J.M.L. Costa

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis: 1. Padrões histopatológicos e estudo evolutivo das lesões

The Authors describe the histopathological findings observed in biopsies from 378 cases of Mucocutaneous Leishmaniasis, caused by Leishmania braziliensis braziliensis. All the patients lived in the locality of Tres Bracos, State of Bahia, an endemic area of Leishmaniasis in Brazil. Parasites were found in 63.7% of patients with cutaneous form and in 35.7% of cases with mucous lesions, although always in reduced number. Histopathologic findings allowed the caracterization of five different patterns: 1. Exsudative-cellular reaction, due to infiltraction of histiocytes, lymphocytes and plasm cells; 2. Exsudative-necrotic reaction, characterized by the association of necrosis with cellular infiltration; 3. Exsudative and necrotic-granulomatous reaction, corresponding to pattern described as chronic-granulomatous inflammation with necrosis; 4. Exsudativegranulomatous reaction, characterized a disorganized granulomatous reaction, without tissue necrosis; 5. Exsudative-tuberculoid reaction — in which a typical tuberculoid granuloma is formed. The follow-up study in 49 patients showed, in sucessive biopsies, changes in the histopathologic patterns in 63.2% of cutaneous forms and in 45.4% of the mucous forms. It was concluded that the exsudative-cellular reaction represents both the inicial and final pattern of Mucocutaneous Leishmaniasis lesion. The other four histopathologic patterns characterize intermediate forms found during the evolution of the disease.

Long-term follow-up of patients with Leishmania (Viannia) braziliensis infection and treated with Glucantime®

Seventy-nine patients with cutaneous (62) or mucosal (17) infection with Leishmania (Viannia) braziliensis in Três Braços, Bahia, Brazil, were followed for at least 4 years after initiating treatment with antimony. Cutaneous relapses occurred in 6/62 (10%), mucosal relapse after cutaneous infection in 2/62 (3%), and mucosal relapse after mucosal disease in 2/17 (17%). It is concluded that relapse (cutaneous and mucosal) is rare after adequate antimony therapy and that no definite prediction of relapse (clinical, serological or by skin reaction) is possible.

Leishmaniose mucocutânea humana em Três Braços, Bahia - Brasil: uma área de transmissão de Leishmania braziliensis braziliensis. III. Comprometimento mucoso e evolução inicial

In an analysis of 57 patients mucosal disease was commonestin males(77%) in the third decade of life although the age range was wide and even two children were affected. All but nine patients (16%) had signs of cutaneous leishmaniasis but in only 8(14%) was this lesion active. The nose was affected in 100% of 19 patients with multiple lesions and 92% of 38 patients with single lesions. The pharynx, palate, larynx and upper lip were affected in this order. 42% of patients with multiple lesions had laryngeal disease and in two patients this site existed as a lone lesion. No age difference could be discemed as to whether lesions were single or multiple. Duration of mucosal disease was very variable from less than 4 months to 264 months. Only 7% developed mucosal disease more than ten years after the cutaneous lesion. Usually patients responded to adequate antimonial treatment but there were exceptions, when amphotericin B had to be used Three patients who refused to collaborate regarding treatment died Only 18% of patients in whom measurements were made had positive fluorescent antibodies two years after treatment.

Estudo comparativo da leishmaniose tegumentar americana em crianças e adolescentes procedentes das áreas endêmicas de Buriticupu (Maranhão) e Corte de Pedra (Bahia), Brasil

A comparative study on children aged 0-15 years, with American tegumentary leishmaniasis (ATL), in the endemic regions of Buriticupu (MA) and Corte de Pedra (BA), whereby 214 cases were detected between 1982 and 1993, 78 (36.4%) of them originated from Corte de Pedra and 136 (63.6%) from Buriticupu. In Corte de Pedra, most cases were observed in patients aged between 0-5 years. Twenty nine (37.2%) cases; 62% of those were male. In the Buriticupu region, 88 (64.7%) cases occured in patients of 11-15 years of age, where in 73.8% consisted of male. In both researched regions, brunetts were predominant, with a ratio of 65.4% in Corte de Pedra and 75% in Buriticupu. Twenty six (33.3%) children in the village of Corte de Pedra were farmers, predominantly male (57.7%), generating statistical significance (c2 = 11.21). Twenty one (80.8%) farmers were aged 11-15 years. Thirty seven and a half per cent of the children from Buriticupu were students, however, 41 (30.2%) were farmers, representing 39 (44.3%) cases; all of them male. Both in Buriticupu and Corte de Pedra, the unique wound was predominant, corresponding to 57.7% and 53.7%, respectively. The wounding time stood out from one to three months, with 45 (69.2%) cases in Corte de Pedra and 73 (61%) in Buriticupu (c2 = 11.82). As to the wound locations, it has been observed that they were most constantly present on the lower limbs, with 77.2% in Corte de Pedra and 58.9% in Buriticupu (c2 = 27.9). The cutaneous case mostly found in Corte de Pedra was the ulcerous one (91%). IDRM was positive in 61 (78.2%) children originated from Corte de Pedra, wherein no statistical difference was detected between age ratio and positivity of the test (c2 = 0.0669).

