Organising Pneumonia

An inflammatory lung disease with plugs of granulation tissue (Masson bodies) in the alveolar ducts and bronchioles, with chronic inflammation of the surrounding alveoli.

• Cryptogenic (idiopathic) in about half; secondary forms are caused by infection (bacterial, viral including SARS-CoV-2, Mycoplasma, Legionella), drugs (amiodarone, nitrofurantoin, methotrexate, bleomycin, immune checkpoint inhibitors, sulfasalazine, statins), connective tissue disease (rheumatoid arthritis, myositis, Sjogren syndrome, lupus), breast radiotherapy, haematological malignancy, inflammatory bowel disease, transplant, and aspiration.
• Incidence is about 2 per 100,000 per year; mean age 50 to 60 years; both sexes; smoking is not a cause.
• Mechanism: repair of alveolar injury leads to fibroblast and myofibroblast proliferation in the airspaces rather than resolution, usually reversible with corticosteroids.

Subacute illness (2 to 10 weeks) with fever, dry cough, breathlessness, malaise and weight loss, mimicking pneumonia that does not respond to antibiotics.

• Examination: localised or bilateral crackles; clubbing is uncommon.
• Radiological relapse and migration of consolidation without new symptoms in some patients.
• Differential diagnosis: bacterial pneumonia, chronic eosinophilic pneumonia, lung adenocarcinoma (lepidic type), lymphoma, tuberculosis, vasculitis (granulomatosis with polyangiitis), hypersensitivity pneumonitis, fibrotic nonspecific interstitial pneumonia, drug reaction, sarcoidosis.
• Complications: respiratory failure (the rapidly progressive form), relapse in 30 to 50% on tapering, steroid adverse effects, fibrosis (about 5 to 10%), pneumothorax, and death in rapid forms.

Chest X-ray: patchy, bilateral, peripheral consolidations, often migratory.

• High-resolution CT: subpleural or peribronchial consolidation with air bronchograms, ground glass opacities, the reversed halo sign (atoll sign: central ground glass surrounded by consolidation), nodules, and perilobular pattern.
• Spirometry restrictive with reduced diffusing capacity; arterial blood gas; CRP raised (often 50 to 150 mg/L), mild leucocytosis, raised erythrocyte sedimentation rate.
• Bronchoalveolar lavage: lymphocytes 20 to 40% with a reduced CD4 to CD8 ratio, foamy macrophages, mast cells, neutrophils and eosinophils; cultures excluding infection.
• Transbronchial cryobiopsy or surgical biopsy when imaging is atypical or the patient is not improving: intra-alveolar buds of loose connective tissue with preserved architecture.
• Exclusions: sputum and bronchoalveolar culture, Xpert MTB/RIF, fungal tests, autoimmune serology (antinuclear antibody, rheumatoid factor, anti-cyclic citrullinated peptide, antineutrophil cytoplasmic antibody, myositis panel), drug history, and imaging for malignancy.

Remove the cause: stop the drug (amiodarone, nitrofurantoin, methotrexate), treat infection, and manage the underlying disease.

• Mild disease with few symptoms and minimal changes: observe with CT at 4 to 6 weeks (some resolve spontaneously); clarithromycin 500 mg twice daily for 3 months is an option (evidence limited).
• Moderate to severe disease: prednisolone 0.75 mg/kg daily (usual 40 to 60 mg) for 4 weeks, then reduce by 10 mg every 2 weeks to 20 mg, then by 5 mg every 2 weeks, stopping after a total of 6 to 12 months; improvement is usually seen in 1 to 3 weeks.
• Fulminant or rapidly progressive disease: methylprednisolone 500 to 1000 mg IV daily for 3 days, then prednisolone 1 mg/kg daily; intensive care and ventilation with lung protective settings (tidal volume 6 mL/kg predicted body weight).
• Relapse (30 to 50%): restart prednisolone at 20 to 30 mg daily and taper more slowly over a longer period, and add a steroid sparing drug when repeated or on prednisolone of more than 15 mg: azathioprine 1 to 2 mg/kg daily (check thiopurine methyltransferase), mycophenolate mofetil 500 mg twice daily rising to 1 g twice daily, or cyclophosphamide 500 mg/m2 IV every 4 weeks for 3 to 6 doses in severe refractory disease; rituximab 1 g twice, 2 weeks apart (evidence limited).
• Steroid safety: co-trimoxazole 480 mg daily or 960 mg three times weekly for Pneumocystis prophylaxis during prednisolone of 20 mg or more for 4 weeks or more; omeprazole 20 mg daily; calcium 1000 mg and vitamin D 800 units daily, alendronate 70 mg weekly; glucose and blood pressure monitoring.
• Oxygen to SpO2 94 to 98% (88 to 92% if hypercapnic); pulmonary rehabilitation; annual influenza vaccination.
• Special groups: children (rare; prednisolone 1 mg/kg daily for 4 weeks then tapered over 6 to 12 months, and look for infection and drug causes); pregnancy (prednisolone is acceptable; avoid cyclophosphamide, mycophenolate, methotrexate and clarithromycin in the first trimester); elderly (bone and glucose care); renal impairment (adjust azathioprine and mycophenolate); immunosuppression (exclude opportunistic infection before escalation).
• Red flags: respiratory failure, rapidly progressive disease, no response to steroids by 3 weeks, cavitation, new nodules, fever on steroids, haemoptysis.
• Follow-up: clinical review and chest X-ray at 2 to 4 weeks, spirometry and diffusing capacity at 3 and 6 months, CT at 3 to 6 months, review every 3 months during taper and for 1 year afterward; relapse most often occurs within 3 months of stopping steroids.