Histoplasmosis-Associated Hemophagocytic Lymphohistiocytosis: A Review of the Literature

Abstract

Background Histoplasmosis is an endemic fungal disease with diverse clinical presentations. Histoplasmosis-associated hemophagocytic lymphohistiocytosis (HLH) is a rare disorder with limited data regarding treatment and outcome. We described the clinical features, treatment, and outcomes of five patients in our institution with histoplasmosis-associated HLH. This review also summarizes the current literature about presentation, treatment, and outcome of this infection-related HLH entity. Methods We searched the electronic medical records for patients with histoplasmosis-associated HLH at our institution from 1/1/2006 to 9/30/2017. Diagnosis of HLH was confirmed by chart review using the HLH-04 criteria. We also searched the current literature for case reports and case series. Results Five cases of histoplasmosis-associated HLH were included from our institution. All five patients were diagnosed after 2010. The literature review yielded 60 additional cases of histoplasmosis-associated HLH. The most common underlying condition was HIV in 61% of cases. The majority of histoplasmosis patients (81%) were treated with amphotericin B formulations. Documented specific treatments for HLH were as follows: nine patients received steroids only, six patients received intravenous immunoglobulin (IVIG) only, three patients received dexamethasone and etoposide, two patients received etoposide, dexamethasone, and cyclosporine, two patients received steroids and IVIG, and one patient received Anakinra and IVIG. The inpatient case fatality rate was 31% with most of the deaths occurring within two weeks of hospital admission. Conclusions Histoplasmosis-associated HLH among adults is an uncommon but serious complication with high associated mortality. Early antifungal therapy with a lipid formulation amphotericin B is critical. The initiation of immunosuppressive therapy with regimens like HLH-04 in this disease entity should be individualized.

Hemophagocytic Lymphohistiocytosis During HIV Infection in Cayenne Hospital 2012–2015: First Think Histoplasmosis

“…HLH has been previously reported among HIV patients with and without disseminated infections. HLH is notably a known complication of acute disseminated histoplasmosis in both HIV+ and HIV- patients (Subedee and Van Sickels, 2015 ; Townsend et al, 2015 ; Jabr et al, 2019 ). Besides histoplamosis, the main etiology for HLH in AIDS patients are Kaposi sarcoma or lymphoma (B cell, T cell, or primary effusion lymphoma), but also toxoplasmosis, CMV disease, mycobacterial infections, and other opportunistic infections, such as candidiasis and pneumocystosis (Bhatia et al, 2003 ).…”

A Case of Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Histoplasmosis

“…Liver biochemistries are universally abnormal, and neurological manifestations such as ataxia, mental status changes and seizures are present in up to a third of the patients with HLH [13,14]. Our patient met all of the above criteria and also had a bone marrow biopsy which is recommended early in the evaluation of patients meeting HLH 2004 diagnostic criteria [15]. Infection-related HLH cases should be treated aggressively with standard HLH protocols that include dexamethasone, etoposide, and cyclosporine [10,14].…”

“…Infection-related HLH cases should be treated aggressively with standard HLH protocols that include dexamethasone, etoposide, and cyclosporine [10,14]. Mortality rates have been found to be high regardless of treatment modality in a previous case series [15].…”

Central Nervous System Histoplasma-Associated Post-infectious Inflammatory Response Syndrome (Histo-PIIRS)

“…1 ). Soluble CD25 reflects immune activation and is used in the diagnosis of histoplasmosis-associated hemophagocytic lymphohistiocytosis [ 14 ]. IL-6 is involved in naïve T cell polarization, classically Th17 differentiation, and is released by activated astrocytes during CNS inflammation [ 15 ].…”