Original article

Medical Science. 2014 Dec.;2(4):157-63.PMHID - 1035

    Retrospective analysis of extrapulmonary tuberculosis: a cross sectional study from a medical college, Chitwan, Nepal

    Tiwari M1, Maharjan S2, Ranabhat S3

    Corresponding Author

    Tiwari M

        Author Information

    1 Dr. Mamata Tiwari,   MBBS, MD, Associate Professor, Department of Pathology, Chitwan Medical College, Bharatpur-10, Chitwan, Nepal.

    2 Dr. Sushna Maharjan,   MBBS, MD, Assistant Professor, Department of Pathology, Chitwan Medical College, Bharatpur-10, Chitwan, Nepal.

    3 Dr. Sabin Ranabhat,   MBBS, MD, Associate Professor, Department of Pathology, Chitwan Medical College, Bharatpur-10, Chitwan, Nepal.

  • Tuberculosis (TB) is considered as a major global public health problem. According to a survey, one-third of the world's population is infected with mycobacterium tuberculosis [1]. After primary infection with the bacillas, there is a chance of reactivation and other organ involvement. Recent scientific reports have suggested that sites of infection of extra-pulmonary tuberculosis (EPTB) in the human body vary with geographic location [2-5]. Immunocompetence is a cause of EPTB infection about 15 to 20% of all cases of tuberculosis and a major risk factor 50% among the HIV-positive individuals. The most common site of infection in EPTB is Lymph node which is followed by pleural effusion and any other human body organs [6, 7]. Cervical adenopathy, inguinal, axillary, mesenteric, mediastinal, and intramammary infections in EPTB is well documented [8-12].

    In most of the cases, lymphadenitis occurs at the age of 20 to 40 years, and in the patients without HIV infection shows chronic, nontender lymphadenopathy [10-12]. Lymph node biopsy including histological characteristics, AFB stain, and mycobacterial culture is the most useful choice of diagnosis for this disease [11-12]. In EPTB, there is involvement of other organs like skin, abscess wall, joints, intestine, perianal fistula, sinus tract, pleura, breast, testes, larynx, other# [13-22]. Organ involvement severity also varies in different conditions. Although less, pleural tuberculosis in United States responsible for 5% of total cases [20]. In contrast, bone and joint TB relatively more, 35% of cases, which sometimes involves spine, followed by tuberculous arthritis, a clinical condition which affects weight-bearing joints and extraspinal tuberculous osteomyelitis [15-17]. Abdominal tuberculosis affects gastrointestinal tract, peritoneum, mesenteric lymph nodes. Military tuberculosis is responsible for EPTB in other organs like liver, spleen, adrenal glands [23].

    In developing countries, TB is considered as the major infectious disease, accountable for maximum death. According to the Global Tuberculosis Report 2014, WHO, Tuberculosis was considered as one of the world’s deadliest communicable diseases. Most striking finding by the WHO, in the year 2013, 9.0 million people developed TB and mortality was 1.5 million, 360 000 of whom were diagnosed with HIV infections. There is a progressive slowness in the growth rate each year. 37 million lives were saved worldwide, between a period of 2000 and 2013 through effective diagnosis and treatment. Globally, there is also a decline in the TB mortality rate around 45% between 1990 and 2013 and the TB prevalence rate fell by 41% during the same period [24]. Estimates of the burden of diseases caused by TB in the SAARC Region 2012 shows highest rate of TB in Pakistan followed by Bangladesh, Bhutan, Afghanistan, India, Nepal, Sri Lanka and Maldives. For the detection of cases, Nepal is in 3rd position. According to the report, prevalence of TB (all cases / 100 000 population) is 243 and mortality (deaths/100 000 population) is 51 in Nepal [25]. Neighboring country India, responsible for one-fifth of the global TB incidence, around 1.98million cases each year. Diagnosis of EPTB is a clinical challenge for physicians because of frequently atypical clinical presentation mimicking other inflammatory and neoplastic conditions. So, a high index of suspicion helps in the early detection, and more than one procedure is required for the diagnosis. This is a difficult challenge for underdeveloped countries due to poor diagnostic infrastructure potential [26].

