Achiléa L. Bittencourt

Disseminated Leishmaniasis: A New and Emerging Form of Leishmaniasis Observed in Northeastern Brazil

During the past decade, there has been an increase in the number of patients with disseminated leishmaniasis (DL), which is characterized by a large number of acneiform and papular skin lesions, with very few or no parasites in the skin tissue. The present report describes 42 cases of DL identified between 1992 and 1998 in an area where Leishmania braziliensis transmission is endemic; 8 of the patients were prospectively diagnosed. In a contrast to localized cutaneous leishmaniasis (LCL), acquisition of DL was associated with age >19 years (P<.05), male sex (P<.05), and agricultural occupation (P<.001). Patients with DL presented with 10-300 lesions that were a mixture of acneiform, papular, nodular, and ulcerated types. Twelve (29%) of 42 patients had mucosal involvement. Patients with DL had lower levels of interferon-gamma (P<.05) and tumor necrosis factor-alpha (P<.05) production, compared with patients with LCL. DL is an emerging clinical distinct form of leishmaniasis associated with agricultural activities and host immunological response.

Evaluation of the histopathological classifications of American cutaneous and mucocutaneous leishmaniasis

In order to evaluate the reliability of histopathological classifications of cutaneous and mucocutaneous leishmaniasis the authors compared the histopathological patterns of two biopsies taken simultaneously from the same patient, and classified the material according to Ridley et al. (1980), to Magalhães et al. (1986a), and to a more simplified classification with only three patterns. Distinct histopathological aspects were observed in different lesions or even in the same lesion. The authors concluded that histopathological patterns do not represent a stage of tegumentary leishmaniasis, thus they can not be correlated with prognosis and therapeutical response as suggested in the literature.

Human T-cell lymphotropic virus type 1 infection among pregnant women in northeastern Brazil.

Summary: An evaluation of human T‐cell lymphotropic virus type 1 (HTLV‐1) infection among 6754 pregnant women in Salvador, Bahia, Brazil using enzyme‐linked immunosorbent assay, Western blot analysis, and polymerase chain reaction assay found a rate of infection of 0.84% (57 of 6754 women). Epidemiologic and obstetric data on the HTLV‐1‐positive pregnant women were analyzed and compared with data on a control group of HTLV‐1‐negative pregnant women. The mean age of the HTLV‐1‐positive women was 26.2 years. All were seronegative for HIV and syphilis, and only 2 reported a past history of sexually transmitted infection and more than 10 sexual partners. Of the HTLV‐1‐positive women, 88.5% were breast‐fed, 4% were bottle fed, and 7.5% did not know. Six women had received blood transfusions, and only 1 reported intravenous drug use. Fifty‐two HTLV‐1‐positive women could be followed: 45 had full‐term deliveries, 5 had premature deliveries, and 2 had abortions. Our results indicate that (1) the frequency of HTLV‐1 infection among pregnant women is relatively high in Salvador, Bahia, Brazil; (2) maternal infection was probably acquired more frequently through breast‐feeding, but the sexual route was cer tainly the second most important means of transmission; (3) HTLV‐1‐positive women had a history of eczema‐like infections in childhood more frequently than the control group; (4) HTLV‐1 infection did not interfere in the course of pregnancy; and (5) no associated congenital infections were observed in the HTLV‐1‐positive women.

Adult T-cell leukemia/lymphoma (ATL) presenting in the skin: Clinical, histological and immunohistochemical features of 52 cases

