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International Journal of Dermatology 2008, 47, 40–43 © 2008 The International Society of Dermatology
40
Abstract
Taiwan is not considered an endemic area of leishmaniasis. Imported cases are encountered
infrequently, and only two cases of indigenous cutaneous leishmaniasis have been reported. 1
We found one new case in the past 20 years. The patient presented with erythematous plaques
on the nasal bridge and right thumb. Skin biopsy specimens from both sites revealed numerous
Leishman–Donovan bodies in macrophages. There was no history of travel outside the country,
and the diagnosis of indigenous cutaneous leishmaniasis was made. Polymerase chain
reactions (PCR) identified the species as Leishmania tropica
. The route of infection in this
patient is unclear. Because pentavalent antimony, the drug of choice for leishmaniasis, is not
available in Taiwan, the patient was treated with levamisole and potassium iodide, with an
excellent response.
BlackwellPublishingLtdOxford,UKIJDInternationalJournalofDermatology0011-9059©2007The InternationalSocietyofDermatologyXXX
Tropical medicine rounds
IndigenousleishmaniasisinTaiwanWang
etal.
TROPICALMEDICINEROUNDS
Indigenous leishmaniasis in Taiwan: report of a case
Jia-Ru Wang
1
, MD
, Sho-Tone Lee
2
, PhD
, Wei-Hsin Juan
1
, MD
, Wei-Lin Chuang
2
, MS
,Shuen-Iu Hung
3
, PhD
, Wen-Hung Chung
1
, MD,
and Hong-Shang Hong
4
, MD, PhD
From the 1
Department of Dermatology, Chang
Gung Memorial Hospital, Taipei, 2
Institute of
Biomedical Sciences, Academia Sinica,
Taipei, 3
Institute of Pharmacology, National
Yang-Ming University, Taipei, 4
Chang Gung
University, Kwei-Shan Tao-Yuan, Taiwan
Correspondence
Yue-Zon Kuan, MD
Department of Dermatology
Chang Gung Memorial Hospital
199, Tun Hwa North Road
Taipei
Taiwan
E-mail: [email protected]
Introduction
Leishmaniasis is a protozoan disease caused by the parasite
Leishmania
and transmitted by infected phlebotomine sand
flies. The parasite has a digenetic life cycle shuttling between
a flagellated promastigote in the gut of a sand fly and an intra-
cellular amastigote in mammalian macrophages, which are
the obligate hosts of the parasite. The term leishmaniasisincludes cutaneous, mucocutaneous, and visceral types.
2
Case Report
In May 2005, a 57-year-old woman presented with a 1-month
history of an erythematous plaque on the nasal bridge (Fig. 1),
and a 1-week history of a papule involving her right thumb.
The lesions were mildly pruritic but not painful. The patient
had chronic diabetes mellitus and Graves disease. She has
worked as a fruit farmer on Mount Takuan in northern
Taiwan, but she had not contacted exotic fruit or traveled
outside the country. There was no history of trauma or insectbite. She had an apparently healthy dog and previously had
a dog that died from an unknown disease.
The skin lesions measured 1.2 cm and 0.5 cm in diameter,
respectively. There was no nasal deformity, lymphadenopathy,
or hepatosplenomegaly. Biopsy was obtained from the nasal
bridge lesion, and the papule of the right thumb was excised
completely. Histologic examination of both lesions revealed
multiple small granulomas on a background of heavy
lymphoplasmacytic dermal infiltrates (Fig. 2a). There were
numerous small organisms in histiocytes, compatible with
Leishman–Donovan bodies on Giemsa-stained sections
(Fig. 2b). Because the history was negative for travel outside
the country, a diagnosis of indigenous cutaneous leishmaniasis
was made.
