99m Tc-ethambutol Uptake In Case Of Leprosy Case Report.

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99m

Tc-ETHAMBUTOL UPTAKE IN CASE OF
LEPROSY
Case Report

AH Gunawan and AHS Kartamihardja
Department of Nuclear Medicine
Faculty of Medicine, Universitas Padjadjaran/Dr. HasanSadikin General Hospital,
Bandung, Indonesia

POSTER PRESENTATION
4 International Conference on Radiopharmaceutical Therapy
New World Hotel, Ho Chi Minh City, Vietnam
28 Nov – 2 Dec 2011
th

99m


Tc-ETHAMBUTOL UPTAKE IN CASE OF
LEPROSY
Case Report

AH Gunawan and AHS Kartamihardja
Department of Nuclear Medicine
Faculty of Medicine, Universitas Padjadjaran/Dr. HasanSadikin General Hospital,
Bandung, Indonesia
Abstract
Introduction:

99m

Mycobacterium

Tc--Ethambutol scintigraphy has recently been used for active
tuberculosis

infection


imaging,

both

pulmonary

and

extrapulmonary infection. Ethambutol is taken up by mycobacteria’s cell wall
based on the drug inhibitory ability on arabinosyl transferase, an essential enzyme
which is involved in polymeryzation reaction of arabinoglycan, an important
component of mycobacterial cell wall. We present a case of leprosy patient
suffering low back pain that was referred to our department.
Case: A 53-year-old females who suffered low back pain and lower limb paralysis
with unknown etiology, was referred to our department for ethambuthol
scintigraphy to investigate any tuberculosis infection. No trauma history was
recorded, neither was tuberculosis history or treatment. The patient had been
diagnosed as leprosy and being treated with multidrug of antileprosy. Prior X-ray
examination showed destructive lesions on the thoracal and lumbar spines, as well
as lytic lesion on head of the left hip bone and acetabulum. We performed an MDP

(methylene-diphosphonate) bone scintigraphy, that showed pathological uptake on
multiple thoracal and lumbar spines. The Tc-99m-Ethambuthol scintigraphy

performed two days later showed pathological uptake on multiple lumbar vertebrae
consistent with the X-Ray and bone scintigraphy result, with another additional
uptake seen on soft tissue of the left elbow.
Discussion: Leprosy is a disease affecting skin and nerves caused by M. leprae. Its
distribution is widespreading in tropical or subtropical regions, including in
Indonesia. The diagnosis is considered based on clinical signs (i.e. existence of
neurologic and cutaneous lesions) and laboratory findings (acid-fast bacilli on slitsmear or biopsy of the skin). Several years after a person afflicted with leprosy,
especially with multibacillary spectrum of this disease, bone changes can occur.
In this case, the diagnosis of Hansen’s disease had been confirmed by laboratory.
No clinical sign of skin tuberculosis was noted. Regarding to patient complaint of
back pain and lower limb weakness, bone scintigraphy was then performed during
the reactive phase of leprosy (ENL) to find any bone changes. The positive bone
scintigraphy result showed some bones/spines involvement, consistent with the
prior X-Ray result. There were not any indicator or findings that supported any
malignancies. The bone involvement was seen as osteolytic with predominantly
sclerotic


pattern in the

affected spines. This pattern could refer to

Charcot/neuropathic osteoarthropathy, a spectrum of bone or joint destructive
processes associated with neurosensory deficit. This manifestation in spine is one
of non-spesific bone changes in leprosy.
Interestingly, there was ethambutol uptake on soft tissue of the left elbow
scintigraphy showed possible uptake by M. leprae. There were no ethambutol
uptake seen in spines. This indicated that the bone changes recorded in bone

scintigraphy was not caused by direct involvement of mycobacteria, and supported
the suggestion of Charcot osteoarthropathy in the prior bone scintigraphy result.
Unfortunately, there were no further examination we could perform to ensure the
absence of direct bone invasion.
Concluding Remark: Soft tissue uptake in this case might be caused by direct
infection of Mycobacterium leprae. Bone scintigraphy can detect any bone
involvement, while ethambutol scintigraphy can detect infection caused by
mycobacteria.


Introduction
Tuberculosis (TB) is an infection disease due to Mycobacterium tuberculosis
affected not only lungs, but also other organs. This infection disease could be
totally cured if appropriate treatment with anti tuberculous drug are given, but if not
it could be lead to fatal condition within 5 years or more in more than half cases.1
TB is remains an important worldwide health problem. WHO reported in
2009, more than 5.8 million new cases of pulmonary and extra-pulmonary TB
every year. More than 95% found in developing countries. It was estimated that 1.7
million (1.5-1.9 million) patients with TB were died. Early and accurate diagnostic
have an important key in controlling TB. 1
There are many diagnostic modalities can be used to diagnose TB, but every
modality has their own advantages and disadvantages. Nuclear Medicine
technology has its role on detecting and localizing infection diseases in early stage.
This is non-invasive with high sensitivity and specificity diagnostic modality using

radionuclide.1,2
Many

radiopharmaceuticals


infection/inflammation.

can

be

used

to

detect

and

localize

67

Ga-citrate is the first radionuclide used, but this


radionuclide has disadvantages since it could not differentiated infection from
inflammation and malignant diseases. HMPAO-WBC labeled by
have been widely used, but as

67

99m

Tc or

111

In

Ga-citrate, those radiopharmaceuticals also could

not differentiated infection from sterile inflammation.

