Association of Serum Adenosine Deaminase Levels in Cytologically Suggested Cases of Tubercular Lymphadenitis: The Experience of a Tertiary Care Centre

Abstract

Background: Tuberculosis (TB), a communicable disease, caused by Mycobacterium tuberculosis requires a simple, rapid test, which can be easily carried out in a laboratory. Unfortunately, despite a battery of investigations, no definite test is available till date. Adenosine deaminase (ADA), a biochemical marker has been proposed as a useful surrogate marker for TB as its levels can be measured in body fluids.


Methods: A one-and-a-half-year prospective study of 154 cases presenting with lymphadenitis from January 2019 to June 2020 was undertaken. Using cytology, lymphadenitis subjects were divided into two groups: Tubercular (104 patients) as a case group and Reactive (50 patients) as a control group. All cases were followed by serum ADA assay by colorimetric method. Nonparametric tests were performed to compare the two groups.


Results: The mean age of the participants was 28.99 ± 13.26 years with a F:M ratio of 1.81:1. Involvement of cervical lymph nodes was most frequent (89.42% cases). The mean S.ADA level for tubercular and reactive lymphadenitis was 41.71 ± 11.53 U/L and 21.16 ± 4.16 U/L, respectively (P-value < 0.05). The cut-off value calculated was 32.6 U/L. The sensitivity, specificity, PPV, NPV, and accuracy were calculated as 79.81%, 100%, 100%, 70.42%, and 86.36%, respectively.


Conclusion: A statistically significant increase was found in serum ADA levels in tubercular lymphadenitis cases compared to reactive lymphadenitis. Hence, it can be used as an adjunct to FNAC and is a fairly sensitive and specific test. Since it is difficult to always demonstrate AFB in FNAC smears, ADA can be helpful in establishing a definite diagnosis despite smear negativity.


Keywords: adenosine deaminase, lymphadenitis, tuberculosis

References
[1] World Health Organization (WHO). (2020). Global Tuberculosis Report 2020. Geneva: WHO. Retrieved from: https://www.who.int/tb/publications/global_report/ en/

[2] Grange, J. M. and Zumla, A. (2002). The global emergency of tuberculosis: what is the cause? Journal of the Royal Society for the Promotion of Health, vol. 122, no. 2.

[3] Stevanovic, G., Pelemis, M., Pavlovic, M., et al. (2011). Significance of adenosine deaminase serum concentration in the diagnosis of extra-pulmonary tuberculosis. Journal of IMAB, vol. 17, no. 2011, pp. 130–134.

[4] Golden, M. P. and Vikram, H. R. (2005). Extrapulmonary tuberculosis: an overview. American Family Physician, vol. 72, no. 9, pp. 1761–1768.

[5] Jawahar, M. S., Rajaram, K., Sivasubramanian, S., et al. (2005). Treatment of lymph node tuberculosis - a randomized clinical trial of two 6-month regimens. Tropical Medicine & International Health, vol. 10, no. 11, pp. 1090–1098.

[6] Subrahmanyam, M. (1993). Role of surgery and chemotherapy for peripheral lymph node tuberculosis. British Journal of Surgery, vol. 80, no. 12, pp. 1547–1548.

[7] Dandapat, M. C., Mishra, B. M., Dash, S. P., et al. (1990). Peripheral lymph node tuberculosis: a review of 80 cases. British Journal of Surgery, vol. 77, no. 8, pp. 911–912.

[8] Jay, S. J. (1985). Diagnostic procedures for pleural disease. Clinics in Chest Medicine, vol. 6, no. 1, pp. 33–48.

[9] Achkar, J. M., Lawn, S. D., Moosa, M.-Y. S., et al. (2011). Adjunctive tests for diagnosis of tuberculosis: serology, ELISPOT for site-specific lymphocytes, urinary lipoarabinomannan, string test, and fine needle aspiration. Journal of Infectious Diseases, vol. 204, no. 4, pp. S1130–S1141.

[10] Purohit, M. and Mustafa, T. (2015). Laboratory diagnosis of extra-pulmonary tuberculosis (EPTB) in resource-constrained setting: state of the art, challenges and the need. Journal of Clinical and Diagnostic Research, vol. 9, no. 4, pp. EE01–EE06.

