Arm ulcer on a Latin American immigrant

Leishmaniasis is caused by more than 15 species of Leishmania, which are flagellated protozoa parasites. The parasites are transmitted by the bite of the Phlebotomus and Lutzomyia species of sand fly. Once inoculated into the skin, the parasites are taken...

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Leishmaniasis is caused by more than 15 species of Leishmania, which are flagellated protozoa parasites. The parasites are transmitted by the bite of the Phlebotomus and Lutzomyia species of sand fly. Once inoculated into the skin, the parasites are taken up by macrophages and clinical disease ensues.^1,2

Leishmaniasis occurs worldwide but primarily affects people in South America, Central America, the Mediterranean basin, Asia, and Africa. The three clinical subtypes are cutaneous (affecting only the skin), mucocutaneous (affecting both skin and mucous membranes), and visceral (affecting the liver, spleen, and lymph nodes).

Leishmaniasis is subdivided by geographic region, with the New World type occurring in the Americas and the Old World type occurring in Asia, Africa, and the Mediterranean basin. More than 400,000 cases of leishmaniasis are reported yearly, with the vast majority found in Saudi Arabia, Afghanistan, Syria, Brazil, and Peru^.1,2

Old World cutaneous leishmaniasis is primarily caused by L. major and L. tropica. In the New World, cutaneous disease is caused by L. mexicana, and mucocutaneous disease is caused by L. braziliensis. L. donovani (Kenya, India, Bangladesh, Sudan), L. infantum (in a geographic belt from Portugal to China), and L. chagasi (in Mexico and South and Central America) cause visceral leishmaniasis.

In cutaneous leishmaniasis, a small papule initially develops at the site of inoculation and subsequently may become ulcerated or warty. The lesions may be solitary, or they may spread by means of the lymphatic system to produce satellite lesions. Frequently, the cutaneous lesions heal spontaneously with scarring; however, some lesions may become chronic or even disseminated.^1.2

Mucocutaneous leishmaniasis starts as cutaneous disease; within months to years, the patient develops mucosal disease. The lips, nose, and oropharynx are characteristically affected. Lesions appear clinically as edema, infiltrated plaques, ulceration, or even frank destruction of cartilage.^1,2

In visceral leishmaniasis, also referred to as kala-azar, patients develop symptoms of fever, cough, lymphadenopathy, hepatosplenomegaly, and wasting in one to 36 months after inoculation. The GI, renal, and pulmonary systems may be affected, leading to death. A curious syndrome known as post-kala-azar dermal leishmaniasis may occur after successful treatment of visceral leishmaniasis. In this syndrome, patients develop dermal nodules, verrucous papules, and hypopigmented macules. The skin eruption may occur many years after the original treatment period.

Confirming the presence of the parasites by skin biopsy, scraping, or fine-needle aspiration makes the diagnosis of leishmaniasis. On histology, the skin lesions demonstrate ulceration overlying pseudoepitheliomatous hyperplasia. Look for a mixed inflammatory infiltrate consisting of plasma cells, neutrophils, lymphocytes, and macrophages. The parasites are found within the macrophages and appear as 2-µm to 4-µm oval structures that lack a capsule. The abscence of a capsule helps to distinguish leishmaniasis from Histoplasma capsulatum, which may otherwise appear similar histologically. The organisms localize around the periphery of the macrophages and are better visualized using a special Giemsa stain.

Leishmania may be cultured on specialized media, but cultures are only positive in 40% of cases.^1,2 Polymerase chain reaction (PCR) is considered the most sensitive test.3 Other tests include indirect immunofluorescence, enzyme-linked immunosorbent assay, immunoprecipitation, and isoenzyme electrophoresis.

The differential diagnosis includes such infections as syphilis, noma (also called gangrenous stomatitis, this necrotizing is infection caused by various bacteria in an immunocompromised host), paracoccidioidomycosis, and various other deep fungal or atypical mycobacterial infections.

Clinically, the cutaneous lesions may occur as basal or squamous cell carcinomas. Ulcerative lesions affecting the mucous membranes of the central face may mimic angiocentric natural-killer/T-cell lymphoma or Wegener’s granulomatosis. The ulcers of leishmaniasis may even mimic pyoderma gangrenosum. The presence of pseudoepitheliomatous hyperplasia on histology may mimic squamous cell carcinoma, and the presence of parasitized macrophages may mimic such infections as histoplasmosis and penicilliosis.

The treatment of leishmaniasis varies based on the subtype of infection and the severity of the clinical presentation. Old World cutaneous disease is frequently self-limited and does not necessarily require treatment.4 New World disease caused by L. brasiliensis may progress to destructive mucocutaneous disease and therefore requires treatment. Standard systemic therapy consists of a pentavalent antimonial medication, such as sodium stibogluconate or meglumine antimoniate.

Significant side effects of these medications include cardiotoxicity leading to QT prolongation, pancreatitis, hepatitis, thrombocytopenia, and renal failure. Other systemic therapies include amphotericin B (Amphocin, Fungizone), itraconazole (Onmel, Sporanox), ketoconazole (Nizoral) and others.^5-7 Leishmaniasis may be prevented through the use of insect repellants and through public-health measures to reduce animal reservoirs of disease.

In this case, the initial biopsy indicated squamous cell carcinoma. Since there was clinical suspicion for an infectious rather than a malignant etiology of the skin lesions, a second biopsy was performed. In the second biopsy the pathologist noted unencapsulated organisms within tissue macrophages. This histologic finding, along with the clinical picture of an expanding ulcer and the history of weeks spent in Central America, made leishmaniasis highly likely.

Experts at the CDC provided support in obtaining a tissue culture and performing a PCR on the specimen. The CDC also provided guidance regarding treatment. At the time of this writing, the patient had been admitted to the hospital for treatment with IV sodium stibogluconate for 20 days.

More information regarding the diagnosis and treatment of leishmaniasis can be found at the CDC website. This website is an invaluable resource for any health-care professional managing leishmaniasis in the United States.

Adam Rees, MD, is a first-year dermatology resident at Baylor College of Medicine in Houston.

References

1. Lupi O. Protozoa and worms. In: Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. St. Louis, Mo.: Mosby/Elsevier; 2008:1263-1268.
2. Grekin RC, Samalaska CP, Vin-Christian K. Parasitic infestations, stings, and bites. In: James WD, Berger TG, Elston DM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia, Pa.: Saunders Elsevier; 2006:415-419.
3. Lemrani M, Hamdi S, Laamrani A, Hassar M. PCR detection of Leishmania in skin biopsies. J Infect Dev Ctries. 2009;3:115-122. Available at www.jidc.org/index.php/journal/article/view/19755741.
4. Lee SA, Hasbun R. Therapy of cutaneous leishmaniasis. Int J Infect Dis. 2003;7:86-93.
5. Sundar S, Chakravarty J, Agarwal D, et al. Single-dose liposomal amphotericin B for visceral leishmaniasis in India. N Engl J Med. 2010;362:504-512. 
6. Berman J. Current treatment approaches to leishmaniasis. Curr Opin Infect Dis. 2003;16:397-401.
7. Murray HW. Leishmaniasis in the United States: treatment in 2012. Am J Trop Med Hyg. 2012;86:434-440.

All electronic documents accessed February 15, 2013.