Diagnostic evaluation of pleural effusion in adults: Additional tests for undetermined etiology
- YC Gary Lee, MBChB, PhD
YC Gary Lee, MBChB, PhD
- Professor of Respiratory Medicine
- University of Western Australia, Perth, Australia
Pleural effusions can develop as a result of over 50 different pleuropulmonary or systemic disorders. Following diagnostic thoracentesis, the cause of a pleural effusion is not evident in up to 25 percent of patients [1,2]. However, no universally accepted definition exists for an "undiagnosed effusion."
This topic will review the approach to pleural effusions for which the diagnosis is unclear after initial clinical assessment and investigation. The initial assessment of a patient with a pleural effusion is presented separately. (See "Imaging of pleural effusions in adults" and "Diagnostic evaluation of a pleural effusion in adults: Initial testing" and "Diagnostic thoracentesis".)
The first step for the clinician is to revisit the patient's history, paying particular attention to drugs, occupational exposures, risk factors for pulmonary embolism or tuberculosis, and comorbid conditions.
A careful drug history may reveal that the patient is taking nitrofurantoin, amiodarone, ovarian stimulation therapy, or a drug that can produce a lupus-like syndrome [3,4]. (See "Drug-induced lupus".)
Occupational asbestos exposure, which might suggest a benign asbestos pleural effusion, may have occurred many years earlier . Benign asbestos effusions are usually unilateral, exudative, and about a third have an elevated pleural eosinophil count .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Collins TR, Sahn SA. Thoracocentesis. Clinical value, complications, technical problems, and patient experience. Chest 1987; 91:817.
- Venekamp LN, Velkeniers B, Noppen M. Does 'idiopathic pleuritis' exist? Natural history of non-specific pleuritis diagnosed after thoracoscopy. Respiration 2005; 72:74.
- Huggins JT, Sahn SA. Drug-induced pleural disease. Clin Chest Med 2004; 25:141.
- Abramov Y, Elchalal U, Schenker JG. Pulmonary manifestations of severe ovarian hyperstimulation syndrome: a multicenter study. Fertil Steril 1999; 71:645.
- Robinson BW, Musk AW. Benign asbestos pleural effusion: diagnosis and course. Thorax 1981; 36:896.
- Cugell DW, Kamp DW. Asbestos and the pleura: a review. Chest 2004; 125:1103.
- Maldonado F, Tazelaar HD, Wang CW, Ryu JH. Yellow nail syndrome: analysis of 41 consecutive patients. Chest 2008; 134:375.
- Nordkild P, Kromann-Andersen H, Struve-Christensen E. Yellow nail syndrome--the triad of yellow nails, lymphedema and pleural effusions. A review of the literature and a case report. Acta Med Scand 1986; 219:221.
- Huggins JT, Sahn SA, Heidecker J, et al. Characteristics of trapped lung: pleural fluid analysis, manometry, and air-contrast chest CT. Chest 2007; 131:206.
- Porcel JM, Chorda J, Cao G, et al. Comparing serum and pleural fluid pro-brain natriuretic peptide (NT-proBNP) levels with pleural-to-serum albumin gradient for the identification of cardiac effusions misclassified by Light's criteria. Respirology 2007; 12:654.
- Long AC, O'Neal HR Jr, Peng S, et al. Comparison of pleural fluid N-terminal pro-brain natriuretic peptide and brain natriuretic-32 peptide levels. Chest 2010; 137:1369.
- Hooper CE, Lee YC, Maskell NA, et al. Investigation of a unilateral pleural effusion in adults: the British Thoracic Society Guidelines. Thorax 2010; 76 (Suppl2):In press.
- Romero-Candeira S, Fernández C, Martín C, et al. Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure. Am J Med 2001; 110:681.
- STEAD WW, EICHENHOLZ A, STAUSS HK. Operative and pathologic findings in twenty-four patients with syndrome of idiopathic pleurisy with effusion, presumably tuberculous. Am Rev Tuberc 1955; 71:473.
- Thomas R, Cheah HM, Creaney J, et al. Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions. Chest 2016; 149:1494.
- Wrightson JM, Stanton AE, Maskell NA, et al. Pseudochylothorax without pleural thickening: time to reconsider pathogenesis? Chest 2009; 136:1144.
- Das DK. Serous effusions in malignant lymphomas: a review. Diagn Cytopathol 2006; 34:335.
- Hooper CE, Lee YC, Maskell NA. Interferon-gamma release assays for the diagnosis of TB pleural effusions: hype or real hope? Curr Opin Pulm Med 2009; 15:358.
- Liang QL, Shi HZ, Wang K, et al. Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis. Respir Med 2008; 102:744.
- Nestor J, Huggins T, Kummerfeldt C, et al. Viral diseases affecting the pleura. J Clin Virol 2013; 58:367.
