Desquamative Interstitial Pneumonia

Desquamative interstitial pneumonia is a smoking related interstitial lung disease with diffuse accumulation of pigmented macrophages in the alveolar spaces. Over 90% of adults are current or former smokers.

It presents in the fourth and fifth decades, more in men, with a subacute course. Other causes are occupational dusts, drugs (nitrofurantoin, sirolimus), infection (hepatitis C, Pneumocystis) and, in children, surfactant protein gene variants and systemic disease. Outlook is better than for most fibrosing diseases.

Pathophysiology. Smoke and other inhaled agents cause a macrophage predominant alveolitis, with macrophages filling the airspaces, with mild septal thickening, and variable fibrosis. The cells are not desquamated epithelial cells, as the name originally suggested.

Progressive dyspnoea and dry cough over weeks to months, with clubbing in up to half, fine basal crackles and, in some, weight loss. Respiratory failure is less common than in other interstitial pneumonias.

Rapid worsening, fever or hypoxaemia at rest needs urgent evaluation for infection or an acute exacerbation.

• High resolution CT: diffuse ground glass opacity, often predominating in the lower and peripheral zones, with small cysts in the ground glass areas in many, and little or no honeycombing.
• Lung function: restrictive defect with reduced DLCO, and often mild airway obstruction.
• Bronchoalveolar lavage: many pigmented (smoker) macrophages, sometimes with eosinophils, and a normal or mildly raised lymphocyte count.
• Lung biopsy when the picture is uncertain: macrophages in airspaces with uniform septal thickening.
• Serology for connective tissue disease, hepatitis C and HIV tests, and drug and exposure history.

Differential diagnosis.

• Respiratory bronchiolitis associated interstitial lung disease
• Nonspecific interstitial pneumonia
• Hypersensitivity pneumonitis
• Pulmonary alveolar proteinosis
• Eosinophilic pneumonia
• Pneumocystis pneumonia
• Pulmonary Langerhans cell histiocytosis

• Stop smoking and eliminate exposures: this is the most important step and can lead to improvement alone. Varenicline 0.5 mg daily for days 1 to 3, 0.5 mg twice daily for days 4 to 7, then 1 mg twice daily for 12 weeks (reduce to 0.5 mg twice daily at eGFR under 30), or nicotine replacement with a patch and a short acting form.
• Corticosteroid for symptomatic or progressive disease: prednisolone 0.5 mg/kg daily (usually 30 to 40 mg) for 4 to 8 weeks, then tapered over 3 to 6 months, with response judged by symptoms, spirometry and CT.
• Steroid sparing agent for those who relapse or do not respond: azathioprine 1 to 2 mg/kg daily or mycophenolate mofetil 1 to 1.5 g twice 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, and vaccination against influenza, pneumococcus and COVID-19.
• Oxygen when PaO2 is 7.3 kPa or less, and pulmonary rehabilitation.

Complications and prognosis. Most improve with smoking cessation and steroids, with 10-year survival of about 70%. A minority progress to fibrosis, and emphysema and lung cancer are risks in smokers.

Monitoring. Review at 4 to 8 weeks with spirometry and DLCO, then every 3 to 6 months, with CT at 6 to 12 months.

Referral and escalation. Refer to an interstitial lung disease service, and refer for progressive disease or when the diagnosis is uncertain.