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American Cutaneous Leishmaniasis

A Cluster of 3 Cases During Military Training in Panama


MAJ Michael Royer, MC, USA; COL Mark Crowe, MC, USA

● We present 3 cases of American cutaneous leishmaniasis ical Asia, India, Africa and the Mediterranean, and the
occurring in soldiers of a unit of US Army Rangers who New World (Americas). Old World cutaneous leishmani-
parachuted into the jungles of Panama. Shortly after re- asis is most often caused by members of the L tropica com-
turning to the United States, these 3 soldiers each devel- plex. New World cutaneous leishmaniasis is caused by or-
oped a crusted, indurated papule, which slowly enlarged ganisms of the Leishmania braziliensis complex and the
during the following 6 weeks. Routine microscopy of skin Leishmania mexicana complex.1,3 Leishmania braziliensis is ca-
biopsies revealed a dermal granulomatous inflammation pable of producing a destructive mucocutaneous form of
and a predominantly lymphoid infiltrate. Numerous histio- leishmaniasis, known as espundia.
cytes contained small oval organisms with bar-shaped par- Humans are infected with Leishmania species through
anuclear kinetoplasts, morphologically consistent with the bite of a Phlebotomus sand fly. Occasional leishmaniasis
leishmanial parasites. Cultures grew Leishmaniasis brasi- infections have been reported in Texas, but most infections
liensis, subspecies panamensis. The soldiers were treated identified in the United States have resulted from travel
with intravenous pentavalent antimonial therapy daily for to endemic areas. The incidence of leishmaniasis in the
20 days with good clinical improvement. Epidemics of United States is increasing due to international travel and
leishmaniasis occur periodically in tropical regions of the factors such as human immunodeficiency virus infection,
world, and leishmaniasis has emerged in new settings, for which may increase the pathogenicity or transmission of
example, as an acquired immunodeficiency syndrome–as- disease.2 Rapid diagnosis and effective treatment of infec-
sociated opportunistic infection. With an increasingly mo- tion with Leishmania continues to be a major challenge.
bile society, it is important to be familiar with the clinical
and histopathologic appearance of conditions such as REPORT OF CASES
leishmaniasis, which are common in tropical and subtrop- Approximately 60 US Army Rangers parachuted into the jun-
ical regions and are increasingly significant in other regions gles of Panama as part of a training exercise in November 1997.
of the world. For 2 weeks, the Rangers alternated spending 3 days out in the
(Arch Pathol Lab Med. 2002;126:471–473) jungle with 1 day in barracks. While in the jungle, they slept on
the ground or on ponchos. Insect netting and repellant were
available and used to varying degrees. The terrain was described

