Interstitial Pneumonia with Autoimmune Features

Interstitial pneumonia with autoimmune features describes patients with idiopathic interstitial pneumonia who have signs, serology or lung patterns suggesting an autoimmune cause but do not meet the diagnostic definition for a defined connective tissue disease. It is a research classification and a practical label for these cases.

It accounts for about 7 to 15% of interstitial lung disease, mostly in women over 50 years. The commonest patterns are nonspecific interstitial pneumonia, organising pneumonia and usual interstitial pneumonia. Some develop a connective tissue disease over time, in about 10 to 30% in follow up.

Pathophysiology. Systemic autoimmunity is limited or lung dominant, and may reflect a connective tissue disease that has not declared itself yet. Mechanisms are shared with other autoimmune interstitial lung diseases, with immune mediated alveolar injury and fibrosis.

Progressive dyspnoea and cough, with extrapulmonary features that may be mild: Raynaud phenomenon, morning joint stiffness, digital ulceration or fissuring, mechanic's hands, Gottron sign, unexplained digital swelling and palmar telangiectasia.

Rapid worsening, hypoxaemia at rest, fever or new haemoptysis needs urgent assessment.

• High resolution CT: interstitial pneumonia of a nonspecific interstitial pneumonia, organising pneumonia, mixed or lymphoid pattern, or usual interstitial pneumonia, with extra-parenchymal features (pleural or pericardial effusion, airway disease, pulmonary vascular disease).
• Exclusion of other causes: hypersensitivity pneumonitis (exposure history), drugs, occupational disease, infection and heart failure.
• Does not meet the definition of a connective tissue disease after rheumatology review.
• At least one feature in one of three domains: clinical (distal digital fissuring or ulceration, inflammatory arthritis or morning stiffness over 60 minutes, palmar telangiectasia, Raynaud phenomenon, unexplained digital oedema, or Gottron sign), serological (antinuclear antibody 1:320 or more in a diffuse, speckled or homogeneous pattern, or nucleolar or centromere pattern at any titre, rheumatoid factor over twice the upper limit of normal, anti-CCP, anti-dsDNA, anti-Ro, anti-La, anti-Sm, anti-RNP, anti-Scl-70, anti-synthetase, anti-PM-Scl, anti-MDA5), or morphological (nonspecific interstitial pneumonia, organising pneumonia, mixed pattern or lymphoid interstitial pneumonia, or multi-compartment involvement).
• Creatine kinase, inflammatory markers, bronchoalveolar lavage, and multidisciplinary discussion.

Differential diagnosis.

• Idiopathic pulmonary fibrosis with a positive antinuclear antibody
• Established connective tissue disease associated interstitial lung disease
• Hypersensitivity pneumonitis
• Drug induced lung disease
• Occupational interstitial lung disease
• Cryptogenic organising pneumonia

• No treatment is proven by controlled study, and therapy follows the pattern and severity, using the approach for connective tissue disease associated interstitial lung disease.
• Inflammatory patterns (nonspecific interstitial pneumonia, organising pneumonia): prednisolone 0.5 mg/kg daily (30 to 40 mg) for 4 to 8 weeks then tapered, with mycophenolate mofetil 500 mg twice daily increased to 1 to 1.5 g twice daily, or azathioprine 1 to 2 mg/kg daily.
• Refractory disease: rituximab 1 g intravenously on days 1 and 15, or cyclophosphamide 600 mg/m2 intravenously monthly for 6 months.
• Fibrosing or progressive disease, especially a usual interstitial pneumonia pattern: nintedanib 150 mg twice daily with food (100 mg twice daily in mild hepatic impairment), or pirfenidone titrated to 801 mg three times daily.
• Prophylaxis against Pneumocystis when prednisolone is 20 mg or more daily for over 4 weeks: co-trimoxazole 960 mg three times weekly.
• Bone protection, glucose and blood pressure monitoring on steroids, smoking cessation, vaccination against influenza, pneumococcus and COVID-19, pulmonary rehabilitation and oxygen when PaO2 is 7.3 kPa or less.
• Reassess regularly for evolution to a defined connective tissue disease.

Complications and prognosis. Outlook is intermediate: better than idiopathic pulmonary fibrosis and variable, with a usual interstitial pneumonia pattern doing worse. Progression, acute exacerbation and pulmonary hypertension occur.

Monitoring. Spirometry, DLCO and walk test every 3 to 6 months, CT at 6 to 12 months or with decline, and rheumatology review every 6 months for new autoimmune features and serology.

Referral and escalation. Refer to an interstitial lung disease service with rheumatology for shared care, and to a transplant centre for advanced fibrosis.