C68-12 A Rare Case of Mycobacterium Kansasii-induced Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare yet life-threatening hyperinflammatory immunologic syndrome characterized by uncontrolled activation of cytotoxic T lymphocytes and macrophages, resulting in excessive cytokine release, progressive multiorgan dysfunction, and bone marrow hemophagocytosis. Although viral infections are among the most frequently recognized triggers, HLH associated with nontuberculous mycobacterial (NTM) infection is exceptionally uncommon, making timely recognition and management particularly challenging. We report the case of a 33-year-old man who presented with altered mental status and incoherent speech. Initial evaluation revealed persistent high-grade fevers, pancytopenia, hyponatremia, ferritin elevation exceeding 23,000 ng/mL, and markedly increased soluble IL-2 receptor levels with liver enzyme elevations. Bone marrow biopsy demonstrated hypercellular marrow with granulomatous inflammation and focal hemophagocytosis, while CT imaging revealed pulmonary micronodules, mild splenomegaly, and mesenteric fat stranding. Based on fulfillment of HLH-2004 diagnostic criteria, treatment with dexamethasone and etoposide was initiated. Microbiologic investigation subsequently identified Mycobacterium kansasii in bronchoalveolar lavage cultures, prompting the introduction of rifampin, ethambutol, and azithromycin. Despite appropriate immune-modulating and antimycobacterial therapy, the patient developed acute respiratory distress syndrome, diffuse alveolar hemorrhage, persistent cytopenias, and neurologic deterioration consistent with posterior reversible encephalopathy syndrome. His course required multiple transfers for escalating levels of critical care, ultimately necessitating intensive management in a tertiary-care ICU. This case underscores the complexity of diagnosing HLH in the context of an NTM infection, where overlapping manifestations with sepsis, malignancy, and other inflammatory disorders may obscure early recognition. The immunopathogenesis likely reflects a maladaptive hyperinflammatory response to persistent intracellular infection, with macrophage activation and cytokine storm driving rapid clinical decline. Optimal outcomes hinge on concurrent suppression of excessive immune activation and aggressive treatment of the underlying infection. Clinicians should maintain heightened suspicion for NTM as a potential HLH trigger in the presence of granulomatous inflammation, pulmonary involvement, or delayed culture positivity, as early therapeutic intervention remains critical to reducing the high mortality associated with this entity.