Abstract Introduction Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by NADPH oxidase defects, leading to impaired reactive oxygen species (ROS) production and defective intracellular pathogen killing. Typically diagnosed in childhood, CGD manifests as recurrent infections by catalase-positive bacteria and fungi. Immune dysregulation with hyperinflammatory responses may occur even without infection. We present a case of severe immune dysregulation in CGD with concomitant pulmonary nocardiosis. Case Summary A 37-year-old man presented with one month of progressive productive cough, fevers, malaise, vomiting, poor oral intake and high ileostomy output. He was diagnosed with X-linked CGD at age 5 which was complicated by recurrent skin infections and fulminant colitis requiring subtotal colectomy. Laboratory studies showed elevated WBC and CRP of 282.77mg/l. CT scan of chest showed widespread pulmonary nodules and dense consolidation in the left upper lobe with heterogeneous diminished enhancement suggesting necrosis (Fig 1). Cell-free pathogen DNA sequencing testing on sputum identified Nocardia cyriacigeorgica DNA. Fungal cultures on bronchoalveolar lavage grew Nocardia cyriacigeorgica. He was treated with imipinem-cilastin, sulfamethoxazole-trimethoprim, and posaconazole. His course was complicated by refractory fevers (T.max 40.5 C), septic shock, and ARDS. He had two episodes of extubation failure characterized by sudden recrudescence of fever, hemodynamic change, and worsening oxygenation. Each of these episodes occurred during steroid tapers and improved after reinitiating full stress doses. Immune dysregulation was suspected, and he was maintained on 0.8mg/kg/day of methylprednisone with plans for a prolonged taper. He gradually improved, was weaned off oxygen, and discharged home. Discussion Pulmonary nocardiosis is common in CGD, particularly without prophylaxis. Case series report that some patients fail to improve with antimicrobials alone and require adjunctive corticosteroids to control excessive inflammation, as seen in this patient. Immune dysregulation in CGD involves both defective microbial killing and excessive inflammation. Absent ROS results in persistent NF-κB and inflammasome activation, driving production of pro-inflammatory cytokines, leading to granuloma formation, autoimmunity, and IBD-like colitis. Granulomatous inflammation may cause gastrointestinal or genitourinary obstruction, and up to half of patients develop colitis. Exaggerated inflammatory responses to infection or environmental triggers can also mimic hemophagocytic lymphohistiocytosis (HLH). Concurrent susceptibility to infections and inflammation complicates diagnosis and management. Corticosteroids remain first-line for inflammatory episodes and may be combined with antibiotics, as in disseminated nocardiosis, to control hyperinflammation. However, long-term use is limited by adverse effects, and steroid-sparing agents lack proven efficacy in CGD. Hematopoietic stem cell transplantation remains the only curative option in CGD. This abstract is funded by: None
Gyimah et al. (Fri,) studied this question.