It is a lymphocytic exudate whose main diagnoses are tumor and tuberculous pleuritis. They do not give the value of glucose which should be lowered, but if the cytology shows absence of malignant cells so we are left with tuberculous pleuritis. Other possible diagnoses such as lymphoma are not mentioned in the answers.

A 50-year-old patient presenting with a pleural effusion with the following features: straw-like appearance, pH 7.3, pleural protein/serum ratio 0.8, pleural LDH/serum ratio 0.9, Gram and Ziehl's negative, total lipids, cholesterol and triglycerides normal, mesothelial cells <5%, intense lymphocytosis without atypia, ADA 64 U/L. What diagnosis would you suggest?

Pleural effusion due to heart failure (transudate).

Effusion secondary to pulmonary infarction.

Pleural diseases.

In the United States, approximately one million patients each year develop a pleural effusion. Pleural effusions have classically been divided into transudative and exudative pleural effusions. A transudative pleural effusion occurs when the systemic factors influencing pleural fluid formation and reabsorption are altered so that pleural fluid accumulates; an exudative pleural effusion occurs when the local factors influencing pleural fluid formation and reabsorption are altered, allowing accumulation of pleural fluid. The leading causes of transudative pleural effusions are left ventricular failure and cirrhosis with ascites. The leading causes of exudative pleural effusions are pneumonia, malignancy, and pulmonary embolization. Transudative pleural effusions can be differentiated from exudative pleural effusions by measurement of the pleural fluid protein and lactic dehydrogenase (LDH) levels. The ratio of the pleural fluid protein to the serum protein is less than 0.5, the ratio of the pleural fluid LDH to the serum LDH is less than 0.6, and the absolute value of the pleural fluid LDH level is less than two thirds of the upper normal limit for serum with transudative pleural effusions while at least one of these criteria is not met with exudative effusions. Most patients who have a pleural effusion with congestive heart failure have left ventricular failure. It is believed that the transudation of the pulmonary interstitial fluid across the visceral pleura overwhelms the capacity of the lymphatics to remove the fluid. Most patients with cirrhosis who have a pleural effusion also have ascites. It is also believed that the pleural effusions form when fluid moves directly from the peritoneal cavity into the pleural cavity through pores in the diaphragm. Approximately 40% of patients with pneumonia will have a pleural effusion. If these patients have a significant amount of pleural fluid, a diagnostic thoracentesis should be performed. Chest tubes should be inserted if the pleural fluid is gross pus, if the Gram stain of the pleural fluid is positive, if the pleural fluid glucose level is below 40 mg/dl, or if the pleural fluid pH level is less than 7.00. If drainage with the chest tubes is unsatisfactory, either streptokinase or urokinase should be injected intrapleurally. If drainage is still unsatisfactory, a decortication should be considered. The three leading malignancies that have an associated pleural effusion are breast carcinoma, lung carcinoma, lymphomas and leukemias. The diagnosis of pleural malignancy is made most commonly with pleural fluid cytology; in recent years immunohistochemical tests have proved invaluable in differentiating benign from malignant pleural effusions.(ABSTRACT TRUNCATED AT 400 WORDS)

[Contribution of pleural fluid analysis to the diagnosis of pleural effusion].

Analysis of pleural fluid can have, on its own, a high diagnostic value. In addition to thoracocentesis, a diagnostic hypothesis based on medical history, physical examination, blood analysis and imaging tests, the diagnostic effectiveness will significantly increase in order to establish a definite or high probable diagnosis in a substantial number of patients. Differentiating transudates from exudates by the classical Light's criteria helps knowing the pathogenic mechanism resulting in pleural effusion, and it is also useful for differential diagnosis purposes. An increased N-terminal pro-brain natriuretic peptide, both in the fluid and in blood, in a due clinical context, is highly suggestive of heart failure. The presence of an increased inflammatory marker, such as C-reactive protein, together with the presence of over 50% of neutrophils is highly suggestive of parapneumonic pleural effusion. If, in these cases, the pH is<7.20, then the likelihood of complicated pleural effusion is high. There remains to be demonstrated the usefulness of other markers to differentiate complicated from uncomplicated effusions. An adenosine deaminase > 45 U/L and>50% lymphocytes is suggestive of tuberculosis. If a malignant effusion is suspected but the cytological result is negative, increased concentrations of some markers in the pleural fluid can yield high specificity values. Increased levels of mesothelin and fibruline-3 are suggestive of mesothelioma. Immunohistochemical studies can be useful to differentiate reactive mesothelial cells, mesothelioma and metastatic adenocarcinoma. An inadequate use of the information provided by the analysis of pleural fluid would results in a high rate of undiagnosed effusions, which is unacceptable in current clinical practice.

[Differential diagnosis between exudate and transudate in pleural effusion].

The objective was 1) to determine the usefulness of different criteria in the differential diagnosis between exudate and transudate in pleural effusion, 2) to evaluate albumin gradient changes in pleural effusion fluids characterized as transudates in patients who do and do not receive diuretic therapy, 3) to define the specificity of pleural effusions of neoplastic etiology. All patients with pleural effusion admitted to the hospital between January 15 and August 15 1994 were evaluated consecutively. Serum and pleural effusion, total protein, LDH, albumin and cholesterol levels were measured and the etiologic diagnosis of the pleural effusion (gold standard) was established. Out of the total of 112 evaluated patients, 7 were excluded because it was impossible to reach a final diagnosis. Based on the etiologic diagnosis, 47 patients (44.8%), average age of 69.6 +/- 12.07, had pleural effusions defined as transudate and 58 patients (55.2%), average age of 66.5 +/- 14.26, had pleural effusions defined as exudate. Sixty-six percent of the transudates were secondary to heart failure, while 40% of the exudates were of neoplastic origin. Using the criteria of Light et al, we obtained a diagnostic accuracy (DA) of 82.7% (CI 95% 73.1-90.0)%. However, when the cut-off point was modified according to Valdez and the value of cholesterol in pleural effusion and its relation to serum cholesterol was added, the DA rose to 90.2 (83.2-96.0)% (p < 0.05). The effusion-serum cholesterol ratio demonstrated 100 (85.1-100)% sensitivity for neoplastic effusions, whereas for non-neoplastic exudative effusions the sensitivity was 89 (73.2-96.8)%. The tests, however, showed only 17.4 (6.56-33.6)% specificity. The albumin gradient (the difference between serum and pleural effusion albumin) did no vary in patients with transudates who received diuretics, allowing a correct diagnosis of transudate in 93 (82.4-97.8)% of the cases. However, in patients who were taking diuretics, the classic criteria of protein index defined correctly only 66 (53.4-82.1)% of the cases (p < 0.05). It can be concluded that the variation of cut-off points originally established by Light et al. and the addition of cholesterol determination in pleural effusion and its relation to the serum cholesterol level allowed us to increase the DA. This appears to be the best way to differentiate a transudate from an exudate. The relation between pleural effusion and serum cholesterol levels showed a very low specificity for the differentiation of neoplastic and non-neoplastic exudative pleural effusions. Unlike the pleural effusion-serum total protein ratio, the albumin gradient allowed us to establish the correct diagnosis of transudate even in patients taking diuretics.

