Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World

Background  Comorbidity from tegumentary leishmaniasis and AIDS is poorly characterized.
Objectives  To describe a series of patients coinfected with Leishmania and human immunodeficiency virus (HIV).
Methods  Clinical records from patients were analysed by demographic data, clinical manifestations, diagnoses, treatments and outcomes.
Results  Fifteen cases of AIDS/tegumentary leishmaniasis were found. The diagnosis of leishmaniasis was confirmed by the detection of Leishmania amastigotes or antigens from the cutaneous or mucosal lesions. The mean CD4+ T-cell count was 84 cells mm⁻³ (range 8–258) and all patients were classified as having AIDS according to the Centers for Disease Control and Prevention. A wide range of manifestations was found, varying from a single ulcer to multiple and polymorphic lesions. Mucosal lesions were present in 80% and cutaneous lesions in 73% of patients (53% with mucocutaneous form), disseminated lesions in 60% and genital lesions in 27% of patients. All patients received anti- Leishmania therapy and 53% showed relapses. Sixty-seven per cent received highly active antiretroviral therapy but showed no difference in outcomes and relapses compared with those not using medication. Forty per cent died during the study period. In these patients, the anti- Leishmania antibody and Montenegro skin test were useful in the diagnosis of leishmaniasis, probably because leishmaniasis preceded immunosuppression due to HIV infection.
Conclusions  Clinical manifestations of tegumentary leishmaniasis in HIV-infected patients are diverse. Our data emphasize possible unusual manifestations of this disease in HIV-infected patients, particularly in severely immunosuppressed cases (< 200 CD4+ cells mm⁻³).     

American cutaneous leishmaniasis due to Leishmania (Viannia) guyanensis as an initial clinical presentation of human immunodeficiency virus infection

The authors present the first report of Leishmania (Viannia) guyanensis (L.(V.) guyanenesis ) associated with human immunodeficiency virus (HIV) in a Brazilian heterosexual man. It is also the first case of HIV infection associated with American cutaneous leishmaniasis in Brazilian Western Amazonia. The patient had cutaneous and mucous lesions with a negative Montenegro skin test. Histopathology showed large numbers of amastigotes, even in a lesion which had clinically healed. L.(V.) guyanenesis was typed by an immunoenzymatic technique. Various therapies were attempted, but the patient relapsed after each episode of treatment.     

Treatment of cutaneous leishmaniasis with 20% paromomycin ointment

Cutaneous leishmaniasis is an infectious disease caused by flagellate protozoa of the genus Leishmania. In Mediterranean countries, the most common causative agents are Leishmania (L.) major, L. infantum and L. tropica. In Croatia, cutaneous leishmaniasis is a rare disease, the last case being reported in 1988. Our patient was a 5-year-old boy with a left cheek skin lesion in the form of papule with central exulceration, hyperkeratotic crust and erythema of a 6-month duration. The diagnosis of cutaneous leishmaniasis was based on history data (stay in the southernmost region of Croatia and multiple mosquito bites), light microscopic histology (dense infiltrates of large histiocytes with extracellular bodies), and positive Montenegro (leishmanin) test. A new therapy with aminosidine (paromomycin), an aminoglycoside antibiotic, in the form of ointment at a concentration of 20%, was for the first time used in Croatia. Four-week therapy resulted in complete regression of the skin lesions with residual hyperpigmentation. During therapy, no local or systemic side effects were observed. Thus, topical therapy with paromomycin could be considered an efficient therapeutic alternative in the management of cutaneous leishmaniasis.     

Cutaneous Leishmaniasis from Belize–treatment with ketoconazole

Eight patients suffering from cutaneous leishmaniasis acquired in Belize were treated with 800 mg oral ketoconazole daily for 28 days. Four were infected with Leishmania mexicana mexicana and four with Leishmania braziliensis brazitiensis. On completion of therapy, all cases of Leishmania mexicana mexicana infection and one of Leishtaania braziliensis braziliensis infection showed significant clinical improvement. Clearance of infection was confirmed by the absence of amastigotes in post-treatment biopsy specimens and negative post-treatment cultures. The possibility of spontaneous clinical healing of these ulcers within such a short period of time is discussed but considered most unlikely. No side-effects were observed during this study which suggests that ketoconazole might be a safe and effective form of therapy for cutaneous leishmaniasis caused by Leishmania mexicana mexicana.     

A pilot study comparing low‐dose liposomal amphotericin B with N‐methyl glucamine for the treatment of American cutaneous leishmaniasis

Background Cutaneous leishmaniasis is an infectious re‐emerging disease that has increased in incidence worldwide. Antimony, a highly toxic drug, remains the first choice therapy to treat it. Liposomal amphotericin B is active against Leishmania and is less toxic than antimony. Objective To compare low‐dose liposomal amphotericin B with N‐methyl glucamine for the treatment of American cutaneous leishmaniasis. Patients/Methods In a controlled open‐label trial 35 patients with a localized form of American cutaneous leishmaniasis were included. They were allocated to a first group treated with 1.5 mg/kg/day of liposomal amphotericin B for 5 days, or to a second one treated with 20 mgSbV/kg/day of N‐methyl glucamine for 20 days. Results In the first group, 50% and 81% of patients experienced a clinical cure and clinical improvement respectively. There was a 100% clinical cure in the second group. Conclusion Liposomal amphotericin B seems to be promising and safe for the treatment of American cutaneous leishmaniasis.     

Intralesional therapy of American cutaneous leishmaniasis with pentavalent antimony in Rio de Janeiro, Brazil – an area of Leishmania (V.) braziliensis transmission

Background The drug of choice for leishmaniasis is pentavalent antimony and different regimens are under continuous evaluation. The ideal therapy should be simple, effective, and with no or minor side-effects, in this paper we have studied the efficacy of intralesionally applied antimony in New World cutaneous leishmaniasis. Methods Seventy-four patients from Rio de Janeiro state, Brazil, and presenting with single ulcerative cutaneous lesions mainly located on the trunk or extremities were enrolled in the study. The drug employed was N-methyl glucamine (425 mg of Sb^v in each 5 ml ampoule). Each lesion was infiltrated with the drug at the four cardinal points in order to achieve complete blanching. Results Of the 74 patients, 59 (80%) were healed after a 12–week interval. Extensive follow-up (up to 10 years) disclosed no relapses or the development of mucosal lesions. Conclusions The aim of therapy in New World cutaneous leishmaniasis is the healing of the cutaneous lesion and the prevention of late mucosal damage. Both conditions were achieved with the treatment employed with no side-effects and a considerable decrease in costs. In addition, the method is easy to apply in the field.     

Sporotrichoid cutaneous leishmaniasis in Tunisia: a clinical and histological study

BACKGROUND: The sporotrichoid variety of cutaneous leishmaniasis is defined by the presence of dermal and hypodermal nodules along the lymphatic stream, and remote from the primary inoculation lesions. This clinical form is usually considered rare. The aim of our study was to investigate the epidemiological, clinical, histological and evolutionary particularities of sporotrichoid cutaneous leishmaniasis in the south of Tunisia. PATIENTS AND METHODS: During a systematic study of all cases of cutaneous leishmaniasis from the south of Tunisia diagnosed in our hospital in 2002, sporotrichoid forms were diagnosed on the basis of clinical criteria. In all cases of sporotrichoid cutaneous leishmaniasis, the principal clinical characters were systematically specified. Cutaneous biopsies of subcutaneous nodules were performed in six cases. RESULTS: Of 102 patients with cutaneous leishmaniasis, 19 presented sporotrichoid cutaneous leishmaniasis, that is, a frequency of 19%. Between two and 20 painless subcutaneous nodules were arranged in linear strings on the upper leg in 79% of cases. Time to appearance varied between 12 days and one year after the primary lesions. Fourteen appeared without any preliminary treatment for cutaneous leishmaniasis and five appeared after Glucantime infiltration in the primary lesions. Biopsies of the nodules showed an inflammatory infiltrate composed of lymphocytes and histiocytes. This infiltrate was particularly dense and rich in plasmocytes at the level of the deep dermis. The biopsies were deep enough to involve the hypoderm in one case and the same type of infiltrate was noted at the level of interlobular septa. A small number amastigotes was seen in one deep biopsy sample. Outcome was favourable in all cases under treatment. CONCLUSION: Sporotrichoid cutaneous leishmaniasis appears to be common in the south of Tunisia, were cutaneous leishmaniasis is dominant because of Leishmania major. It is not associated with a poor prognosis.     

