Cutaneous leishmaniasis

Abstract

p> ABSTRACT

Leishmaniasis is considered to be zoonotic disease, caused by a protozoan parasite of the genus Leishmania, and transmitted by a bite of infected female sandfly. Primary cutaneous leishmaniasis is not common disease in Nepal, however, there were cases reported from Terai region of Nepal. The patients with cutaneous leishmaniasis present with a papule or nodule at the site of inoculation, followed by formation of crusts. Differential diagnoses of cutaneous leishmaniasis include variety of skin diseases, inflammatory like impetigo, eczema, or granulomatous like sarcoidosis, lupus vulgaris, to skin tumor like basal cell carcinoma & squamous cell carcinoma. There are various procedures and laboratory techniques used to diagnose leishmaniasis. Punch skin biopsy is widely used & popular technique to diagnose cutaneous leishmaniasis. Different drugs like sodium stibogluconate, sodium antimony gluconate, Amphotericin B and Miltefosine: are used for its treatment. No vaccines are available for prevention. </p

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Journal of
of Nepal
PATHOLOGY
www.acpnepal.com
Journal of Pathology of Nepal (2017) Vol. 7, 1212 -
Review Article
Cutaneous leishmaniasis
Leishmaniasis is considered to be zoonotic disease, caused by a protozoan parasite of the genus
Leishmania, and transmitted by a bite of infected female sandy. Primary cutaneous leishmaniasis is not
common disease in Nepal, however, there were cases reported from Terai region of Nepal. The patients
with cutaneous leishmaniasis present with a papule or nodule at the site of inoculation, followed by
formation of crusts. Differential diagnoses of cutaneous leishmaniasis include variety of skin diseases,
inammatory like impetigo, eczema, or granulomatous like sarcoidosis, lupus vulgaris, to skin tumor like
basal cell carcinoma & squamous cell carcinoma. There are various procedures and laboratory techniques
used to diagnose leishmaniasis. Punch skin biopsy is widely used & popular technique to diagnose
cutaneous leishmaniasis. Different drugs like sodium stibogluconate, sodium antimony gluconate,
Amphotericin B and Miltefosine: are used for its treatment. No vaccines are available for prevention.
ABSTRACT
Adhikari Ram Chandra1, Shah Mahesh2
1Department of Pathology, Tribhuvan University Teaching Hospital, Maharajgunj, Kathmandu, Nepal.
2Department of Dermatology, Anandban Leprosy Hospital, Lalitpur, Nepal
INTRODUCTION
At the turn of nineteenth century, Cunningham, Borovsky,
Leishman, Donovan, Wright, Lindenberg and Vianna
each independently identied the parasite that causes
leishmaniasis.1 In 1903, the term “Leishmania” was
coined by Ronald Ross.2 Carini identied leishmania in
mucosal lesions of patients with leishmaniasis in Brazil
in 1912. Bramachari described Post Kala-azar dermal
leishmaniasis (PKDL) in India in 1922. Thereafter the
clinical and geographical features of the human disease
were supplemented by other studies.
Leishmaniasis is considered to be zoonotic disease,
encountered in endemic areas in dogs, wild rodents or other
mammals. It is caused by a protozoan parasite of the genus
Leishmania, and transmitted by a bite of infected female
sandy of the genus phlebotomus in the old world and the
genus Lutzomyia in the new world.3 The disease is prevalent
in 98 countries and regions of the world and responsible for
increasing health problems.4,5
Keywords:
Granulomatous;
Kala-azar;
Papulo-nodular;
Skin
1217
DOI : 10.3126/jpn.v7i2.18031
Correspondence:
Dr. Ram Chandra Adhikari, MBBS,MD
Professor, Department of Pathology
Tribhuvan University Teaching Hospital, Maharajgunj, Kathmandu, Nepal.
ORCID ID:0000-0002-1605-2898
Email: rcadhikari@hotmail.com
Reveived : July 1st, 2017 ; Accepted : August 9th, 2017; Published : September 1, 2017
Citation: Adhikari RC, Shah M. Cutaneous leishmaniasis. J Pathol Nep. 2017;7: 1212-7. doi:
10.3126/jpn.v7i2.18031
Copyright: This is an open-access article distributed under the terms of the Creative Commons
Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original author and source are credited.

