Abstract Background Autoimmune Pulmonary Alveolar Proteinosis (aPAP) is a rare lung disease characterized by autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF). Defective GM-CSF signaling leads to dysfunctional alveolar macrophage development and activation, predisposing patients to opportunistic infections in otherwise immunocompetent patients. The anti-GM CSF activity in aPAP predisposes patients to disseminated nocardiosis, due to impaired phagocytosis. Our case describes a patient with brain abscesses due to disseminated nocardiosis as the presenting manifestation of aPAP. Case description A 53-year-old male smoker with history of hypertension and daily alcohol use presented as a transfer from an outside hospital with tonic-clonic seizure in the setting of several weeks of memory changes and phantosmia. Head computed tomography (CT) was notable for multiple cystic rim-enhancing left frontal and right parietal brain lesions with extensive vasogenic edema, midline shift, and right ventricle effacement. These were redemonstrated on brain magnetic resonance imaging (MRI) and concerning for large conglomerates of abscesses. CT of the chest, abdomen and pelvis revealed extensive symmetric bilateral pulmonary cystic cavities and bronchiectasis associated with diffuse interlobular septal thickening, apical predominant ground-glass opacities consistent with a “crazy paving” pattern. Seizure prophylaxis and empiric broad-spectrum antibiotics were started. Stereotactic aspiration of the right parietal abscess revealed beaded filamentous gram-positive bacilli on modified acid-fast stain suspicious for Nocardia, later confirmed withculture as Nocardia beijingensis, with antibiotics directed to sensitivities. Interval imaging showed significant improvement in brain MRI, but persistent abnormalities in chest CT. This was associated with worsening hypoxemia and pulmonology was consulted. Based on his chest imaging, alternate diagnosis was suspected and evaluated with bronchoscopy. Transbronchial biopsy revealed eosinophilic alveolar filling most compatible with PAP. Serum anti-GM-CSF autoantibodies were positive, confirming autoimmune PAP. He is waiting for therapeutic whole lung lavage due to worsening hypoxemia. Discussion Most patients with aPAP present with insidious dyspnea and cough. Opportunistic infections like nocardiosis are a rare initial presentation of aPAP. In a review of published studies, 61% of the opportunistic infections in aPAP were due to nocardiosis. This bacterium induces GM-CSF-mediated STAT5 phosphorylation in monocytes. In the presence of anti GM-CSF autoantibody, this immune response is evaded, making the aPAP patient susceptible to nocardiosis. Macrophage dysfunction may result in ineffective pulmonary barrier, thus increasing the risk of dissemination. Our case highlights an unusual presentation of a rare disease and emphasizes the importance of suspicion for anti-cytokine pathologies in immunocompetent patients presenting with opportunistic infections. This abstract is funded by: None
Savani et al. (Fri,) studied this question.