Short communication: mucocutaneous leishmaniasis in HIV-related immune reconstitution syndrome.

Immune reconstitution inflammatory syndrome (IRIS) is an immuno-pathologic reaction to quiescent opportunistic microbial pathogens upon restoration of underlying immune defects. Here we report a Honduran patient with HIV/AIDS who developed a facial rash worsening on antiretroviral therapy and increasing CD4 count. Culture and PCR analysis from the skin biopsy identified Leishmania panamensis, which was effectively treated with long-term liposomal amphotericin B. This is the first report of mucocutaneous leishmaniasis (MCL)-associated IRIS due to L. panamensis.

Reactivation of mucosal and cutaneous leishmaniasis in a renal transplanted patient.

Mucosal leishmaniasis (ML) is a chronic form of tegumentary leishmaniasis, which causes destructive lesions of nasal, pharyngeal, and laryngeal mucosa. We describe a case of leishmaniasis reactivation with simultaneous cutaneous and mucosal forms in a renal transplanted patient with no history of prior leishmaniasis. Reactivation after renal transplantation was not reported in Brazil. A 67-year-old woman receiving prednisone 20 mg/day, tacrolimus 1 mg/day, and mycophenolic acid 360 mg/day presented with nose edema with erythema and cutaneous lesions. Amastigotes were identified on biopsies and the polymerase chain reaction confirmed Leishmania (Viannia) braziliensis. The patient was treated with liposomal amphotericin B but died 3 weeks after as a result of bacterial septic shock. In conclusion, tegumentary leishmaniasis can reactivate with simultaneous cutaneous and mucosal forms in a renal transplanted patient during the immunosuppressant therapy.

Molecular diagnosis and species identification of mucosal leishmaniasis in Iran and correlation with cytological findings.

OBJECTIVE: Mucosal leishmaniasis (ML) is a rare destructive disease that mainly affects the mucous membranes of the mouth and nose. The etiologic agent(s) of ML are not well known in the Middle East. STUDY DESIGN: Cytologic smears of ML from the mucosal lesions of 7 patients were prepared by scraping. In 2 patients with nasal lesions, exfoliative cytology was made by washing the nasal cavity. The smears were both air dried and fixed in alcohol and stained. Scrapings from the same smears were then tested for leishmanial DNA by nested PCR. RESULTS: This study characterized 9 isolates of ML, with 7 cases identified as Leishmania major and 2 as Leishmania tropica. While 6 patients were found to be positive by the cytology technique, the nested PCR was positive for all of these samples. CONCLUSIONS: Presence of granuloma and multinucleated giant cells in the negative smears of the patients who showed clinical manifestation of ML was an important clue for diagnosis of this disease. The PCR-based method not only appears to be a precise diagnostic approach in the identification of suspected cases of ML but is also efficient in determining the species of the parasite. L. major and L. tropica can lead to ML, but they result in different cytologic features.

[Mucosal complication of cutaneous leishmaniasis]. / Complicación mucosa de la leishmaniasis cutánea.

A 74-year-old man from the rural area of Caicedonia, Valle del Cauca Province, was diagnosed with uncontrolled hypertension, stage IV chronic renal failure and severe anemia. Fifteen years earlier, while living in Guaviare Province, he was diagnosed with leishmaniasis-with lesions located on the right upper and lower eyelids, left auricle and limbs. At that time, he received an incomplete treatment with antimonials. The patient had experienced 8 years of progressive mucosal lesions located in the upper lip, nasal mucosa and right upper and lower eyelids (figure 1). A histopathological diagnosis of leishmaniasis was made and confirmed by polymerase chain reaction (figure 2). Treatment with antimonials (Glucantime) was contraindicated due to the patient's comorbidities. Inpatient supervised treatment with miltefosine (Impavido 50 mg capsules) was initiated according to the national guidelines of 1.8 mg/kg/day for 28 days. Clinical follow up and routine laboratory tests (creatinine, BUN, liver function tests and complete blood counts) were done during and after treatment; no complications were reported. Medical follow up was continued until the Internal medicine, ophthalmology, and plastic surgery consultations were provided for subsequent management of the pathology. Mucocutaneous leishmaniasis is a serious preventable complication of cutaneous leishmaniasis. This case illustrated a failure in opportune diagnosis and treatment of this disease as a consequence of an inadequate leishmaniasis control program. The case indicated the effectiveness of miltefosine as a therapeutic option in patients for whom antimonial treatment is contraindicated.

