|Year : 2012 | Volume
| Issue : 3 | Page : 364-366
Primary disseminated extrapulmonary multidrug resistant tuberculosis
SK Das, A Das, A Gangopadhyay, AK Sinha
Department of Respiratory Medicine, Medical College, Kolkata - 700 073, West Bengal, India
|Date of Submission||03-Jan-2012|
|Date of Acceptance||21-Feb-2012|
|Date of Web Publication||8-Aug-2012|
S K Das
Department of Respiratory Medicine, Medical College, Kolkata - 700 073, West Bengal
Source of Support: None, Conflict of Interest: None
Disseminated tuberculosis is a common mode of presentation of tuberculosis in patients both with and without HIV/AIDS in India. However, primary multidrug resistance in disseminated tuberculosis involving only the extrapulmonary sites in an immunocompetent adult is rare. Here, we report a case of a 19-year-old man who had disseminated tuberculosis involving left pleura, pericardium, peritoneum and intraabdominal lymph nodes. He was initially taking WHO category I antituberculous drugs, but was not responding in spite of 5 months of chemotherapy. Culture of the pleural biopsy specimen grew Mycobacterium tuberculosis which was resistant to isoniazid and rifampicin. He was put on therapy for multidrug resistant tuberculosis,following 24 months of chemotherapyhe had an uneventful recovery.
Keywords: Disseminated tuberculosis, extrapulmonary tuberculosis, multidrug resistance, primary resistance
|How to cite this article:|
Das S K, Das A, Gangopadhyay A, Sinha A K. Primary disseminated extrapulmonary multidrug resistant tuberculosis. Indian J Med Microbiol 2012;30:364-6
|How to cite this URL:|
Das S K, Das A, Gangopadhyay A, Sinha A K. Primary disseminated extrapulmonary multidrug resistant tuberculosis. Indian J Med Microbiol [serial online] 2012 [cited 2019 Dec 14];30:364-6. Available from: http://www.ijmm.org/text.asp?2012/30/3/364/99509
| ~ Introduction|| |
Tuberculosis (TB) is broadly divided into two categories according to the site of involvement. TB involving only the lung parenchyma is called pulmonary TB, while TB of organs other than the lungs is called extrapulmonary TB. Disseminated TB refers to concurrent involvement of at least two non-contiguous organ sites of the body or involvement of the blood or bone marrow by tuberculous process. 
Drug resistance in TB develops due to genetic mutation that makes a drug ineffective against the mutant bacilli. Spontaneous mutation causing resistance to isoniazid occurs in about 1 in 10 6 replications while that causing rifampicin resistance occurs in 1 in 10 8 replications. So, spontaneous mutation causing resistance to both isoniazid and rifampicin would be 1 in 10 14 replications.  As this number of bacilli is rarely present even in extensive cavitary pulmonary TB, the chance of spontaneous development of multidrug resistant TB (MDR-TB) (defined as resistance to both isoniazid and rifampicin with or without other drugs) is very remote.  MDR-TB occurring in extrapulmonary sites is very rare because of paucity of the bacilli.  MDR-TB is basically a manmade problem produced by inadequate or poorly administered treatment. It sometimes occurs in a patient without previous history of antituberculous drug (ATD) therapy because of infection from an individual harbouring MDR-TB bacilli, when it is called primary MDR-TB. We are repor a case of primary disseminated extrapulmonary TB affecting left pleura, pericardium, peritoneum and abdominal lymph nodes.
| ~ Case Report|| |
A 19-year-old male presented to the local physician with high fever and shortness of breath for 1 month. His chest radiograph done at that time showed pericardial effusion [Figure 1]. Echocardiography showed large pericardial effusion without evidence of tamponade [Figure 2]. Ultrasonography (USG) of the whole abdomen showed ascites with multiple thin and thick septa and multiple enlarged para- and pre-aortic lymph nodes [Figure 3]. Sputum for acid-fast bacilli (AFB) was negative. He was put on WHO category I ATD with oral prednisolone 40 mg/day for 1 month, followed by tapering of the dose over 6 weeks at the local hospital. His shortness of breath improved, but fever persisted in spite of 5 months of chemotherapy. He was then referred to us for further evaluation. On interrogation at our clinic, he reaffirmed persistence of fever for last 5 months and also complained of weight loss of 10 kg. He denied any non-compliance with ATD and had no history of contact with TB patient.