    There are few retrospective studies and case report available mainly from the valley of Kathmandu, not from any other places in Nepal. Therefore, we carried out this study to find out the most common sites of infections in EPTB prevailing in the central region of Nepal, correlating demographic factors [27-29].
  • Study Period

    This retrospective study was carried out in Pathology Department of Chitwan Medical College Teaching Hospital (CMCTH) from April 2009 to March 2011.

    Study design and collection of data

    A total of 89 cases of EPTB were diagnosed in histopathology department of CMCTH in these three years period in biopsy specimens. Age, gender, site and histopathological findings were retrieved from the biopsy records of pathology department. Cases with epithelioid cell granuloma with Langhans giant cells and, with or without caseation necrosis were diagnosed as tuberculosis. The cases of EPTB were divided into two groups, depending on the association of lymph nodes, which was further classified according to the involved group of lymph nodes.

    Inclusion criteria

    All the cases diagnosed as EPTB in biopsy specimens were included in the study.

    Exclusion criteria

    Level of serum creatinine more than 2 mg/dL, under medication of corticosteroids or other immunosuppressive agents during diagnosis, malignancy and diabetes mellitus were set up as exclusion criteria.

    Outcome variable

    Site of extra-pulmonary tuberculosis, involvement of lymph Node was considered as outcome variable Explanatory variables Demographic factors like age group, gender were set up as explanatory variable

    Ethical committee approval

    The samples used in this study were from routine clinical specimens. Acquiring the samples did not involve direct patient contact and did not interrupt routine clinical care, consent was not required. Permission to conduct the study was obtained from the Head of the Pathology Department.

    Data management and statistical analysis

    The collected data was analyzed using Statistical Package for the Social Sciences (SPSS) for Windows Version 20.0 (SPSS Inc; Chicago, IL, USA). The associations between different variables (age group, gender, site of infection etc.) were tested using the Chi-square test. A p value less than 0.05 was considered statistically significant.
  • A total of 89 cases (47 male, 42 female) of EPTB were diagnosed in pathology department during the two years period. Among 89 cases, 37 cases (42%) were associated with lymph nodes and remaining 52 cases (58%) were in extra nodal sites. On histopathological examination, caseation necrosis was absent in 10 cases (11%) and Ziehl– Neelsen stain (Z-N stain) was positive in only 7 cases (8%). Females were more prone for lymph node tuberculosis than males.

    Among males infections were more in other organs (Table - 1).

    Table 2 explains gender variation, groups of lymph nodes and involvement of other organs in EPTB. Among males, cervical, inguinal lymph node infections were more. Axillary and supraclavicular regions were affected more in females. Considering other organs, males were infected more in EPTB with abscess wall, joints, perianal fistula sinus tract, pleura; whereas skin, intestine and other# were more frequent site of infection in females, apart from respective reproductive organs.

    Majority of the lymph node infections were observed in the age group below 20 years. On contrast, other organ involvement were relatively more in the age group 20-40 years and >40 years (Table 3).

    Table 4 represents relation between age groups, involvement of lymph nodes and other organs in EPTB. Maximum infection in cervical lymph node was observed in the age group below 20 years. Axillary lymph node involvement was only observed in 20-40 years of age group; same as supraclavicular lymph node infection in >40 age group. Submandibular lymph node affected more in 20-40 years of age. 20-40 years age was most vulnerable for EPTB in skin, abscess wall, intestine, perianal fistula, pleura and others. On contrary, among the >40 years of age group, ECT infection was evident in joints, sinus tract and larynx.

  • Out of the investigated samples from the various extrapulmonary sites, most of the isolates were obtained from urinary, pelvic and cold abscess. Some researchers found caseating granuloma in 62-72% of cases and Z-N stain is positive for acid fast bacilli (AFB) in 8% of cases, in our study we observed caseation necrosis was absent in 11% cases and Z-N stain is positive for 8% [30]. Another obtained a wide range of AFB positivity, upto 75% [31].

    Influence of gender and site of infection in EPTB.

    EPTB can involve different organs of the body at any age and gender. Cases of EPTB are increased with human immunodeficiency virus infection. Our study shows higher number of EPTB in male than in female with male to female ratio 1.17:1. This finding is in accordance with several other studies [2, 4, 32] but contradictory to other researchers, where, female preponderance was observed, which explain sociocultural factors leading to malnutrition in females as main cause [33-37].

