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No Germs, Just Cytokines: A Case of Immunotherapy-Induced Hemophagocytic Lymphohistiocytosis Masquerading as Neutropenic Sepsis in a Patient With Inflammatory Breast Cancer.

Created on 16 Jul 2026

Authors

Nnaemeka H Ugwuchukwu

Published in

Cureus. Volume 18. Issue 6. Pages e110906. Epub Jun 15, 2026.

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition leading to organ dysfunction and death. Primary HLH, driven by genetic mutations that impair immune regulation, predominantly affects children, whereas the secondary (acquired) form is more common in adults. Secondary HLH may be precipitated by various drivers, including medications such as immune checkpoint inhibitors (ICIs). Diagnosing this condition is difficult, as initial signs are often vague and overlap with those of other disorders; consequently, clinicians commonly use the Hemophagocytic Lymphohistiocytosis-2004 (HLH-2004) diagnostic criteria and the H-Score to support the diagnostic evaluation. We report a case of a patient with triple-negative inflammatory breast cancer who developed HLH following anticancer therapy with pembrolizumab. The patient's presentation with fever and cytopenias led to the initial management of neutropenic sepsis. However, following non-response to standard sepsis management, the patient was worked up for HLH. Diagnosis of HLH was supported by histopathological and laboratory findings; the patient fulfilled five HLH-2004 diagnostic criteria and responded to high-dose corticosteroid therapy. This case highlights the importance of considering HLH as a rare immune-related adverse event (irAE) in patients receiving ICIs when presumed diagnosis fails to respond as expected. It further illustrates the value of applying validated diagnostic tools to expedite immunosuppressive therapy.

PMID:
42460212
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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