Natalizumab-induced pneumonitis

Abstract

Natalizumab is an anti-α4 integrin humanised monoclonal antibody approved for treatment of multiple sclerosis (MS) and Crohn’s disease. Recognised treatment complications include infusion reactions and progressive multifocal leukoencephalopathy. We report pneumonitis associated with peripheral blood eosinophilia attributable to Natalizumab in a patient with co-existent MS and Crohn’s disease. A 39-year-old man presented with worsening dyspnoea and cough. Symptoms had been intermittent over several months and had not improved with antibiotics. There was a history of relapsing–remitting MS, Crohn’s disease with short gut syndrome, and a chronic perianal abscess and pancreatitis. Monthly Natalizumab infusions had been commenced 6 months prior to presentation (Fig. 1). Additional medications included vitamin D, folate, and multivitamins. He smoked and had no history of drug allergy. On examination, there was scattered expiratory wheeze on auscultation and O2 saturations on air were 80%, rising to > 98% with 5 L O2. Inflammatory markers were elevated (C-reactive protein 115 mg/L and plasma viscosity 1.97 mPa/s). There was a raised white cell count (21.55 × 109/L) with neutrophilia (15.09 × 109/L) and eosinophilia (2.87 × 109/L). Alkaline phosphatase was elevated (200 U/L) and the D-dimer was positive. Total immunoglobulin E was normal, but there was a newly identified, low concentration lambda monoclonal paraprotein. Normal or negative investigations included urea and electrolytes, ferritin, anti-nuclear and anti-neutrophil cytoplasm antibodies, as well as screening for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-19). Vitamin D level in the peri-admission period was normal. A CT pulmonary angiogram demonstrated extensive broncho-centric and peripheral ground glass opacification with superimposed interlobular septal thickening consistent with interstitial lung disease but no evidence of acute or chronic thromboembolic disease (Fig. 2). Bronchoalveolar lavage fluid was clear and contained bronchial epithelial cells and alveolar macrophages; semiquantitative assessment of the cell count demonstrated 80% macrophages, 15% neutrophils, and 5% lymphocytes. No significant organisms were identified on culture including prolonged culture for mycobacteria. A diagnosis of Natalizumab-induced pneumonitis was made; the drug was withdrawn and Prednisolone 30 mg was commenced. Follow-up CT chest performed at 2 months and