A Complex Case of Disseminated Mycobacterium Kansasii, Hemophagocytic Lymphohistiocytosis, and Chronic Myelogenous Leukemia in a Patient With Multiple Sclerosis on Ocrelizumab Therapy

Abstract Introduction This a case of a patient with relapsing-remitting multiple sclerosis (RRMS) on ocrelizumab with a complex clinical course that involved diagnoses of disseminated Mycobacterium Kansasii, Macrophage Activation Syndrome (MAS)-hemophagocytic lymphohistiocytosis (HLH), and chronic myelogenous leukemia (CML). This case highlights the challenges in diagnosing and managing multiple severe conditions in an immunocompromised patient. Case Presentation 45-year-old female with RRMS on ocrelizumab arrived at the emergency department with confusion, abdominal pain, weakness, and recurrent fevers for weeks. She was febrile (103.4°F), tachypneic, tachycardic, and disoriented. Physical examination was unremarkable, and initial labs were remarkable for thrombocytosis, normal white blood cell count, hyponatremia, hypokalemia, transaminitis, elevated ferritin, and CRP. Broad-spectrum antibiotics were initiated. CT imaging revealed a 3.4cm right hilar mass, pulmonary nodules, atelectasis, and hepatosplenomegaly. Bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial ultrasound (EBUS) revealed acid-fast bacilli, though Mycobacterium tuberculosis PCR was negative. Persistent hyperferritinemia (>7000 ng/mL) and elevated IL-2 receptor (IL-2R) levels (26335 pg/mL) suggested HLH. Bone marrow biopsy showed fibrotic marrow, lymphohistiocytic infiltrates, necrotizing granulomas, and positive acid-fast bacilli. The combination of findings supported a diagnosis of HLH and disseminated non-tuberculous mycobacteria(dNTM). During her ICU stay, the patient's condition deteriorated with shock, encephalopathy, and worsening pulmonary infiltrates requiring high-flow nasal cannula. Mycobacterium kansasii was eventually cultured, and she was treated with azithromycin, ethambutol, and rifampin. Concurrently, dexamethasone and anakinra were administered for Macrophage activation syndrome (MAS)-HLH, leading to clinical improvement. Genetic analysis of the bone marrow biopsy later revealed the Philadelphia chromosome (t 9; 22), confirming a new diagnosis of CML. After a prolonged ICU stay, the patient was transferred to a rehabilitation center with plans to start CML treatment as an outpatient. Discussion dNTM is more prevalent in those with an immunologic defect either acquired or genetic. The patient's immunosuppressed state due to ocrelizumab therapy and CML contributed to her susceptibility to dNTM. HLH is a hyperinflammatory, hyperferritinemic syndrome induced by aberrantly activated macrophages, cytotoxic T cells and cytokine storm. HLH can be classified as primary or secondary. Secondary HLH is usually triggered by infections, malignancies, and/or autoinflammatory/autoimmune disorders. Differentiating MAS-HLH from other forms of secondary HLH is crucial due to differences in treatment strategies. The overlap of symptoms and the presence of multiple severe diagnoses (dNTM, HLH, and CML) required careful coordination and discussions among specialists to optimize patient outcomes. This case underscores the importance of a multidisciplinary approach in managing complex presentations in immunocompromised patients.