Progressive interstitial lung disease nonresponse to cyclophosphamide

Abstract

A 27-year-old Caucasian woman presented at 23 6/7 weeks gestational age with seizure and hypoxic respiratory failure. While initially thought to have eclampsia, she was found to have a positive ANA, a positive anti-Scl-70 antibody, and abnormal nailfold capillaroscopy and, thus, was diagnosed with systemic sclerosis. Several months into her disease course, she developed interstitial lung disease (ILD) diagnosed by high-resolution computed tomography (HRCT). She was started on treatment with cyclophosphamide based on data from the Scleroderma Lung Study I. Unfortunately, her pulmonary function tests (PFTs) and imaging continued to worsen despite treatment with cyclophosphamide. She was then treated with mycophenolate mofetil (MMF) and an experimental therapy with a tyrosine kinase inhibitor (imatinib), both of which yielded similarly poor results. In addition to immunosuppression, she underwent drastic measures to control her gastroesophageal reflux disease, a risk factor known to correlate with more severe ILD. In spite of all of these therapies, she progressed to end-stage lung disease and is currently undergoing evaluation for lung transplant. When initial treatment with cyclophosphamide for SSc-ILD fails, where does one go from there? Several new potential agents are on the horizon. Two new antifibrotic agents, which have been approved for the treatment of idiopathic pulmonary fibrosis, are currently being studied in SSc-ILD. Additionally, a number of other immunosuppressive agents, such as rituximab and tocilizumab, are under investigation in patients with SSc-ILD. While lung transplantation and autologous hematopoietic stem cell transplantation (HSCT) remain potential treatment options, these should generally be reserved for when all other therapies have failed.