Background. Adult T-cell leukemia/lymphoma (ATL) is a severe disease caused by HTLV-I. This paper describes the clinicopathological and immunohistochemical findings of 52 cases of ATL with skin involvement and investigates whether there is any relationship between median survival time (MST) and histological patterns, primary cutaneous involvement and CD8 positivity.Material and methods. All cases were HTLV-I+ and HIV- and were clinically classified. HTLV-I proviral integration was investigated in atypical cases. Immunohistochemistry was performed using CD3, CD4, CD5, CD7, CD8, CD20, CD25, CD30 and CD45RO markers. Ki-67 was used to evaluate the proliferative index. Results. Twenty-seven cases were primary, while 25 were secondary. Monoclonal viral integration was demonstrated in all atypical cases. Patterns resembling mycosis fungoides (MF) were found in 19 cases and anaplastic large-cell lymphoma (ALCL) in two cases. Fifteen cases had an atypical immunophenotype and expressed CD8. Primary cutaneous ATL had a longer MST (48 months) than the secondary cutaneous ATL (7 months) and the difference was statistically significant, but no statistically significant difference was found between the MST of CD8-positive and negative cases.Conclusions. It is important to differentiate between primary and secondary cutaneous ATL and classify the cases histologically in order to better evaluate the prognosis. The two forms of primary cutaneous ATL, primary cutaneous smoldering and primary cutaneous tumoral (PCT), should also be identified. The smoldering type presented a longer survival (58 months) and histological aspects suggestive of better prognosis in contrast to the PCT type that had a shorter survival (20 months) and histological characteristics suggestive of worse outcome.

Adult T-cell leukemia/lymphoma in Bahia, Brazil: analysis of prognostic factors in a group of 70 patients.

The purpose of this study was to evaluate whether subdivision of adult T-cell leukemia/lymphoma (ATL) on the basis of clinical types, skin involvement, histologic features, cell size, and proliferative index (PI) was clinically relevant. Skin lesions were present in 47 cases (67%). Five cases were classified as primary cutaneous tumoral (PCT) type not included in the Shimoyama classification and characterized by skin tumors and absence of systemic involvement, lymphocytosis, and hypercalcemia. Mortality was high (61/70 [87%]). The overall median survival time (MST) was 12 months. The following variables were adversely related to survival: acute, lymphoma, and PCT types; absence of skin lesions; large cells; and PI more than 18%. The longer MST observed in cases with skin lesions was probably due to prolonged survival of the smoldering type (58 months). The MST of the PCT type (21 months) was shorter than that of the smoldering type, confirming the importance of clearly defining these 2 types of ATL.

Failure of Early Treatment of Cutaneous Leishmaniasis in Preventing the Development of an Ulcer

The clinical characteristics and treatment outcome were determined for 26 patients who presented with early-stage cutaneous leishmaniasis. Illness duration ranged from 8 to 20 days, and the commonest clinical presentation was the presence of a papule with small central crust on a lower extremity. Prominent regional adenopathy was found in 22 (85%) of 26 patients. The results of an intradermal skin test for Leishmania were positive for 96% of those patients, and results of serologic testing were positive for 61% of patients tested. Ten (46%) of 22 patients for whom follow-up data were available developed enlargement and ulceration of the lesion despite early antimony therapy and required additional courses of treatment. Histopathological studies of samples from the lesions of 3 patients showed vasculitis. These data show that early therapy for cutaneous leishmaniasis does not prevent the development of an ulcer in one-half of patients. This unfavorable outcome underlines the relevance of local exacerbated inflammatory and immune response in the pathogenesis of the disease.

Frequent expansion of Epstein–Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV‐associated lymphoma

