Successful Management of Autoimmune Pulmonary Alveolar Proteinosis Complicating Rheumatoid Arthritis with Whole-lung Lavage and De-escalation of Anti-rheumatic Therapy: A Report of Two Cases

Abstract Background Autoimmune pulmonary alveolar proteinosis (APAP) is characterized by elevated levels of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), resulting in the accumulation of surfactant proteins within the alveoli. Immunosuppressive therapy is generally considered harmful in APAP, but the clinical impact of reducing immunosuppressive therapy on concomitant connective tissue disease remains unclear. Case presentation Case 1: A 69-year-old woman with rheumatoid arthritis (RA) in clinical remission on methotrexate, iguratimod, and salazosulfapyridine developed exertional dyspnea. Chest High-resolution computed tomography showed bilateral ground-glass opacities with a crazy-paving appearance, and APAP was diagnosed based on bronchoalveolar lavage findings and elevated serum anti-GM-CSF autoantibody levels. Whole-lung lavage (WLL) resulted in improvement, but APAP recurred one year later and required a second WLL. During APAP management, anti-rheumatic therapy was gradually tapered and discontinued, and she remained free of both APAP recurrence and RA flare for two years after the second WLL. Case 2: A 67-year-old man with RA treated with salazosulfapyridine was found to have bilateral diffuse bilateral ground-grass opacities on routine chest imaging and was subsequently diagnosed with APAP based on a positive serum anti-GM-CSF autoantibody testing. Because he was initially asymptomatic with preserved oxygenation, careful observation was chosen. After disease progression, WLL was performed, followed by gradual tapering of salazosulfapyridine. APAP relapsed three months later and improved after a second WLL, by which time salazosulfapyridine had been discontinued. He has remained free of respiratory symptoms and RA flare without medication for more than five years. Conclusion In selected patients with RA who develop APAP, tapering anti-rheumatic medication may allow APAP to be managed without loss of RA control. These cases suggest a possible immunomodulatory role of anti-GM-CSF autoantibodies and indicate that careful re-evaluation and adjustment of RA treatment after the onset of APAP may help achieve a more favorable balance between APAP control and RA disease activity.