What is the recommended immunosuppressive therapy for a patient with microscopic polyangiitis (MPA) presenting with interstitial lung disease (ILD) as the sole manifestation?

Immunosuppressive Therapy for Microscopic Polyangiitis with Isolated Interstitial Lung Disease

For patients with microscopic polyangiitis (MPA) presenting with interstitial lung disease (ILD) as the sole manifestation, mycophenolate mofetil is the preferred first-line immunosuppressive therapy, followed by rituximab or cyclophosphamide as alternative options. 1

First-Line Treatment Algorithm

Preferred First-Line Agent:

• Mycophenolate mofetil
  • Favorable safety profile compared to cyclophosphamide
  • Effective for controlling ILD progression
  • Recommended by ACR/CHEST guidelines as preferred first-line therapy for SARD-ILD

Alternative First-Line Options (if mycophenolate is contraindicated or not tolerated):

1. Rituximab

   • Particularly effective in ANCA-positive MPA
   • May have dual benefit for both ILD and underlying vasculitis

2. Cyclophosphamide

   • Traditionally used for severe MPA manifestations
   • Consider for rapidly progressive disease
   • Typically administered as pulse therapy to minimize toxicity

Treatment Considerations for MPA-ILD

Glucocorticoid Use:

• Short-term glucocorticoids (≤3 months) are conditionally recommended as adjunctive therapy
• Consider pulse intravenous methylprednisolone for initial control in rapidly progressive cases
• Taper to lowest effective dose to minimize adverse effects

Combination Therapy for Severe/Progressive Disease:

• For rapidly progressive MPA-ILD, consider upfront combination therapy:
  • Glucocorticoids plus mycophenolate or cyclophosphamide
  • Triple therapy may be considered in severe cases (glucocorticoids + two immunosuppressants)

Medications to Avoid:

• Leflunomide
• Methotrexate
• TNF inhibitors
• Abatacept

Monitoring and Assessment

• Regular pulmonary function tests (PFTs) every 3-6 months
• High-resolution CT scans at baseline and as needed to assess progression
• Monitor for extrapulmonary manifestations, particularly renal involvement
• Regular ANCA testing, though treatment should not be based solely on ANCA titers 1

Management of Treatment Failure or Disease Progression

If disease progresses despite first-line therapy:

1. Add or switch to rituximab or cyclophosphamide if not already used 1
2. Consider calcineurin inhibitors (tacrolimus, cyclosporine) for refractory disease 1
3. Consider IVIG for patients unable to receive other immunomodulatory therapy 1
4. Consider nintedanib as add-on therapy for progressive fibrotic ILD 1
5. Early referral for lung transplantation evaluation in cases of severe, progressive disease 1

Clinical Pearls and Pitfalls

• MPA-ILD can present as isolated pulmonary fibrosis before other manifestations of vasculitis develop 2, 3
• The most common radiographic pattern in MPA-ILD is usual interstitial pneumonia (UIP), similar to idiopathic pulmonary fibrosis 4
• Subclinical episodes of alveolar hemorrhage may be the underlying mechanism of ILD in MPA 2
• Delay in treatment can lead to irreversible fibrosis; early intervention is crucial
• Monitor closely for development of other organ involvement, particularly renal disease
• Pneumocystis jirovecii pneumonia prophylaxis is conditionally recommended for patients receiving rituximab or cyclophosphamide 1

Special Considerations

• For patients with rapidly progressive disease, early referral for lung transplantation evaluation is recommended 1
• Long-term immunosuppression is typically required, with treatment duration guided by clinical response and disease activity
• The overall 5-year survival for MPA without poor prognostic factors is approximately 92%, but outcomes are worse with significant pulmonary involvement 5

MPA-ILD requires prompt recognition and treatment to prevent irreversible fibrotic changes. While mycophenolate is the preferred first-line agent based on current guidelines, treatment should be escalated to more potent immunosuppression if there is evidence of disease progression.