Pleural effusion differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Prince Tano Djan, BSc, MBChB [2]; Nate Michalak, B.A.

Overview

Evaluation of a patient with a pleural effusion requires a thorough clinical history and physical examination in conjunction with pertinent laboratory tests and imaging studies. According to the British Thoracic Society Pleural Disease Guideline 2010, thoracentesis should not be performed for bilateral effusions in a clinical setting strongly suggestive of a transudate unless there are atypical features or they fail to respond to therapy. Pleural fluid should always be sent for protein, lactate dehydrogenase, Gram stain, cytology and microbiological culture. Additional studies which may be indicated in selected cases include pH, glucose, acid-fast bacilli and tuberculosis culture, triglyceride, cholesterol, amylase, and hematocrit. Light's criteria is applied to distinguish the fluid between transudative or exudative. A broad array of underlying conditions result in exudative effusions, while a limited number of disorders are assoicated with transudative effusions, which include congestive heart failure, cirrhosis, nephrotic syndrome, peritoneal dialysis, hypoalbuminemia, urinothorax, atelectasis, constrictive pericarditis, trapped lung, superior vena cava obstruction, and duropleural fistula.

Differentiating Pleural Effusion from other Diseases

Exudative Pleural Effusions

Etiology	Underlying conditions
Infectious	Bacterial pneumonia, tuberculous effusion, fungal disease, atypical pneumonia, nocardia, actinomyces, subphrenic abscess, hepatic abscess, splenic abscess, hepatitis, parasites
Iatrogenic	Drug-induced, esophageal perforation, esophageal sclerotherapy, central venous catheter misplacement or migration, enteral feeding tube in pleural space
Vasculitis	Wegener granulomatosis, Churg–Strauss syndrome, familial Mediterranean fever
Malignancy	Carcinoma, lymphoma, mesothelioma, leukemia, chylothorax
Inflammatory	Pancreatitis, benign asbestos pleural effusion (BAPE), pulmonary infarction, radiation therapy, sarcoidosis, post-cardiac injury syndrome (PCIS), hemothorax, acute respiratory distress syndrome (ARDS), cholesterol effusion
Increased negative intrapleural pressure	Atelectasis, trapped lung
Connective tissue disease	Lupus pleuritis, rheumatoid pleuritis, mixed connective tissue disease, Sjögren syndrome
Endocrine dysfunction	Hypothyroidism, ovarian hyperstimulation syndrome
Lymphatic abnormalities	Chylothorax, yellow nail syndrome, lymphangiomyomatosis, lymphangiectasis
Movement of fluid from abdomen to pleural space	Acute pancreatitis, pancreatic pseudocyst, Meigs syndrome, chylous ascites

Other Differentials

Pleural effusions should be differentiated from other diseases presenting with chronic cough, shortness of breath and tachypnea. The differentials include the following:

