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At least 19 recordsLinked to original sources
PubMed1996

Variation of cytokine patterns related to therapeutic response in diffuse cutaneous leishmaniasis.

Diffuse cutaneous leishmaniasis is a rare entity characterized by disseminated cutaneous nodules associated with specific anergy to leishmanial antigens. A low but not absent IFN-gamma expression by cells present in cutaneous lesions has been documented during the active phase of diffuse cutaneous leishmaniasis. In this study we confirm this observation, and extend it by showing a similar pattern in peripheral blood mononuclear cells and the variation of mRNA cytokine expression pattern during different stages of the disease. During active disease, patients did not express mRNA for IFN-gamma, while expressing mRNA for IL-2, IL-4, and IL-10. In contrast, an expression of IFN-gamma and low IL-10 was observed after treatment-induced transient healing of cutaneous lesions. In three patients we have been able to analyze a third PBMC sample obtained after clinical relapse, documenting in all of them decreased IFN-gamma expression with no expression of IL-10. Although there was an association between the appearance of IFN-gamma expression and clinical improvement, with marked expression of IFN-gamma mRNA and decreased expression of mRNA for IL-10 after treatment, this was not sufficient to prevent relapse in these patients. Therefore, it is possible that factors other than the cytokines characteristic of the Th1 and Th2 balance are implicated in the inability of diffuse cutaneous leishmaniasis patients to mount an anti-Leishmania immune response causing clinical improvement.

Adolescent↗
PubMed1997

Leishmania major in an Egyptian patient manifested as diffuse cutaneous leishmaniasis.

Diffuse cutaneous leishmaniasis (DCL) is an unusual form of cutaneous leishmaniasis mainly caused by infection with Leishmania aethiopica in the Old World. In this paper, diffuse cutaneous leishmaniasis was reported for the first time, in an Egyptian patient from Sinai Peninsula resulting from infection with L. major zymodeme LOND-1 as proved by enzymatic characterization, using seven enzymes.

Adult↗
PubMed1982

Specific inhibition of lymphocyte-proliferation responses by adherent suppressor cells in diffuse cutaneous leishmaniasis.

Diffuse cutaneous leishmaniasis is characterized by multiple nonulcerative skin lesions. Histologically, these lesions are dominated by vacuolated, heavily infected macrophages, with only a few lymphocytes present. A unique focus of diffuse cutaneous leishmaniasis is present in the Dominican Republic. We studied four patients with this disease. None had a delayed reaction to leishmanial antigen on skin tests. The total numbers of lymphocytes and T cells were normal. None of these patients had a lymphocyte-proliferation response to leishmanial antigens, although their responses to other antigens were normal. Adding indomethacin to cultures or decreasing the number of adherent cells by passage of cells over nylon wool reconstituted the lymphocyte responses to leishmanial antigens. Thus, our studies demonstrate that patients with diffuse cutaneous leishmaniasis have a selective anergy to leishmanial antigen, and that an adherent suppressor cell is one mechanism by which this selective immunosuppressive state is modulated.

Adolescent↗
PubMed1997

Association of Leishmania heat shock protein 83 antigen and immunoglobulin G4 antibody titers in Brazilian patients with diffuse cutaneous leishmaniasis.

Diffuse cutaneous leishmaniasis (DCL) is characterized by the presence of numerous nonulcerated nodules and plaques containing large numbers of Leishmania amazonensis parasites and few lymphoid elements. The immune responses of DCL patients reflect severe antigen-specific T-cell deficiencies, while the antibody response to Leishmania antigens is often accentuated. We report herein on the Leishmania antigen-specific antibody subclass distribution in DCL patients and demonstrate that a dominant antigen contributing to the biased immunoglobulin G4 antibody subclass in sera of DCL patients is Leishmania heat shock protein 83.

Animals↗
PubMed1994

High serum-soluble interleukin-2 receptor is not associated with the immunosuppression in diffuse cutaneous leishmaniasis.

Diffuse Cutaneous Leishmaniasis (DCL) is a rare complication of Leishmania aethiopica-induced cutaneous leishmaniasis which is associated with non-self healing and in vivo and in vitro antigen-specific non-responsiveness. Such antigen-specific unresponsiveness is also observed in visceral leishmaniasis (VL). The non-responsiveness seen in VL disease is believed to be due, in part, to serum-derived factors, including raised serum soluble IL-2 receptor (sIL-2R). Raised sIL-2R in serum was not a consistent feature of DCL in our study (range: 787-4546 U/ml) but was frequently observed in sera of patients with other dermatological disorders (range: 474-3313 U/ml) and some patients with the simple local cutaneous leishmaniasis (LCL; range: 556-4247 U/ml). The level of sIL-2R in the sera of DCL patients was not indicative of the disease state. Sera from DCL patients did not reduce proliferation of the IL-2-dependent CTLL cell line nor reduce PHA-driven mononuclear cell proliferation, although sera from VL patients could. Both DCL and VL sera could reduce the L. aethiopica-driven proliferation. Furthermore addition of serial dilutions of recombinant IL-2 to CTLL cultured in VL or DCL sera containing high sIL-2R levels did not alter the effect of such sera on proliferation. We conclude therefore, that raised sIL-2R in serum is not associated with the immunosuppression in DCL.

Adolescent↗
PubMed1978

Comparative study of American cutaneous leishmaniasis and diffuse cutaneous leishmaniasis in two strains of inbred mice.

Two Leishmania strains, AZV (isolated from a typical case of American cutaneous leishmaniasis) and AMP (from a case of diffuse cutaneous leishmaniasis), were studied in C57BL/6 and BALB/c mice. After infection with 10(4) amastigotes of either strain, C57BL/6 mice developed self-resolving lesions lasting 20 to 23 weeks and showed both delayed hypersensitivity response to leishmanial antigen and specific agglutinating antibodies. On the other hand, BALB/c mice infected with 10(4) AZV or AMP amastigotes developed chronic, large, ulcerated lesions and showed impaired cellular and humoral responses to the parasite. When BALB/c and C57BL/6 mice received 10(2) AMP amastigotes, patterns of infection were similar to those observed after inoculation of 10(4) amastigotes. In vitro studies revealed that spleen cells from AZV- or AMP-infected C57BL/6 mice showed an increased DNA-synthetic response to leishmanial antigen, concanavalin A, and phytohemagglutinin. Spleen cells from AZV- or AMP-infected BALB/c mice showed an increased response to concanavalin A and diminished responses to leishmanial antigen, phytohemagglutinin, and lipopolysaccharide.

Animals↗
PubMed1993

The role of interferon-gamma in the treatment of visceral and diffuse cutaneous leishmaniasis.

Traditionally, the mainstay of visceral and diffuse cutaneous leishmaniasis therapy has been pentavalent antimony, with pentamidine and amphotericin B reserved for refractory cases. Interferon-gamma (IFN-gamma) in combination with pentavalent antimony has been used successfully in treating patients refractory to pentavalent antimony and in patients with previously untreated visceral leishmaniasis (39 total). In addition, 6 patients with diffuse cutaneous leishmaniasis have been treated with combination IFN-gamma and antimony therapy. Preliminary experience with these patients indicates that IFN-gamma is a useful adjunct therapy for severe or refractory cases of visceral leishmaniasis; however, the potential of IFN-gamma in treating diffuse cutaneous leishmaniasis cannot be assessed as current clinical experience is too limited.

Antimony↗
PubMedDate not supplied

Spontaneous regional healing of extensive skin lesions in diffuse cutaneous Leishmaniasis (DCL).

The authors report a case of diffuse cutaneous leishmaniasis, with longstanding evolution and presenting with diffuse infiltrated lesions rich in amastigotes in the absence of mucosal involvement. In situ characterization with monoclonal antibodies revealed Leishmania amazonensis. Large regional lesions have presented spontaneous healing without specific therapy. Considering that DCL presents with a defect in the cellular immune response, this fact demonstrate that this patient may develop a regional cellular immune response enough to destroy the parasites and to produce clearing of some lesions.

Child↗
PubMed1995

Polar and subpolar diffuse cutaneous leishmaniasis in Brazil: clinical and immunopathologic aspects.

BACKGROUND: Diffuse cutaneous leishmaniasis (DCL) is a rare manifestation of human leishmaniasis, characterized by multiple, slowly progressive nodules or plaques without ulceration, involving almost the entire body. It has been suggested, that DCL results from a lack of cell-mediated immunity to leishmanial antigen, leading to uncontrolled parasite growth. METHODS: We have performed detailed clinical, histopathologic, and immunologic investigations in six patients with DCL. Biopsies were taken from the nodules, processed, and examined for determination of the macrophagic pattern present, based on the intensity of vacuolation and the frequency of vacuolated cells, the parasite index, and the presence of eosinophils. Immunologically, patients were evaluated by their response to intradermal skin test to PPD or leishmania antigen, determination of antileishmania antibodies by immunofluorescent assay, and lymphocyte proliferation assay. RESULTS: There seemed to be a negative relation between nodules and skin ulcerations, whereas the highest number of parasites were observed in patients with the greatest number of vacuolated macrophages. The delayed hypersensitivity skin test to leishmanial antigen was negative, and antileishmania IgG antibodies were positive in all patients. CONCLUSIONS: Although all cases fulfill the criteria for being classified as DCL, they present a wide spectrum. Three cases were clearly at the unresponsive pole, and three other cases belonged to the subpolar form of DCL, exhibiting varying weak signs of antiparasite responsiveness.

Adolescent↗
PubMedDate not supplied

Aminosidine and its combination with sodium stibogluconate in the treatment of diffuse cutaneous leishmaniasis caused by Leishmania aethiopica.

