Lieshmaniasis_0912 Derm Dx
A 34-year-old man presents with an ulcer on his arm that has been present many weeks and is expanding. He states that it started as a small papule, which he ignored until it started expanding into a larger nodule that eventually ulcerated.
The patient confides that he recently entered the United States illegally. Originally from Cuba, he traveled to Central America and then spent weeks trekking through the jungles of Costa Rica and Guatemala before arriving in Mexico. He was then transported to the U.S. border and smuggled across with the assistance of human smugglers.
The patient is otherwise healthy and takes no medications. He denies fevers. A punch biopsy is performed,which demonstrates ulceration with pseudoepitheliomatous hyperplasia and multiple macrophages filled with small parasites. What’s your diagnosis?
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More than 15 species of Leishmania, a type of flagellated protozoa parasite transmitted by sandfly bites, cause leishmaniasis.
Leishmaniasis occurs worldwide, affecting South and Central America, the Mediterranean basin, Asia and Africa. There are three clinical subtypes:
- Cutaneous — affecting only the skin
- Mucocutaneous — affecting both the skin and mucous membranes
- Visceral — affecting the liver, spleen and lymph nodes
Leishmaniasis is also subdivided by geographic region, with “New World” types referring to disease contracted in the Americas, and “Old World” types referring to those contracted in Asia, Africa and the Mediterranean.
More than 400,000 leishmaniasis cases are reported annually. The vast majority of disease occur in Afghanistan, Brazil, Peru, Saudi Arabia and Syria. Other affected regions include Sub-Saharan Africa, Central America, Central Asia, India, the Mediterranean basin, and South America’s northern regions.
L. major and L. Tropica are typically responsible for Old World cases of cutaneous leishmaniasis. In the New World, L. mexicana causes cutaneous diseases, whereas L. braziliensis is responsible for most mucocutaneous disease
Visceral leishmaniasis is caused by different species depending on geographic region:
- L. donovani — Bangladesh, India, Kenya and Sudan
- L. infantum — a geographic belt spanning from Portugal to China
- L. chagasi — Mexico, South and Central America
Two species of sandfly transmit leishmaniasis via bite – Phlebotomus and Lutzomyia. The Phlebotomus species is responsible for Old World leishmaniasis, and the Lutzomyia species is responsible for New World disease. Once inoculated into the skin, microphages take up the parasites and clinical disease ensues.
In cutaneous leishmaniasis, a small papule initially develops at the site of inoculation, which may subsequently become ulcerated or warty. Lesions may be solitary or may spread via the lymphatic system to produce satellite lesions. Cutaneous lesions frequently heal spontaneously with scarring; however, some lesions may become chronic or disseminated.
Mucocutaneous leishmaniasis starts as cutaneous disease, with the patient developing mucosal disease within months to years. The lips, nose and oropharynx are characteristically affected and appear clinically as edema, infiltrated plaques, ulceration, or even frank destruction of cartilage.
In visceral leishmaniasis — also called kala-azar, black fever and Dumdum fever — patients’ develop fever, cough, lymphadenopathy, hepatosplenomegaly and wasting one to 36 months after inoculation. With visceral leishmaniasis, the gastrointestinal, renal and pulmonary systems may be affected, which can lead to death.
A curious syndrome known as “post-kala-azar dermal leishmaniasis” may occur after visceral leishmaniasis is successfully treated. In this syndrome, patients develop dermal nodules, verrucous papules and hypopigmented macules. The skin eruption may occur many years after the original treatment period.
A skin biopsy, scraping or fine needle aspiration is necessary to detect the presence of parasites and confirm a diagnosis of leishmaniasis.
On histology, leishmaniasis skin lesions demonstrate ulceration overlying pseudoepitheliomatous hyperplasia, and a mixed inflammatory infiltrate, consisting of plasma cells, neutrophils, lymphocytes and macrophages. The parasites are found within the macrophages and appear as oval 2-4 µm structures that lack a capsule. The lack of a capsule helps to distinguish leishmaniasis from Histoplasma capsulatum, which may otherwise appear histologically similar. 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. Polymerase chain reaction (PCR) is considered the most sensitive test. Other tests include indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation and isoenzyme electrophoresis.
The differential diagnosis includes other infections, including syphilis; noma, a gangrenous stomatitis that occurs in immunocompromised hosts; paracoccidioidomycosis; and various other deep fungal or atypical mycobacterial infections.
Clinically, 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. Leishmaniasis ulcers 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 other infections, such as histoplasmosis and penicilliosis.
Leishmaniasis treatment varies based on the subtype of infection and the severity of clinical presentation.
Old World cutaneous disease is frequently self-limited and does not necessarily require treatment. However, New World disease caused by L. brasiliensis may progress to destructive mucocutaneous disease, and therefore requires treatment.
The standard systemic therapy is pentavalent antimonial medication, such as sodium stibogluconate or meglumine antimoniate. These medications have significant side effects including cardiotoxicity leading to Q-T prolongation, pancreatitis, hepatitis, thrombocytopenia and renal failure.
Other systemic therapies include amphotericin B, itraconazole, ketoconazole and others. Use of insect repellants and public health measures to reduce animal reservoirs of disease can help prevent leishmaniasis from occurring.
Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine in Houston.
- Bolognia J, Jorizzo JL, Rapini RP. “Chapter 82: Protozoa and Worms.” Dermatology. St. Louis, Mo.: Mosby/Elsevier, 2008.
- James WD, Berger TG, Elston DM et al. “Chapter 20: Parasitic Infestations, Stings, and Bites.” Andrews’ Diseases of the Skin: Clinical Dermatology. Philadelphia: Saunders Elsevier, 2006.