Characterization of the Histopathologic Features in Patients in the Early and Late Phases of Cutaneous Leishmaniasis

Abstract

Cutaneous leishmaniasis (CL), characterized by an ulcerated lesion, is the most common clinical form of human leishmaniasis. Before the ulcer develops, patients infected with Leishmania (Viannia) braziliensis present a small papule at the site of the sandfly bite, referred to as early cutaneous leishmaniasis (E-CL). Two to four weeks later the typical ulcer develops, which is considered here as late CL (L-CL). Although there is a great deal known about T-cell responses in patients with L-CL, there is little information about the in situ inflammatory response in E-CL. Histological sections of skin biopsies from 15 E-CL and 28 L-CL patients were stained by hematoxilin and eosin to measure the area infiltrated by cells, as well as tissue necrosis. Leishmania braziliensis amastigotes, CD4+, CD8+, CD20+, and CD68+ cells were identified and quantified by immunohistochemistry. The number of amastigotes in E-CL was higher than in L-CL, and the inflammation area was larger in classical ulcers than in E-CL. There was no relationship between the number of parasites and magnitude of the inflammation area, or with the lesion size. However, there was a direct correlation between the number of macrophages and the lesion size in E-CL, and between the number of macrophages and necrotic area throughout the course of the disease. These positive correlations suggest that macrophages are directly involved in the pathology of L. braziliensis–induced lesions.

Arginase activity of Leishmania isolated from patients with cutaneous leishmaniasis

“…Moreover, they showed that the increased ARG levels in lesions of CL patients may play a role in the pathogenesis of the disease, but did not specify the ARG on isolated parasites . Furthermore, a recent study showed that no significant correlation was seen between the number of parasite amastigotes and the duration of illness and its size . Their data were in agreement with the present study.…”

“…In particular, it has been elucidated that knocking down of parasite ARG restricts the parasite growth and replication; however, as we could not find any correlation between the type, size, number and duration of lesions and parasite ARG activity, we favour the hypothesis that isolated wild‐type Leishmania from CL patients had higher ARG activity. Although the immunopathology of the CL lesions and its features is well described, there is a lack of information about the exact mechanism of lesion development and its relationship with the parasite . The most probable explanation for this is that the different wild‐type isolates of Leishmania inoculated directly from sandflies have higher virulence and infectivity than the parasites cultured in mice or in in vitro situations .…”

Leishmaniasis cutánea inducida por especies de Leishmania Viannia en ratones BALB/c y eficacia de un tratamiento tópico

“…Microscópicamente se observan diferentes patrones histológicos en humanos siendo el más común el de dermatitis difusa (85% de los pacientes con LC) que muestra una epidermis hiperplásica, ulcerada, escamocostras e infiltrado dérmico difuso con macrófagos vacuolados, plasmocitos, linfocitos y amastigotes intracelulares en las papilas dérmicas. Otros patrones como el de dermatitis granulomatosa (de granulomas epitelioides, linfocitos y plasmocitos y escasas células gigantes y amastigotes), el de dermatitis granulomatosa tipo tuberculoide (con vasculitis y áreas de necrosis fibrinoide) o el de dermatitis difusa con epidermis normal o atrófica y macrófagos vacuolados conteniendo abundante amastigotes, pueden ser observados [7][8] .…”

“…El perfil inflamatorio revela la predominancia de macrófagos, linfocitos en la unión epidermis-dermis, algunos granulomas y áreas con necrosis. También se observan células plasmáticas, células gigantes y vasculitis [6][7][8] . La LC producida por L. (V.) braziliensis ha mostrado lesiones nodulares eritematosas, induradas con ulceración central y presencia de exudado 6 .…”

Combination of paromomycin plus human anti-TNF-α antibodies to control the local inflammatory response in BALB/ mice with cutaneous leishmaniasis lesions

“…Therefore, T helper 1 (Th1) inflammatory cytokines, especially interferon-g (IFN-g), tumor necrosis factor-α (TNF-α), and interleukin (IL)-12, are crucial in the initiation of protective immunity against L. major infection [2,3]. However, it has been observed that the onset of inflammatory reactions in the skin due to the presence of the parasite leads to collateral tissue damage and to ulcer formation through upregulation of these pro-inflammatory mediators [4]. In order to balance the immune response, T regulatory cells produce regulatory cytokines such as transforming growth factor-β (TGF-β) and IL-10 that might inhibit possible Abbreviations: Ab, anti-TNF-α antibodies; BMDM, bone marrow derived macrophages; CL, cutaneous leishmaniasis; IFN-g, interferon-g; IL, interleukin; IMQ, imiquimod; LPS, lipopolysaccharide; MCL, mucocutaneous leishmaniasis; NO, nitric oxide; PM, paromomycin; PBS, phosphate buffered saline; TNF-α, tumor necrosis factor-α; TNFR, TNF-receptor; VL, visceral leishmaniasis.…”