Pleural effusion

The ratio of pleural fluid protein to serum protein is greater than 0.5 The ratio of pleural fluid LDH and serum LDH is greater than 0.6 Pleural fluid LDH is greater than 0.6 or times the normal upper limit for serum. Different laboratories have different values for the upper limit of serum LDH, but examples include 200 and 300 IU/l.

Frequency and characteristics of pleural effusions in pulmonary embolism.

Pulmonary embolism (PE) is the fourth cause of pleural effusions, after pneumonia, neoinfiltrates and tuberculosis. Several questions are yet unanswered: are the pleural effusions in PE exudates or transudates, what is their size, are they unilateral or bilateral, are they only haemorrhagic, etc. The aim of this study is to determine the frequency, side, size, biochemical and cytological characteristics of pleural effusions in PE. In this study, 100 patients with suspicion of PE were examined and treated and in all the diagnosis of PE was establish. 31 of them had pleural effusions. Of 31 patients with PE and pleural effusions, six (9.84%), had bilateral pleural effusions, 14 (22.95%) patients had right-sided pleural effusion, and 11 (18.03%) had pleural effusion on the left side. 22 (36.07%) had small pleural effusions, 8 (13.11%) had medium and 1 (1.64%) had a large pleural effusion.18 (29.51%) had yellowish colored pleural effusions, 12 (19.67%) had haemorrhagic pleural effusions and 1 (1.64%) had transparent pleural effusion. Values of the total protein in pleural effusions varied in the interval 45.70±7.25 gr/l., 30 patients had LDH an effusion/sera ratio bigger than 0.6, and 1 patient had an LDH p/s ratio<0.6. 15 patients (24.59) had neutrophil cells, 10 (16.39%) had lymphocytes, and eosinophil cells dominated in 5 (8.20%). One patient (1.64%) had a negative cytological finding. We can conclude that pleural effusions secondary to PE can be found in around one third of all cases with PE. They are small, mostly unilateral, often but not always haemorrhagic. They are always exudates with a predomination of neutrofil cells.

Pleural cavity

If malignant cells are present, a pathologist may perform additional studies including immunohistochemistry to determine the etiology of the malignancy. Chemical analysis Chemistry studies may be performed including pH, pleural fluid:serum protein ratio, LDH ratio, specific gravity, cholesterol and bilirubin levels. These studies may help clarify the etiology of a pleural effusion (exudative vs transudative). Amylase may be elevated in pleural effusions related to gastric/esophageal perforations, pancreatitis or malignancy. Pleural effusions are classified as exudative (high protein) or transudative (low protein).

Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure.

Diuretic therapy increases the total protein and lactate dehydrogenase concentrations in pleural fluid in patients with transudates due to heart failure, but the effect of diuresis on other substances in pleural fluid constituents is not known. Twenty-one patients with transudative pleural effusions due to congestive heart failure were prospectively studied. Repeated diagnostic thoracentesis (mean +/- SD = 3 +/- 1; range, 2 to 6) was performed until the effusions were radiographically unapparent (5 +/- 2 days). Thirty-one patients with congestive heart failure who underwent only a single thoracentesis after diuretic therapy served as controls. We measured the concentrations of various components of pleural effusions in the serum and in the pleural fluid, and determined the serum-pleural fluid gradient (serum concentration minus pleural fluid concentration) and ratio (serum concentration divided by pleural fluid concentration). The pleural concentrations of most components increased significantly (P <0.001) from the initial specimen to the final specimen: total protein, from 23 +/- 7 g/L to 33 +/- 9 g/L; albumin, from 13 +/- 4 g/L to 18 +/- 6 g/L; lactate dehydrogenase, from 177 +/- 62 U/L to 288 +/- 90 U/L; cholesterol, from 31 +/- 16 mg/dL to 52 +/- 22 mg/dL; and cholinesterase, from 1,304 +/- 616 U/L to 1,884 +/- 674 U/L. Expressed as percentage change, the increases in the serum-pleural fluid gradients for albumin (12% +/- 22%) and total protein (11% +/- 12%) were significantly less than the increases in their concentrations in pleural fluid (albumin, 47% +/- 49%; total protein, 48% +/- 40%) or in their pleural fluid/serum ratios (albumin, 27% +/- 29%; total protein, 38% +/- 34%). The concentrations of the biochemical components commonly measured in pleural fluid increase progressively during diuretic therapy. Calculation of the serum-pleural fluid gradients for protein and albumin may be the most useful way to distinguish transudates from exudates in patients with congestive heart failure who have undergone diuresis.

[Cuttoff values of biochemical tests on pleural fluid: their usefulness in differential diagnosis of 1,040 patients with pleural effusion].

The aim of biochemical pleural fluid testing is to reach an etiological diagnosis of the pleural effusion. We assessed the utility of considering cuttoff points for the wide range of analytes used to investigate pleural fluid. Among 1,040 patients with pleural effusion, we sought the etiologies of those fluids which showed any of the following characteristics: red blood cell count = 10 x 109/L, leukocytes = 10 x 109/L, percentage of neutrophils or lymphocytes >50%, protein = 50 g/L, glucose = 60 mg/dL, pH = 7.2, lactate dehydrogenase = 1,000 U/L, adenosine deaminase = 40 U/L, amylase = 100 U/L or cholesterol = 60 mg/dL. Some of the more prominent findings were: a) a sixth of transudates were blood-tinged or contained predominantly neutrophils; b) a groosly bloody fluid suggests malignant disease, trauma, or pulmonary embolization; c) nearly 90% of fluids containing = 10 x 10(9) leukocytes/L were parapneumonics; d) 73% of tuberculous pleural fluids had protein > or = 50 g/L, e) tuberculosis and parapneumonics explained more than 90% of fluids with high adenosine deaminase content; f) one third of amylase-rich pleural effusions were malignant; g) a low pleural glucose or pH levels indicate that patient probably has a parapneumonic, tuberculous or malignant etiology; y h) the diagnostic yield of pleural fluid cytology in malignant effusions was 57%, a percentage which raised to 94% in those with low glucose fluid level. Cuttof values of biochemical pleural fluid tests may greatly support particular causes of pleural effusions.

Thoracentesis

Transudate Congestive heart failure Nephrotic syndrome Hypoalbuminemia Cirrhosis Atelectasis trapped lung Peritoneal dialysis Superior vena cava obstruction Amylase A high amylase level (twice the serum level or the absolute value is greater than 160 Somogy units) in the pleural fluid is indicative of either acute or chronic pancreatitis, pancreatic pseudocyst that has dissected or ruptured into the pleural space, cancer or esophageal rupture. Glucose This is considered low if pleural fluid value is less than 50% of normal serum value. The differential diagnosis for this is: rheumatoid effusion. The levels are characteristically low (<15 mg/dL). lupus effusion bacterial empyema malignancy tuberculosis esophageal rupture (Boerhaave syndrome) pH Normal pleural fluid pH is approximately 7.60. A pleural fluid pH below 7.30 with normal arterial blood pH has the same differential diagnosis as low pleural fluid glucose.

Chylothorax

The fluid of a chylothorax may appear milky, serous or serosanguineous. If the appearance of the fluid is not milky, that does not exclude a chylothorax from consideration. Since chyle is rich in triglycerides, a pleural effusion that is rich in triglycerides (>110 mg/dL) confirms the presence of a chylothorax; a pleural effusion that is low in triglyceride content (<50 mg/dL) virtually excludes the diagnosis. If a pleural effusion contains triglycerides between 50–110 mg/dL, analysis of the lipoprotein content of the pleural effusion to evaluate for chylomicrons is recommended. If that procedure detects chylomicrons in the fluid, that confirms a chylothorax. Chylothoraces are typically exudative and often contain a high number of lymphocytes and have low levels of the enzyme lactate dehydrogenase (LDH). However, atypical chylothoraces can occur and are transudative in 14% of cases. A milky appearance of pleural fluid is insufficient to confirm the diagnosis of chylothorax as

Behaviour of nucleated cells in various types of pleural effusion.

To know the behavior of cellular components of pleural fluid can help focus the differential diagnosis of a pleural effusion. Our objective was to assess their composition in different types of pleural effusions and assess whether it provides relevant clinical information. Observational, cross-sectional and retrospective study in which the cellular components of pleural effusions of different etiology were analyzed. Pleural effusions were classified as neutrophilic, lymphocytic (≥50% of each one of them), eosinophilic (≥10%) or mesothelial (>5%) and were grouped into six diagnostic categories RESULTS: 1.467 patients were studied (354 heart failure; 59 other transudates; 349 paraneumonic; 133 tuberculous; 397 malignant and 175 other exudates). The predominance cell was lymphocytic in heart failure (44,4%), uncomplicated parapneumonic (29,2%), tuberculosis (88%) and malignant (49,6%); neutrophilic in parapneumonic (57%) and malignant (9,6%); eosinophilic in malignant (6,3%) and mesotelial in tuberculosis (12%). The most frequent etiologies with lymphocyte count ≥80% were tuberculosis (35,1%) and malignant (23,3%). Parameters with higher discriminating accuracy were: leukocytes (transudates: AUC 0,835) and percentage of neutrophils (empyemas: AUC 0,906 and complicated parapneumonic+empyemas: AUC 0,907). Nucleated cell counts will help focus the etiology of pleural effusions, since each etiology often have a characteristic cell predominance. The percentage of nucleated cells in pleural fluid not ruled out tuberculosis if there is a high count of mesothelial cells, nor a parapneumonic effusion with lymphocytic predominance, or malignancy with ≥80% lymphocytes.

Thoracentesis

A transudate is defined as pleural fluid to serum total protein ratio of less than 0.5, pleural fluid to serum LDH ratio > 0.6, and absolute pleural fluid LDH > 200 IU or > 2/3 of the normal. An exudate is defined as pleural fluid that filters from the circulatory system into lesions or areas of inflammation. Its composition varies but generally includes water and the dissolved solutes of the main circulatory fluid such as blood. In the case of blood it will contain some or all plasma proteins, white blood cells, platelets and (in the case of local vascular damage) red blood cells. Exudate hemorrhage Infection Inflammation Malignancy Iatrogenic Connective tissue disease Endocrine disorders Lymphatic disorders vs Constrictive pericarditis Transudate Congestive heart failure Nephrotic syndrome Hypoalbuminemia Cirrhosis Atelectasis trapped lung Peritoneal dialysis Superior vena cava obstruction

Transudative pleural effusions.

A transudative pleural effusion develops when the systemic factors influencing the formation or absorption of the pleural fluid are altered. The pleural surfaces are not involved by the primary pathologic process. The diagnosis of transudative effusion is simple to establish by examining the characteristics of the pleural fluid. Transudates have all of the following three characteristics: The ratio of the pleural fluid to the serum protein is less than 0.5. The ratio of the pleural fluid to the serum LDH is less than 0.6. The pleural fluid LDH is less than two thirds the upper limit of normal for the serum LDH. Among the conditions that produce transudative pleural effusion, congestive heart failure is by far the most common. Pulmonary embolism, cirrhosis of the liver with ascites, and the nephrotic syndrome are the other common causes. Management of transudative pleural effusions involves managing the primary disease. Refractory, massive effusions can be controlled by tetracycline pleurodesis.

Pleural effusion

The sensitivity and specificity of Light's criteria for detection of exudates have been measured in many studies and are usually reported to be around 98% and 80%, respectively. This means that although Light's criteria are relatively accurate, twenty percent of patients that are identified by Light's criteria as having exudative pleural effusions actually have transudative pleural effusions. Therefore, if a patient identified by Light's criteria as having an exudative pleural effusion appears clinically to have a condition that usually produces transudative effusions, additional testing is needed. In such cases, albumin levels in blood and pleural fluid are measured. If the difference between the albumin level in the blood and the pleural fluid is greater than 1.2 g/dL (12 g/L), this suggests that the patient has a transudative pleural effusion. However, pleural fluid testing is not perfect, and the final decision about whether a fluid is a transudate or an exudate is based not on

Management of pleural effusions.

