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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



© 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)



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



© 2008 The International Society of Dermatology International Journal of Dermatology 2008, 47, 40–43

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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