An outbreak of human Leishmania (Viannia) braziliensis infection

The occurrence of acute cutaneous leishmaniasis among inhabitants of 10 farms within 10 Km of the hamlet of Corte de Pedra, Bahia, Brazil was studied prospectively from 1984-1989. A mean population of 1,056 inhabitants living in 146 houses were visited every 6 months and the number of skin ulcers recorded. A leishmanin skin test survey was done people with suggestive skin scars or active disease in 1984. The incidence of skin ulcers due to Leishmania (Viannia) braziliensis (Lvb) reached 83/1,000 inhabitants but declined sharply in the subsequent 2 years. Retrospective data shows that leishmaniasis is a sporadic endemic disease. Although the reasons for this epidemic are unclear some possible aetiological factors are discussed.

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 4. Classificação histopatológica

The Authors have analysed the histopathological alterations observed in 162 cases of Mucocutaneous Leishmaniasis from Tres Bracos, Bahia, of whom 131 (80,9%) had purely cutaneous lesions and 31 (19,1%) had only mucosal lesions. The clinical behavior of 5 histopathological forms was documented in relation to treatment. The best prognosis was associated with the exudative granulomatous histopathology, a phase where the a host mechanism to use the parasite is evident leading to necrosis and granuloma formation as a residual sign. Therapy in this phase merely hastened the process. In a further large group the lesions were classified as exudative cellular reaction (cutaneous forms), an exudative necrotic reaction and an exudative necrotic gra- nulomatous reaction. In these cases the mechanisms of host defense are still being developed and the effect of therapy is to reduce the time to healing. Cutaneous cases with an exudative tuberculoid reaction had a worse prognosis, although there was a favourable response to treatment if the patient was young, the lesion was of short duration and the intradermal leishmanin test was not exaggerated Lastly are a group of mucosal cases with an exudative cellular reaction where this infiltrate may be a manifestation of auto agression. These cases, also classified as exudative tuberculoid, occur in adult patients with longstanding lesions and an exaggerated leishmanin skin test. They have a poor prognosis. This study develops suggestions for a classification based on the histopathological picture which could be valuable in predicting prognosis and influencing the choice of treatment. This classification is strictly morphological and is easy for the pathologist to apply. It appears to, correspond to the clinical course of the illness and could aid the clinician in the initial case evaluation.

Função renal em pacientes com leishmaniose muco-cutânea tratados com antimoniais pentavalentes

The renal function in ten patients with mucocutaneous leishmaniasis treated with Glucantime (meglumine antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome) was assessed. During the use of these drugs a defect in concentrating capacity of the kidney was observed expressed as low values of maximun urinary osmolarity and negative maximun clearance of free water in relation to tests made before treatment. The urinary concentrating capacity returned to normal in 5 of the 8 patients studied 15-30 days after the end of treatment. However the maximal urinary osmolarity values where still inferior to those obtained before treatment. In two patients there was a proteinuria above 150 mg/24 hours after antimoniais which disappeared later. The clearance of endogenous creatinine do not alter significatly with the use of these drugs. The results suggest that pentavalent antimoniais can resue in a defect in urine concentrating capacity which is partially reversible after antimonial therapy has ceased.

Aspectos psicossociais e estigmatizantes da leishmaniose cutâneo-mucosa

The authors selected 15 patients with severe mucocutaneous leishmaniasis. By means of an interview concentrating on sociopsychological aspects they sought to understand aspects of the life of each patient before, during and after treatment of the disease. At the same time similar interviews were recorded on 25 healthy members of the same community to gauge their reaction to subjects with leishmaniasis. Among the patients interviewed, in 14(93.3%) their lives were affected by the disease and (73.3%) were suffering from discrimination. Nine (60%) felt di vorced from society and 10(66.6%) had difficulty in returning to work. Of the healthy community members interviewed 11(44%) associated the disease with bodily deformities and 8(32%) were afraid of catching the disease due its destructive nature. Twenty-four (96%) thought patients had social problems.

