Abstract Introduction Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment. Case presentation A 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-clonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics. Conclusion The patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.</p

Bimal, Sanjiva

Das, Pradeep

Das, Vidyanand R

Kumar, Nawin

Lal, Chandra S

Pandey, Krishna

Siddiqui, NA

Singh, Dharmendra

Sinha, Prabhat K

Topno, Roshan K

Verma, Neena

Verma, Rakesh B

English

PubMed

Abstract Introduction Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires life long treatment. Case presentation A 15-year-old Indian patient, presented to the outpatient department of our institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-clonic convulsions since childhood. The clinical and laboratory findings suggested visceral leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics. Conclusion The patient responded well and in a follow up six months after presentation, she was found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of diseases is difficult.</p

Pandey Krishna

Sinha Prabhat K

Das Vidyanand R

Kumar Nawin

Bimal Sanjiva

Verma Rakesh B

Verma Neena

Lal Chandra S

Topno Roshan K

Siddiqui NA

Singh Dharmendra

Das Pradeep

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Journal of Medical Case Reports

Tuberous sclerosis with visceral leishmaniasis: a case report

Krishna Pandey

Prabhat K Sinha

Vidyanand R Das

Nawin Kumar

Sanjiva Bimal

Rakesh B Verma

Neena Verma

Chandra S Lal

Roshan K Topno

NA Siddiqui

Dharmendra Singh

Pradeep Das

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Springer - Publisher Connector