Clinical features of cutaneous and disseminated cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis in Paraty, Rio de Janeiro

Background  American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis is endemic in Rio de Janeiro State (RJ), where the disease shows epidemiologic and clinical characteristics distinct from those of ATL in other Brazilian regions. Paraty is the second most important endemic area in RJ; however, reports on leishmaniasis in this region refer to the occurrence of the disease without describing its characteristics.
Methods  The clinical features of 71 cases of ATL reported between 1991 and 1997 in Paraty are presented. Thirty patients were re-evaluated 10 years later.
Results  Males and females were affected in similar proportions, and the disease was more prevalent in patients aged between 10 and 49 years (63.4%). Cutaneous leishmaniasis was the most prevalent clinical form observed. Unique lesions were present in 69% of cases, 91.6% of which displayed an ulcerated aspect. Although mucosal leishmaniasis was not observed, severe clinical manifestations, such as disseminated cutaneous lesions caused by L. braziliensis , were diagnosed in two patients. These patients presented skin lesions with different clinical aspects spread throughout the body, as well as low cellular immune responses. Montenegro skin test (92% positivity) and serology (8% IgM and 56% IgG anti- Leishmania positive results) were the most utilized tests for supporting the diagnosis of leishmaniasis. Parasites, detected in 27 of the 33 cases analyzed, were characterized as L. braziliensis .
Conclusion  ATL in Paraty shares the clinical and laboratory characteristics reported for ATL in other regions of RJ, probably because of the similar epidemiologic context related to the Atlantic rainforest region.     

Value of diagnostic techniques for cutaneous leishmaniasis

BACKGROUND: Traditional diagnostic tests, ie, smear, culture, and histopathology of a skin biopsy specimen, are not always conclusive in patients with a clinical diagnosis of cutaneous leishmaniasis (CL). OBJECTIVE: Our purpose was to find out if a polymerase chain reaction (PCR) specific for Leishmania organisms might be more sensitive than the traditional diagnostic techniques, thereby decreasing the number of false-negative diagnoses. METHODS: In a prospective study, smear, culture, and histopathology of skin biopsy specimens from 46 patients with a possible diagnosis of CL were compared with PCR specific for Leishmania. In addition, the Montenegro test as a measure of cellular immunity against the Leishmania parasite was performed. Proven CL was defined as a case in which at least 1 of the 3 traditional tests showed the presence of Leishmania parasites. RESULTS: Of our 46 patients, 22 had leishmaniasis. Of the traditional tests, culture was the most sensitive but there were no statistically significant differences between the sensitivities of the various tests. PCR results were positive in all cases of proven leishmaniasis. Moreover, 3 patients with the clinical diagnosis of CL and negative findings on traditional tests had positive PCR results. Only 1 patient with a strong clinical suggestion of CL and positive Montenegro test results had negative PCR findings; this patient also had negative smear, culture, and histopathology results. CONCLUSION: PCR appears to be the most sensitive single diagnostic test for CL.     

Leishmania infantum/HIV co-infection: cutaneous lesions following treatment of visceral leishmaniasis