Western blot analysis, using the patient’s serum as an
immuno-probe, showed strong reactivity to Leishmania
tropica
(BTO11) and
Leishmania infantum
(Bman), but not
to Leishmania donovani
(Jeddah) and
Leishmania major
(LH32) (Fig. 3). Total DNA was extracted from a fresh nasal
skin biopsy specimen. PCR primers [5
′
LITSR (5
′
-CTGGAT-
CATTTTCCGATG-3
′
) and 3
′
L5.8S (5
′
-TGATACCACT-
TATCGCACTT-3
′
)] were designed to amplify a 300–350-bp
region in the ribosomal internal transcribed spacer 1 (ITS1)
flanking between the genes coding for SSU and 5.8S rRNA
gene. Amplification reactions were performed in 50 μ
L
containing the following: 1.5 m
m
MgCl
2
; 200 μ
m
each of
dNTPs; 500 n
m
primers; and 2 units of Taq
DNA polymerase.
Amplification was performed by a GenAmp PCR System 9700
(Applied Biosystems) with an initial step of denaturation
for 3 min at 96 °
C, followed by 35 cycles, with each cycleconsisting of 30 s at 94 °
C, 1 min at 53 °
C, and 2 min at
72 °
C, and finally, a final extension for 5 min at 72 °
C. PCR
products were analyzed by DNA gel electrophoresis on a 2%
(wt/vol) agarose gel, stained with ethidium bromide, and
visualized on a UV transilluminator (Fig. 4). The sequencing
result was comparable with the ITS1 region of L. tropica
deposited in GenBank (accession no. AJ000301 to AJ000302).
Ketoconazole 400 mg daily for 8 weeks was prescribed
because pentavalent antimony, the drug of choice for leish-
maniasis, was not available in Taiwan. After a poor clinical
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© 2008 The International Society of Dermatology International Journal of Dermatology
2008, 47
, 40–43
41
Wang
et al. Indigenous leishmaniasis in Taiwan
Tropical medicine rounds
response to ketoconazole, subtotal excision of the nasal lesion
was performed, and systemic fluconazole 150 mg daily for
8 weeks was prescribed. However, the nasal lesion enlarged.
Levamisole hydrochloride 50 mg t.i.d. for 3 days every
2 weeks and potassium iodide 300 mg orally t.i.d. were then
prescribed. In 1 month, the lesion appeared smaller, softer,
and less erythematous.
Discussion
In 1903, Leishman and Donovan, working separately, described
the protozoan Leishmania
. Leishmaniasis is a collective
term used to describe the diseases caused by 20 Leishmania
species pathogenic to mammals. Worldwide, approximately
12 million people have leishmaniasis, with 1.5–2 million new
cases reported each year.
3
Leishmaniasis is widespread in 22
countries in the New World and in 66 countries in the Old
World. The disease is not found in Southeast Asia, except in
Vietnam; kala-azar was diagnosed in three HIV-positivewomen in Vietnam in 2002.
4
Leishmaniasis is transmitted by
the female phlebotomine sand fly. Thirty out of 500 phleboto-
mine species have been identified as vectors of the disease.
Leishmaniasis is an important infectious disease in
mainland China, especially the regions north of the Yangtze
River, such as Xinjiang, Sichuan, Gansu, Shanxi, Shaanxi,
Neimenggu, and Shandong.
5
Taiwan is not considered to be
an endemic area, and leishmaniasis was not seen in Taiwan
prior to World War II. About 100 imported cases of kala-azar
were observed in civilians and military personnel from
Figure 1 A poorly demarcated, indurated erythematous plaque
involving the nasal bridge
Figure 2 (a) Multiple small granulomas embedded in a dense
lymphoplasmacytic infiltrate, and numerous small cellular
organisms within histiocytes (hematoxylin and eosin, ×100).