Case report
Open Access
Tuberous sclerosis with visceral leishmaniasis: a case report
Krishna Pandey1*, Prabhat K Sinha1, Vidyanand R Das1, Nawin Kumar1,
Sanjiva Bimal2, Rakesh B Verma1, Neena Verma3, Chandra S Lal4,
Roshan K Topno5, NA Siddiqui5, Dharmendra Singh6 and Pradeep Das6
Addresses: 1Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research),
Agamkuan, Patna - 800 007, Bihar, India
2Department of Immunology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan,
Patna - 800 007, Bihar, India
3Department of Pathology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan,
Patna - 800 007, Bihar, India
4Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan,
Patna - 800 007, Bihar, India
5Department of Epidemiology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan,
Patna - 800 007, Bihar, India
6Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan,
Patna - 800 007, Bihar, India
Email: KP* - drkrishnapandey@yahoo.com; PKS - pksinha18@yahoo.com; VRD - drvnrdas@yahoo.com; NK - drnawinkumar@gmail.com;
SB - drsbimal@yahoo.com; RBV - rbihariverma@yahoo.com; NV - verma_neena@yahoo.com; CSL - drcslal@sify.com;
RKT - roshanktopno@yahoo.com; NAS - niyamatalisiddiqui@yahoo.com; DS - singhd72@yahoo.co.in; PD - drpradeep.das@gmail.com
*Corresponding author
Received: 20 December 2008 Accepted: 28 March 2009 Published: 8 September 2009
Journal of Medical Case Reports 2009, 3:9027 doi: 10.4076/1752-1947-3-9027
This article is available from: http://jmedicalcasereports.com/jmedicalcasereports/article/view/9027
© 2009 Pandey et al.; licensee Cases Network Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introduction: Visceral leishmaniasis, a tropical infectious disease, is a major public health problem in
India. Tuberous sclerosis, a congenital neuro-ectodermosis, is an uncommon disease which requires
life long treatment.
Case presentation: A 15-year-old Indian patient, presented to the outpatient department of our
institute with a high-grade fever for two months, splenomegaly and a history of generalized tonic-
clonic convulsions since childhood. The clinical and laboratory findings suggested visceral
leishmaniasis with tuberous sclerosis. The patient was treated with miltefosine and antiepileptics.
Conclusion: The patient responded well and in a follow up six months after presentation, she was
found free of visceral leishmaniasis and seizures. Diagnosis and treatment of this rare combination of
diseases is difficult.
Page 1 of 4
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Introduction
Leishmania donovani, is a protozoan parasite that causes
visceral leishmaniasis (VL) in India. The disease is
transmitted by the bite of infected female sand flies
(phlebotomus argentipes). About 350 million people are
at risk worldwide with an estimated prevalence of
2.5 million and incidence of 0.5 million new cases every
year. India, Nepal, Bangladesh, Sudan and Brazil account
for 90% of the cases worldwide. Bihar accounts for about
80% of the total Indian cases. The disease affects those
from a lower socio-economic background and it is
estimated that about 90% of people with VL earn less
than $2 a day [1].
Tuberous sclerosis is an example of a phakomatosis as are
neurofibromatosis, Sturge-Weber syndrome and Von
Hippel-Lindau disease, among others. These diseases are
known to have autosomal dominant hereditary transmis-
sion as well as involvement of organs of ectodermal origin,
such as the nervous system, the eyes and the skin. Slow
evolution of lesions in childhood and adolescence,
tendency to form hamartomas and a pre-disposition to
malignant transformation are also characteristic. The
disease is transmitted as an autosomal dominant trait
and has a prevalence of 1 in 20,000 to 1 in 30,000 [2].
Case presentation
A 15-year-old girl of Indian origin born to non-con-
sanguineous parents presented to our outpatient depart-
ment in Feb. 2007. She had two younger brothers who
were asymptomatic. She presented with fever of 39∞C
along with chills of two months duration with weakness
and malaise. The fever had not responded to antimalarials
or antibiotics. The patient also complained of repeated
episodes of generalized tonic-clonic convulsions since
childhood. She hadmultiple acne-like spots on the cheeks.
The patient’s mother complained that the child was very
weak in studies and had failed to pass class eight at school
three times. On clinical examination, her weight was
45 kg, pulse rate 120/min, respiratory rate 22/min and
blood pressure 110/70mmHg in the left arm in the supine
position. She appeared pale but had no jaundice, cyanosis,
clubbing or lymphadenopathy. Chest examination and
cardiovascular system examination were normal. An
abdominal examination revealed the liver to be about
2 cm and the spleen about 4 cm below the respective costal
margin in the mid-axillary line.
The patient’s face was covered with acne like patches
(adenoma sebaceum) which had persisted for the last
12 years. The patient’s mother apparently thought that this
might have been due to an allergic drug reaction. Her back
was examined for a shagreen patch and freckles were
present in the lumbosacral region. The neurological
examination was otherwise normal.
Laboratory examination
The total count was 4200/mm3 with hemoglobin of
7.5 gm/dl. The platelet count was 100,000/mm3. The renal
and liver function tests were within normal limits. The
prothrombin time was 3 seconds above the normal limit
of control of 12 seconds. Splenic aspiration was performed
and amastigotes of Leishmania donovani (LD, 2+ according
to WHO criteria) were found. A chest X-ray of the
posteroanterior view, an electrocardiogram and echocar-
diography were normal. Ultra sonography of the abdomen
showed hepatosplenomegaly. Electroencephalogram
showed irregular dysrhythmic bursts of high voltage spikes
and slow waves bilaterally. Computed tomography (CT)
scan of the brain showed multiple subependymal periven-
tricular calcified lesions. A chromosomal examination was
not carried out. The eye examination conducted by an
ophthalmologist was normal.
Considering the above facts, and the clinical triad of
mental retardation, epilepsy and adenoma sebaceum, a
diagnosis of tuberous sclerosis with visceral leishmaniasis
was made. Treatment was initiated with miltefosine
capsules (50 mg) twice daily after meals for 28 days. She
