Acute Fibrinous Organising Pneumonia

A rare acute or subacute lung injury pattern with intra-alveolar fibrin balls ("fibrin balls") and organising pneumonia, without hyaline membranes or eosinophils, causing severe hypoxaemia that often resembles acute respiratory distress syndrome.

• Causes: infection (influenza, SARS-CoV-2, Pneumocystis, Mycoplasma, Legionella, cytomegalovirus), drugs (amiodarone, nitrofurantoin, rituximab, statins, checkpoint inhibitors), connective tissue disease (systemic lupus, rheumatoid arthritis, myositis), haematopoietic cell or lung transplantation, inhalation (dusts, fumes, cocaine), malignancy, and idiopathic.
• Mean age about 50 to 60 years; it is rare and incidence is unknown. In the acute fulminant form mortality is about 50% and in the subacute form about 20 to 30%.
• Mechanism: severe alveolar epithelial injury with intra-alveolar coagulation and fibrin deposition that is organised into fibroblast plugs.

Acute or subacute onset (days to weeks) of fever, cough, breathlessness, pleuritic pain, and hypoxaemia; progression to respiratory failure in days in the acute form.

• Examination: tachypnoea, fever, bilateral crackles, cyanosis in severe disease.
• Differential diagnosis: acute respiratory distress syndrome (diffuse alveolar damage), organising pneumonia, acute eosinophilic pneumonia, pneumonia (bacterial, viral, Pneumocystis), diffuse alveolar haemorrhage, acute interstitial pneumonia, drug induced lung injury, pulmonary oedema, pulmonary embolism.
• Complications: acute respiratory failure and need for ventilation (about 50 to 70% in acute form), refractory hypoxaemia, pneumothorax, secondary infection, pulmonary fibrosis, and death.

Chest X-ray and CT: bilateral consolidation or ground glass opacities, often peripheral and basal, with air bronchograms, sometimes nodules, with a less consistent distribution than organising pneumonia.

• Arterial blood gas (PaO2 to FiO2 ratio), CRP, procalcitonin, lactate, lactate dehydrogenase, ferritin, D-dimer.
• Infection screen: blood cultures, respiratory viral polymerase chain reaction (influenza, SARS-CoV-2, respiratory syncytial virus), Pneumocystis polymerase chain reaction, urinary Legionella and pneumococcal antigens, Xpert MTB/RIF, fungal markers, cytomegalovirus polymerase chain reaction.
• Autoimmune serology: antinuclear antibody, anti-double stranded DNA, rheumatoid factor, anti-cyclic citrullinated peptide, antineutrophil cytoplasmic antibody, myositis antibodies, complement.
• Bronchoalveolar lavage (neutrophils and lymphocytes, exclusion of infection and haemorrhage), then transbronchial cryobiopsy or surgical lung biopsy (when safe) because the diagnosis requires histology: fibrin balls in at least some airspaces in a patchy distribution, with organising pneumonia and no hyaline membranes.

Remove and treat causes:

• Stop the suspected drug.
• Treat infection:
  • Oseltamivir 75 mg twice daily for 5 days, 150 mg twice daily in critical illness or immunosuppression.
  • Remdesivir 200 mg IV then 100 mg daily for 5 days for SARS-CoV-2.
  • Co-trimoxazole 120 mg/kg/day in divided doses for 21 days for Pneumocystis.
  • Azithromycin 500 mg daily and levofloxacin 750 mg daily for Legionella.
• Treat the underlying connective tissue disease.

• Corticosteroids (the main treatment):
  • Methylprednisolone 1 mg/kg IV daily (up to 500 to 1000 mg IV daily for 3 days in fulminant disease), followed by prednisolone 1 mg/kg daily (usual 40 to 60 mg) for 4 weeks then taper over 3 to 6 months guided by response.
  • Response may take 3 to 7 days; the acute form often needs the pulse dose.
• Steroid sparing or escalation for refractory or relapsing disease (evidence limited):
  • Cyclophosphamide 500 to 1000 mg/m2 IV monthly.
  • Rituximab 1 g IV twice 2 weeks apart.
  • Mycophenolate mofetil 1 g twice daily.
  • Azathioprine 1 to 2 mg/kg daily.
  • Intravenous immunoglobulin 2 g/kg over 2 to 5 days.
• Respiratory support:
  • High-flow nasal oxygen 40 to 60 L/min with FiO2 titrated to SpO2 92 to 96%.
  • Non-invasive ventilation in a monitored setting.
  • Intubation for failure, with lung protective ventilation (tidal volume 6 mL/kg predicted body weight, plateau pressure less than 30 cmH2O, positive end-expiratory pressure titrated).
  • Prone positioning for at least 12 to 16 hours daily when PaO2 to FiO2 ratio is less than 150 mmHg.
  • Neuromuscular blockade for the first 24 to 48 hours in severe disease.
  • Venovenous ECMO for refractory hypoxaemia at specialised centres.
• Supportive: conservative fluid balance, thromboprophylaxis with enoxaparin 40 mg SC daily (reduce to 20 mg if creatinine clearance is less than 30 mL/min), stress ulcer prophylaxis with omeprazole 40 mg daily, glycaemic control, nutrition.
• Steroid safety: co-trimoxazole 480 mg daily or 960 mg three times weekly for Pneumocystis prophylaxis, calcium and vitamin D, bone protection, glucose and blood pressure monitoring.
• Special groups: children (rare, usually with infection or immune disease; prednisolone or methylprednisolone 1 to 2 mg/kg daily with specialist care); pregnancy (steroids are acceptable, avoid cyclophosphamide and mycophenolate, deliver in an intensive care centre; ECMO has been used); elderly (higher mortality, discuss goals of care); renal impairment (adjust cyclophosphamide and enoxaparin); immunosuppression and transplant (cover opportunistic infection, review immunosuppression).
• Red flags: PaO2 to FiO2 ratio of less than 200 mmHg, rapid progression, shock, new infection while on steroids, failure to improve in 7 days, pneumothorax.
• Follow-up: chest X-ray and spirometry at 4 to 6 weeks, CT at 3 months, steroid taper with review every 2 to 4 weeks, diffusing capacity at 3 and 6 months; relapse on tapering is possible, and some patients develop fibrosis.