[Mucocutaneous leishmaniasis due to Leishmania guyanensis: a case report in an HIV-infected patient]. / Leishmaniose cutanéo-muqueuse à Leishmania guyanensis: une observation chez un patient infecté par le VIH.

In French Guiana cutaneous leishmaniasis occurs mainly in the localized form with L. guyanensis accounting for more than 90% of cases. Mucocutaneous leishmaniasis is uncommon (less than 2% of cases) with L. braziliensis accounting for all previously reported cases. The purpose of this report is to describe a case of mucocutaneous leishmaniasis due to L. guyanensis that led to diagnosis of HIV infection in a patient living in French Guiana.

Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis.

Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant type 1 immune response (IFN-gamma and TNF-alpha production) and strong inflammatory response in the lesions with few parasites. This exacerbated type 1 response is more evident in ML as compared to CL. Our main hypothesis is that a differential immune regulation of T cell activation leads to over reactive T cells in ML. In the present study, we investigated immunological factors that could explain the mechanisms behind it by comparing some immune regulatory mechanisms between ML and CL patients: frequency of cells expressing co-stimulatory molecules, apoptotic markers, T cell activation markers; and ability of neutralizing antibodies to IL-2, IL-12 and IL-15 do down-regulate IFN-gamma production in leishmania antigen-stimulated peripheral blood mononuclear cells (PBMC). Interestingly, in CL anti-IL-2 and anti-IL-15 significantly suppressed antigen-specific IFN-gamma production, while in ML only anti-IL-2 suppressed IFN-gamma production. Finally, higher frequency of CD4+ T cells expressing CD28-, CD69+ and CD62L(low) were observed in ML as compared to CL. These data indicate that an exacerbated type 1 response in ML is differentially regulated and not appropriately down modulated, with increased frequencies of activated effectors T cells, maintaining the persistent inflammatory response and tissue damage observed in ML.

Analysis of the CC chemokine receptor 5 delta32 polymorphism in a Brazilian population with cutaneous leishmaniasis.

Patients with mucocutaneous leishmaniasis (MCL) show a vigorous T-cell immune response against Leishmania braziliensis. Because the Th response is associated with inflammation, the non-functional CC chemokine receptor 5 (CCR5) may rely in a less severe inflammatory state. The aim of this study was to investigate the CCR5 gene in a Brazilian population with leishmaniasis compared with healthy control subjects and to determine the progression from cutaneous to MCL in the Delta32 allele carriers. Among 100 patients with Montenegro skin test and indirect immunofluorescence assay (IIF) values positive for leishmaniasis, there were 32% women and 68% men. The patients were 89% CCR5/CCR5, 10% CCR5/Delta32, and 1% Delta32/Delta32, while healthy subjects showed a 91% incidence of CCR5/CCR5, 8% of CCR5/Delta32, and 1% of Delta32/Delta32. The CCR5/CCR5 patients (89%) showed a large spectrum of clinical manifestations, where 22.47% had active mucous lesions and 77.53% had cutaneous lesions. In this work, the Delta32 allele carriers (10%) showed only cutaneous manifestations when compared with wild-type individuals. Finally, with regard to the Delta32 allele carriers, a less severe spectrum of clinical manifestations was observed in comparison with wild-type individuals. Although a lack of mucocutaneous lesions was evident among Delta32 allele carriers, the number of individuals studied was small. Therefore, further investigations are needed to elucidate the role of CCR5 in the clinical aspects of leishmaniasis.

