Steroid refractory desquamative interstitial pneumonia responsive to intravenous cyclophosphamide

A 39-year-old female presented with 1 month of dyspnoea and dry cough. Her medical history included asthma diagnosed in childhood and World Health Organization class 2 obesity. She recently quit smoking cigarettes and marijuana via bongs and had a 20-pack-year smoking history. Initial computed tomography (CT) chest demonstrated basal predominant ground glass opacity with fine reticulations (Fig. 1A). Viral panel results were negative and connective tissue disease screen was unremarkable. C-reactive protein was mildly elevated at 5.8 mg/L and full blood cell examination demonstrated a mild neutrophilia. Detailed exposure history did not reveal any additional occupational or environmental exposures. As the differential included both infective and non-infective causes, she was treated with a course of antibiotics with improvement in symptoms. The patient re-presented a week later with progressive symptoms. Non-specific interstitial pneumonia was considered as a diagnosis, and prednisolone 50 mg daily was commenced while a surgical lung biopsy was organised. The histopathology demonstrated diffuse accumulation of macrophages within the airspaces with mild interstitial fibrosis (Fig 1B) and a diagnosis of desquamative interstitial pneumonia (DIP; also recently classified as alveolar macrophage pneumonia) was made. Bacterial and fungal cultures from the biopsy were negative. The patient was continued on prednisolone and counselled strongly on ongoing smoking cessation. Despite adherence, she was later readmitted with severe hypoxia. Repeat CT chest demonstrated marked progression of ground glass changes and interlobular septal thickening with subpleural cysts (Fig 1C). Due to the critical nature of her condition, her case was discussed in a multidisciplinary meeting, and she was commenced on 3 days of intravenous (IV) methylprednisolone followed by a trial 6-month course of monthly IV cyclophosphamide (600 mg/m2) and oral prednisolone in conjunction with nintedanib to reduce progression of fibrosis. A CT scan after the fifth cycle of treatment demonstrated significant improvement in ground glass opacities with residual subpleural fibrosis and cystic change (Fig 1D). Due to ongoing symptoms, she received a single dose of 500 mg IV rituximab at conclusion of cyclophosphamide and then transitioned to oral mycophenolate mofetil. Six-minute walk tests conducted at 8 months and 20 months post-treatment initiation demonstrated walking distances of 180 and 275 m respectively, and she continued to demonstrate slow symptomatic improvement. DIP is a rare type of smoking-related interstitial lung disease (ILD), although 10% of cases occur in patients without a smoking history.1 Prognosis is generally better than idiopathic pulmonary fibrosis, as the majority respond to complete abstinence from smoking and prednisolone.2 Despite this, mortality is between 6% and 28%, as some cases progress despite adherence to standard therapy.3 A case report from 1991 described steroid refractory DIP that responded promptly to intravenous cyclophosphamide but returned when cyclophosphamide was withdrawn.4 Conversely, rituximab has not been reported as a treatment for refractory DIP specifically but has been used for other progressive fibrosing ILDs.5 To our knowledge, this is the first reported case of successful treatment of rapidly progressive steroid-refractory DIP with a complex multi-drug regimen. Although there is remaining residual fibrosis and scarring, resolution of the ground glass infiltrate suggests the acute inflammatory phase has resolved. A considerable proportion of patients with DIP progress despite smoking cessation and steroids, and our case highlights the potential need for aggressive intervention in these cases. Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.