

• ANCA titers are only modestly informative as indicators of disease activity 1
• Persistence of ANCA positivity does not necessarily indicate continued immunosuppressive therapy is required 1

Management of Treatment Failure or Relapse

For Refractory Disease

If orbital GPA is refractory to rituximab, switch to cyclophosphamide rather than combining the two therapies. 1, 4

• Cyclophosphamide dosing: up to 2 mg/kg/day orally for 3-6 months, or 15 mg/kg IV every 2 weeks for 3 doses, then every 3 weeks 1
• Consider adding IVIG (2 g/kg divided over 5 days) to current therapy for refractory cases 1, 5

For Disease Relapse

For patients experiencing relapse with severe manifestations while not on rituximab maintenance, treat with rituximab for remission re-induction. 1, 4

For patients who relapse while receiving rituximab maintenance, switch to cyclophosphamide for remission re-induction. 1, 4

Common Pitfalls to Avoid

• Do not delay treatment initiation, as GPA can progress rapidly and cause irreversible vision loss 2
• Do not base treatment escalation solely on rising ANCA titers without corresponding clinical symptoms 1
• Do not omit Pneumocystis prophylaxis in patients receiving rituximab or cyclophosphamide, as this significantly increases infection risk 2, 5
• Do not perform surgical removal as initial therapy unless there is acute vision-threatening compression requiring urgent decompression 1
• Do not use inadequate glucocorticoid tapering, which can lead to unnecessary treatment-related complications 2

Adjunctive Measures

Nasal rinses and topical nasal therapies (antibiotics, lubricants, glucocorticoids) may be beneficial for patients with sinonasal involvement. 1, 4

• Collaboration with an otolaryngologist with expertise in treating GPA is recommended 1