BACKGROUND: The Mediterranean basin is an endemic region of leishmaniasis caused by Leishmania infantum. With the advent of human immunodeficiency virus (HIV) infection, the number of cases of visceral leishmaniasis has dramatically increased in this area over the last years, mainly in adults. Moreover, the presence of cutaneous lesions infested with Leishmania has been frequently reported in these patients. CASE-REPORT: A 35-year-old Portuguese woman, a former intravenous drug user HIV1-positive since 1997, developed visceral leishmaniasis in 2000, with several relapses in 2001 and 2002, treated successively with pentavalent antimonial salts (Glucantime), liposomal amphotericin B and Glucantime associated with itraconazole. Several weeks after therapy for the second relapse of visceral leishmaniasis, physical examination revealed asymptomatic erythematous papules on the face that later spread to the trunk and upper limbs. Histopathologic studies of a skin biopsy revealed a granulomatous infiltrate in the dermis with the presence of Leishmania amastigotes. After culture, the parasite was identified as L. infantum MON-1. In spite of improvement of the patient's visceral leishmaniasis with the above-mentioned treatment, the cutaneous lesions became increasingly numerous and infiltrated. After 2 months of therapy with intravenous pentamidine (4 mg/kg/3 times a week) and oral dapsone (100 mg b.i.d), the cutaneous lesions disappeared completely. Prevention with dapsone was successfully maintained for 6 months. Several weeks after discontinuation of treatment, further lesions appeared. The patient improved again on reintroduction of dapsone. DISCUSSION: This case confirmed the existence of a clinical form similar to post-kala-azar dermal leishmaniasis in a patient co-infected with L. infantum MON-1/HIV. The cutaneous lesions were resistant to classical antileishmanial drugs but disappeared on treatment with dapsone.     

The T cell phenotypes in the lesion of patients with cutaneous leishmaniasis

Immunohistological analysis of the lesions of patients with cutaneous leishmaniasis showed that the OKT8 positive/cytotoxic T suppressor lymphocyte was the predominant cell in the mononuclear cell infiltrate. These patients were nor immunocompromised, had normal cellular immune functions and had developed specific cellular immunity to the infecting parasite, Leishmania tropica major (L. major). These findings support the contention that in patients with cutaneous leishmaniasis inappropriate sensitization of T suppressor lymphocytes occurs, which may, by inhibiting the positive inducer signals of T helper Lymphocytes, account for the chronicity of these lesions.     

Unusually extensive disease caused by Leishmania major parasites

Simple cutaneous leishmaniasis (CL), which is endemic in several areas of Israel, is usually caused by Leishmania major. CL, which is caused by replication of parasites within dermal macrophages, is self-limited and almost always confined to the skin. We recently encountered two cases of CL in which skin defenses were breached and lesions appeared in subcutaneous locations. In one case, abnormal cell-mediated immune function was detected. The purpose of this article is to present these data and to comment on the immunological aspects of leishmaniasis.     

Molecular diagnosis of cutaneous leishmaniasis and species identification: analysis of 122 biopsies with varied parasite index

Background: Cutaneous leishmaniasis is endemic in the Middle East and North Africa. Confirming the diagnosis histologically depends on amastigote identification, which varies significantly depending on the inoculum, strain type, host response and disease stage. Accurate histological diagnosis is mandatory for appropriate therapy. Methods: Skin biopsies from 122 patients from Lebanon, Syria and Saudi Arabia with clinical diagnosis of untreated leishmaniasis were reviewed and clinical data extracted. Cases were classified according to the modified Ridley's parasitic index. DNA was extracted from formalin‐fixed paraffin‐embedded blocks. Polymerase chain reaction (PCR) was performed using Leishmania‐specific ribosomal internal transcribed spacer 1 (ITS1‐PCR). Nested ITS1‐PCR was performed on cases negative for conventional ITS1‐PCR. ITS1‐PCR amplicons were digested with HaeIII for subsequent restriction fragment length polymorphism (RFLP) subspeciation. Results: Of 122 cases, 54 (44.3%) showed a parasitic index of 0–1+ (no unequivocal amastigotes). ITS1‐PCR (conventional and nested) was positive for all cases as compared with negative control tissue. RFLP identified Leishmania tropica in all cases. Patients with clinically suspected leishmaniasis, whose skin biopsies failed to detect amastigotes represented 44.3% of our cases. Conclusions: In this study, we describe a rapid and optimized protocol from DNA extraction to leishmaniasis subspeciation. ITS1‐PCR showed high sensitivity and specificity in confirming clinically suspected cases. Yehia L, Adib‐Houreih M, Raslan WF, Kibbi A‐G, Loya A, Firooz A, Satti M, El‐Sabban M, Khalifeh I. Molecular diagnosis of cutaneous leishmaniasis and species identification: analysis of 122 biopsies with varied parasite index.     

