Abstract Introduction Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disorder characterized by the accumulation of surfactant within alveoli, resulting in progressive respiratory failure and increased susceptibility to secondary infections. The current mainstay of therapy is widely known to be whole-lung lavage (WLL). We present a case of refractory aPAP refractory to standard WLL and requiring rituximab infusion and plasmapheresis. Case Presentation An 18-year-old female was recently diagnosed with biopsy-proven pulmonary alveolar proteinosis. She was found to have elevated anti-GM-CSF antibodies. Two months following her initial WLL, she presented with worsening dyspnea and hypoxemia requiring high oxygen supplementation. CT of the chest revealed bilateral ground-glass opacities with interlobular septal thickening, consistent with a “crazy-paving” pattern Figure 1. She was also noted to have a concurrent COVID-19 infection. She underwent treatment with remdesivir but remained with refractory hypoxemia. Thus, she underwent a second WLL that could not be completed without worsening hypoxemia. She then required support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) to complete the procedure. Despite this, her oxygen requirement remained high after WLL. Due to the refractory nature of her disease, she underwent five sessions of plasmapheresis followed by an infusion of rituximab 1000mg, resulting in marked clinical improvement and discharge on 5 L/min supplemental oxygen. She received another dose of rituximab 1000 mg two weeks later, with further improvement of oxygen requirement to 3 L/min on ambulation. Discussion Autoimmune PAP, the most common form of primary PAP, has a prevalence of approximately 6.7-6.9 per million and is caused by autoantibodies against GM-CSF, which impair alveolar macrophage and neutrophil function. WLL remains first-line therapy for severely symptomatic disease, with recombinant inhaled GM-CSF suggested on an off-label basis. Rituximab, an anti-CD20 monoclonal antibody, reduces B-cell production of anti-GM-CSF antibodies and has shown benefit in small prospective and observational studies, with reports of improved oxygenation and radiographic findings in most treated patients. Plasmapheresis can rapidly remove circulating antibodies and has been associated with short-term clinical improvement in severe or refractory cases. Combining plasmapheresis with rituximab may provide both immediate and sustained antibody reduction. Current consensus statements from the European Respiratory Society and others support considering rituximab for symptomatic, refractory aPAP and reserving plasmapheresis for rescue therapy in severe cases. This case highlights the potential efficacy of sequential immunomodulatory therapy in aPAP unresponsive to conventional interventions. This abstract is funded by: None
Saenz et al. (Fri,) studied this question.