This review summarizes current strategies in the treatment of patients with pleural effusion. To determine whether a patient has a transudative or exudative pleural effusion, Light's criteria should be applied to measure the concentrations of protein and lactate dehydrogenase (LDH) in the pleural fluid and serum. If the effusion is transudative, therapy should be directed toward the underlying congestive heart failure, cirrhosis, or nephrosis. Consideration should be given to pleurodesis with a sclerosant if patients with recurrent transudative effusion have severe dyspnea due to their effusion. If the effusion is exudative, attempts should be made to define the etiology. The diagnosis of pleural malignancy is most easily established via pleural fluid cytology. If this is negative and the patient is suspected of having pleural malignancy, thoracoscopy is indicated. The concentrations of adenosine deaminase and gamma-interferon in pleural fluid are useful in the diagnosis of pleural tuberculosis. Patients with pneumonia and pleural effusion should undergo therapeutic thoracentesis; the pleural fluid should be Gram-stained and cultured, and the differential cell count, glucose and LDH concentration, and pH should be determined. Indicators of a poor prognosis include the presence of frank pus, a positive Gram-stain, a pleural glucose concentration of less than 2.2 mmol/L, a pH less than 7.00, the presence of pleural loculations, and an LDH concentration greater than three times the upper limit of normal in serum. If the pleural fluid cannot be completely evacuated because of loculations, intrapleural thrombolytic therapy should be considered. If thrombolytics are ineffective, thoracoscopy or thoracotomy with decortication should be performed. Dyspneic patients with malignant pleural effusions whose dyspnea is relieved with therapeutic thoracentesis should be considered for pleurodesis using a tetracycline derivative. Talc is not recommended because it induces acute respiratory distress syndrome in about 5% of patients, with an overall mortality of 1%.

Pleural effusion

When a pleural effusion has been determined to be exudative, additional evaluation is needed to determine its cause, and amylase, glucose, pH and cell counts should be measured. Red blood cell counts are elevated in cases of bloody effusions (for example after heart surgery or hemothorax from incomplete evacuation of blood). Amylase levels are elevated in cases of esophageal rupture, pancreatic pleural effusion, or cancer. Glucose is decreased with cancer, bacterial infections, or rheumatoid pleuritis. pH is low in empyema (<7.2) and maybe low in cancer. If cancer is suspected, the pleural fluid is sent for cytology. If cytology is negative, and cancer is still suspected, either a thoracoscopy, or needle biopsy of the pleura may be performed. Gram staining and culture should also be done.

Thoracentesis

pH Normal pleural fluid pH is approximately 7.60. A pleural fluid pH below 7.30 with normal arterial blood pH has the same differential diagnosis as low pleural fluid glucose. Triglyceride and cholesterol Chylothorax (fluid from lymph vessels leaking into the pleural cavity) may be identified by determining triglyceride and cholesterol levels, which are relatively high in lymph. A triglyceride level over 110 mg/dl and the presence of chylomicrons indicate a chylous effusion. The appearance is generally milky but can be serous. The main cause for chylothorax is rupture of the thoracic duct, most frequently as a result of trauma or malignancy (such as lymphoma). Cell count and differential The number of white blood cells can give an indication of infection. The specific subtypes can also give clues as to the type on infection. The amount of red blood cells are an obvious sign of bleeding.

Pleural effusion

By pathophysiology: Transudative pleural effusion Exudative pleural effusion By the underlying cause (see next section). Causes Transudative The most common causes of transudative pleural effusion in the United States are heart failure and cirrhosis. Nephrotic syndrome, leading to the loss of large amounts of albumin in urine and resultant low albumin levels in the blood and reduced colloid osmotic pressure, is another less common cause of pleural effusion. Pulmonary emboli were once thought to cause transudative effusions, but have been recently shown to be exudative. The mechanism for the exudative pleural effusion in pulmonary thromboembolism is probably related to increased permeability of the capillaries in the lung, which results from the release of cytokines or inflammatory mediators (e.g. vascular endothelial growth factor) from the platelet-rich blood clots. The excessive interstitial lung fluid traverses the visceral pleura and accumulates in the pleural space.

Pleural cavity

Absorption occurs into lymphatic vessels at the level of the diaphragmatic pleura. Clinical significance Pleural effusion A pathologic collection of pleural fluid is called a pleural effusion. Mechanisms: Lymphatic obstruction Increased capillary permeability Decreased plasma colloid osmotic pressure Increased capillary venous pressure Increased negative intrapleural pressure Pleural effusions are classified as exudative (high protein) or transudative (low protein). Exudative pleural effusions are generally caused by infections such as pneumonia (parapneumonic pleural effusion), malignancy, granulomatous disease such as tuberculosis or coccidioidomycosis, collagen vascular diseases, and other inflammatory states. Transudative pleural effusions occur in congestive heart failure (CHF), cirrhosis or nephrotic syndrome.

Role of pleural fluid cholesterol in differentiating transudative from exudative pleural effusion.

Pleural fluid cholesterol has been reported to be useful in distinguishing between transudative and exudative pleural effusion. However, the difference in lipid profile between tubercular and non-tubercular pleural effusion has not been studied. The lipid profile of pleural fluid in 50 patients with exudative (25 tubercular and 25 non-tubercular) and 25 with transudative effusion was studied. The diagnosis was based on clinical criteria and/or a positive diagnosis from another site. The criteria that best identified an exudative pleural effusion were pleural fluid cholesterol > or = 60 mg/dl, pleural fluid to serum cholesterol ratio > or = 0.4, pleural fluid triglyceride > or = 40 mg/dl and pleural fluid to serum triglyceride ratio > or = 0.3. Pleural fluid cholesterol had a sensitivity of 88% and a specificity of 100% for exudates with an accuracy of 92%. Pleural fluid to serum cholesterol ratio had a sensitivity of 98% and a specificity of 84%. These results were superior to the criteria proposed by Light et al. (sensitivity 98% and specificity 80%). Pleural fluid cholesterol estimation is an effective and cost-efficient method of differentiating exudative from transudative pleural effusion. The lipid profile does not help in diagnosing tubercular effusion.

[Clinical evaluation and tissue distribution of CA125 in patients with pleural effusion].

CA125 in serum and pleural effusion was measured in 51 patients with malignant effusion and 38 patients with benign effusion, and the tissue distribution of CA125 was investigated by immunohistochemical technique. The 51 malignant effusions were secondary to primary lung cancer. The 38 benign effusions were taken from 23 patients with tuberculous pleurisy, 9 patients with empyema, 5 patients with congestive heart failure and one patient with nephrosis. In the mean level and the positive rate of serum CA125, no significant difference was shown between primary lung cancer and tuberculosis or the other benign diseases. The mean level of CA125 in pleural effusion of primary lung cancer was significantly higher than that in pleural effusion of tuberculosis (p less than 0.01), and showed a tendency to increase compared to that in pleural effusion of the other benign diseases (p less than 0.1). The mean level of CA125 in pleural effusion of tuberculosis was significantly lower than that in the other benign diseases (p less than 0.02). The positive rate of CA125 in malignant effusion was 43.1% and the diagnostic specificity of it was 86.7%. CA125 was detected in carcinoma cells and activated mesothelial cells in pleural effusion and mesothelial cells of normal pleural tissue by immunohistochemical staining. These results suggest that the measurement of CA125 in pleural effusion is useful for differential diagnosis of the malignant effusion from the benign effusion and that CA125 in pleural effusion of pleuritis carcinomatosa is produced by not only carcinoma cells but also activated mesothelial cells.