Old World eyelid cutaneous leishmaniasis: a case report

Leishmania is a protozoa that may infect the skin, mucous, and viscera. The geographical distribution of cutaneous leishmaniasis (CL) is mainly determined by the sandfly vectors. The Old World type is mainly attributed to Leishmania major and Leishmania tropica, and in South of Europe only to Leishmania infantum. A 63-year-old woman, who noted a pimple on the external third of the left upper eyelid 6 months before. The lesion was nodular, well-defined and measured 1.1 cm in diameter and in height, simulating a basal cell carcinoma. It was surgically excised. CL diagnosis was made upon the histologic examination, which showed histiocytes with intracellular leishmania organisms. At 2 years followup, no evidence exists of cutaneous, mucous, or visceral involvement. Apart from carcinomas, nodular lesions with central ulceration are rare on the eyelid. A single cutaneous lesion of leishmania (oriental sore) has to be considered in the differential diagnosis, along with malignant eyelid neoplasms.     

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.     

Leishmaniasis

Infections with Leishmania spp. rank among the top three most common travel‐associated dermatoses. Depending on the country where the infection was acquired and the patient's immune status, different disease manifestations may be observed. Ninety percent of cases present as cutaneous leishmaniasis, but the infection may also affect internal organs (visceral leishmaniasis). Without treatment, the latter is often fatal. Intermediate types include recurrent, diffuse, or mucocutaneous forms. Nodular lesions on exposed skin with a tendency to ulcerate over time in combination with a travel history should therefore prompt workup for leishmaniasis. The diagnosis is made through histology, parasite culture, and PCR using biopsy material. Therapeutic options range from local therapies in cases with singular lesions to systemic therapy in patients with more severe forms. The present review discusses the most important clinical features, details about diagnostic measures, and current therapeutic approaches.     

A Case of Post-kala-azar Dermal Leishmaniasis

Only a few cases of Post-kala-azar dermal leishmaniasis have been reported in Japan, especially recently. We describe a case of a 32-year-old woman who developed rose-colored nodules on her forearms two years after Kala-azar. A skin biopsy specimen from a nodule revealed not only granulomatous changes but also many amastigotes of Leishmania donovani in macrophages. Rose-colored nodules were also distributed on her face and neck. Treatment with antimony compound was very effective.     

Cutaneous leishmaniasis in a child treated with oral fluconazole

We report a case of cutaneous leishmaniasis in a 3‐year‐old West African girl with a 3‐month history of multiple disfiguring, infiltrated, ulcerating and variably necrotic granulomatous plaques on the limbs and face that occurred after swimming in a river approximately 6 weeks before arriving in Australia. A diagnosis of cutaneous leishmaniasis, a protozoal zoonosis usually transmitted by the Phlebotomus species of sandfly, was considered. The clinico‐pathological features were consistent with Leishmania major infection, known to be the major endemic species causing cutaneous leishmaniasis in the country of origin. Because of the presence of lesions on the face, active treatment was instituted. Continuing resolution of all lesions over 6 weeks was noted to occur with cribiform scarring with the use of oral fluconazole 150 mg daily. Oral fluconazole appears to be emerging as a therapy for uncomplicated cutaneous leishmaniasis, with advantages particularly important in paediatrics.     

Peripheral Nerve Involvement in Cutaneous Leishmaniasis (Old World)

A review of 288 skin biopsy specimens from cutaneous leishmaniasis lesions caused by Leishmania major showed assorted nerve changes in 14 biopsy specimens (5%). Ten patients had perineural inflammatory cell infiltrate consisting of either lymphocytes or a mixture of lymphocytes, plasma cells, and macrophages. Four patients had inflammatory cell invasion of the nerves (neuritis), and in one of them the inflammation was granulomatous and associated with nerve destruction. Amastigotes were seen inside the nerves in two patients. Sensory testing of 50 consecutive patients with cutaneous leishmaniasis identified two patients with diminished sensations over the lesions.