Treatment of diffuse cutaneous leishmaniasis (DCL) caused by Leishmania aethiopica remains unsatisfactory as the parasite is relatively insensitive to antimonial compounds. Reports of the clinical effectiveness of aminosidine sulphate, especially in combination with sodium stibogluconate, in visceral leishmaniasis and the finding that this antibiotic is potent against L. aethiopica in vitro, prompted us to evaluate its usefulness in DCL. Two patients with long-standing, active DCL were treated for 60 d with aminosidine sulphate, 14 mg/kg/d parenterally. The skin lesions resolved completely in both patients although they relapsed subsequently. Synergism between aminosidine and stibogluconate was demonstrated in vitro against parasites isolated from the patients. This led us to administer combined therapy, aminosidine sulphate 14 mg/kg/d and sodium stibogluconate 10 mg/kg/d, to the 2 patients in relapse and to another, third patient. Treatment was continued for 2 months beyond parasitological cure. Side effects were minimal. Following treatment, a return of specific cell-mediated immunity occurred, as expressed by a moderate infiltration of lymphocytes into the lesions and by lymphocyte proliferation in vitro in the presence of live Leishmania antigen, with synthesis of interleukin-2 and interferon gamma with one patient and interleukin 4 with the other. During follow-up periods of 2 to 21 months after treatment, no sign of relapse was seen.

Animals↗
PubMed1990

Diffuse cutaneous leishmaniasis acquired in Peru.

A case of diffuse cutaneous leishmaniasis (DCL) acquired in Peru is described. The causative agent was Leishmania mexicana amazonensis as determined by isoenzyme analysis and species-specific monoclonal antibody binding characteristics. Histological examination of biopsy material showed a large number of intracellular and extracellular amastigotes and few lymphocytes. Treatment with meglumine antimoniate (Glucantime) administered iv at a dosage of 20 mg antimony/kg body weight/day for 60 days resulted in visible improvement of the lesions, but not in clinical or parasitological cure.

Adult↗
PubMed1992

Diffuse cutaneous leishmaniasis with atypical aspects.

A 16-year-old man had long-standing diffuse cutaneous leishmaniasis with the following characteristics: diffuse infiltrated lesions rich in amastigotes, absence of mucosal involvement, and lack of parasite-specific cell-mediated immune response. In situ identification of Leishmania mexicana amazonensis was achieved by the use of monoclonal antibodies. Clinically, as an atypical finding there was deep and extensive ulceration in the lower limbs. Histologically, an atypical characteristic was the presence of a high number of eosinophils in the infiltrate predominantly in the ulcerated lesion. Ultrastructurally, parasitized and lysed eosinophils with dispersion of their granules were seen in the vicinity of parasitized or lysed macrophages.

Adolescent↗
PubMed1984

Monocyte suppression of antigen-specific lymphocyte responses in diffuse cutaneous leishmaniasis patients from the Dominican Republic.

Patients from the Dominican Republic with diffuse cutaneous leishmaniasis showed in vivo and in vitro anergy to leishmanial antigen. Relatives of these DCL patients living in the same endemic area frequently showed skin test and lymphocyte reactivity to leishmanial antigens. This further supports the concept of specific anergy in patients with diffuse cutaneous leishmaniasis. Adherent suppressor cells modulate the antigen-specific lymphocyte proliferative response. Suppressor cells could also be isolated by Percoll gradient centrifugation. Co-culturing of lymphocytes and monocytes from HLA-identical leishmanin responders and nonresponders also identified the suppressor cell as a monocyte. In one patient, this suppression disappeared when clinical cure had been accomplished.

Adolescent↗
PubMed1989

Diffuse cutaneous leishmaniasis in Mexico.

In Mexico, 6 cases of diffuse cutaneous leishmaniasis (DCL) were found in widely separated geographic regions. Information was also available on 2 other cases. In addition to the typical clinical features, half of the patients had evidence of nasopharyngeal mucosal involvement. All isolates from the DCL patients were identified as Leishmania mexicana mexicana by isoenzyme analysis and monoclonal antibody typing. In 1 region of Tabasco state where DCL was found, uncomplicated cutaneous leishmaniasis appeared to be highly endemic, and isolates from a few such patients were identified as L. mexicana mexicana. An incidental finding was the recovery of an isolate of L. braziliensis braziliensis from a patient with chiclero ulcer in Oaxaca state. The clinical and epidemiological significance of the reported cases are discussed.

Adolescent↗
PubMedDate not supplied

Diabetes mellitus associated with pentamidine isethionate in diffuse cutaneous leishmaniasis.

The authors report a case of a male patient from Bacabal, MA with diffuse cutaneous leishmaniasis (DCL), for at least nine years, with 168 lesions on his body. These were tumour-like nodules with some ulceration. He used pentavalent antimonial (glucantime) and an association of gamma interferon plus glucantime with improvement of the lesions but relapsed later. Recently, pentamidine isethionate (pentacarinat) was given a dosage of 4mg/kg/weight/day on alternate days for 20 applications. After 3 months a similar course of 10 application was given 2 times. Later he developed diabetic signs with weight loss of 10kg, polydypsia, polyuria and xerostomia. The lower limbs lesions showed signs of activity. Blood glucose levels normalised and remain like this at moment. Attention is drawn to the fact that pentamidine isethionate should be used as a therapy option with care, obeying rigorous laboratory controls including a glucose tolerance test.

Adult↗