    Gender variation, groups of lymph nodes and involvement of other organs in EPTB

    Earlier researches show that cervical lymph node is the commonest area for infection and Lymph nodes were the most common site of EPTB, involved in 66.4% of the cases [34]. Our findings resemble this result, where maximum numbers of cases were in the cervical Lymph nodes. This is also in accordance with some other findings, where pleura, or bone and joints as the commonest site of EPTB [2, 38]. Researchers from Nepal, and the Netherlands have also reported high number of cases with lymph node involvement [33, 35].

    In the earlier studies, it was observed that females were more prone for Lymph node TB, central nervous system (CNS) tuberculosis and tuberculosis of bones, joints and males with pleural TB and abdominal TB. In our research, we observed that males were infected more in EPTB with abscess wall, joints, perianal fistula sinus tract, pleura; whereas skin, intestine and other# were more frequent site of infection in females [39].

    Age distribution and site of EPTB

    In the present study maximum number of lymphnode infection was observed in the age group of 20-40 years. This findings resembles to other studies [10] but contradictory to the findings of Prakasha SR et al., where lymph node manifestatios occurred mostly, less than 14 years’ age group [40]. This may be related to duration of exposure of bacilli.

    [# - there were two cases amongst male – tuberculosis of phalynx and peritoneal tuberculosis. In females, there were 7 cases – tuberculosis of right kidney, omentum, tonsil, fallopian tube, nasopharynx, corn on left sole and ureter].
  • EPTB can occur in various parts of the body and lymph nodes. Among them, cervical lymph node is the most commonest one. It is frequent in 2nd to 4th decades and less common in children and old age. Biopsy with histopathological exanimation is important for its diagnosis as clinical presentation may vary according to the site of infection. This present study gives a relatively clear scenario in the Bharatpur, which facilitate the govt. policy makers to plan health care programme in this area.
  • This was a retrospective study with small number of cases with limited available data. Further study can be done on the basis of socioeconomic details, caste, area of residence rural or urban, to find out the correlation with the risk factors of EPTB. Detailed study, comparing various parameters of pulmonary tuberculosis with EPTB will also help to understand the clinical scenario.
  • Authors do not have any competing interests.
  • Acid fast bacilli (AFB), Chitwan medical college teaching hospital (CMCTH), Extrapulmonary tuberculosis (EPTB), Human immunodeficiency virus (HIV), Tuberculosis (TB), World health organization (WHO), Ziehl-Neelsen Stain (Z-N stain)
  • Dr. Mamata Tiwari designed the study, collected and interpreted the data, drafted the manuscript, and revised it. Dr. Sushna Maharjan and Dr. Sabin Ranabhat took part in data collection and critically revision of the manuscript. Final manuscript was approved by all authors.
  • Dr. Mamata Tiwari, MBBS, MD, Associate Professor. Department of Pathology, Chitwan Medical College, Bharatpur-10, Chitwan, Nepal. Dr. Sushna Maharjan, MBBS, MD, Assistant Professor. Department of Pathology, Chitwan Medical College, Bharatpur-10, Chitwan, Nepal.

    Dr. Sabin Ranabhat, MBBS, MD, Associate Professor. Department of Pathology, Chitwan Medical College, Bharatpur-10, Chitwan, Nepal.
  • We would like to thank Mr. Anil Shah and Mr. Santosh Gautam, staffs of histopathology department for their technical assistance in histopathological processing of the specimen.
  • 1. Sudre P, Tendam G, Kochi A.Tuberculosis: a global overview of the situation today. Bull World Health Organ.1992;70(2):149-59.

    2. Yang Z, Kong Y, Wilson F, Foxman B, Fowler AH, Marrs CF et al. Identification of risk factors of extrapulmonary tuberculosis. Clin Infect Dis. 2004; 38(2):199-205.

    3. Noertjojo K, Tam CM, Chan SL, Chan-Yeung MM. Extra-pulmonary and pulmonary tuberculosis in Hong Kong. Int J Tuberc Lung Dis. 2002;6(10):879- 86.

    4. Musellim B, Erturan S, Sonmez Duman E, Ongen G. Comparison of extrapulmonary and pulmonary tuberculosis cases: factors influencing the site of reactivation. Int J Tuberc Lung Dis. 2005;9(11): 1220-3.