1213
Nepal is an endemic zone for visceral leishmaniasis and
L. donovani is endemic in south Asian countries like
Nepal, India, Bangladesh and in east African countries like
Ethiopia, Kenya and Sudan.6 So, there are series of cases
of Post-Kala-azar dermal leishmaniasis (PKDL) reported
from Nepal.7,8 Primary cutaneous leishmaniasis is not
common disease in Nepal, however, there were few cases
reported from Terai region of Nepal.9,10 Here cutaneous
and muco-cutaneous leishmaniases are discussed. Visceral
leishmaniasis is not included as the scope of this article.
DISCUSSION
Several leishmanial species (21 species) are responsible for
leishmaniasis in humans. (Table 1).
Leishmania is clinically classied in 3 forms.
Visceral leishmaniasis
Cutaneous leishmaniasis
Muco-cutaneous leishmaniasis
Cutaneous leishmaniasis
The clinical features of cutaneous leishmaniasis tend to
vary between and within regions due to different species
of Leishmania. The patients with cutaneous leishmaniasis
do not show visceral manifestation. A classical lesion starts
as a papule or nodule at the site of inoculation, followed by
formation of crusts (g. 1).
Cutaneous leishmaniases are of following types.
Old world cutaneous leishmaniasis:
It is usually caused by L. major, L. tropica, and L. aethiopica.
Cutaneous leishmaniasis caused by L. major is found in
central Asia, Middle east, North Africa, North India and
Pakistan. There are few reports from Nepal and authors have
also seen cases of cutaneous leishmaniasis (g.1). Multiple
inammed lesions are seen on the nose, lips and limbs. In
our experience, common locations are nose, thigh and arms.
Cutaneous leishmaniasis caused by L. tropica produces
painless dry ulcers of the skin on the face, feet, legs and
arms. Children are usually affected and this disease is
prevalent in Afghanistan, Greece, North India, Iran, Iraq,
Israel, Kuwait, Lebanon, Morocco, Pakistan, Saudi Arabia,
Syria, Tunisia and Turkey.2
Leishmaniasis recidivans (LR) also known as lupoid or
tuberculoid leishmaniasis is also caused by L. tropica and
characterized by slowly progressive skin lesion on the face.
Cutaneous leishmaniasis caused by L. aethiopica gives rise
to small cutaneous lesion on the face. Ulceration is absent.
Rarely this type of leishmaniasis may distort the nostrils and
lips. Diffuse cutaneous leishmaniasis results from specic
deciency of cell-mediated immunity to leishmania antigen.
It is caused by L. aethiopica and reported from Ethiopia and
Kenya. It starts with single lesion and spreads over the face,
extremities and whole body.
In Nepal, cutaneous leishmaniasis is caused by L. tropica9
and L. major11 reported from Dharan (eastern part of Nepal).
Nepalese cutaneous leishmaniasis presented with inltrating
erythematous plaque with ill-dened border and extensive
crusting (g.1). Ulceration is noted in some cases. These
lesions were localized in face & neck region12, however
other sites like wrist, leg and arm are also involved.
New world cutaneous leishmaniasis:
Multiple leishmania species cause wide range of clinical
features in South and Central America. A substantial
proportion of infections are asymptomatic. The clinical
forms are localized, disseminated, diffuse and atypical
cutaneous and muco-cutaneous leishmaniasis. Localized
cutaneous leishmaniasis is caused by multiple species of
both the Leishmania and Viannia subgenera. Cutaneous
lesions are characterized by macule at the site of inoculation,
followed by papule that ulcerates. Lymphadenitis may be
seen especially when it is caused by Vianna subgenus.
Post Kala-azar dermal leishmaniasis (PKDL):
It is caused by L. donovani and common in East Africa and
on the Indian subcontinent, where upto 50% and 10% of
patients with Kala-azar develop PKDL respectively. The
lesion develops about 1 to 2 years after recovery from
visceral leishmaniasis. Though visceral leishmaniasis is
endemic in Nepal, the systematic epidemiological data on
PKDL are still lacking.
The PKDL lesions are of 3 types:
a. Macular & hypopigmented lesion
b. Erythematous patch
c. Nodules
These lesions do not ulcerate. Based on study done by
Garg VK et al,8 Nepalese PKDL is more common in males
(59%) than females (41%) and these patients presented with
hypopigmented macules, papules, plaques or nodules. These
lesions were of variable sizes and distributed symmetrically
over face, trunk and extremities. Oral mucosa & nasal
mucosa involvements were also noted.
Muco-cutaneous leishmaniasis:
Muco-cutaneous leishmaniasis is caused by L. braziliensis
and L. panamensis. Most cases are reported from Bolivia,
DOI : 10.3126/jpn.v7i2.18031
Cutaneous leishmaniasis