Parapneumonic effusion

A parapneumonic effusion is a type of pleural effusion that arises as a result of a pneumonia, lung abscess, or bronchiectasis. There are three types of parapneumonic effusions: uncomplicated effusions, complicated effusions, and empyema. Uncomplicated effusions generally respond well to appropriate antibiotic treatment. Diagnosis The criteria for a complicated parapneumonic effusion include Gram stain–positive or culture-positive pleural fluid, pleural fluid pH <7.20, and pleural fluid LDH that is greater than three times the upper limit of normal of serum LDH. Diagnostic techniques available include plain film chest x-ray, computed tomography (CT), and ultrasound. Ultrasound can be useful in differentiating between empyema and other transudative and exudative effusions due in part to relative echogenicity of different organs such as the liver (often isoechogenic with empyema).

InternalMed_Harrison

Perform diagnostic thoracentesis Measure pleural fluid protein and LDH Exudate Further diagnostic procedures Transudate Treat CHF, cirrhosis, nephrosis Measure PF glucose Obtain PF cytology Obtain differential cell count Culture, stain PF PF marker for TB Consider:Malignancy Bacterial infections Rheumatoid pleuritis Glucose < 60 mg/dL No diagnosis Consider pulmonary embolus (spiral CT or lung scan) Treat for PE Treat for TB PF marker for TB Observe Consider thoracoscopy or image-guided pleural biopsy Any of following met? PF/serum protein > 0.5 PF/serum LDH > 0.6 PF LDH > 2/3 upper normal serum limit Pleural effusion Yes No Yes Yes Yes No No No SYMPTOMS IMPROVING FIGURE 316-1 Approach to the diagnosis of pleural effusions. CHF, congestive heart failure; CT, computed tomography; LDH, lactate dehydrogenase; PE, pulmonary embolism; PF, pleural fluid; TB, tuberculosis.

Thoracentesis

The use of ultrasound for needle guidance can minimize the complication rate. Follow-up imaging While chest X-ray has traditionally been performed to assess for pneumothorax following the procedure, it may no longer be necessary to do so in asymptomatic, non-ventilated persons given the widespread use of ultrasound to guide this procedure. Interpretation of pleural fluid analysis Several diagnostic tools are available to determine the etiology of pleural fluid. Transudate versus exudate First the fluid is either transudate or exudate. A transudate is defined as pleural fluid to serum total protein ratio of less than 0.5, pleural fluid to serum LDH ratio > 0.6, and absolute pleural fluid LDH > 200 IU or > 2/3 of the normal.

Malignant pleural effusion

Malignant pleural effusion is a condition in which cancer causes an abnormal amount of fluid to collect between the thin layers of tissue (pleura) lining the outside of the lung and the wall of the chest cavity. Lung cancer and breast cancer account for about 50-65% of malignant pleural effusions. Other common causes include pleural mesothelioma and lymphoma. Diagnosis Clinical evaluation Clinical factors predicting the diagnosis of malignant pleural effusions are symptoms lasting more than 1 month and the absence of fever.

The etiology of pleural effusions in an area with high incidence of tuberculosis.

To investigate the etiology of pleural effusions in our region, we undertook a prospective study of patients with this condition in our centers. During a 5-year period, we studied 642 pleural effusion patients aged 57.1 +/- 21.1 years, of whom 401 were men aged 56.5 +/- 21 years and 241 were women aged 57.8 +/- 21.4 years; the male/female ratio was 1.6:1. The most frequent cause of pleural effusion was tuberculosis (25%), followed by neoplasia (22.9%) and congestive heart failure (17.9%). The etiology of 48 cases (7.5%) remained uncertain. In the neoplastic effusion group, the most frequent locations of the primary tumor were lung (32.6%), breast (11.5%), lymphoma (10.8%), and ovary (7.5%); in 21 cases (14.3% of the neoplastic group), it was not possible to identify the primary tumor. The 111 patients aged younger than 40 years with tuberculous effusions made up 69.4% of tuberculous effusion cases and the same percentage of patients younger than 40 years; the proportion of effusions that were tuberculous peaked in the 11- to 30-year-old age group and declined steadily thereafter. Of the patients with neoplastic effusions, 83% were older than 50 years; the proportion of effusions that were neoplastic rose steadily from zero in the 0- to 30-year-old age group to a peak among 60- to 70-year-olds. The age-wise distribution of effusions secondary to congestive heart failure was similar to that of neoplastic effusions. Of the effusions secondary to congestive heart failure, 86% (99/115) affected the right pleura or both, and 83% of effusions secondary to pulmonary thromboembolism (15/18) affected the right side. Neoplastic, tuberculous, parapneumonic, empyematous, and other exudative effusions showed no preference for either side. Of the 97 bilateral effusions, 77 (79.4%) were secondary to heart failure (59, 60.8%) or neoplasia (18, 18.6%). We conclude that in our region, the most frequent cause of pleural effusion is tuberculosis, followed by neoplasia and congestive heart failure. We suggest that all those interested in pleural disease should determine the etiologic pattern of pleural effusion in their region with a view to the adoption of regionally optimized diagnostic and therapeutic attitudes.

InternalMed_Harrison

If a patient has an exudative pleural effusion, the following tests on the pleural fluid should be obtained: description of the appearance of the fluid, glucose level, differential cell count, microbiologic studies, and cytology. Effusion Due to Heart Failure The most common cause of pleural effusion is left ventricular failure. The effusion occurs because the increased amounts of fluid in the lung interstitial spaces exit in part across the visceral pleura; this overwhelms the capacity of the lymphatics in the parietal pleura to remove fluid. In patients with heart failure,

Malignant pleural effusion

Diagnosis Clinical evaluation Clinical factors predicting the diagnosis of malignant pleural effusions are symptoms lasting more than 1 month and the absence of fever. Imaging This is needed to confirm the presence of a pleural effusion. Chest radiograph is usually performed first and may demonstrate an underlying lung cancer as well as the pleural effusion. Ultrasound has a sensitivity of 73% and specificity of 100% at distinguishing malignant pleural effusions from other causes of pleural effusion, based on the presence of visible pleural metastases, pleural thickening greater than 1 cm, pleural nodularity, diaphragmatic thickening measuring greater than 7mm and an echogenic swirling pattern visible in the pleural fluid. Biochemical analysis Malignant pleural effusions are exudates. A low pleural fluid pH is associated with poorer survival and reduced pleurodesis efficacy.

Pleural effusion

Transudative pleural effusions are defined as effusions that are caused by systemic factors that alter the pleural equilibrium, or Starling forces. The components of the Starling forces – hydrostatic pressure, permeability, and oncotic pressure (effective pressure due to the composition of the pleural fluid and blood) – are altered in many diseases, e.g., left ventricular failure, kidney failure, liver failure, and cirrhosis. Exudative pleural effusions, by contrast, are caused by alterations in local factors that influence the formation and absorption of pleural fluid (e.g., bacterial pneumonia, cancer, pulmonary embolism, and viral infection). An accurate diagnosis of the cause of the effusion, transudate versus exudate, relies on a comparison of the chemistries in the pleural fluid to those in the blood, using Light's criteria. According to Light's criteria (Light, et al. 1972), a pleural effusion is likely exudative if at least one of the following exists:

Pleural effusion

The most common causes of exudative pleural effusions are bacterial pneumonia, cancer (with lung cancer, breast cancer, and lymphoma causing approximately 75% of all malignant pleural effusions), viral infection, and pulmonary embolism. Another common cause is after heart surgery when incompletely drained blood can lead to an inflammatory response that causes exudative pleural fluid. Conditions associated with exudative pleural effusions: Parapneumonic effusion due to pneumonia Malignancy (either lung cancer or metastases to the pleura from elsewhere) Infection (empyema due to bacterial pneumonia) Trauma Pulmonary infarction Pulmonary embolism Autoimmune disorders Pancreatitis Ruptured esophagus (Boerhaave's syndrome) Rheumatoid pleurisy Drug-induced lupus

Pleural Effusion -- Evaluation

Commonly performed tests on the pleural fluid to determine etiology are a measurement of fluid pH, fluid protein, albumin and LDH, fluid glucose, fluid triglyceride, fluid cell count differential, fluid gram stain and culture, and fluid cytology. Exudates are characterized by elevated protein, elevated LDH, and decreased glucose. Pleural fluid LDH greater than 1000 U/L may be seen in tuberculosis, lymphoma, and empyema. Low pH (pH less than 7.2) indicates complex pleural effusion in the setting of pneumonia and almost always requires chest tube insertion for drainage. Other causes of low pH may be an esophageal rupture and rheumatoid arthritis.

Pleural effusion

See also Pleural disease Empyema Heart failure Pulmonary embolism Subpulmonic effusion Thoracentesis References External links Pleural Effusion Images from MedPix Disorders of fascia Diseases of pleura Articles containing video clips


Let's see, if that subject was not in any risk group, the positive is in the 15mm, therefore both tests are negative, and as only one answer refers to negative, that's it. But both could be false negatives.

Let's see, if that subject was not in any risk group, the positive is in the 15mm, therefore both tests are negative, and as only one answer refers to negative, [HIDDEN]. But both could be false negatives.

In a subject over 65 years of age a tuberculin test has shown an induration of 3 mm. The induration on a second test, performed 10 days later, is 13 mm. Point out the correct answer:

The second reaction is a false positive.

TUBERCULIN reaction size on five consecutive days.

The present paper gives the results of a study on tuberculin reaction size-erythema and induration-at different intervals after intradermal testing with 1 TU.In the course of tuberculin-testing some 18,000 textile workers in Mehalla el Kobra, Egypt, the tuberculin reactions of 417 men were read daily for five days after the tests had been given. The successive readings were made by the same observer without reference to his previous readings.No difference of any practical significance was found between the results of readings made on the second through the fifth day. Almost all the reactions of over 6 mm of induration on any one day (except the first) remained above 6 mm on the subsequent days, and those measuring 0-6 mm did not exceed 6 mm on the later days. Thus, whether the reactions had been read on the second, third, fourth, or fifth day, essentially the same persons would have been classified as positive and negative according to the induration-reaction size.Erythema could have served as well as induration for separating the study population into the same two groups, had 0-8 mm of erythema been defined as negative and erythema of 9 mm or more as positive for reactions read on the second through the fifth day.In tuberculin surveys of the population under study there would thus have been no need to adhere to a fixed reading interval.The material included in the present paper illustrates how the results of a relatively small and inexpensive preliminary study may serve to simplify and rationalize subsequent large-scale work.

Four-stage tuberculin testing in elderly subjects induces age-dependent progressive boosting.

We administered four sequential tuberculin skin tests (5 TU, PPD) with intervals of one week to 223 subjects older than 65 years of age to evaluate whether elderly subjects demonstrated progressive boosting. Indurations of at least 10 mm with increases of at least 6 mm (over the previous test) were considered significant reactions, and these were found in 29 percent of the subjects after test 1, in 43 percent after test 2, in 53 percent after test 3, and in 57 percent after test 4 (p less than 0.05), ie, only about 50 percent of all the positives were detected after the first test. The percentage of positive reactors was inversely related to age (p less than 0.001), yet this age-dependent difference decreased with increasing number of tests. For the 65- to 74-year-old age group, 44 percent reacted positively after the first test and after three tests almost a plateau of 65 to 70 percent positive reactors was reached, suggesting that a minority only of about 30 to 35 percent of these geriatric patients might have outlived their bacilli or were never infected. For the 75- to 84-year-old age group, 24 percent reacted after the first test and 55 percent reacted after the fourth one. For the older than 85-year-old age group, 19 percent positive reactors were found after the first test and 46 percent were found after the fourth test, without clear-cut leveling off toward a plateau value, suggesting that additional tests would induce further boosting. Mean diameters of positive reactions were 15 to 24 mm, and were mostly at least 12 mm larger than in the previous tests. These data support the hypothesis that the negative tuberculin reaction, which is often found in elderly subjects, is mainly due to the failing immune response to tuberculin antigen that can be restored progressively by repeated administrations. These findings, furthermore, emphasize that especially in elderly, care should be taken not to interpret a boosting reaction as a conversion and especially that neither a two-step testing as recommended by the ATS and CDC (Am Rev Respir Dis 1990; 142:723-35) nor even a four-step testing may suffice to detect all positives in this type of population.

Two-stage tuberculin skin testing in an HIV-infected population: a preliminary report.

