Ocrelizumab-Induced Hemophagocytic Lymphohistiocytosis: A Case Report

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon disorder marked by severe immune system dysfunction and excessive inflammation. Its clinical features often mimic those of severe sepsis, including persistent high fevers, multiorgan failure, cytopenia, and coagulation abnormalities. HLH can be triggered by infections, malignancies, rheumatological disorders, genetic factors, and medications, particularly those that cause immunosuppression. Ocrelizumab, an anti-CD20 monoclonal antibody used in the treatment of multiple sclerosis, has been associated with rare immune-mediated complications. In this case, the patient presented with generalized fatigue, fever, and neutropenia and was initially treated for neutropenic sepsis. Despite standard antibiotic therapy, there was no clinical improvement. A CT scan of the chest, abdomen, and pelvis revealed multiple lung nodules with surrounding ground-glass halos, suggestive of an invasive fungal infection, along with hepatosplenomegaly, raising concern for an underlying hematological malignancy. The patient was managed with intravenous antibiotics and antifungal therapy. However, due to persistent high fevers, markedly elevated ferritin levels (peaking at 20,695 ng/mL), and pancytopenia, an H-score for HLH was calculated, yielding a score of 302, indicating a greater than 99% probability of the condition. Based on these findings, intravenous anakinra (100 mg) was initiated. A bone marrow biopsy showed features suggestive of HLH but no evidence of hematological malignancy. The case was discussed at the HLH multidisciplinary team meeting with the HLH team at University College London Hospitals NHS Foundation Trust, and methylprednisolone (500 mg) was subsequently started. Consultations with the rheumatology and respiratory teams were also arranged. The patient's condition gradually improved, and she was discharged on Day 31 with a tapering course of prednisolone, continued oral antifungal therapy, and a follow-up PET scan scheduled. This case highlights the importance of recognizing HLH as a potential complication in patients receiving immunosuppressive therapies such as ocrelizumab. Prompt diagnosis and aggressive management are critical for improving outcomes and preventing further complications.