FULL PAPER
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
thInternational Conference on Radiopharmaceutical Therapy
New World Hotel, Ho Chi Minh City, Vietnam
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 Tc--Ethambutol scintigraphy has recently been used for active Mycobacterium 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
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 slit-smear 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.
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
radionuclide.1,2
Many radiopharmaceuticals can be used to detect and localize infection/inflammation. 67Ga-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 99mTc or 111In have been widely used, but as 67Ga-citrate, those radiopharmaceuticals also could not differentiated infection from sterile inflammation. 99mTc-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 extra-pulmonary 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. 99mTc-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
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 99mTc-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
scintigraphy was performed during the reactive phase of leprosy (ENL) to find any bone changes. The positive 99mTc-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 99m Tc-MDP, this imaging modality has low specificity. Since 99mTc-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.
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 of99mTc-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 99mTc-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,.