Histopathological Features in Both the Eschar and Erythematous Lesions of Tsutsugamushi Disease: Identification of CD30+ Cell Infiltration in Tsutsugamushi Disease

Abstract

Tsutsugamushi disease is an acute febrile infectious disease caused by Rickettsia tsutsugamushi. An infection is heralded by the presence of an eschar at the site of the inoculating chigger bite and followed by the development of a disseminated erythematous macular rash. CD30 expression is found in anaplastic large cell lymphoma; however, expression in nonneoplastic cutaneous disorders, such as atopic dermatitis, drug reactions, scabies, and various infectious diseases, has also been reported. Study of the cutaneous histopathology of tsutsugamushi disease has been limited. In this study, we performed biopsies of both the eschar and erythematous lesions of 15 cases of tsutsugamushi disease to assess the histopathological changes including the CD3, CD4, CD20, CD30, and CD68 reactivity. Twelve women and 3 men were included with an age range from 21 to 73 years. The most common location of the eschar was the trunk (53.3%). The histological features showed increased leukocytoclastic vasculitis in the eschar (93.3%) compared with the erythematous lesions (33.3%); basal vacuolar changes were more common in the erythematous (100%) than in the eschar lesions (20%). The inflammatory infiltrate had a majority of CD3-and CD68-positive cells. Seven erythematous lesions and 7 eschar lesions showed atypical cells that were CD30-positive cells. Here, we report on the cutaneous histopathology and pattern of inflammatory infiltrates of tsutsugamushi disease. Leukocytoclastic vasculitis and basal vacuolar changes were the characteristic features of the eschar and the erythematous lesions, respectively. In addition, CD30-positive cell infiltration was identified for the first time in this disease.

The Role of Chiggers as Human Pathogens

“…The basic histopathologic findings reveal multiplication of O. tsutsugamushi in the endothelial cells lining the small blood vessels, perivasculitis and focal interstitial mononuclear cell infiltrations, and edema. Perivasculitis may involve the lung, heart, brain, kidneys, gastrointestinal tract, liver, spleen, and lymph node [73].…”

Orientia tsutsugamushi in Human Scrub Typhus Eschars Shows Tropism for Dendritic Cells and Monocytes Rather than Endothelium

“…Histopathological studies of eschars in humans [14]–[18] and cynomolgus monkeys [19] have described perivascular collections of mononuclear cells, including lymphocytes, plasma cells and macrophages. In recent studies, immunophenotyping revealed a dominance of CD3+ T-cells and CD68+ monocyte/macrophages within infiltrates [15] and an association of O. tsutsugamushi with the epithelial lining covering the surface of the sweat ducts and glands [14]. Eschars can have high bacterial loads and have been shown to be useful specimens for both PCR-based and immunohistochemical diagnosis [14], [20].…”

Approaches to vaccines against Orientia tsutsugamushi

“…Clues of those effects could be obtained from the study of eschars from human cases. Indeed, a recent study of 11 eschars from patients with confirmed scrub typhus confirmed the classic histological finding of epidermal necrosis and ulceration accompanied by significant neutrophilic infiltration adjacent to the area of necrosis and mononuclear cell infiltrates in the dermis (Lee et al, 2009; Paris et al, 2012). Those infiltrates consisted of T cells, monocytes, and dermal dendritic cells.…”