    5. Ilgazli A, Boyaci H, Basyigit I, Yildiz F.Extra pulmonary tuberculosis: clinical and epidemiologic spectrum of 636 cases. Arch Med Res 2004, 35(5):435-41.

    6. Sharma SK, Mohan A.Extrapulmonary tuberculosis.Indian J Med Res. 2004;120(4):316-53.

    7. Shafer RW, Kim DS, Weiss JP, Quale JM. Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection. Medicine (Baltimore) 1991;70(6):384-97.

    8. Mert A, Tabak F, Ozaras R, Tahan V, Ozturk R, Aktuglu Y. Tuberculous lymphadenopathy in adults: a review of 35 cases. Acta Chir Belg 2002;102(2):118-21.

    9. Ebdrup L, Storgaard M, Jensen-Fangel S, Obel N. Ten years of extrapulmonary tuberculosis in a Danish university clinic. Scand J Infect Dis 2003;35(4):244-6.

    10. Jha BC, Dass A, Nagarkar NM, Gupta R, Singhal S. Cervical tuberculous lymphadenopathy: changing clinical pattern and concepts in management. Postgrad Med J. 2001;77(905):185-7.

    11. American Thoracic Society, CDC. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med 2000;161(4 pt 1):1376-95.

    12. Artenstein AW, Kim JH, Williams WJ, Chung RC. Isolated peripheral tuberculous lymphadenitis in adults: current clinical and diagnostic issues. Clin Infect Dis 1995;20(4):876-82.

    13. Frankel A, Penrose C, Emer J. Cutaneous Tuberculosis.J Clin Aesthet Dermatol.2009;2(10): 19–27.

    14. Gaude GS, Reyas AK. Tuberculosis of the chest wall without pulmonary involvement. Lung India.2008; 25(3): 135–7.

    15. Grosskopf I, Ben David A, Charach G, Hochman I, Pitlik S. Bone and joint tuberculosis-a 10-year review. Isr J Med Sci. 1994;30(4):278-83.

    16. Watts HG, Lifeso RM. Tuberculosis of bones and joints. J Bone Joint Surg Am 1996;78(2):288-98.

    17. Lifeso RM, Weaver P, Harder EH. Tuberculous spondylitis in adults. J Bone Joint Surg Am 1985;67(9):1405-13.

    18. Molodtsov VG, Biriukova LA, Shipkov AV, Dobzhanskii AV. A case of extrapulmonary tuberculosis with laryngeal and intestinal involvement. Vestn Otorinolaringol. 2001;(4):57.

    19. Gupta PJ. Ano-perianal tuberculosis - solving a clinical dilemma. Afr Health Sci. Dec 2005;5(4): 345– 7.

    20. Seibert AF, Haynes J Jr, Middleton R, Bass JB Jr. Tuberculous pleural effusion. Twenty-year experience. Chest 1991;99(4):883-6.

    21. Baharoon S. Tuberculosis of the breast. Ann Thorac Med. 2008;3(3):110–14.

    22. Bhargava A, Davenport C, Gibbons N, McConkey S. TB or not TB?: a case of isolated testicular TB with scrotal involvement. Ir J Med Sci. 2009;178(2):231- 3.

    23. Golden MP. Extrapulmonary Tuberculosis: An Overview. Am Fam Physician. 2005;72(9):1761-8.

    24. Global Tuberculosis Report 2014, WHO. Accessed on 12-12-2014 from URL:http://apps.who.int/iris/bitstream/10665/1370 94/1/9789241564809_eng.pdf?ua=1

    25. Tuberculosis Control SAARC Region Update 2013. SAARC Tuberculosis and HIV/AIDS Centre. Kathmandu, Nepal. Accessed on 12-12-2014 from URL:http://www.saarctb.org/attachments/article/2 3/TB%20update%202013.pdf

    26. Central TB Division. 2010. TB India 2010: RNTCP status report. Ministry of Health and Family Welfare, New Delhi, India. Accessed on 12-12-2014 from URL: http://tbcindia.nic.in/pdfs/TB%20India%202010.pdf

    27. Rijal B, Ghimire P, Tuladhar NR. Comparison of Acid Fast Bacilli Smear and Culture for the Diagnosis of Extra-Pulmonary Tuberculosis. Journal of Nepal Medical Association.2004;43(155):235-8.

