Cutaneous Leishmaniasis

AUTHORS:
Laure Cundiff, BS
Third-Year Medical Student, Texas A&M University College of Medicine, Houston, Texas

Richard L. Byrd, MD
Clinical Assistant Professor, Texas A&M University College of Medicine, Houston, Texas; Pediatrician, Kelsey-Seybold Clinic, Houston, Texas

Catherine M. Short, RN, BSN, CWOCN
Houston Methodist Hospital, Houston, Texas

CITATION:
Cundiff L, Byrd R, Short C. Cutaneous leishmaniasis [published online December 6, 2019]. Consultant360.

During a medical mission to the indigenous Cabécar people of Costa Rica, a 9-year-old girl presented with a chief concern of fleabites of several months’ duration. On physical examination, the girl was noted to have large painless ulcerations of her left forearm (Figure 1), right upper arm (Figure 2), and chin (Figure 3).

Figure 1. Ulceration on the patient’s left forearm (photo by Richard L. Byrd, MD).

Figure 2. Ulceration on the patient’s right upper arm (photo by Richard L. Byrd, MD).

Figure 3. Ulceration on the patient’s chin (photo by Richard L. Byrd, MD).

A clinical diagnosis of cutaneous leishmaniasis was made. The girl was given a 10-day course of cephalexin for suspected secondary infection of the lesions and was referred to the state health department for confirmation of diagnosis and further treatment.

EPIDEMIOLOGY

Leishmaniasis is a vector-borne parasitic disease endemic to 98 countries worldwide. It is primarily found in the tropical regions of Southern Europe, Northern Africa, the Middle East, Central and South America, and the Indian subcontinent.^1,2 With an estimated global annual incidence rate of between 0.9 million and 1.7 million new cases, leishmaniasis remains one of the most common neglected tropical diseases.² The Centers for Disease Control and Prevention reports isolated cases of leishmaniasis originating in Texas and Oklahoma, although this disease does not typically arise in the United States. However, cases may be diagnosed in travelers, immigrants, and military personnel upon their return to the United States and therefore remains an important clinical consideration.¹

The causative organism is the protozoan Leishmania. At least 20 species of Leishmania have been identified, causing a range of clinical manifestations in different geographical areas.¹ The parasite is transmitted by the bite of infected Phlebotomus sand flies, with more than 98 species of this vector having been identified.² Rodents, canines, and humans serve as the primary reservoirs of Leishmania, and thus this disease undergoes both zoonotic (animal-to-human) and anthroponotic (human-to-animal) transmission when female sand flies take blood meals from their mammalian hosts.²

Three clinical syndromes are possible, depending on the Leishmania species. Once inside the host, the promastigote develops into an amastigote within macrophages of the skin, causing the cutaneous form of this disease.² Mucosal leishmaniasis can evolve from dissemination of the parasite from the skin to the laryngeal or naso-oropharyngeal mucosa, which can erode the nasal cartilage and produce a disfiguring scar.² When development occurs within the reticuloendothelial system of the spleen, liver, and bone marrow, the visceral form of leishmaniasis (kala-azar) occurs.² (This review focuses primarily on the diagnosis and treatment of cutaneous manifestations, as seen in our patient.)

DIAGNOSIS

Cutaneous leishmaniasis most commonly presents with a painless papule developing at the site of a sand fly bite. It increases in size and eventually crusts and ulcerates.¹ Lesions may develop between 2 weeks and several months after the initial bite; some people never develop clinical manifestations.¹ Laboratory evaluation is necessary to rule out other etiologies (Table).^3,4

The diagnosis of cutaneous leishmaniasis can be confirmed with microscopic examination of a tissue biopsy or skin scraping of the lesion where amastigotes may be identified.¹ While cost-effective, this method is subjective and time-consuming and comes with highly variable sensitivity.⁵ Samples of the lesion can be taken for polymerase chain reaction analysis, allowing for highly sensitive molecular speciation of the parasite.¹

Immunological testing is achieved using the Montenegro skin test (MST). Similar to a tuberculin skin test, the MST relies on a delayed-type hypersensitivity reaction after injection of phenol-killed promastigotes. Greater than 5 mm induration after 48 to 72 hours is considered a positive test.⁵ This method is widely available in regions without access to specialized medical care and has a reported sensitivity of greater than 90%.⁵ Serology testing is not traditionally recommended as a means of diagnosis due to poor antibody production in cutaneous leishmaniasis and significant cross-reactivity with other diseases, including Chagas disease. However, one recent study showed improved sensitivity of enzyme-linked immunosorbent assay (ELISA) when novel recombinant antigens are used as opposed to more traditional soluble antigens of Leishmania.⁶ If visceral involvement is suspected, bone marrow biopsy may be required for detection of the amastigote.¹

TREATMENT

While skin lesions caused by certain species of Leishmania heal spontaneously within 3 to 18 months, intervention is recommended to reduce scarring and prevent mucosal or visceral spread.¹ Local therapy may be effective for small, single lesions without evidence of systemic involvement. These include cryotherapy, heat lamps, paromomycin ointment, and most commonly intralesional injection of trivalent antimony, which has a 75% cure rate after 8 treatments at 2 week intervals.¹ Antimony is an elemental metalloid that works by causing trypanothione and glutathione efflux from the parasite and inhibiting trypanothione reductase activity, thus halting thiol redox metabolism in the parasite.⁷ Refractory or disseminated cases may require oral antimony, which has a 96% cure rate after a 20-day course, or antiprotozoal agents including fluconazole, ketoconazole, miltefosine, and amphotericin B with cure rates between 53% and 79%.¹

One study describes upregulation of antimony resistance marker (ARM) in certain species of Leishmania, suggesting the utility of this marker in determining effective species-specific treatment.⁸ Another study describes the development of a chloroquinolin derivative useful in cases of antimony resistance and with better results when compared with amphotericin.⁹ This chloroquinolin compound works by inducing formation of reactive oxygen species and causing changes to the mitochondrial membrane potential.⁹

While leishmaniasis related-death is rare, when it does occur it is most commonly due to untreated secondary bacterial infection.¹ Cure is expected, and our patient’s prognosis is favorable, given her successful completion of cephalexin therapy followed by a series of intralesional antimony injections at the Costa Rican health department. No long-term follow-up is necessary. Infection usually provides immunity, but recurrence is possible in immunosuppressed individuals.^1,10 Preventive measures include utilization of pyrethroid-containing insect repellants, protective clothing, and bed nets.^1,11 Many potential vaccines are in early clinical trial; if combined with anti-Leishmania drugs, they may provide safer and shorter treatment regimens in the future.¹²