What is the treatment for interstitial lung disease (ILD) in a patient with ankylosing spondylitis (AS)?

Etiology, Diagnosis and Treatment of Interstitial Lung Disease in Ankylosing Spondylitis

For patients with ankylosing spondylitis (AS) who develop interstitial lung disease (ILD), mycophenolate is the preferred first-line treatment, along with short-term glucocorticoids, while TNF inhibitors should be avoided due to potential exacerbation of ILD. 1

Etiology

ILD in AS is uncommon compared to other pulmonary manifestations. The primary pulmonary complications of AS include:

• Chest wall restriction due to costovertebral joint fusion
• Apical fibrobullous disease (most common parenchymal manifestation)
• Spontaneous pneumothorax
• Obstructive sleep apnea 2

When ILD does occur in AS patients, it may be related to:

• Underlying autoimmune mechanisms of AS
• Medication-induced lung disease (particularly from TNF inhibitors)
• Overlap with other systemic autoimmune rheumatic diseases (SARDs) 3

Diagnosis

Clinical Presentation

• Progressive dyspnea on exertion
• Dry cough
• Decreased exercise tolerance
• Bibasilar crackles on auscultation

Diagnostic Workup

1. Pulmonary Function Tests:

   • Restrictive pattern (decreased FVC and TLC)
   • Reduced diffusion capacity (DLCO)

2. High-Resolution CT (HRCT) of the chest:

   • Ground-glass opacities
   • Reticular patterns
   • Honeycombing in advanced disease

3. Laboratory Testing:

   • Inflammatory markers (ESR, CRP)
   • Autoantibody screening to rule out overlap syndromes
   • HLA-B27 testing (if not already done)

4. Bronchoscopy with bronchoalveolar lavage:

   • To exclude infection
   • May show lymphocytosis

5. Lung biopsy (rarely needed):

   • Only if diagnosis remains uncertain after less invasive testing

Treatment Algorithm

First-Line Treatment for AS-ILD 1

1. Preferred medication:

   • Mycophenolate mofetil (starting dose 500mg twice daily, titrating to 1000-1500mg twice daily as tolerated)

2. Short-term glucocorticoids:

   • Oral prednisone (starting at 0.5mg/kg/day with tapering over 2-3 months)
   • IV pulse methylprednisolone (1000mg daily for 3 days) for severe or rapidly progressive disease

3. Additional options (if inadequate response to mycophenolate):

   • Azathioprine (1-2.5mg/kg/day)
   • Rituximab (1000mg IV at 0 and 2 weeks, repeated every 6 months)
   • Cyclophosphamide (for severe, rapidly progressive disease)

Medications to Avoid in AS-ILD

• TNF inhibitors (infliximab, adalimumab, etanercept, golimumab, certolizumab) - despite being effective for joint manifestations of AS 1, these should be avoided in AS-ILD as they may potentially worsen ILD
• Methotrexate - conditionally recommended against as first-line ILD treatment 1
• Leflunomide - conditionally recommended against as first-line ILD treatment 1

Management of Progressive ILD Despite First-Line Treatment 1

For patients with AS-ILD who show progression despite first-line treatment (defined as decline in FVC ≥10% or decline in FVC 5-10% with worsening symptoms/HRCT findings):

1. Consider switching to or adding:

   • Rituximab
   • Cyclophosphamide
   • Nintedanib (especially if fibrosing phenotype)

2. Avoid long-term glucocorticoids - conditionally recommended against due to risk of adverse effects 1

Monitoring

• Pulmonary function tests (FVC, DLCO) every 3-6 months
• HRCT chest at baseline and as clinically indicated (typically every 6-12 months)
• Regular assessment of respiratory symptoms
• Monitor for medication side effects

Special Considerations

1. Rapidly Progressive ILD:

   • Combination therapy recommended (e.g., glucocorticoids + cyclophosphamide + mycophenolate)
   • Early referral for lung transplantation evaluation 1

2. Management of AS Joint Symptoms:

   • NSAIDs remain first-line for AS joint symptoms but may need to be used cautiously in ILD 1
   • IL-17 inhibitors (secukinumab, ixekizumab) may be considered for joint symptoms in patients with AS-ILD, as they have not been associated with ILD exacerbation 1

3. Rare Association with Sjögren's Syndrome:

   • Consider screening for Sjögren's syndrome in AS patients with ILD, as this association has been reported 3
   • May require adjustment of treatment approach if overlap exists

Pitfalls and Caveats

• Don't confuse restrictive lung disease due to chest wall involvement with parenchymal ILD
• Always rule out infectious complications, particularly in apical fibrobullous disease
• Monitor for drug-induced pneumonitis, especially if using methotrexate
• Consider pulmonary rehabilitation to optimize functional status
• Ensure regular monitoring for extra-articular manifestations of AS (uveitis, inflammatory bowel disease, psoriasis) 4

The prognosis of AS-ILD depends on early recognition and appropriate treatment. Regular monitoring of pulmonary function and prompt intervention for disease progression are essential to improve outcomes and quality of life.