- Feinsilver SH, Barrows AA, Braman SS. Fiberoptic bronchoscopy and pleural effusion of unknown origin. Chest 1986; 90:516.
- Poe RH, Levy PC, Israel RH, et al. Use of fiberoptic bronchoscopy in the diagnosis of bronchogenic carcinoma. A study in patients with idiopathic pleural effusions. Chest 1994; 105:1663.
- Chang SC, Perng RP. The role of fiberoptic bronchoscopy in evaluating the causes of pleural effusions. Arch Intern Med 1989; 149:855.
- Yilmaz U, Polat G, Sahin N, et al. CT in differential diagnosis of benign and malignant pleural disease. Monaldi Arch Chest Dis 2005; 63:17.
- Porcel JM, Madroñero AB, Pardina M, et al. Analysis of pleural effusions in acute pulmonary embolism: radiological and pleural fluid data from 230 patients. Respirology 2007; 12:234.
- Toaff JS, Metser U, Gottfried M, et al. Differentiation between malignant and benign pleural effusion in patients with extra-pleural primary malignancies: assessment with positron emission tomography-computed tomography. Invest Radiol 2005; 40:204.
- Orki A, Akin O, Tasci AE, et al. The role of positron emission tomography/computed tomography in the diagnosis of pleural diseases. Thorac Cardiovasc Surg 2009; 57:217.
- Koegelenberg CF, Bolliger CT, Theron J, et al. Direct comparison of the diagnostic yield of ultrasound-assisted Abrams and Tru-Cut needle biopsies for pleural tuberculosis. Thorax 2010; 65:857.
- Maskell NA, Gleeson FV, Davies RJ. Standard pleural biopsy versus CT-guided cutting-needle biopsy for diagnosis of malignant disease in pleural effusions: a randomised controlled trial. Lancet 2003; 361:1326.
- Metintas M, Ak G, Dundar E, et al. Medical thoracoscopy vs CT scan-guided Abrams pleural needle biopsy for diagnosis of patients with pleural effusions: a randomized, controlled trial. Chest 2010; 137:1362.
- Ryan CJ, Rodgers RF, Unni KK, Hepper NG. The outcome of patients with pleural effusion of indeterminate cause at thoracotomy. Mayo Clin Proc 1981; 56:145.
- Chakrabarti B, Ryland I, Sheard J, et al. The role of Abrams percutaneous pleural biopsy in the investigation of exudative pleural effusions. Chest 2006; 129:1549.
- Kirsch CM, Kroe DM, Azzi RL, et al. The optimal number of pleural biopsy specimens for a diagnosis of tuberculous pleurisy. Chest 1997; 112:702.
- Diacon AH, Van de Wal BW, Wyser C, et al. Diagnostic tools in tuberculous pleurisy: a direct comparative study. Eur Respir J 2003; 22:589.
- Benamore RE, Scott K, Richards CJ, Entwisle JJ. Image-guided pleural biopsy: diagnostic yield and complications. Clin Radiol 2006; 61:700.
- Rahman NM, Ali NJ, Brown G, et al . Local anaesthetic thoracoscopy: British Thoracic Society plerual disease guidelines 2010. Thorax 2010; 65:Suppl 2.
- McLean AN, Bicknell SR, McAlpine LG, Peacock AJ. Investigation of pleural effusion: an evaluation of the new Olympus LTF semiflexible thoracofiberscope and comparison with Abram's needle biopsy. Chest 1998; 114:150.
- Davies HE, Nicholson JE, Rahman NM, et al. Outcome of patients with nonspecific pleuritis/fibrosis on thoracoscopic pleural biopsies. Eur J Cardiothorac Surg 2010; 38:472.
- ROPER WH, WARING JJ. Primary serofibrinous pleural effusion in military personnel. Am Rev Tuberc 1955; 71:616.
- Gopi A, Madhavan SM, Sharma SK, Sahn SA. Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest 2007; 131:880.
- Poe RH, Israel RH, Utell MJ, et al. Sensitivity, specificity, and predictive values of closed pleural biopsy. Arch Intern Med 1984; 144:325.
- Leslie WK, Kinasewitz GT. Clinical characteristics of the patient with nonspecific pleuritis. Chest 1988; 94:603.
- Alemán C, Sanchez L, Alegre J, et al. Differentiating between malignant and idiopathic pleural effusions: the value of diagnostic procedures. QJM 2007; 100:351.
- Maskell, NA. Undiagnosed pleural effusions. In: Textbook of Pleural Diseases, 2nd, Light, RW, Lee, YCG (Eds), Arnold Press, London 2008. p.491.
- TIME COURSE
- REANALYSIS OF PLEURAL FLUID
- TRAPPED LUNG
- DIAGNOSTIC EVALUATION
- Pleural pressure
- Pleural biopsy
- - Closed pleural biopsy
- - CT-guided cutting needle biopsy
- - Thoracoscopic pleural biopsy
- TUBERCULOUS PLEURISY
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS