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Adenosine Deaminase Diagnostic Testing in Pericardial Fluid

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 65-year-old Vietnamese man with hypertension, type 2 diabetes mellitus, and chronic hepatitis B with cirrhosis presented with a 2-week history of shortness of breath at rest, orthopnea, and lower extremity edema. He reported a 4-month history of nonproductive cough, 5-kg weight loss, and fatigue. He immigrated to the United States as an adult more than 20 years before presentation. His temperature was 37°C, heart rate was 78/min, respiratory rate was 17/min, and blood pressure was 158/95 mm Hg. A chest radiographic image suggested cardiomegaly and a computed tomographic scan demonstrated a moderate to large pericardial effusion. A pericardial drain was placed and pericardial fluid was sent to the laboratory for evaluation. Initial pericardial fluid study results are presented in the Table. Empirical treatment for tuberculosis was initiated. Three days later, an adenosine deaminase (ADA) level of 118.1 U/L (normal range, 0.0-11.3 U/L) from pericardial fluid was reported from the laboratory.

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B. Stop further nontubercular diagnostic testing and continue antitubercular therapy

ADA is an enzyme in lymphocytes and myeloid cells that recycles toxic purine pathway metabolites, which are essential for DNA metabolism and cell viability.1,2 ADA levels are elevated in inflammatory effusions, including pleural, pericardial, and joint effusion, caused by bacterial infections, granulomatous inflammation (eg, tuberculosis, sarcoidosis), malignancy, and autoimmune diseases (eg, lupus, vasculitis).1,2 ADA is normally elevated in neutrophil-predominant effusions and is not a useful diagnostic test in the setting of neutrophil-predominant effusions.3 However, among lymphocyte-predominant effusions, levels of ADA are typically higher in those caused by tuberculosis (TB) than those caused by other conditions.1,2

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Article Information

Corresponding Author: Brad Spellberg, MD, LAC+USC Medical Center, 2051 Marengo St, Los Angeles, CA 90033 (spellber@usc.edu).

Published Online: June 14, 2019. doi:10.1001/jama.2019.7535

Conflict of Interest Disclosures: Dr Spellberg reported receiving personal fees from Alexion, Synthetic Biologics, Paratek, TheoremDx, Acurx, and Merck and equity from Motif, BioAIM, Synthetic Biogogics, Mycomed, and ExBaq. No other disclosures were reported.

References
1.
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2.
Reuter  H, Burgess  L, van Vuuren  W, Doubell  A.  Diagnosing tuberculous pericarditis.  QJM. 2006;99(12):827-839. doi:10.1093/qjmed/hcl123PubMedGoogle ScholarCrossref
3.
Porcel  JM, Esquerda  A, Bielsa  S.  Diagnostic performance of adenosine deaminase activity in pleural fluid: a single-center experience with over 2100 consecutive patients.  Eur J Intern Med. 2010;21(5):419-423. doi:10.1016/j.ejim.2010.03.011PubMedGoogle ScholarCrossref
4.
Koh  KK, Kim  EJ, Cho  CH,  et al.  Adenosine deaminase and carcinoembryonic antigen in pericardial effusion diagnosis, especially in suspected tuberculous pericarditis.  Circulation. 1994;89(6):2728-2735. doi:10.1161/01.CIR.89.6.2728PubMedGoogle ScholarCrossref
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Pandie  S, Peter  JG, Kerbelker  ZS,  et al.  Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous pericarditis compared to adenosine deaminase and unstimulated interferon-γ in a high burden setting: a prospective study.  BMC Med. 2014;12(1):101. doi:10.1186/1741-7015-12-101PubMedGoogle ScholarCrossref
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Mayosi  BM, Burgess  LJ, Doubell  AF.  Tuberculous pericarditis.  Circulation. 2005;112(23):3608-3616. doi:10.1161/CIRCULATIONAHA.105.543066PubMedGoogle ScholarCrossref
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Syed  FF, Mayosi  BM.  A modern approach to tuberculous pericarditis.  Prog Cardiovasc Dis. 2007;50(3):218-236. doi:10.1016/j.pcad.2007.03.002PubMedGoogle ScholarCrossref
8.
Lewinsohn  DM, Leonard  MK, LoBue  PA,  et al.  Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children.  Clin Infect Dis. 2017;64(2):e1-e33. doi:10.1093/cid/ciw694PubMedGoogle ScholarCrossref
9.
Talati  NJ, Seybold  U, Humphrey  B,  et al.  Poor concordance between interferon-γ release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals.  BMC Infect Dis. 2009;9(15):15. doi:10.1186/1471-2334-9-15PubMedGoogle ScholarCrossref
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