To identify differences in purified protein derivative (PPD) tuberculin positivity rates and to assess the utility of sequential PPD testing among persons with HIV infection, we performed two sequential administrations of 5 tuberculin units of PPD in a group of persons with HIV infection. Eligible patients were skin-tested with the tuberculin using the Mantoux method. Patients who tested < 5 mm of induration were skin-tested seven days later along with Candida and mumps antigens. Of 37 tested patients, only 18 (49%) returned to have the first test read. Using a > or = 5 mm cutoff, 5 (28%) tested positive. Positivity varied markedly between patients with CD4+ cell counts under and at or over 400 cells/mm3 (0% vs. 56%). Among patients who had a reaction to the first test, the reaction was smaller in patients with CD4+ cell counts under 400 than in those with counts at or over 400 cells/mm3 (mean induration: 2.8 vs. 30.4 mm). Positivity was also less frequent in intravenous drug users than in nonusers (9% vs. 57%); these two groups did not differ with respect to CD4+ cell counts. Of the 13 patients who tested < 5 mm, only 8 (62%) kept their appointments to have the second test placed and read. Only 1 of these, a drug user with a CD4+ count of 6 cells/mm3, had a positive reaction with boosting from 4 mm on the first test to 10 mm on the second. These data indicate that PPD testing may be unreliable in screening for tuberculosis infection in persons with CD4+ counts < 400 cell/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

[Two-step tuberculin skin testing in our hospital employees].

To evaluate the baseline values of tuberculin reaction, two-step tuberculin skin testing was carried out in 365 employees of our hospital. We defined strongly response group when the size of erythema showed more than 30 mm or who showed strongly positive reaction. Two-step tuberculin skin testing was carried out in 165 hospital employees excluding those who were defined as the strongly response group in the first testing. 80 hospital employees (48.5%) became strongly response group by the second tuberculin skin testing. Altogether, 76.7% of all employees were strongly response group either by the first time or the second tuberculin skin testing. The size of erythema and that of induration showed 13.2 +/- 12.6 mm (mean +/- SD), 6.9 +/- 9.2 mm increase, respectively, in the two-step tuberculin skin testing, so-called Booster phenomenon. We could not know the true tuberculin reaction status by the single tuberculin skin testing. Therefore, two-step tuberculin skin testing is important as one of an infection prevention countermeasures in the hospital workers.

Stability of positive tuberculin tests: are boosted reactions valid?

To determine the stability and presumed significance of tuberculin skin tests, we followed a cohort of 380 tuberculin-positive patients living in chronic care facilities. Each patient had a positive reaction (greater than or equal to 10 mm induration to 5 tuberculin units of purified protein derivative) to one of three sequential baseline tuberculin tests. One year after the initial series, each patient had a single repeat skin test. Reversion to a negative test occurred in 98 (26%) of the 380 patients. Decreases in induration of 6 mm or more occurred in 88 (90%) of the reverters. Initially positive tests were more likely (p less than 0.001) to remain stable than tests that were "boosted" to positive reactions on the second or third initial administration. Stable responses were found in 96% of those whose tests had greater than or equal to 15 mm induration compared with 61% of those with reactions of 10 to 14 mm induration. Increasing age also was associated with a high rate of reversion. The instability of boosted tuberculin reactions brings into question the clinical significance of these tests. We propose limiting tuberculin testing to two sequential tests.

Choosing an appropriate criterion for true or false conversion in serial tuberculin testing.

This study evaluates five different criteria of true conversion in relation to the annual tuberculosis infection rate or risk of infection. It also examines prospective results of a general population, 16 to 69 yr of age, who had less than 6 mm of induration at first PPD test. This population received a second PPD test between 1976 and 1986. In about 95% of cases, the interval was 1 to 5 yr. In 1,355 bacillus Calmette-Guerin (BCG)-vaccinated subjects, none of the criteria is acceptable for true conversion. Among 1,834 nonvaccinated BCG, only the criterion of a change from less than 10 to 18 mm or more with an increase of 12 mm or more, or the criterion of change from less than 10 to 18 mm or more with an increase of 18 mm or more, is compatible with true conversion and with the correspondent annual risk of infection. But we must accept that with smaller increases, recently infected persons may escape diagnosis of infection. A third test was performed in 81 subjects with two negative test results. In all cases except one, the annual conversion rate observed was much higher than the annual risk of infection. These data reveal shortcomings of the current criterion for conversion. They show that the tuberculin conversion at retesting is not epidemiologically related to new infection and that none of the criteria assures the discovery of true converters. Other factors must be taken into account.

The presence of a booster phenomenon among contacts of active pulmonary tuberculosis cases: a retrospective cohort.

Assuming a higher risk of latent tuberculosis (TB) infection in the population of Rio de Janeiro, Brazil, in October of 1998 the TB Control Program of Clementino Fraga Filho Hospital (CFFH) routinely started to recommend a two-step tuberculin skin test (TST) in contacts of pulmonary TB cases in order to distinguish a boosting reaction due to a recall of delayed hypersensitivity previously established by infection with Mycobacterium tuberculosis (M.tb) or BCG vaccination from a tuberculin conversion. The aim of this study was to assess the prevalence of boosted tuberculin skin tests among contacts of individuals with active pulmonary tuberculosis (TB). Retrospective cohort of TB contacts > or = 12 years old who were evaluated between October 1st, 1998 and October 31st 2001. Contacts with an initial TST < or = 4 mm were considered negative and had a second TST applied after 7-14 days. Boosting reaction was defined as a second TST > or = 10 mm with an increase in induration > or = 6 mm related to the first TST. All contacts with either a positive initial or repeat TST had a chest x-ray to rule out active TB disease, and initially positive contacts were offered isoniazid preventive therapy. Contacts that boosted did not receive treatment for latent TB infection and were followed for 24 months to monitor the development of TB. Statistical analysis of dichotomous variables was performed using Chi-square test. Differences were considered significant at a p < 0.05. Fifty four percent (572/1060) of contacts had an initial negative TST and 79% of them (455/572) had a second TST. Boosting was identified in 6% (28/455). The mean age of contacts with a boosting reaction was 42.3 +/- 21.1 and with no boosting was 28.7 +/- 21.7 (p = 0.01). Fifty percent (14/28) of individuals whose test boosted met criteria for TST conversion on the second TST (increase in induration > or = 10 mm). None of the 28 contacts whose reaction boosted developed TB disease within two years following the TST. The low number of contacts with boosting and the difficulty in distinguishing boosting from TST conversion in the second TST suggests that the strategy of two-step TST testing among contacts of active TB cases may not be useful. However, this conclusion must be taken with caution because of the small number of subjects followed.

Mantoux test

Use of two-step testing is recommended for initial skin testing of adults who will be retested periodically (e.g., health care workers). This ensures any future positive tests can be interpreted as being caused by a new infection, rather than simply a reaction to an old infection. The first test is read 48–72 hours after injection. If the first test is positive, consider the person infected. If the first test is negative, give a second test one to three weeks after the first injection. The second test is read 48–72 hours after injection. If the second test is positive, consider the person infected in the distant past If the second test is negative, consider the person uninfected. A person who is diagnosed as "infected in the distant past" on two-step testing is called a "tuberculin reactor". The US recommendation that prior BCG vaccination be ignored results in almost universal false diagnosis of tuberculosis infection in people who have had BCG (mostly foreign nationals).