[11] Gupta, B. (2010). Sensitivity, specificity, negative and positive predictive values of adenosine deaminase in patients of tubercular and non-tubercular serosal effusion in India. Journal of Clinical Medicine Research, vol. 2, no. 3, pp. 121–126.

[12] Greco, S., Girardi, E., Masciangelo, R., et al. (2003). Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a metaanalysis. International Journal of Tuberculosis and Lung Disease, vol. 7, no. 8, pp. 777–786.

[13] Dasgupta, A., Ghosh, R. N., Poddar, A. K., et al. (1994). Fine needle aspiration cytology of cervical lymphadenopathy with special reference to tuberculosis. Journal of Indian Medical Association, vol. 92, no. 2, pp. 44–46.

[14] Piras, M. A., Gakis, C., Budroni, M., et al. (1978). Adenosine deaminase activity in pleural effusions: an aid to differential diagnosis. British Medical Journal, vol. 2, no. 6154, pp. 1751–1752.

[15] Mugulkod, P., Chavan S., S. (2017). Serum adenosine deaminase levels and other laboratory parameters in the diagnosis of extrapulmonary tuberculosis: a clinicopathological study. International Journal of Research in Medical Sciences, vol. 5, no. 7, p. 3140.

[16] Khajuria, R., Goswami, K. C., Singh, K., et al. (2006). Pattern of lymphadenopathy on fine needle aspiration cytology in Jammu. JK Science, vol. 8, no. 3, pp. 157–159.

[17] Purohit, M. R., Mustafa, T., Mørkve, O., et al. (2009). Gender differences in the clinical diagnosis of tuberculous lymphadenitis-a hospital-based study from central India. International Journal of Infectious Diseases, vol. 13, no. 5, pp. 600–605.

[18] Bhattacharya, S., Raghuveer, C. V., and Adhikari, P. (1998). FNAC diagnosis of tuberculosis–an eight years study at Mangalore. Indian Journal of Medical Sciences, vol. 52, no. 11, pp. 498–506.

[19] Khanna, A., Khanna, M., and Manjari, M. (2013). Cytomorphological patterns in the diagnosis of tuberculous lymphadenitis. International Journal of Medical and Dental Sciences, vol. 2, no. 2, pp. 182–188.

[20] Nassaji, M., Azarhoush, R., Ghorbani, R., et al. (2014). Acid fast staining in formalinfixed tissue specimen of patients with extrapulmonary tuberculosis. International Journal of Scientific and Research Publication, vol. 4, no. 1, pp. 2250–3153.

[21] Sulakshana, M. S., Ahmed, S. M., and Jayakumar, C. K. (2015). Study of serum adenosine deaminase levels in FNAC confirmed cases of tuberculous lymphadenitis. International Journal of Recent Advances in Multidisciplinary Research, vol. 2, no. 6, pp. 0476–0480.

[22] Ahmed, I., Sabah, S., Alam, B., et al. (2020). Role of serum ADA in patients of extra-pulmonary tuberculosis in a tertiary care hospital of Bangladesh. International Journal of Medical Research Professionals, vol. 6, no. 3, pp. 63–67.

[23] Alaarag, A., Mohammad, O., and Farag, N. (2016). Diagnostic utility of serum adenosine deaminase level in the diagnosis of pulmonary tuberculosis. Egyptian Journal of Bronchology, vol. 10, no. 2, pp. 133–139.

[24] Conde, M. B., Marinho, S. R., De Fatima Pereira, M., et al. (2002). The usefulness of serum adenosine deaminase 2 (ADA2) activity in adults for the diagnosis of pulmonary tuberculosis. Respiratory Medicine, vol. 96, no. 8, pp. 607–610.

[25] Salmanzadeh, S., Tavakkol, H., Bavieh, K., et al. (2015). Diagnostic value of serum adenosine deaminase (ADA) level for pulmonary tuberculosis. Jundishapur Journal of Microbiology, vol. 8, no. 3, p. e21760.

[26] Farazi, A., Moharamkhani, A., and Sofian, M. (2013). Validity of serum adenosine deaminase in diagnosis of tuberculosis. Pan African Medical Journal, vol. 15, p. 133.