Histopathologic Finding of Perieschar Lesions in Tsutsugamushi Disease Shows Lymphocytic Vasculitis Mimicking Angiocentric Lymphoma

Abstract

BackgroundTsutsugamushi disease is an acute, febrile, infectious disease caused by Orientia tsutsugamushi. Several studies investigating the histopathologic findings of eschars in tsutsugamushi disease reported leukocytoclastic vasculitis and neutrophil infiltration as the major findings. However, these findings may result from secondary changes following tissue necrosis. The histopathologic findings of perieschar lesions may be important to understand the primary changes associated with tsutsugamushi disease.ObjectiveTo investigate characteristic histopathologic features of perieschar lesions and suppose the mechanism of vascular pathophysiological changes associated with tsutsugamushi disease.MethodsWe analyzed histopathological slides of perieschar lesions in 12 patients diagnosed with tsutsugamushi disease.ResultsIn the epidermis, exocytosis of mononuclear cells (75.0%) and basal vacuolar changes (66.7%) were frequent. In the dermis, perivascular, interstitial, and perineural mononuclear cell infiltration (100.0%, 83.3%, and 83.3%, respectively), as well as thrombosis (83.3%), atypical lymphocyte infiltration (91.7%), and mitotic figures (83.3%) were commonly seen. Lymphocytic vasculitis and mononuclear cell infiltration around eccrine glands were found in all cases, but eosinophil infiltration was only found in one patient (8.3%). However, the characteristic findings of eschar lesions, such as leukocytoclastic vasculitis and neutrophil infiltration, were not found in perieschar lesions.ConclusionThe major histopathologic findings in the perieschar lesions of tsutsugamushi disease were lymphocytic vasculitis and atypical lymphocytic infiltration, mimicking lymphoma. Therefore, we suggest that this lesion should be added to the list of pseudolymphomas. To observe these characteristic histopathologic features, we also recommend that skin biopsies should be performed on perieschar lesions, not eschar lesions.

Ultrastructural visualization of Orientia tsutsugamushi in biopsied eschars and monocytes from scrub typhus patients in South Korea

“…The bacteria bore the characteristic features of O . tsutsugamushi , including a nearly round shape with a diameter of ~1 µm 19 – 22 and a double membrane with a clear “halo”-like outermost layer 15 , 19 . The bacteria also had the typical morphology of gram-negative bacteria 23 , including under higher magnification a cell wall, an outer membrane (OM, black arrowhead) associated with an external surface microcapsular layer, an internal plasma membrane (PM, white arrowhead) layer surrounding the cytoplasm, and a periplasmic space that appeared as an electron lucent gap between the outer and cytoplasmic membranes (Fig.…”

“…tsutsugamushi invades dermal cells and infects antigen-presenting cells in the sub-epidermal zone, including the basal epidermis and superficial dermis 8 . The dry eschar consists of thick layers of compressed epidermis and dermis 15 with necrosis of the overlying epidermis. Our TEM analysis of an eschar and its surrounding skin showed that O .…”

“…tsutsugamushi strain 4 . Eschar biopsies can be used for PCR-based 13 and immunohistochemical diagnosis 8 , 14 , 15 . Serological tests are also widely used to diagnosis scrub typhus 4 .…”

“…The presence of O . tsutsugamushi in eschar from patients with scrub typhus has been demonstrated using an immunofluorescence assay and light microscopy with immunohistostaining 8 – 10 , 14 , 15 . Here, transmission electron microscopy (TEM) was performed to observe the ultrastructure of O .…”

Buerger’s Disease May be a Chronic Rickettsial Infection with Superimposed Thrombosis: Literature Review and Efficacy of Doxycycline in Three Patients

“…In tsutsugamushi disease the overall pathological features are similar to epidemic typhus [ 82 ]; however, overt thrombosis is somewhat uncommon and typhus nodules are seldom observed. In biopsy specimens of eschars and erythematous rashes in tsutsugamushi disease, the immunophenotypes of infiltrating cells are predominantly CD8 + T lymphocytes and CD68 + monocytes/macrophages; CD4 + T cells are present in smaller numbers than CD8 + T cells; CD30 + -positive large atypical cells were observed in approximately half of the patients; CD20 + B lymphocytes were infrequent [ 83 84 ]. Kawamura described in his monograph that giant cells were observed in the eschar, primary lymph nodes, spleen, and bone marrow in tsutsugamushi disease [ 85 ].…”