Concurrent Nocardia, Cryptococcus and Mycobacterium Infections Unmask Anti-GM-CSF Antibody-Associated...

Anti-granulocyte macrophage colony stimulating factor (anti-GM-CSF) antibodies, classically associated with pulmonary alveolar proteinosis (PAP), are increasingly recognised as a cause of adult-onset immunodeficiency predisposing to opportunistic infections. Coinfections with multiple opportunistic pathogens in this context are uncommon. We describe a rare case of disseminated Nocardia paucivorans, pulmonary Cryptococcus gattii, pulmonary Mycobacterium chelonae, and subsequent PAP in a patient with high-level anti-GM-CSF antibodies. A 64-year-old man presented with subacute bilateral shoulder pain and was diagnosed with acromioclavicular septic arthritis. N. paucivorans was isolated, and subsequent evaluation demonstrated disseminated infection with numerous brain abscesses, left eye endophthalmitis and pulmonary involvement. Interval computed tomography of the chest revealed new right lower lobe consolidation, a biopsy of which identified C. gattii and M. chelonae. Immunological testing confirmed high-level anti-GM-CSF antibodies. The patient received prolonged combination antimicrobial therapy, including meropenem, ceftriaxone, linezolid, trimethoprim-sulfamethoxazole, moxifloxacin, fluconazole, tigecycline and clofazimine, with clinical and radiological improvement of infectious lesions. Despite microbiological clearance, progressive bilateral ground-glass opacities developed on serial chest imaging consistent with PAP, with no pathogens identified on bronchoscopic sampling. Given minimal respiratory symptoms, PAP-directed therapy was deferred. The patient remains clinically stable on trimethoprim-sulfamethoxazole prophylaxis with ongoing clinical and radiological surveillance. This case illustrates the expanding clinical spectrum of anti-GM-CSF antibody-associated disease and underscores the importance of considering this diagnosis in patients presenting with opportunistic infections, in particular, disseminated nocardiosis or C. gattii infection. It also highlights the need for vigilance in evaluating for coinfections, recognition of PAP as a noninfectious codiagnosis, and the importance of long-term follow-up in affected patients.