L eishmaniasis is a protozoal disease affecting people on


all continents, except Australia and Antarctica, and is
endemic in all tropical American countries. Estimates by
as tropical jungle with numerous streams and areas of marsh.
Within 1 to 2 weeks of returning to the United States, 3 soldiers
each developed a single crusted papule. Lesions were located on
the World Health Organization suggest that worldwide exposed areas of skin, including the temporal scalp, face, and
there are approximately 1 to 2 million new cases of leish- dorsum of the hand. The lesions slowly enlarged during the fol-
maniasis each year.1 In addition, new clinical presentations lowing 6 weeks and were evaluated by a dermatologist. At the
time of presentation, the lesions had increased in size to approx-
of Leishmania infection continue to be described. Following imately 2 cm in diameter and were indurated, erythematous, cen-
the Persian Gulf War, a viscerotropic form of Leishmania trally crusted plaques (Figure 1). No adenopathy or systemic
tropica infection was described, and acquired immunode- symptoms were noted in any of the soldiers. Tissue was obtained
ficiency syndrome–associated disease is increasingly im- by punch biopsy for histologic examination and culture on NNN
portant.2 Leishmaniasis ranges in severity from a relative- (Novy-Nicolle-McNeal) media.
ly benign, self-limiting cutaneous form to a potentially fa-
tal systemic illness. The clinical presentation and prog- PATHOLOGIC FINDINGS
nosis depends on the infecting species, the duration of Tissue was processed for histologic examination using
infection, and the host immune response. conventional methods. Histopathologic examination of he-
Leishmaniasis is broadly divided into infections ac- matoxylin-eosin–stained tissue revealed a dermal granu-
quired in the Old World regions of tropical and subtrop- lomatous inflammation with a predominantly lymphoid
infiltrate (Figure 2) and numerous, small (2–4 mm in di-
ameter), oval to round organisms with bar-shaped par-
Accepted for publication August 20, 2001.
From the Department of Anatomic and Clinical Pathology, Womack
anuclear kinetoplasts, morphologically consistent with
Army Medical Center, Fort Bragg, NC (Dr Royer); and the Dermatology leishmanial parasites (Figure 3). Cultures of tissue done
Service, Madigan Army Medical Center, Tacoma, Wash (Dr Crowe). on NNN media revealed L braziliensis panamensis in all 3
Reprints not available from the author. soldiers.
Arch Pathol Lab Med—Vol 126, April 2002 Cutaneous Leishmaniasis—Royer & Crowe 471
COMMENT
More than 20 species of Leishmania are capable of pro-
ducing disease. The clinical presentation and prognosis
differ greatly depending on the species, the duration of
infection, and the immune status of the infected person.
There are 3 general groups of clinical disease presentation
associated with Leishmania infection: cutaneous, mucocu-
taneous, and visceral. Leishmania infections are also sub-
divided into Old World and New World acquired disease.
Leishmania infections acquired in Old World and New
World regions may produce cutaneous or visceral disease,
but Leishmania species capable of producing mucocutane-
ous disease are generally restricted to the New World.1,3
Cutaneous leishmaniasis is subdivided into localized
cutaneous, disseminated cutaneous, recidivans cutaneous,
and post–kala azar (postvisceral) dermal leishmaniasis.
Localized cutaneous disease is usually restricted to ex-
posed areas of the skin, such as the face, scalp, and arms.
The lesions caused by L mexicana typically (60% of cases)
involve the earlobes and are known as ‘‘Chiclero ulcers.’’ 1
Chicle is a sap harvested by natives, called chicleros, from
wild trees in the rain forests. Chicle is used in making
chewing gum, such as Chiclets. Disseminated cutaneous
disease has been reported in both New and Old World
infections and occurs when the human immune system
does not respond to the invading parasites. Recurrent or
recidivans leishmaniasis occurs when lesions develop in
the site of prior infection, 1 to 15 years after the primary
infection. Post–kala azar dermal leishmaniasis is rare and
occurs years after recovering from visceral disease.
Mucocutaneous leishmaniasis is predominantly a New
World disease and is predominantly a disease of rural and
jungle regions. It is endemic in all tropical American coun-
tries and occurs when primary cutaneous infection with
L braziliensis subspecies braziliensis or panamensis becomes
disseminated to the upper respiratory tract. Clinically, in-
fections tend to start as chronic cutaneous ulcers. Hema-
togenous and lymphatic dissemination of the parasite can
occur after the primary infection and produce lesions in
the mucous membranes of the oral, pharyngeal, and nasal
cavities.1,3 The earliest mucosal lesion is usually character-
ized by hyperemia of the nasal septum and subsequent
ulceration. The lesion progresses to invade the nasal sep-
tum and later the paranasal fossae. Perforation of the sep-
tum with unrelenting disease involving the entire nose
and oropharynx results in severe mutilation of the mid-
face and sometimes death. There are no tests to predict
which patients will progress from localized cutaneous dis-
ease to this form of infection, know as espundia. The fre-
Figure 1. This lesion of New World (American) cutaneous leishman- quency of mucous membrane involvement is variable.
