# The Paucity of Typical Pathology: An Autopsy Series of Typhus Group Rickettsiosis-Associated Hemophagocytic Lymphohistiocytosis

## TL;DR

This paper reports two fatal cases of a severe immune reaction triggered by murine typhus, a bacterial infection, highlighting an unusual pathology.

## Contribution

The study presents new clinical insights into hemophagocytic lymphohistiocytosis caused by typhus group rickettsiosis.

## Key findings

- Murine typhus can lead to fatal hemophagocytic lymphohistiocytosis.
- Classic histopathologic features of rickettsial infection were absent in the reported cases.

## Abstract

Murine typhus (also called flea-borne or endemic typhus) is an undifferentiated febrile illness caused by the bacterium Rickettsia typhi. The disease, transmitted by rat and cat fleas, is endemic to seaboard regions worldwide. Recently, murine typhus has reemerged as an increasingly recognized cause of febrile illness in the United States, especially in Texas and Southern California. In addition to fever, manifestations often include headache, malaise, myalgias, and a maculopapular rash in approximately half of cases. Although usually considered a mild illness, when untreated, symptoms can last up to 3 weeks. Severe manifestations such as pneumonitis, acute kidney injury, and meningoencephalitis may occur. Historically, death has occurred in 0.4%, but in Southern California, the case fatality rate has been recently recorded at 1.8%. As murine typhus has reemerged, there have been growing reports that this infection has triggered hemophagocytic lymphohistiocytosis, a life-threatening hyperinflammatory syndrome. We herein report two fatal cases of hemophagocytic lymphohistiocytosis secondary to murine typhus. Autopsy revealed typhus group rickettsial antigen in tissues via immunohistochemistry, along with hemophagocytosis. Interestingly, the classic vascular and perivascular histopathologic findings associated with disseminated rickettsial infection were absent. These findings highlight an aberrant inflammatory cascade leading to hemophagocytic lymphohistiocytosis.