Diseases	Diagnostic tests			Physical Examination			Symptoms							Past medical history	Other Findings
	CT scan and MRI	EKG	Chest X-ray	Tachypnea	Tachycardia	Fever	Chest Pain	Hemoptysis	Dyspnea on Exertion	Wheezing	Chest Tenderness	Nasalopharyngeal Ulceration	Carotid Bruit
Chronic obstructive pulmonary disease (COPD)	On CT scan: Chronic bronchitis may show bronchial wall thickening, scarring with bronchovascular irregularity, fibrosis Emphysema may show alveolar septal destruction and airspace enlargement (Centrilobular- upper lobe, panlobular- lower lobe) Giant bubbles On MRI: Increased diameter of pulmonary arteries Peripheral pulmonary vasculature attentuation Loss of retrosternal airspace due to right ventricular enlargement Hyperpolarized Helium MRI may show progressively poor ventilation and destruction of lung	Multifocal atrial tachycardia (atleast 3 distinct P wave morphologies)	Enlarged lung shadows (emphysema) Flattening of diaphragm (emphysema)	✔	✔	-	-	-	✔	✔	-	-	-	Smoking Alpha-1 antitrypsin deficiency Increased sputum production (chronic bronchitis) Cough	Alpha 1 antitrypsin deficiency may be associated with hepatomegaly
Pneumonia	On CT scan: (not generally indicated) Consolidation (alveolar/lobar pneumonia) Peribronchial nodules (bronchopneumonia) Ground-glass opacity (GGO) Abscess Pleural effusion On MRI: Not indicated	Prolonged PR interval Transient T wave inversions	Consolidation (alveolar/lobar pneumonia) Peribronchial nodules (bronchopneumonia) Ground-glass opacity (GGO)	✔	✔	✔	✔	-	✔	✔	-	-	-	Ill-contact Travelling Smoking Diabetic Recent hospitalization Chronic obstructive pulmonary disease	Requires sputum stain and culture for diagnosis Empiric management usually started before culture results
Congestive heart failure	On CT scan: Mediastinal lymphadenopathy Hazy mediastinal fat On MRI: Abnormality of cardiac chambers (hypertrophy, dilation) Delayed enhancement MRI may help characterize the myocardial tissue (fibrosis) Late enhancement of contrast in conditions such as myocarditis, sarcoidosis, amyloidosis, Anderson-Fabry's disease, Chagas disease)	Goldberg's criteria may aid in diagnosis of left ventricular dysfunction: (High specificity) SV1 or SV2 + RV5 or RV6 ≥3.5 mV Total QRS amplitude in each of the limb leads ≤0.8 mV R/S ratio <1 in lead V4	Cardiomegaly	✔	✔	✔	-	-	✔	-	-	-	-	Previous myocardial infarction Hypertension (systemic and pulmonary) Cardiac arrythmias Viral infections (myocarditis) Congenital heart defects	Right heart failure associated with: Hepatomegaly Positive hepato-jugular reflex Increased jugular venous pressure Peripheral edema Left heart failure associated with: Pulmonary edema Eventual right heart failure
Pulmonary embolism	On CT angiography: Intra-luminal filling defect On MRI: Narrowing of involved vessel No contrast seen distal to obstruction Polo-mint sign (partial filling defect surrounded by contrast)	S1Q3T3 pattern representing acute right heart strain	Fleischner sign (enlarged pulmonary artery), Hampton hump, Westermark's sign	✔	✔	✔ (Low grade)	✔	✔ (In case of massive PE)	✔	-	-	-	-	Hypercoagulating conditions (Factor V Leiden, thrombophilia, deep vein thrombosis, immobilization, malignancy, pregnancy)	May be associated with metabolic alkalosis and syncope
Percarditis	On contrast enhanced CT scan: Enhancement of the pericardium (due to inflammation) Pericardial effusion Pericardial calcification On gadolinium-enhanced fat-saturated T1-weighted MRI: Pericardial enhancement (due to inflammation) Pericardial effusion	ST elevation PR depression	Large collection of fluid inside the pericardial sac (pericardial effusion) Calcification of pericardial sac	✔	✔	✔ (Low grade)	✔ (Relieved by sitting up and leaning forward)	-	✔	-	-	-	-	Infections: Viral (Coxsackie virus, Herpes virus, Mumps virus, HIV) Bacteria (Mycobacterium tuberculosis-common in developing countries) Fungal (Histoplasmosis) Idiopathic in a large number of cases Autoimmune Uremia Malignancy Previous myocardial infarction	May be clinically classified into: Acute (< 6 weeks) Sub-acute (6 weeks - 6 months) Chronic (> 6 months)
Vasculitis	On CT scan: (Takayasu arteritis) Vessel wall thickening Luminal narrowing of pulmonary artery Masses or nodules (ANCA-associated granulomatous vasculitis) On MRI: Homogeneous, circumferential vessel wall swelling	Right or left bundle-branch block (Churg-Strauss syndrome) Atrial fibrillation (Churg-Strauss syndrome) Non-specific ST segment and T wave changes	Nodules Cavitation	✔	✔	✔	✔	✔	✔	-	✔	✔	✔	Takayasu arteritis usually found in persons aged 4-60 years with a mean of 30 Giant-cell arteritis usually occurrs in persons aged > 60 years Churg-Strauss syndrome may present with asthma, sinusitis, transient pulmonary infiltrates and neuropathy alongwith cardiac involvement Granulomatous vasculitides may present with nephritis and upper airway (nasopharyngeal) destruction