iasis was located on the dorsum of the hand and shows a characteristic Whereas in Yucatan and Guatemala it is an exception, in
centrally ulcerated plaque measuring approximately 2 cm in diameter. other countries, such as Brazil, it may occur in 80% of
Most lesions of cutaneous leishmaniasis occur on exposed areas of cases.1
skin.
Visceral leishmaniasis, also known as kala azar, is the
Figure 2. Dermal granulomatous inflammation with a predominantly most serious form of infection and has been reported to
lymphoid infiltrate is seen in this punch biopsy of a cutaneous Leish- occur in both New and Old World infections. Infections in
mania lesion (hematoxylin-eosin, low-power view 310).
these patients localize to the viscera rather than the skin,
Figure 3. Small, 2- to 4-mm, round or oval organisms with bar-shaped and parasites are found throughout the reticuloendothelial
paranuclear kinetoplasts are characteristic of leishmanial parasites. The system. As a result, patients present with fever, malaise,
kinetoplast is a rod-shaped, specialized mitochondrial structure that
contains extranuclear DNA. Numerous organisms may be seen in this hepatosplenomegaly, anorexia, wasting, pancytopenia,
high-power view (hematoxylin-eosin, original magnification 31000). and hypergammaglobulinemia. The skin is rarely in-
volved, but may show irregular areas of dark pigmenta-
tion, leading to the name kala azar, or ‘‘black sickness.’’
Untreated it frequently causes death, and epidemics have
472 Arch Pathol Lab Med—Vol 126, April 2002 Cutaneous Leishmaniasis—Royer & Crowe
killed thousands in Brazil, India, and the Sudan during granulomatous reaction. Ulcerative mucosal lesions of es-
the past 30 years.1 pundia show predominantly a nonspecific inflammatory
Following the Persian Gulf War, 12 veterans were dis- infiltrate with few or no Leishmania organisms within mac-
covered to have a viscerotropic infection with L tropica.1,4 rophages and few or no tuberculoid formations.1,5
They presented with symptoms of unexplained fever, The diagnosis of leishmaniasis can be confirmed by var-
chronic fatigue, malaise, cough, diarrhea, and abdominal ious methods. The Montenegro (leishmanin) test is an in-
pain. These cases appeared to represent a mild form of tradermal test of delayed hypersensitivity that is highly
visceral disease and did not progress to the more severe specific but is not widely available. Leishmanial organisms
form of kala azar. may be grown on NNN media. Organisms may also be
In immunosuppressed patients, particularly patients demonstrated in smears taken from an ulcer. Direct de-
positive for human immunodeficiency virus, diffuse an- tection by enzyme-linked immunosorbent assay methods,
ergic cutaneous leishmaniasis may be seen.2,5 With increas- DNA probes, and a variety of molecular methods have
ing incidence of acquired immunodeficiency syndrome in been used.3 Polymerase chain reaction can be used both
Old World countries and elsewhere, it is increasingly ap- for diagnosis and for speciation on fresh tissue or forma-
parent that blood-borne transmission of this parasite does lin-fixed tissue.6–8 Serum antibodies have been detected
occur. Transfusion-associated leishmaniasis may occur using direct agglutination tests. Advances in molecular
from blood contaminated with Leishmania parasites for up methods have the potential to lead to improved, rapid,
to 30 days of routine blood bank storage.1 field-applicable diagnostic techniques.9
Phlebotomine sand flies are the vector for Leishmania Cutaneous leishmaniasis is generally sensitive to pen-
parasites. They are smaller than mosquitoes and can pen- tavalent antimonials (Pentostam, sodium stibogluconate).9
etrate standard mosquito nets. They feed on mammalian Mucocutaneous leishmaniasis and diffuse anergic cuta-
blood, ingesting the amastigote form of Leishmania from neous leishmaniasis are often refractory to treatment. In
an infected animal. On reaching the gut of the sand fly, cases in which there is resistance or intolerance to anti-
the organism converts to a promastigote (flagellated) mony, amphotericin B or pentamidine may be used.10
form, reproduces, and migrates to the buccal cavity. These The subspecies of L brasiliensis panamensis identified in
promastigotes infect another mammal during subsequent these soldiers is known to be capable of producing mu-
feedings by the sand fly. There is activation of complement cocutaneous leishmaniasis. All soldiers were given intra-
in the new host, and the promastigotes are opsonized and venous sodium stibogluconate therapy daily for 20 days
phagocytized by macrophages. The promastigotes lose with good clinical improvement. There was no evidence
their flagella, multiply within the macrophage, and, after of recurrence during 24 months of follow-up, and the sol-
rupturing the cell, invade neighboring cells. The process diers continue to be monitored for evidence of mucocu-
continues with the development of a cellular immune re- taneous disease.
sponse and a characteristic cutaneous lesion. References
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maniasis. Dermatol Clin. 1999;17:77–92, viii.
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filtrate of mixed inflammatory cells. Organisms can be 3. Herwaldt BL. Leishmaniasis. Lancet. 1999;354(9185):1191–1199.
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Arch Pathol Lab Med—Vol 126, April 2002 Cutaneous Leishmaniasis—Royer & Crowe 473