was also started on iron supplements and 300 mg tablets
of the anti-epileptic phenytoin sodium at bed time were
prescribed. After one month her platelet count was
normal. The spleen regressed and no LD bodies were
demonstrated in the bone-marrow aspirate. She had no
Figure 1. Computerized tomography (CT) of the brain
showing bilateral subependymal periventricular tubers.
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Journal of Medical Case Reports 2009, 3:9027 http://jmedicalcasereports.com/jmedicalcasereports/article/view/9027
fever and appeared cheerful. The patient was told to
continue taking iron and folic acid supplements along
with phenytoin sodium. One month after presentation,
there was no fever; her spleen and liver were not palpable
and she did not have any seizures. She was told to
continue taking phenytoin sodium, indefinitely. The
patient was free from VL and seizures at six month
follow-up.
Discussion
Our case report describes a rare combination of tuberous
sclerosis and visceral leishmaniasis. VL has a high
prevalence in India, particularly in eastern states like
Bihar, Bengal and Eastern Uttar Pradesh. The diagnosis
and management of this disease is difficult. However,
newer diagnostic tools like the rK39 strip test (which has a
sensitivity and specificity close to 98%) can be applied in
field conditions [3]. This, along with splenic and bone
marrow aspiration and other sophisticated tests like the
direct agglutination test (DAT) and nested polymerase
chain reaction (PCR) can be help in making a diagnosis.
Regarding management, sodium antimony gluconate is
developing resistance and a response rate of less than 40%
has been reported in Bihar [4]. Pentamidine use has been
stopped of late particularly because of multiple toxic
effects such as diabetes and anaphylactic shock. Ampho-
tericin B can be an effective drug but requires hospital
admission and monitoring particularly for hypokalaemia
and nephrotoxicity.
Miltefosine can be given orally and has a cure rate of about
95% with limited toxicity - mainly gastrointestinal
according to the observations of Phase III and Phase IV
trials at our institute and other clinical centres of Bihar
[5,6]. Sitamaquine, another oral drug, is being tried but
is still at Phase II. Injectable aminoglycosides, namely
paromomycin, has completed Phase III trial and its Phase
IV clinical trial is in progress. This drug has a cure rate of
about 95% [7]. Miltefosine and Amphotericin B appear to
be the best available drugs for VL therapy at present.
Miltefosine has been recommended for use in the VL
elimination program in India at pilot level by the Central
Government. However, being a teratogenic drug, its use is
limited in pregnant women.
Tuberous sclerosis is an autosomal dominant disorder
caused by mutation in either of the two genes TSC1
(located on chromosome 9q34) or TSC2 (located on 16p
13.3). In about 50% of these cases there are grey or yellow
plaques (gliomatous tumors) in the retina or optic disc
(phakoma), as well as renal hamartomas. Rhabdomyomas
are present in the heart in at least 50% of cases. In about
90% of cases, congenital hypomelanotic macules, or “ash
leaf” lesions, can occur on the skin which can be identified
by Wood’s lamp examination. About 90% of these
patients present with adenoma sebaceum on the cheek
with a shagreen patch on the lumbosacral region.
The diagnosis was based on the above mentioned features,
as well as family history although chromosomal analysis
was not done. Death often occurs due to conduction
defects in the heart, intractable epilepsy and renal failure
or malignant transformation. The TSC2 gene has been
associated with polycystic kidney disease. Positron
emission tomography (PET) scanning with 2-deoxy-2-
[F-18]fluoro-D-glucose can assess the full extent of
functional brain abnormality in tuberous sclerosis [8].
The use of alpha (C) methyl-L-tryptophan PET has proved
to be a useful tool in the identification of epileptogenic
tubers and improves the outcome of surgery for epilepsy in
tuberous sclerosis [9].
Various drugs have been used to treat epilepsy but the
disease is usually resistant. Levetiracetam was found to
have good results [10]. Antiepileptic treatment has to be
taken indefinitely. A multi-disciplinary treatment
approach has to be undertaken for lesions in the other
organs like the kidneys, heart and eyes including surgery
for cerebral tubers and subependymal nodules. The drug
interactions between various antileishmanial drugs, in this
case miltefosine, with antiepileptics like phenytoin
sodium (potential enzyme inducers) need to be taken
into consideration.
Conclusion
The diagnosis and management cost of this combination
of diseases is beyond the means of poorer patients,
particularly because treatment has to be given for life,
especially in case of intractable epilepsy. This can require
costly stereotactic brain surgery.
Abbreviations
CT, computed tomography; DAT, direct agglutination test;
LD, Leishmania donovani; PCR, polymerase chain reaction;
PET, positron emission tomography; VL, visceral
leishmanisis.
Consent
Written informed consent for publication of this case
report and accompanying images was obtained from the
patient’s father, as the patient was a minor. A copy of the
written consent is available for review by the Editor-in-
Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Page 3 of 4
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Journal of Medical Case Reports 2009, 3:9027 http://jmedicalcasereports.com/jmedicalcasereports/article/view/9027
Authors’ contributions
KP recorded the patient data and performed clinical
examination and management of the patient. PKS,
VNRD, NK and RKT helped in case management. SB,
NV, CSL and DS did the immunological, pathological,
biochemical and molecular profile of the patient respec-
tively. RBV, NAS and PD were the major contributors in
writing the manuscript. All authors read and approved the
final manuscript.
Acknowledgement
The authors wish to acknowledge the sincere efforts of Sri
Santosh Kumar Singh, laboratory technician, Sri Brijnath
Prasad and Sri Naresh Kumar Sinh for the great help
rendered by them in preparation of the manuscript.
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Tuberous sclerosis with visceral leishmaniasis: a case report

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