    28. Srivastava GN, Meena M, Yadav P, Hussain M, Amrita, Kumar V. A rare extra-pulmonary presentation of tuberculosis as gum tuberculosis. SAARC Journal of Tuberculosis, Lung Diseases and HIV/AIDS. 2013;10(1):37-9.

    29. Makaju R, Mohammad A, Thakur NK. Scenario of extrapulmonary tuberculosis in a tertiary care center. J Nepal Health Res Counc. 2010;8(1):48-50. 30. Fatmi TI, Jamal Q. A morphological study of chronic granulomatous lymphadenitis with the help of special stains. Pakistan Journal of Medical Sciences. 2002; 18(1): 48 -51.

    31. Kamboj S, Goel MM, Tandon P, Natu SM, Nath P. Correlative study of histopathology and bacteriology in patients of tubercular lymphdenitis. The Indian Journal Chest Disease and Allied Science. 1994; 36(4):187-91.

    32. Wiwatworapan T, Anantasetagoon T. Extra pulmonary tuberculosis at a regional hospital in Thailand. Southeast Asian J Trop Med Pub Health. 2008;39(3):521-5.

    33. Sreeramareddy CT, Panduru KV, Verma SC, Joshi HS, Bates MN. Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospitalbased retrospective study. BMC Infect Dis 2008; 8:8.

    34. Ullah S, Shah SH, Aziz-ur-Rehman, Kamal A, Begum N, Khan G. Extrapulmonary tuberculosis in Lady Reading Hospital Peshawar, NWFP, Pakistan: survey of biopsy results. J Ayub Med Coll Abottabad. 2008; 20(2): 43-6.

    35. Lowieke AM. Beek T, Marieke J, Werf V, Richter C, Borgdorff MW. Extrapulmonary Tuberculosis by Nationality, the Netherlands, 1993–2001. Emerging Infectious Diseases. 2006;12(9):1375-82.

    36. Chandir S, Hussain H, Amir M, Lotia I, Javed A Khan, Salahuddin N, Ali F. Extrapulmonary Tuberculosis: A retrospective review of 194 cases at a tertiary care hospital in Karachi, Pakistan, JPMA.2010;60 (2):105- 9.

    37. Solovic I, Jonsson J, Korzeniewska-Kosela M, Chiotan DI, Pace-Asciak A, Slump E, et al. Challenges in diagnosing extrapulmonary tuberculosis in the European Union, 2011. Euro Surveill. 2013; 18(12). pii: 20432.

    38. Sandren A, Hollo V, van der Werf M J. Extrapulmonary tuberculosis in the European Union and Europian Economic Area, 2002 to 2011. Euro Surveill. 2013; 18(12): Accessed on 12-12-2014 from URL:http://www.eurosurveillance.org/images/dyna mic/ee/v18n12/art20431.pdf

    39. Prakasha SR, Suresh G, D’sa IP, Shetty SS, Kumar SG. Mapping the Pattern and Trends of Extrapulmonary Tuberculosis. J Glob Infect Dis. 2013;5(2): 54–9.

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    Tiwari, M., Maharjan, S., & Ranabhat, S. (2014). Retrospective analysis of extrapulmonary tuberculosis: a cross sectional study from a medical college, Chitwan, Nepal. Medical Science, 2 (4), 157-163. Retrieved from http://www.pubmedhouse.com/journals/ms/articles/1035/PMHID1035.pdf


    Tiwari, Mamata, Sushna Maharjan, & Sabin Ranabhat. "Retrospective analysis of extrapulmonary tuberculosis: a cross sectional study from a medical college, Chitwan, Nepal." Medical Science [Online], 2.4 (2014): 157-163. Web. 30 Dec. 2014


    Tiwari M, Maharjan S, Ranabhat S. Retrospective analysis of extrapulmonary tuberculosis: a cross sectional study from a medical college, Chitwan, Nepal. Medical Science. 2014; 2(4): 157-63. Available at: http://www.pubmedhouse.com/journals/ms/articles/1035/PMHID1035.pdf

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Article history

Received : - Oct. 11, 2014

Accepted : - Dec. 3, 2014

Published : - Dec. 30, 2014

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