Clinical History
A 23-year old male with a one month history of non-healing erythematous plaques. Some of the plaques
were ulcerated with rolled borders. The lesions are located on the right forearm and left lateral chest.
He recently returned from Iraq. Biopsy of chest lesion was obtained.
Case 4 - Figure 1 - Punch biopsy of non-ulcerated skin with interface and deep dermal nodular infiltrates.
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Case 4 - Figure 2 - Higher power of skin demonstrates the dense granulomatous inflammation.
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Case 4 - Figure 3 - Oil immersion, reveals intracellular amistigotes of Leishmania species (center of the field) the nucleus and kinetoplast are visible.
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Slide description
The punch biopsy of skin shows non-ulcerated skin with non-caseating granulomatous inflammation.
There is a dense lymphohisitocytic infiltrate at the dermal-epidermal interface and a nodular
lymphohistiocytic infiltrate in the deeper dermis . Occasional amastigotes of Leishmania species are
seen in giant cells and histiocytes.
Diagnosis
Cutaneous Leishmaniasis
Clinical Follow-up
The patient was treated under an experimental protocol
of 20mg/kg/d intravenous Pentostam for 20 days. The lesions resolved.
Discussion
Leishmaniasis is infection by protozoan parasites of the genus Leishmania. The organisms are transmitted to humans by the bite of female
sandflies (Phlebotomus in the East; Lutzomyia in the West). In endemic areas, nonhuman mammalian species
serve as reservoir hosts.
Cutaneous leishmaniasis (CL) is endemic in 82 countries. In the Americas, it is widely distributed
from southern Texas to northern Argentina. Other endemic areas include the Middle East, India, and East
Africa. Worldwide, approximately 300 000 cases of CL are reported annually. Epidemics of CL frequently
occur when a nonimmune population intrudes into a natural enzootic cycle. The population at highest risk
for CL is nonimmune expatriates such as tourists, soldiers, new settlers, and construction or
agricultural workers.
Three serologically and biochemically distinct species of Leishmania : L. tropica, L. aethiopica, and
L. major are responsible for Old World leishmaniasis. They are transmitted by sandflies of the genus
Phlebotomus. New World leishmaniasis with purely cutaneous involvement is caused by L. braziliensis
peruviana, L. braziliensis guyanensis, and L. mexicana, all of which are transmitted by sandflies of the
genus Lutzomyia. L. braziliensis braziliensis is the etiologic agent of mucocutaneous leishmaniasis and
is transmitted by the genus Lutzomyia.
The most common clinical presentations of Old World leishmaniasis are single or multiple localized
ulcers or nodules. Typically, ulcerative CL starts as a small, erythematous papule at the site where
promastigotes, the infective form of the parasite, are inoculated by the bite of a sandfly. The
incubation period is usually several weeks or months, but lesions can appear within a few days or several
years after leaving an endemic area. In most cases, within a few weeks the papule enlarges, crusts over,
and breaks down into a slow-growing ulcer up to several centimeters in diameter. The ulcer is shallow
and well-defined, with a raised erythematous border and central granulation tissue. As the ulcer grows,
patients develop a delayed hypersensitivity reaction to leishmanial antigens. Secondary bacterial
infection is common after ulceration. Surrounding inflammation may be minimal or quite marked. The
ulcer heals slowly, leaving a depressed, atrophic scar. Subcutaneous nodules with a sporotrichoid
pattern and satellite lesions are common, mainly in the West. Lesions may be hyperkeratotic and do not
always ulcerate. There may be involvement of proximal lymph nodes. Macules, papules, plaques, nodules,
and psoriasiform, varicelliform, eczematous, and keloidal lesions are uncommon.
New World leishmaniasis encompasses several clinical entities. The "Bay" sore typically occurs on the
face as one or occasionally multiple erythematous plaques that typically do not ulcerate. "Apple-jelly"
nodules resembling lupus vulgaris are sometimes seen. The "Chiclero" ulcer is similar but is more often
a single erythematous plaque that ulcerates; it affects the ear in 40 percent of cases and can cause
extensive destruction of the cartilage. "Uta" presents as one or several papules on exposed sites;
lesions usually ulcerate and are self-healing. In "pian bois" there is a single skin ulcer. Lymphatic
spread may occur and result in widespread ulceration; but mucocutaneous involvement is extremely
uncommon.
Disseminated cutaneous leishmaniasis presents as a single ulcer, nodule, or plaque on the face and
other exposed areas. Nodular or plaque -like satellite lesions develop from the primary lesion and may
disseminate over the entire body. Patients are anergic to leishmanial antigens and do not mount a
specific cellular immune response to the infection. The organisms proliferate indefinitely, forming many
lesions teeming with parasites.
