An Elusive Diagnosis: Case Reports of Secondary Hemophagocytic Lymphohistiocytosis and Review of Current Literature

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare and serious hematologic disorder characterized by severe immune system dysregulation with a cytokine storm and histologic evidence of hemophagocytosis. It can be inherited or develop secondary to other diseases. We present three cases of secondary HLH in patients with distinct backgrounds. Our objective is to characterize the unique features of the disease, its underlying associations, treatment, and potential prognostic variables. The first case was a 20-year-old male with a history of intravenous (IV) drug abuse who presented with multi-organ failure and septic shock. A diagnosis of HLH was suspected after finding a ferritin of >100,000 ng/mL and confirmed with bone marrow biopsy. Furthermore, the patient was found to have significant Epstein-Barr virus (EBV) viremia. He responded well to the HLH-94 protocol with the addition of rituximab and ganciclovir. The second case was a 50-year-old female with a history of human immunodeficiency virus (HIV) who presented with multi-organ failure and severe anemia. Ferritin was also significantly elevated and a bone marrow biopsy confirmed the diagnosis of HLH. She was started on HLH-94 protocol. Despite treatment, the patient expired due to worsening renal failure and shock. Her autopsy report also showed evidence of Hodgkin’s lymphoma. The third case was a 57-year-old male with a history of Crohn’s disease treated with infliximab and adalimumab, who presented with multi-organ failure and pancytopenia. A diagnosis of HLH was made based on clinical findings and later confirmed on bone marrow biopsy. He responded to HLH-94 protocol but experienced fatal gastrointestinal bleeding. Patients presenting with HLH are often critically ill and deteriorate rapidly. The diagnosis is often challenging to establish due to its variable presentation and association with other pathologies. A moderate index of suspicion should be present for patients who have febrile illness with pancytopenia, multi-organ failure, high ferritin, and low fibrinogen levels. We discuss associations with viral infections, hematologic malignancies and immunosuppressive therapy. Treatment is directed at suppressing the immune response and for secondary HLH, addressing the underlying conditions, such as use of rituximab for EBV viremia and treatment of lymphoma.

Lamotrigine-associated haemophagocytic lymphohistiocytosis (HLH) confounded with underlying rheumatoid arthritis

“…For example, in cases of infection associated with HLH (I-HLH) secondary to Epstein-Barr virus, the concurrent use of rituximab, aiming at the selective killing of B cells, is justified in some literature. There have also been cases supporting repeat stem cell transplantation aiming at a better prognosis 11 12. HLH is an evolving field, and despite the current advancement and treatment options, the 5-year survival rate is still grim.…”

A Case of Severe Epstein–Barr Virus-Associated Hemophagocytic Lymphohistiocytosis Successfully Treated With High Dose Steroids and Ganciclovir

“…Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hematological disorder characterized by immune dysregulation with multiple organ involvement and poor prognosis [ 1 ]. The occurrence of HLH may be familial or sporadic, or secondary causes like infection or malignancy can trigger it [ 2 ]. It is divided into primary or familial HLH and secondary HLH.…”

Secondary Hemophagocytic Lymphohistiocytosis in a Young Hispanic Adult

“…Hemophagocytic lymphohistiocytosis (HLH) is a rare hematologic disorder characterized by severe immune system dysregulation, leading to the overproduction of inflammatory cytokines, hyperinflammation, and histologic evidence of hemophagocytosis. It frequently affects multiple organs and has been associated with poor prognosis [1]. HLH can be inherited as an autosomal recessive disorder or develop secondary to other pathologies.…”