Risk factors for mucosal manifestation of American cutaneous leishmaniasis.

A case-comparison study was carried out to identify risk factors for mucosal manifestations of American cutaneous leishmaniasis (ACL) in southeast Brazil, using a series of 2820 patients, diagnosed with ACL between 1966 and 1999. The significant factors independently associated with mucosal leishmaniasis were: gender, age, nutritional status and length of disease. Mucosal leishmaniasis occurred 1.7 times more frequently among males than females; twice as often in individuals older than 22 years compared with the younger group; almost four times as often in individuals with severe malnutrition compared with those who were well nourished; and almost four times more frequently in individuals reporting the disease for more than 4 months compared with those reporting a shorter duration of the disease. Among individuals older than 22 years the risk of mucosal leishmaniasis increased significantly (from 1.9 to 9.6) as the nutritional status decreased, when compared with younger and well-nourished patients. The characteristics herein described and correlated with severe forms could be used as diagnostic markers as part of clinical screening in areas endemic for ACL.

Ulcerative post-kala azar mucosal leishmaniasis masquerading as a carcinoma--a case report.

Post kala-azar mucosal leishmaniasis (PKML) is relatively rare in the Indian subcontinent. We describe an ulcerative variant of PKML with nasal involvement in a Nepalese adult male. He had ulcerated plaque over the upper lip with extensive involvement of nasal columella and septum. He came from endemic area for kala-azar and had a previous history of kala-azar. There were plenty of LD bodies in microsections and FNA of submandibular lymph node.

Cutaneous leishmaniasis following local trauma: a clinical pearl.

Cutaneous leishmaniasis is acquired from the bite of an infected sand fly and can result in chronic skin lesions that develop within weeks to months after a bite. Local trauma has been implicated as a precipitating event in the development of skin lesions in patients who have been infected with Leishmania species. Here we report a case series and review the literature on patients who developed cutaneous leishmaniasis after local trauma, which may familiarize clinicians with this presentation.

Leishmanioses: visceral e mucocutânea / Leishmaniosis: visceral and mucocutaneous

A autora estuda conceito, etiologia, epidemiologia e apresentação clínica das formas visceral e mucocutânea da leishmaniose, detendo-se nos diversos esquemas de tratamento modernamente disponíveis, considerando as drogas de primeira e segunda linhas, a terapêutica tópica e os critérios de cura.

Risk factors for onset of cutaneous and mucocutaneous leishmaniasis in Bolivia.

A survival analysis was performed on data from an endemic area of Bolivia where two populations, natives and highland migrants, were living, to investigate risk factors for onset of cutaneous leishmaniasis (CL) and its mucosal form (MCL). In a first data set (703 subjects with 242 CL patients), significant risk factors for CL were gender, native/migrant status, activity, and home-forest distance. The instantaneous risk of CL increased until adolescence in both populations, and rapidly decreased thereafter. This risk was 3-10 times higher in migrants than in natives until 20 years of age, and became similar thereafter. Environmental and behavioral factors did not seem sufficient to explain this contrast between the two populations, and this evolution with age may suggest differences in the mechanisms involved in the development of individual protection during childhood. In a second data set (446 CL patients with 34 mucosal forms) the native/migrant status was the main factor associated with the onset of mucosal form.

Eyelid leishmaniasis in a patient with neurogenic ptosis.

A patient with chronic progressive external ophthalmoplegia contracted cutaneous leishmaniasis of the upper eyelid. Infection of this site is rare because eyelid movements usually prevent the sandfly vector from biting the skin there. It is postulated that the relative immobility of the upper eyelid in this patient was a major predisposing factor for the infection.

Histological analysis and the pathogenesis of mucocutaneous leishmaniasis.