Burkitts lymphoma (BL) and Hodgkins disease (HD) occurring in developing regions are frequently associated with Epstein–Barr virus (EBV) infection and have a high incidence in childhood. Recent genotyping studies indicate that the tumour cells of both neoplasms represent B cells that contain somatically mutated immunoglobulin heavy chain genes. This implies that the precursors of these neoplasms have participated in the germinal centre (GC) reaction. We therefore presumed that normal lymphoid tissues from children living in developing regions would harbour an increased number of EBV‐infected cells within the GC, when compared with children living in industrialized nations. To test this hypothesis, hyperplastic tonsils from 40 children living in Bahia (Brazil) and 40 from German children were analysed for the presence of EBV‐encoded small nuclear RNA (EBER) and EBV‐encoded proteins by in situ hybridization and immunohistology, respectively. Although the overall EBV infection rate was similar in both groups (50 per cent of Bahian vs. 45 per cent of German cases), a significantly higher number of EBER‐positive lymphoid cells were found in the GCs of 8/20 EBV‐positive tonsils from Brazil (9–89 cells/GC; mean: 14·5 cells/GC per case), while only 3/18 tonsils from Germany displayed a few EBER positive cells (1–9 cells/GC; mean: 0·5 cell/GC per case) in this compartment (p < 0·007). In addition, the EBV‐infected GC cells in Bahian samples resembled centroblasts, exhibited mitotic activity, and in two cases showed expression of EBV‐encoded latent membrane protein (LMP)‐1, findings not present in German samples. These data show that latently EBV‐infected cells participate more frequently in GC reactions in developing regions than in industrialized countries and may abnormally express the oncogenic protein LMP‐1. This could in part explain the higher incidence in this region of EBV association with lymphomas related to GC cells or their progeny, such as BL and HD. Copyright

Cutaneous manifestations associated with HTLV-1 infection

Skin lesions are frequent in human T‐cell lymphotropic virus type 1 (HTLV‐1) infection and may constitute an alert for the diagnosis of this condition. The most severe skin diseases related to this virus are adult T‐cell leukemia/lymphoma (ATLL), an aggressive form of leukemia/lymphoma that fails to respond to chemotherapy, and infective dermatitis associated with HTLV‐1 (IDH), a severe and recurrent form of eczema occurring in childhood. ATLL affects the skin in 43–72% of cases. In this review, the clinical, histopathological and immunohistochemical aspects of ATLL and IDH will be discussed, as well as the differential diagnoses, giving particular focus to the primary cutaneous ATLL. IDH may progress to HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) and to ATLL. Adult onset IDH and reactional and inflammatory dermatoses found in carriers and also in patients with HAM/TSP will be considered. Other dermatological diseases that occur more frequently in HTLV‐1‐infected individuals such as xerosis, acquired ichthyosis, seborrheic dermatitis and infectious and parasitic dermatoses will also be discussed.

Geographic diversity of adult t-cell leukemia/lymphoma in Brazil

We describe 195 cases of adult T‐cell leukemia/lymphoma (ATLL) reported to the national registry of T‐cell malignancies in Brazil between 1994 and 1998. We compared the effect of demographic differences and clinical features of 150 consecutive ATLL cases in different regions of this diverse country. At diagnosis, the predominant clinical sub‐type was the acute type (60%), followed by lymphoma (22%), chronic (10%) and smoldering (8%) types. Although we expected that different sub‐types would be present in different regions, on the basis of immunogenetic factors determined by ethnicity, we did not demonstrate these differences. There were no significant differences among ATLL subtypes by age or gender. No ethnic group predominated in the total population of patients, but significant differences were noted when examining ethnic distribution by region. Reflecting the general population distribution, white patients were seen more often in São Paulo and black patients in Bahia, than in other regions. In most regions, cases were equally distributed between blacks and mulattos, except in Pernambuco, where blacks were less frequent. The main clinical features were lymphadenopathy, skin lesions, hypercalcemia and hepatomegaly. Fourteen patients (9%) suffered from HTLV‐I‐associated myelopathy (HAM/TSP), either at diagnosis or during follow‐up of ATLL. All cases but one had antibodies to HTLV‐I, with concordant results with ELISA, WB and PCR analyses. For the antibody‐negative case, pol and tax gene sequences were present in tumor cells when subjected to PCR analyses. The prognosis was generally poor, suggesting that the disease in Brazil behaves in similar fashion regardless of ethnic or geographical differences. Int. J. Cancer 83:291–298, 1999.

Occurrence of subcutaneous zygomycosis caused by Basidiobolus haptosporus in Brazil

There were described the first three South American cases of subcutaneous zygomycosis caused by B. haptosporus. The patients were children from nearby towns lying just north of 13 ° latitude S. The diagnosis was based on histopathological aspects plus cultural isolation of the fungus.