(b) Giemsa-stained section demonstrates the intracellular
organisms consistent with Leishman-Donovan bodies (×400)
Figure 3 Western blot result. Serum of the patient showed no
reactivity to L. amazonensis (Promastigote) (1), L. amazonensis
(Amastigote) (2) , L. major (3) and L. donovani (4) while strong
reactivity to L. tropica (5) and L. infantum (6)
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International Journal of Dermatology
2008, 47
, 40–43 © 2008 The International Society of Dermatology
42 Tropical medicine rounds
Indigenous leishmaniasis in Taiwan
Wang
et al.
mainland China during and after the civil war. The first report
of autochthonous leishmaniasis in Taiwan was published in
1985 by John and colleagues.
1
They described two native
born aboriginal Taiwanese, with cutaneous leishmaniasis,
who were from the same village in Hsinchu County of northern
Taiwan and had never traveled far from home.
1
Although a
human-bite sand fly species
Phlebotomus kiangsuensis
had
been identified in Taiwan in 1970,
6
John and colleagues couldidentify only the sand fly Phlebotomus iyengari taiwanensis
that feeds on animals in the area. No disease was found
in other humans, dogs, cats, rodents, birds, reptiles, and
amphibians in the region.
The infectious route in our patient was not clear. Since
the possible species was L. tropica
, the source of infection
probably did not come from mainland China where kala-azar
and post-kala-azar dermal leishmaniasis are caused most
commonly by L. donovani
.
1
Because sand flies have been found
in Taiwan, physical transmission by sand flies was possible,
with village animals as a reservoir, although serum from the
patient’s dog was negative for leishmania. There probably areunrecognized autochthonous foci, such as wild animals, in
the remote mountains of Taiwan.
Treatment of leishmaniasis varies according to the infecting
species and clinical severity (Table 1). Lesions of Old World
cutaneous leishmaniasis may resolve spontaneously. Inter-
vention is necessary only in the following conditions:
cosmetically unacceptable lesions, chronic and large lesions,
mucosal disease, multiple lesions, worsening lesions, and
lesions in immunosuppressed patients.
3
Levamisole and
potassium iodide were beneficial in our patient. Levamisole is
Figure 4 Leishmania PCR result. 1: DNA extracted from skin
lesion of patient, 2: DNA extracted from normal human skin,
3: negative control
Table 1 Treatment of leishmaniasis
Category Type of treatment
Species
Old World New World
Local
treatment
Physical Cryotherapy11 L. tropica L. brasiliensis
L. ethiopica
Local heat12
Surgery
Ointment Paromomycin L. major 13 L. mexicana 14
Paromomycin with methylbenzethonium L. panamensis 15
Imiquimod16
Local infiltration Pentavalent antimony L. major 17 L. mexicana
L. tropica 18
Photodynamic therapy L. donovani 19
Systemic
treatment
Intravenous Pentavalent antimony (Sodium stibogluconate) L. major L. guyanensis
L. tropica L. panamensis
L. donovani L. brasiliensis
Pentamidine L. guyanensis 20
Amphotericin B1
Oral Ketoconazole L. major 21 L. Mexicana 22
L. panamensis 23
Fluconazole L. major 24
(no response to L. tropica 25)
Other: Rifampin26; Dapsone1; Allopurinol1;
Pentoxifiline27; Miltefosine28
Immunotherapy Vaccination29
Interferone-γ 30
Other Sitamaquine (WR6026)31
Phytotherapy32
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43Wang et al. Indigenous leishmaniasis in Taiwan Tropical medicine rounds
a levo-isomer of tetramisole, a potent antihelmintic agent. In
1971, its immunomodulatory effects were documented.7
Levamisole is capable of inducing T-cell differentiation and
restoring depressed effector function of peripheral lymphocytes
and phagocytes. Potassium iodide is used to treat inflammatory
dermatoses such as Sweet’s syndrome, erythema nodosum,subacute nodular migratory panniculitis, and some cutane-
ous infection,9 but its mechanism of action is unknown. These
drugs also may be useful in other countries where pentavalent
antimony is unavailable. More data are needed to establish
the roles of levamisole and potassium iodide in the treatment
of leishmaniasis.
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