On examination, he had pallor and the other findings were: oral temperature 40°C, pulse rate 102/min, blood pressure 110/70 mm Hg, and respiratory rate 22 breaths/min. Examination of the respiratory system revealed diminished vocal resonance, dull percussion note and absent breath sound in left mammary, infra-axillary and infrascapular areas. Examination of the other systems revealed no abnormality. Routine blood examination revealed haemoglobin 9.2 g/dL, fasting plasma glucose 87 mg/dL and normal liver function tests. Sputum for AFB was negative. HIV-I and -II serology were non-reactive. Chest X-ray postero-anterior view showed left-sided encysted pleural effusion with normal cardiac silhouette. USG abdomen showed minimal peritoneal fluid and multiple enlarged lymph nodes in periportal, pre- and para-aortic and mesenteric region. Computed tomography (CT) scan thorax revealed left-sided encysted pleural effusion with mediastinal lymphadenopathy [Figure 4]. Echocardiography revealed chink of pericardial effusion. Pleural fluid aspiration revealed straw-coloured fluid which showed coagulum on standing. Pleural fluid analysis showed glucose 25 mg/dL, protein 6.1 g/dL, lactic acid dehydrogenase 1847 U/L, adenosine deaminase 86.1 U/L, and cell count 700/mm 3 with 20% neutrophils and 80% lymphocytes. Gram stain, AFB stain and Papanicoloau stain were negative. Closed pleural biopsy showed epithelioid granulomas, Langhan's giant cell and few AFB [Figure 5]. Culture of the biopsy material by BACTEC 460 radiometric system showed growth of Mycobacterium tuberculosis which showed resistance to isoniazid and rifampicin in proportion method of drug sensitivity testing.
|Figure 4: CECT thorax showing left-sided encysted pleural effusion and mediastinal lymphadenopathy|
Click here to view
|Figure 5: HPE of pleural tissue showing epithelioid granuloma (H and E, ×40) and few acid-fast bacilli (ZN stain, ×100)|
Click here to view
A diagnosis of MDR-TB involving left pleura, peritoneum, abdominal lymph node and pericardium was made. He was put on daily therapy with ethambutol, pyrazinamide, levofloxacin, kanamycin, prothionamide and cyclocerine. Follow-up was done clinically and radiologically. Inj. kanamycin was stopped after 6 months and all other drugs were continued for another 18 months. He made an uneventful recovery.
| ~ Discussion|| |
The prevalence of MDR-TB is found to be at a low level in India.  The state level drug resistance survey conducted at Gujarat, India, has estimated the prevalence of MDR-TB to be about 3% in new cases and 12-17% in retreatment cases.  Most of the epidemiological studies of MDR-TB included pulmonary TB only. Primary MDR-TB of extrapulmonary site is an uncommon form of disease even in patients with HIV infection.  There are sporadic case reports of extrapulmonary MDR-TB involving lymph node,  peritoneum,  meninges, , ribs , and spine. ,
Extrapulmonary MDR-TB is treated with the same strategy involving the same regimen and duration as pulmonary MDR-TB.  The second-line drugs are generally widely distributed in most body fluids and tissues.  Penetration into cerebrospinal fluid is good with pyrazinamide, ethionamide, prothionamide, cycloserine and newer generations of fluoroquinolones. Aminoglycosides have good penetration in the presence of the meningeal inflammation. Monitoring strategy of the patient is less straightforward and mostly depends on the clinical and radiological observation. Prognosis is relatively better than pulmonary MDR-TB as most of the reported patients with extrapulmonary MDR-TB completed treatment and survived. ,,,,,,
The prevalence of MDR-TB is increasing in number in recent years because of increased awareness of the disease, increased access to culture and drug sensitivity testing, and earlier suspicion of MDR-TB cases among previously treated patients. So, it is expected that MDR-TB affecting extrapulmonary sites will increase in the near future.  Hence, there is an urgent need for increasing awareness of the physicians to such presentation. 