A series of over 400 well-documented biopsies of mucocutaneous leishmaniasis was evaluated to elucidate the histological processes associated with the elimination of parasites, and their correlation with the course of the disease. Non-specific inflammation was the most frequent and least effective response; its onset might be delayed, and in this event particularly the incidence of metastasis from skin to mucosa was high. Lysis of parasite-laden macrophages appeared to be the basic mechanism of parasite reduction, even when it was not overt. When it was acute the onset was usually rapid, and though it resulted in much tissue destruction the prognosis was generally better and mucosal metastasis rare. Lysis and non-specific inflammation both led to the formation of a post-necrotic type of granuloma, but reversion of the process was almost as common as progression. Ultimately a tuberculoid granuloma evolved and proceeded to resolution. In about 5 per cent of cases, macrophage activation appeared to bring about early resolution; neither reversion nor mucosal metastasis was seen.

[Mucocutaneous leishmaniasis in Panama. Etiologic agent, epidemiologic and clinical aspects]. / Leishmaniasis mucocutánea en Panamá. Agente etiológico, aspectos epidemiológicos y clínicos.

From November 1985 to December 1988, 33 patients were enrolled at Santo Tomas Hospital and Gorgas Memorial Laboratory to study the etiology, epidemiology and clinical characteristics of mucocutaneous leishmaniasis. Seventeen were males and 16 females, 14 to 80 years old from the endemic rural areas of the provinces of Panama, Colón, Coclé, Darién, Veraguas, Bocas del Toro and San Blas. In 8 patients the respiratory mucosa involvement occurred at the time of the primary infection and 25 had the involvement after an incubation period of 2 to 30 years. Twenty one of these 25 patients had a clear history of cutaneous leishmaniasis and the characteristic depressed and hyperpigmented scar of a previous leishmanial infection. The Montenegro skin test was positive in all the patients, serology in 84%, direct smear in 47%, histopathology in 37% and culture in 26%. The strains were characterized as L. braziliensis panamensis by electrophoresis of isoenzymes. Possible risk factors in development of MCL were found to be female sex and the lack of past treatment of CL. The mucosal involvement was mild in the majority of the patients, the infection was localized in the nasal mucosal (nasal septum and inferior turbinate) in 91% of the patients, and the most common symptoms were epistaxis, nasal obstruction and rhinorrhea.

Leishmaniasis mucocutanea en Panamá: agente etiologico, aspectos epidemiologicos y clínicos / Mucocutaneous leishmaniasis in Panamá: etiologic agent, epidemiologic and clinical aspects

De noviembre de 1985 a diciembre de 1987 se estudiaron 33 pacientes con leismaniasis mucocutánea, que consultaron en el Hospital Santo Tomás o en el Laboratorio Conmemorativo Gorgas con el objeto de determinar su etiología, la epidemiología y sus características clínicas. Diez y siete pacientes eran del sexo masculino y 16 del femenino. Las edades variaban entre los 14 y los 80 años. Procedían de las áreas rurales endémicas de las provincias de Panamá, Colón, Cocle, Darién, Veraguas, Bocas del Toro y la Comarca de San Blas. En 8 pacientes el compromiso de la mucosa respiratoria ocurrió durante la primoinfección cutánea y en 25 se produjo después de un intervalo se produjo de 2 a 30 años. Veintiuno de los 25 casos tenían historia de LC y presentaban una cicatriz característica. La prueba de Montenegro fue positiva en todos los pacientes, la serología en 84%, el frotis directo en 47%, la histopatología en 37% y el cultivo en el 26%. Las cepas fueron identificadas como L. braziliensis panamensis mediante electroforesis de isoenzimas. Como posibles factores de riesgo se mencionan el sexo femenino y la falta de tratamiento de la LC. El compromiso de la mucosa fie leve en la mayoría de los pacientes; la infección (tabique, cornete inferior) en el 91% de los casos y los síntomas más frecuentes fueron epistaxis, obstrucción nasal y rinorrea