99m


Tc-ciprofloxacine was

developed to over come the problem on differentiation between infection and sterile
inflammation. Several studies showed that 99mTc-ciprofloxacine has high sensitivity
and specificity in diagnosing and localizing bacterial infection, but unfortunately it
could not differentiated between TB and non-TB infection.
99m

Tc-Ethambutol

scintigraphy has

recently

been

used

for


active

Mycobacterium tuberculosis infection imaging, in both pulmonary and extrapulmonary infection. Ethambutol is a narrow spectrum anti-tuberculous drug will
be uptaken by mycobacteria’s cell wall based on the drug inhibitory ability on
arabinosyl transferase. Arabinosyl transferase is an essential enzyme, which is
involved in polymeryzation reaction of arabinoglycan, an important component of
mycobacterial cell wall.

99m

Tc-Ethambutol is 85% labeled efficiency. It is in-vivo

and in-vitro stable binding, consistent bio-distribution and pharmacokinetic
parameter with non-labeled ethambutol and safe to be use as diagnostic modality. 2
Case
A 53-year-old females who suffered low back pain and lower limb paralysis
with unknown etiology, was referred to the Department of Nuclear Medicine Dr.
Hasan Sadikin General Hospital for ethambuthol scintigraphy to investigate any

tuberculosis infection. No history of trauma was recorded, neither was tuberculosis

history or treatment. The patient had been diagnosed as leprosy and being treated
with multidrug of antileprosy. Prior X-ray examination showed destructive lesions
on the thoracal and lumbar spines, as well as lytic lesion on head of the left femoral
bone and its acetabulum. 99mTc-MDP (methylene-diphosphonate) bone scintigraphy
was performed, that showed pathological increase tracer uptake on several thoracal
and lumbar spines. The

99m

Tc-Ethambuthol scintigraphy was performed two days

later showed pathological uptake on multiple lumbar vertebrae consistent with the
X-Ray and bone scintigraphy result, with another additional abnormal increased
tracer uptake seen on soft tissue of the left elbow.
Discussion
Leprosy is a disease affecting skin and nerves caused by M. leprae. The
distribution of this disease is widely spread in tropical or subtropical regions,
including in Indonesia. The diagnosis is considered based on clinical signs (i.e.
existence of neurologic and cutaneous lesions) and laboratory findings. Final
diagnosis is made there is evidence of acid-fast bacilli on slit-smear or biopsy of the

skin lesion. Several years after a person afflicted with leprosy, especially with
multibacillary spectrum of this disease, bone changes can occur.
In this case, there was no clinical sign of skin tuberculosis was noted. The
diagnosis of Hansen’s disease had been confirmed by laboratory.

99m

Tc-MDP bone

scintigraphy due to patient complaint of back pain and lower limb weakness. The
referring physician would like to evaluate whether bone have been involve, since
patient complain of back pain and lower limb weakness.

99m

Tc-MDP bone

scintigraphy was performed during the reactive phase of leprosy (ENL) to find any
bone changes. The positive

99m

Tc-MDP bone scintigraphy result showed some

bones/spines involvement. The abnormal locations were consistent with X-Ray
result done earlier. There were not any indicator or findings that supported any
malignancies. The bone involvement was seen as osteolytic on x-ray with
predominantly sclerotic pattern in the affected spines. This pattern could refer to
Charcot/neuropathic osteoarthropathy, a spectrum of bone or joint destructive
processes associated with neurosensory deficit.
99m

Tc-MDP bone scintigraphy is a high sensitive imaging modality base on

osteoblastic activity. Any condition follow by increase osteoblastic activity as well
as in growth plate will show increase tracer uptake. Normal increase tracer uptake
usually symetrical found in growth plate. Due to its uptake mechanism of
MDP, this imaging modality has low specificity. Since

99m

99m

Tc-

Tc-MDP bone

scintigraphy results in this case was positive in spines, but negative on on

99m

Tc-

Ethambuthol scintigraphy, then we can conclude that the manifestation of
abnormalities in spine was non-spesific bone changes related to leprosy. This
indicated that the bone changes recorded in bone scintigraphy was not caused by
direct involvement of mycobacteria, and supported the suggestion of Charcot
osteoarthropathy in the prior bone scintigraphy result.
Interestingly, there was increased tracer uptake of

99m

Tc-Ethambuthol on soft

tissue of the left elbow, the results of scintigraphy showed a possible abnormal
tracer uptake by M. leprae. Unfortunately, there was no further examination for
confirmation of abnormal finding on

99m

Tc-MDP bone scintigraphy, but negative

on 99mTc-Ethambuthol scintigraphy.
Concluding Remark
99m

Tc-MDP none scintigraphy can detect any bone involvement due to its

sensitivity, while ethambutol scintigraphy can detect infection caused by
mycobacteria. Soft tissue uptake in this case might be caused by direct infection of
Mycobacterium leprae.

References:
1. Kartini NO, Nurlaila Z, Microbiological Characterization of 99mTc-ethambutol –
labelled compounds as the Infection Imaging Radiopharmaceuticals, In:
Regional Seminar on Pharmaceuticals and Biomedicals Analysis; 2005: 15-16
September; School of Pharmacy. Institut Teknologi Bandung; 2005
2. Hussein AK, Kartini NO, Sugiharti RJ, Radionuklid

99m

Tc-ethambutol untuk

Diagnosis Tuberkulosis Extrapulmonal, MKB 2006; XXXVIII; (3); 116-21
3. James WD, Berger T, and Elston DM., Editors. Hansen’s Disease. In: Andrew’s
Diseases of Skin, 10th ed. Philadelphia, Elsevier Inc 2006,.
4. Jones EA, et al. Neuropathic Osteoarthropathy: Diagnostic Dilemmas and
Differential Diagnosis. RadioGraphics 2000; 20: S279–S293