Dermatology Online Journal

Old World cutaneous leishmaniasis
Tracey Newlove MD, Maria Robinson MD, Shane A Meehan MD, Rhonda Pomerantz MD
Dermatology Online Journal 18 (12): 32

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York

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Abstract

The leishmaniases are a group of diseases caused by species of Leishmania and transmitted by the bite of the female sandfly. The major clinical forms include localized or disseminated cutaneous, mucocutaneous, and visceral disease. Localized cutaneous leishmaniasis is most frequently caused by L. major and L. tropica in the Old World and by L. braziliensis, L. mexicana, and related species in the New World. L. donovani generally causes visceral disease in the Old World. We describe a case of disseminated cutaneous leishmaniasis caused by L. donovani in a traveller returning to the United States from Italy. Dermatologists should be aware of the clinical manifestations of leishmaniasis.

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History

Figure 1	Figure 2

A 59-year-old woman began to experience intermittent abdominal pain, diarrhea, and weight loss in January, 2011. She then developed a small, red papule under her right eye and on her left forearm. The patient had travelled to Sicily in October, 2010, on a vacation. In February, 2011, the patient consulted a dermatologist and a biopsy was performed that revealed the diagnosis. Her gastrointestinal symptoms had resolved at that time and a treatment decision was made to await spontaneous resolution of the disease.

Three months later, the initial cutaneous lesions had enlarged and ulcerated. New lesions had developed on the right temple and on the right arm. In May, 2011, the patient presented to a second dermatologist and additional biopsies were performed. Tissue samples were sent to the Centers for Disease Control (CDC) for species confirmation.

After referral to an infectious disease specialist and confirmation of the diagnosis, the patient was treated with oral fluconazole for two weeks without improvement and this medication was discontinued because of undesirable side effects such as intolerable dysgeusia. She was subsequently admitted to the hospital for initiation of liposomal amphotericin B.

Physical examination

Edematous, pink plaques were present on the right temple, right infraorbital crease, left forearm, and right arm. The lesion on the right infraorbital crease was ulcerated. On palpation, the lesions were non-tender. There was no cervical, submental, axillary, or inguinal lymphadenopathy and no hepatosplenomegaly.

Laboratory data

A comprehensive metabolic panel, and hepatic function panel were normal. The hemoglobin was 10.4 g/dL and hematocrit 31.4 percent. Studies performed at the Centers for Disease Control (CDC) included a positive leishmania real-time PCR, positive leishmania microsopy, and negative leishmania culture and leishmania PCR with DNA sequencing. These findings were consistent with Leishmania donovani.

Histopathology

In the dermis, there is a nodular infiltrate of histiocytes and a few lymphocytes. Within many of the histiocytes there are multiple small, round organisms with eccentric kinetoplasts.

Discussion

Leishmaniases are a group of diseases that are caused by more than 20 species of the protozoan genus Leishmania and that are transmitted by the bite of the Phlebotomus and Lutzomyia sandflies. The incubation period ranges from a few weeks to several years. The major clinical forms include localized or disseminated cutaneous, mucocutaneous, and visceral disease.

Localized cutaneous leishmaniasis is most frequently caused by L. major and L. tropica in the Old World and L. braziliensis, L. mexicana, and related species in the New World. The lesion may start as a nodule but eventually ulcerates in most cases and can be associated with regional lymphadenopathy. Spontaneous healing is common but requires months to years and often heals with an atrophic scar. Mucocutaneous leishmaniasis usually occurs months or years after healing of primary cutaneous leishmaniasis. It is most commonly caused by parasites of the L. braziliensis complex and can cause destruction of the nasal septum, palate, and other mucosal structures. Visceral leishmaniasis is most frequently caused by L. donovani and L. infantum (chagasi). The typical patient presents with fever, malaise, weight loss, splenomegaly, hepatomegaly, hypergammaglobulinemia, and pancytopenia.

The diagnosis of cutaneous leishmaniasis (CL) relies on the demonstration of Leishmania in tissue biopsy specimens, scraping or impression preparations by microscopy, and/or culture in a specialized medium [1]. Species identification is recommended because management may vary depending on the infecting species. Assays based on the use of polymerase chain reaction (PCR) include multiplex assays that can distinguish among several species simultaneously [2]. For visceral leishmaniasis, definitive diagnosis requires the demonstration of the parasite by smear or culture in tissue, usually bone marrow or spleen [3]. Specific information about diagnostic modalities is available from the CDC [4].

Treatment of leishmaniasis differs greatly based on the clinical presentation and infecting species. CL ulcers from several Leishmania species may heal without treatment, although healing usually takes months and will leave a scar. For one or a few small lesions not on the face or over a joint, careful follow-up without drug treatment may be appropriate. The exceptions are ulcers caused by L. braziliensis and L. panamensis, which tend not to heal spontaneously and are associated with a small risk (<5%) of subsequent mucocutaneous leishmaniasis [5]. First-line therapeutic options include the pentavalent antimonial drugs, sodium stibogluconate and meglumine antimoniate, oral azoles, and liposomal amphotericin B. Pentostam (sodium stibogluconate) is not approved by the FDA but is available under investigational new drug (IND) protocol from the CDC. Liposomal amphotericin B appears to have efficacy against several cutaneous leishmanial species, but is not currently approved by FDA for this indication. In the absence of treatment, the case-fatality rate of visceral leishmaniasis (kala-azar) is greater than 90 percent. Mortality often relates to hemorrhagic or infectious complications. Liposomal amphotericin B is the drug with the highest therapeutic efficacy and the most favorable safety profile and is currently FDA-approved for visceral leishmaniasis.

Established options for the management of CL caused by L. donovani include topical aminosidine ointment [6], intralesional sodium stibogluconate, intralesional hypertonic saline [7], and liquid nitrogen cryotherapy [8]. For cases requiring systemic treatment, oral azoles, pentavalent antimonials, and amphotericin B have demonstrated efficacy.

With changing globalization patterns, reports of CL in returning travellers are increasing. Between 1985 and 1990, the CDC received 129 requests for sodium stibogluconate (SSG) to treat civilians with leishmaniasis [9]. Between 1991 and 2001, the CDC released SSG over 350 times for the treatment of CL, 75 percent of the time for New World CL and 17 percent for Old World CL [10]. At the beginning of 2004, the USA Department of Defense reported 522 confirmed cases of CL in soldiers deployed in southwest/central Asia [11].

References

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4. Practical Guide for Laboratory Diagnosis of Leishmaniasis. May 2011. (Accessed September 18 2011, at http://www.cdc.gov/parasites/leishmaniasis/ resources/pdf/cdc_diagnosis_guide_leishmaniasis.pdf.)

5. Jones TC, et al. Epidemiology of American cutaneous leishmaniasis due to Leishmania braziliensis braziliensis. J Infect Dis 1987;156:73 [PubMed]

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9. Herwaldt B, et al. American cutaneous leishmaniasis in US travelers. Ann Intern Med 1993;118:779

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11. Update: Cutaneous leishmaniasis in U.S. military personnel--Southwest/Central Asia, 2002- 2004. Morbidity and Mortality Weekly Report 2004;53:264 [PubMed]

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