1214
Brazil and Peru. There are two phases, a primary cutaneous
lesion, sometimes followed by a secondary mucosal
involvement. Nasal mucous membranes, pharynx, larynx
and upper lip are involved. We have no experience about
this type of leishmaniasis and there are no reports published
in the literature from Nepal.
Leishmania and HIV infection
HIV and leishmania reinforce each other. Visceral
leishmaniasis is more likely to develop in HIV-positive
patients. In severely immunocompromised patients,
gastrointestinal tract, peritoneum, pleura & lung may be
infected. These patients show multiple, polymorphic &
relapsing lesions.
Differential diagnosis of cutaneous leishmaniasis
Skin lesions of cutaneous leishmaniasis may clinically
mimic variety of skin diseases, inammatory like impetigo,
eczema, or granulomatous like sarcoidosis, lupus vulgaris,
to skin tumor like basal cell carcinoma & squamous cell
carcinoma.
Uzun et al13 reported a patient with an uncommon cutaneous
leishmaniasis lesion that clinically resembled allergic
contact dermatitis. Unusual clinical forms of cutaneous
leishmaniasis have been reported including the palmoplantar
form, chancriform lesion at the glans penis and penile shaft,
zosteriform lesions at the trunk, erysipeloid form at the
upper lip and adjacent cheek, annular form at the penile shaft
and acute paronychial forms at the nail folds and ngers.
Akman et al14 have observed cutaneous leishmaniasis cases
that mimicked erysipelas, rosacea, hydroa vacciniforme,
eczema, leg ulcer, sarcoidosis, discoid lupus erythematosus,
leprosy, drug eruption, lupus vulgaris, basal cell carcinoma
and squamous cell carcinoma. Akcali C et al15 and Oetken
T et al16 also reported cases of cutaneous leishmaniasis
that mimicked squamous cell carcinoma clinically. Table
2 shows the list of differential diagnoses of cutaneous
leishmaniasis based on clinical ground.
It has been suggested that cutaneous leishmaniasis may
be a “great imitator” in the regions where cutaneous
leishmaniasis is endemic.
Laboratory diagnosis
There are various procedures and laboratory techniques
used to diagnose leishmaniasis.
Slit skin smear test: The affected area of the skin is cleaned
Table 1: Leishmania found in humans1
Subgenus L.(Leishmania) L.(Leishmania) L.(Viannia) L.(Viannia)
Old World L. donovani
L. infantum
L. major
L. tropica
L. killicki
L. aethiopica
L. infantum
New World L. infantum
L. infantum
L. mexicana
L. pifanoi
L. venezuelensis
L. garnhami
L. amazonensis
L. braziliensis
L. guyanensis
L. panamensis
L. shawi
L. naif
L. lainsoni
L. lindenbergi
L. peruviana
L. colombiensis
L. braziliensis
L. panamensis
Principal tropism Viscerotropic Dermotropic Dermotropic Mucotropic
DOI : 10.3126/jpn.v7i2.18031
Table 2: Clinical differential diagnoses of Cutaneous Leishmaniasis15
Erysipelas Wegener’s granulomatosis Sarcoidosis Keloid
Kerion Tuberculosis cutis Rosacea Jessner’s lymphocytic inltrate
Impetigo Syphilitic gummata Swimming pool granuloma Lupus vulgaris
Furuncle Yaws Foreign body granuloma Basal cell carcinoma
Ecthyma Pyogenic granuloma Granuloma faciale Keratoacanthoma
Wart Blastomycosis Eczema Squamous cell carcinoma
Insect bite Histoplasmosis Hydroa vacciniforme Lymphocytoma cutis
Orf Paracoccidiomycosis Leg ulcer Leukaemia
Psoriasis Sporotrichosis Discoid lupus erythematosis Lymphoma
Molluscum contagiosum Chromoblastomycosis Drug eruption Cutaneous metastases
Adhikari RC et al.