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 2. Resposta humoral tissular

The Authors analysed the humoral response in biopsy material from 90 patients with Mucocutaneous Leishmaniasis caused by Leishmania braziliensis braziliensis, utilising the immunoperoxidase method to identify IgA, IgG, IgM, C3 complement fraction and fibrin in the tissue. The presence of IgG, IgA and IgM was found in tissue plasma cells with a predominance of IgG and this was correlated significantly with the number of plasma cells in the lesion. The presence of immunoglobulins in the tissues stimulated the opsonisation of parasites and/or their antigens resulting in necrosis which represents one of the effective mechanisms to reduce parasite load. In ne- crotic areas and the walls of inflammed vessels immunoglobulins were deposited as well as the C3 fraction of complement and fibrin — immunocomplex fractions derived from the host. This tissue necrosis was interpreted as the result of the action of immunocomplexes in a region with equivalent or a smally excess of antigen (Arthus type reaction). The presence of parasite antigens expressed on the macrophage membrane in the initial phase of the lesion when in contact with tissue immunoglobulins, leads to the installation of an antigen-antibody reaction resulting in the appearance of necrosisin Mucocutaneous Leishmaniasis.

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 3. Reação celular nos tecidos

The Authors analyse the histopathological alterations observed in 378 cases of Mucocutaneous Leishmaniasis from Tres Bracos, Bahia, of whom 307 (81,4%) were only cutaneous, 54 (14,2%) only mucosae and in 17 (4,4%) both integuments were involved simultaneously. A cellular infiltration of lymphocytes and plasma cells was invariably present in all forms and during healing. In mucosal cases, this reaction may have an important role in maintaining an auto agression in the presence of few or no parasites. The plasma cell is a constant ele-ment in well developed lesions but not present in healing lesions. Its presence almost always denotes a tendancy to relapse. Mast cells were observed in both cutaneous and mucosal lesions but predominate in the former. Its number was significantly greater in those with an exudative and necrotic granulomatous reaction where necrotic phenomena are marked. Eosinophils were significantly associated with mast cells suggesting the existence of association between these cells in the modulation of the inflammatory response. Two types of granulomatous reaction were observed: a disorganized one, often related to tissue necrosis, and an organized, tuberculoid type granuloma. The first type is interpreted as of post necrotic origin resulting in a reduction in antigenic load with maintenance of antibody levels, creating the conditions to establish a granuloma similar to that observed in immunocomplex lesions with excess of antibody. The other type of rection was the granuloma of epithelioid cells, which tend to arise in two groups of patients. In young patients, with short time cutaneous lesions and normal positive leishmanin skin tests, this type of granuloma perhaps similar to the specific hypersensibility granuloma described by EPSTEIN (1977). In the other group of patients, the leishmanin skin test was always exaggerated. In these cases the hypersensitive granuloma is associated with a cellular hypersensivity, perhaps amplified by sequestration of antigen, reforcing the antigenic stimulus of the granuloma. As a result, treat- ment of this group is more difficult and the prognosis worse in consequence.The Authors analyse the histopathological alterations observed in 378 cases of Mucocutaneous Leishmaniasis from Tres Bracos, Bahia, of whom 307 (81,4%) were only cutaneous, 54 (14,2%) only mucosae and in 17 (4,4%) both integuments were involved simultaneously. A cellular infiltration of lymphocytes and plasma cells was invariably present in all forms and during healing. In mucosal cases, this reaction may have an important role in maintaining an auto agression in the presence of few or no parasites. The plasma cell is a constant ele-ment in well developed lesions but not present in healing lesions. Its presence almost always denotes a tendancy to relapse. Mast cells were observed in both cutaneous and mucosal lesions but predominate in the former. Its number was significantly greater in those with an exudative and necrotic granulomatous reaction where necrotic phenomena are marked. Eosinophils were significantly associated with mast cells suggesting the existence of association between these cells in the modulation of the inflammatory response. Two types of granulomatous reaction were observed: a disorganized one, often related to tissue necrosis, and an organized, tuberculoid type granuloma. The first type is interpreted as of post necrotic origin resulting in a reduction in antigenic load with maintenance of antibody levels, creating the conditions to establish a granuloma similar to that observed in immunocomplex lesions with excess of antibody. The other type of rection was the granuloma of epithelioid cells, which tend to arise in two groups of patients. In young patients, with short time cutaneous lesions and normal positive leishmanin skin tests, this type of granuloma perhaps similar to the specific hypersensibility granuloma described by EPSTEIN (1977). In the other group of patients, the leishmanin skin test was always exaggerated. In these cases the hypersensitive granuloma is associated with a cellular hypersensivity, perhaps amplified by sequestration of antigen, reforcing the antigenic stimulus of the granuloma. As a result, treat- ment of this group is more difficult and the prognosis worse in consequence.