Our patient had extrapulmonary MDR-TB affecting the pleura, pericardium, peritoneum and abdominal lymph node. Surprisingly, his pericardial effusion significantly reduced while abdominal lesions persisted and pleural effusion newly appeared. Transient immunosuppression induced by systemic steroid, used during treatment of tuberculous pericardial effusion, might have been responsible for reactivation of infection in other extrapulmonary sites. But surprisingly, in spite of delay of more than 5 months before the diagnosis of MDR-TB, the disease did not involve the lung parenchyma. He had no history of contact with MDR-TB patient and he had not taken ATD in the past. Probably, the disease was transmitted to the patient unknowingly from a case of sputum-positive multidrug-resistant pulmonary TB. He was diagnosed with culture and drug sensitivity of pleural biopsy specimen, tolerated ATD well and had a favourable outcome after 2 years of chemotherapy.
We have reported this case to emphasise the increasing incidence of extrapulmonary MDR-TB, the importance of rapid and reliable diagnosis, and to create an awareness for early suspicion. Further research is urgently needed to know the prevalence, diagnostic procedure, effective regimen and duration of treatment, monitoring procedure and outcome of the patients of MDR extrapulmonary TB.
| ~ References|| |
|1.||Sharma SK, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res 2004;120:316-53. |
|2.||David HL. Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl Microbiol 1970;20:810-4. |
|3.||Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med 1993;329:784-91. |
|4.||World Health Organization. The WHO/IUATLD global project on antituberculosis surveillance: Anti-tuberculosis drug resistance in the world, report No. 2: prevalence and trends. Geneva: World Health Organization; 2000. |
|5.||Mahadev B, Kumar P, Agarwal SP, Chauhan LS, Srikantaramu N. Surveillance of drug resistance to anti-tuberculosis drugs in districts of Hoogli in West Bengal and Mayurbhanj in Orissa. Indian J Tuberc 2005;52:5-10. |
|6.||Ramachandran R, Nalini S, Chandrasekar V, Dave PV, Sanghvi AS, Wares F, et al. Surveillance of drug-resistant tuberculosis in the state of Gujarat, India. Int J Tuberc Lung Dis 2009;13:1154-60. |
|7.||Rawat J, Sindhwani G, Dua R. Primary multi-drug resistant tubercular lymphadenitis in an HIV infected patient. Indian J Tuberc 2009;56:157-9. |
|8.||Asgeirsson H, Blöndal K, Blöndal T, Gottfredsson M. Multidrug resistant tuberculosis in Iceland- case series and review of the literature. Laeknabladid 2009;95:499-507. |
|9.||Sofia M, Maniscalco M, Honoré N, Molino A, Mormile M, Heym B, et al. Familial outbreak of disseminated multidrug-resistant tuberculosis and meningitis. Int J Tuberc Lung Dis 2001;5:551-8. |
|10.||DeVincenzo JP, Berning SE, Peloquin CA, Husson RN. Multidrug-resistant tuberculosis meningitis: Clinical problems and concentrations of second-line antituberculous medications. Ann Pharmacother 1999;33:1184-8. |
|11.||Sarkar S, Maity GN, Mukhopadhyay KK, Acharyya B, Ghoshal AG. Primary multidrug resistant tuberculosis. Lung India 2007;24:97-9. |
|12.||Krishnan H, Chan KL. Multidrug resistant tuberculosis involving the clavicle, spine and ribs. Malays Orthop J 2011;5:71-4. |
|13.||Pawar UM, Kundnani V, Agashe V, Nene A, Nene A. Multidrug- resistant tuberculosis of the spine-is it the beginning of the end? A study of twenty-five culture proven multidrug-resistant tuberculosis spine patients. Spine 2009;34:E806-10. |
|14.||Guidelines for the programmatic management of drug-resistant tuberculosis. Geneva, World Health Organization, Emergency Update, 2008 (WHO/HTM/TB/2008.402). |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
|This article has been cited by|
||Treatment outcomes of tuberculosis patients in Brazilian prisons: A polytomous regression analysis
| ||Ribeiro Macedo, L., Reis-Santos, B., Riley, L.W., Maciel, E.L. |
| ||International Journal of Tuberculosis and Lung Disease. 2013; 17(11): 1427-1434 |
||Disseminated tuberculosis manifesting as pulmonary, meningeal and spinal tuberculosis in an immunocompetent patient
| ||Verma, R., Patil, T.B., Lalla, R. |
| ||BMJ Case Reports. 2012; 2012 |