1215
and squeezed rmly between the index nger & thumb to
give 3-4 mm incision of 3 mm depth. Then slit smear is
made for Giemsa staining and demonstration of leishmania
species.
Touch imprint test: This technique is suitable for ulcerative
lesion and imprints are prepared directly from ulcer after
cleaning it. Then Giemsa staining is performed to examine
leishmania.
Skin punch biopsy: This is most widely used technique to
diagnose cutaneous leishmaniasis in Nepal.
H&E section reveals granulomatous inltrate in the dermis.
In some cases, the entire dermis is diffusely inltrated by
lymphocytes & histiocytes with ill-formed granulomas,
while discrete granulomas may be encountered in other
cases. In our experience, amastigotes of leishmania are found
in the upper dermis within the cytoplasm of macrophages
(g.2). The overlying epidermis is usually hyperplastic.
Differential diagnoses include other granulomatous disease
of the skin like lupus vulgaris, sarcoidosis, fungal infection,
leprosy etc. However presence of amastigotes rules out most
of these diseases. The spores of Histoplasma capsulatum
may mimic amatigotes of leishmania. PAS stain is used
to differentiate them as spores of Histoplasma are PAS
positive and amastigotes of leishmania are PAS negative.
Immunohistochemistry can be used for conrmation of the
diagnosis.
Fine needle aspiration cytology (FNAC): We have
no experience about FNAC diagnosis of leishmaniasis.
However, nodular and indurated lesions are subjected to ne
needle aspiration and cytological examination may reveal
amastigotes of leishmania. There are several case reports
emphasizing the role of FNAC in diagnosis of cutaneous
leishmaniasis.17-19 Cytology smears reveal granuloma
with intracellular as well as extracellular amastigotes of
leishmania. The following system of grading of parasites
used for splenic punctures20 can be used for cytology smears
if required. Authors have used this grading system to assess
parasitic load in punch biopsy sections.
The average amastigote density is graded as follows.
6+: >100 parasites per eld (viewed with a 10x eyepieces
and 100x oil-immersion lens)
5+: 10-100 parasites per eld
4+: 1-10 parasites per eld
3+: 1-10 parasites per 10 elds
2+: 1-10 parasites per 100 elds
1+: 1-10 parasites per 1000 elds
0: 0 parasites per 1000 elds
Culture: Skin biopsy specimen can be subjected for culture
in following media:21
a. Modied Nicole-Novy-McNeal (NNN) medium
b. Modied NNN medium plus RPMI 1640 medium and
10% heat inactivated fetal bovine serum (HIFBS)
c. Modied NNN medium plus medium 199 and 10%
HIFBS
d. RPMI 1640 medium plus 30% HIFBS
e.Schneider’s Drosophilia medium plus various
concentration of HIFBS.
PCR for characterization of causative organisms: DNA
extracted from cultured organisms can be used for PCR to
identify the species of leishmania.
TREATMENT
Following antileishmanial drugs are used for the treatment
of cutaneous leishmaniasis.
Figure 1: Clinical picture of cutaneous
leishmaniasis. Erythematous plaque with
crusting over nose.
Figure 2: Skin biopsy, showing numerous
intracellular amastigotes of Leishmania
species. (HE stain, X1000).
DOI : 10.3126/jpn.v7i2.18031
Cutaneous leishmaniasis

1216
Pentavalent antimonials:
Intralesional inltration of 1-5 ml (100 mg/ml) sodium
stibogluconate (SSG) can be given to patients with cutaneous
leishmaniasis on alternate days for three days once a month
and this results in complete healing by the end of second
month in most cases.21 A larger dose and > 3 schedules
were needed for multiple and larger lesions. Sharma et
al used intramuscular SSG (800 mg/day) in addition to
intralesional SSG in multiple lesions.21 The alternative drug
is meglumine antimoniate, which is considered to be rst
line choice of drugs in Ecuador.3 In Nepal, PKDL patients
are treated with an intramuscular injection of sodium
antimony gluconate (20 mg/Kg/day) for a period ranging
from 30 to 72 days.8 There are issues of drug resistance and
in Nepal, SSG resistant cases of visceral leishmaniasis were
documented.22,23 So far, this issue was not reported from
Nepal in cutaneous leishmaniasis.
Amphotericin B:
Inj. Amphotericin B in a dose of 25 mg in 5% dextrose can
be administered intravenously 6 hourly with a total dose
of 1980 mg. One of our patients received this therapy with
dramatic improvement and no recurrence is noted till now.
Miltefosine:
Miltefosine is prescribed in a dose of 50 mg thrice a day
for 28 days. One of our patients received Miltefosine with
dramatic improvement and no recurrence till now.
Control of leishmaniasis
There are no organized efforts to control cutaneous
leishmaniasis in Nepal. The disease is prevalent in Terai
region of Nepal and there are cases from hilly region of
Nepal as well. The patients from hilly region have travel
history to India or Terai region of Nepal. The true burden of
this disease in Nepal is not known. In neighboring countries
like India, Bangladesh & Srilanka it represents a major
health problem as in Nepal with case burden as high as
21 cases per 10,000 populations.24-26 There were attempts
to control leishmaniasis in Indian subcontinent24 and
collective efforts in future can bring positive results.
Prophylactic vaccines
There is no vaccine for general use against leishmaniasis.
However, intradermal inoculation of live virulent L.
major promastigotes from a fresh culture has been used
intermittently for many years to protect against L. major
infection.1
CONCLUSION
Case reports and case series published in the literature
indicate that the cutaneous leishmaniasis is a disease
prevalent in Nepal, though its true burden is not known.
Dermatologists should be aware of this disease and it should
be kept as one of the differential diagnoses while suspecting
granulomatous or malignant disease of the skin. Pathologists
should search for amastigotes of leishmania when vague or
discrete granulomas are present in skin biopsies.
Conict of Interest: None
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Cutaneous leishmaniasis