In HIV-infected hosts, visceral leishmaniasis is the predominant clinical presentation of this
protozoal disease. Purely cutaneous and mucosal manifestations of leishmaniasis in HIV co-infection are
rare. Dissemination of the parasite through the lymphatic system can produce sporotricoid-like lesions.
Treatment failure and relapse are also common. Death during the first episode of visceral leishmaniasis
has been reported in up to 19% of patients.
Diagnosis
Smears
Polyparasitic syndromes, such as early-stage and diffuse CL, are easily confirmed with Giemsa-stained
smears. Oligoparasitic syndromes, such as late-stage (healing) CL, are difficult or impossible to
confirm with standard Giemsa-stained smears. Amastigotes are ovoid or round and 1.5–3 µm in diameter (up
to 5 µm in smears). They have a thin cell membrane, a relatively large nucleus, and a rod-shaped
kinetoplast.
Histology
In histologic sections, amastigotes usually stain well with H&E or Brown-Hopps modified tissue
gram stain, and are readily observable if abundant. Parasites may be very sparse in late lesions,
requiring review of multiple tissue sections. Oil-immersion observation with a 100x objective is
mandatory for these cases. In our experience, Brown-Hopps modified tissue gram stain best accentuates
the kinetoplast, and produces minimal background staining and maximum contrast. Giemsa stains are of no
value in tissue sections.
Various admixtures of lymphocytes, neutrophils, and plasma cells are also present. Areas of
ulceration may have pseudoepitheliomatous hyperplasia (PEH) at the edge of the ulcer and show
predominantly nonspecific inflammatory infiltrates . As the lesions age, there tends to be gradual
reduction in the number of both organisms and histiocytes. A granulomatous infiltrate
containing epithelioid cells and multinucleated giant cells develops; caseous necrosis is notably absent.
In vitro culture is more sensitive than histological methods, but because some Leishmania sp. are
difficult to culture, this method should be complementary to microscopy, especially in clinically suspect
cases.
There is currently no sensitive or specific serological assay for detecting Leishmania-specific
antibody in CL. A skin-test antigen can detect prior infection and corroborate the diagnosis of
oligoparasitic syndromes; however, no such test is currently available in the United States for clinical
use.
Differential Diagnosis
The histopathological differential diagnosis includes American trypanosomiasis, histoplasmosis,
rhinoscleroma, granuloma inguinale, leprosy, and atypical mycobacteriosis. Each of these entities is
characterized by an infiltrate or parasitized histiocytes admixed with chronic inflammatory cells.
However, Leishmania amastigotes can generally be differentiated
histologically from other organisms. Differentiation of Leishmania
amastigotes from those of Trypanosoma cruzi may be quite difficult. T. cruzi amastigotes are larger (3 to 5 m m), round to oval with a distinct
cytoplasmic membrane, a round nucleus, and a basophilic kinetoplast. Unlike Leishmania and Histoplasma, Trypanosoma are able to invade mesenchymal cells.
Current Outbreak in US forces:
As of January 2004, CL has been diagnosed in troops deployed in Operation Iraqi freedom. There have
been no cases of visceral leishmaniasis from Iraq. We anticipate having addition cases in troops as well
as contractors returning from the field.
References
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- Abalos FM, Klassen MK, Marty AM, Neafie RC. Brown-Hopps stain for Leishmania amastigotes. Mod Pathol.1998;11:143A.
- Azadeh B, Samad A, Ardehali S. Histological spectrum of cutaneous leishmaniasis due to Leishmania tropica. Trans R Soc Trop Med Hyg. 1985;79:631-636.
- Berman J. Current treatment approaches to leishmaniasis. Curr Opin Infect Dis. 2003;16:397-401.
- Magill AJ. Leishmaniasis. In: Strickland GT, ed. Hunter's Tropical Medicine and Emerging Infectious Diseases. 8th ed. Philadelphia, Pa: WB Saunders; 2000:665-687.
- Magill AJ, Grogl M, Gasser RA Jr, Sun W, Oster CN. Visceral infection caused by Leishmania tropica in veterans of Operation Desert Storm. N Engl J Med. 1993;328:1383-1387.
- Nelson AM, Lemons-Estes F. Protozoal and Algal Infections of the skin. In: Barnhill RL (ed). Textbook of Dermatopathology. New York, NY McGraw-Hill, 1998:457-66.
- Wortmann G, Sweeney C, Houng H, et al. Rapid diagnosis of leishmaniasis by fluorogenic polymerase chain reaction. Am J Trop Med Hyg. 2001;65:583-587.