[Tuberculin screening tests. Open comparative trial of Tine-Test and Monotest versus Mantoux 1:1000 (10 TU) in 119 outpatients].

The two percutaneous tuberculin tests Tine test (TT) (old tuberculin) and Monotest (MT) (PPD-tuberculin) were compared simultaneously with the standard intradermal reaction (Mantoux [MX] 1:1000 = 10 EPPD-RT23-tuberculin) in 119 unselected 16-81 year old outpatients (general medicine) in an open trial. The tests were read after 48 and/or 72 h. Indurations of greater than or equal to 10 mm (MX), greater than or equal to 2 mm (MT) and greater than or equal to 5 mm of one papule or confluescent papules (TT) were considered to be positive. 6-9 mm for MX and 2-4 mm for TT were considered doubtful. The overall agreement with MX (69.7% positive, 27.7% negative reactions) was 92.4% for MT and 68.1% for TT. Regarding sensitivity (false negative reactions), MT provided far better results than TT (8.4% vs. 44.6%). TT performed equally well when the doubtful reactions were reclassified as positive (8.4% false negative). It is recommended that the limit for a positive TT be lowered to greater than or equal to 2 mm, as other authors have suggested. MT always produced easily palpable and measurable indurations, whereas the borderline TT reactions (2-4 mm) were difficult to read and the size of the four papules varied considerably in most instances. Only MT showed significantly more positive readings after 72 h compared to 48 h. MT was better tolerated subjectively than TT with regard to application and skin reaction. The Monotest can be recommended as tuberculin screening test for general practice.

Sensitivity to avian sensitin of tuberculin reactors in Belgium.

It was proposed that a study should be made on the specificity of the reactions of 1068 subjects reacting "weakly to moderately" to an intradermal test with 2 units of PPD RT23; 43% were classified as "positives" (greater than or equal to 10 mm) and Palmer type IV indurations or merely erythema were seen in 81%. Three months later, the same people were retested, this time with 2 units of PPD RT23 and, simultaneously, with 0.1 mcg of avian sensitin: 23% of all reactors (13% of all "positives", but none with a Palmer type I of II induration) had completely lost their sensitivity to RT23. Of the 1068 original reactors, 87% reacted to avian sensitin and 69% did so with a reaction greater than or equal to to human RT23. According to the results of this double test, and depending on the strictness of the comparative criterion, 69% to 84% of the original reactors (65% to 78% of the "positives") would be classified as non-specifically infected. There was a high degree of agreement between an induration greater than or equal to 10 mm to PPD RT23 in the second test and classification as specific infection, based on a comparative criterion.

Underreading of the tuberculin skin test reaction.

The tuberculin skin test is the best diagnostic method to detect tuberculous infection. How accurate is interpretation of the test? Observational study. Both general hospital and university hospital. One hundred seven health-care professionals, including 52 practicing pediatricians, 33 pediatric house officers, 10 pediatric academicians, 11 registered nurses, and 1 pediatric nurse practitioner. A tuberculin skin test (Mantoux) was applied to the arm of a known tuberculin converter. As participants entered/left the room, they were guided to the tuberculin converter. At no time did a participant observe readings other than his/her own. Mantoux tuberculin reaction measuring 15 mm induration was read individually by a group of 52 practicing pediatricians, 33 pediatric house officers, 10 pediatric academicians, 11 registered nurses, and one pediatric nurse practitioner. The median induration recorded by this group of 107 health-care professionals was 10 mm, and 17 (33%) practicing pediatricians read the reaction as <10 mm induration. Using the > or = 15-mm induration indicator to identify a positive reaction, 93% of those in the study (99/107 participants) would have identified our known converter as tuberculin negative. This study confirms a general inaccuracy in interpretation of the tuberculin skin test reaction. It raises two questions. (1) Is there a general tendency toward underreading? (2) Does this general tendency to underread tuberculin skin test reactions raise some question as to the American Academy of Pediatrics, American Thoracic Society, and Centers for Disease Control and Prevention move in raising the amount of induration considered tuberculin positive to 15 mm in low-risk individuals?

A 19-year follow-up of tuberculin reactors. Assessment of skin test reactivity and in vitro lymphocyte responses.

Tuberculin skin test reactivity decreases with time such that repeat PPD skin testing may result in reactions of less than 10 mm. This reactivity may be boosted in some individuals with a second tuberculin skin test. The immunologic basis of these observations remains unclear. We studied the relationship between skin-test reactivity and in vitro blastogenic response to PPD in a cohort of 22 individuals (aged 28 to 81 years) known to be tuberculin reactors (induration greater than or equal to 10 mm) in 1970. In 1989, 18 subjects remained reactive to PPD on the first skin test and responded to PPD in vitro (mean incorporation of 3H-thymidine by peripheral blood mononuclear cells, 22,650 cpm). Three subjects reverted (induration in response to PPD less than 10 mm) and lost in vitro reactivity to PPD (mean incorporation of 3H-thymidine, 2,205 cpm). One subject boosted (increase of induration of at least 6 mm to greater than or equal to 15 mm) on the second skin test and showed a concomitant in vitro boost in the blastogenic response to PPD (from 1,008 cpm to 47,837 cpm). In this cohort, interpretation of the two-step tuberculin skin test correlated closely with in vitro proliferative responses. Over a 19-year period, the majority of individuals maintained skin test reactivity and strong in vitro responses to PPD despite a lack of ongoing exogenous exposure to Mycobacterium tuberculosis. The immunologic basis for reversion appears to depend in part on a loss of lymphocyte blastogenic capacity. In the one individual who exhibited the booster phenomenon, repeat antigen stimulation resulted in a dramatic increase in the in vitro blastogenic responses.

Multiple-puncture tuberculin testing: reason for variable response to tine test.

1040 'Tine Test' (TT) discs from 3 production batches were examined under a dissecting microscope. The dried tuberculin coatings of the 4 metal tines of the test discs were found to vary from being thin and smooth to being thick with droplet formation. Variations in coating were identified in the following proportions: 47% thin, 37% medium, and 16% thick (N = 4160 tines), these proportions varying significantly between the 3 batches (p much less than 0.001). Pairs of thin and thick coated TT discs were selected and applied to 103 tuberculin positive volunteers. When thickly coated TT were applied the sum of the diameters of induration was substantially smaller (p less than 0.001) than when thinly coated TT were used. At a greater than or equal to 2 mm limit for a positive reaction the thick TT failed to detect 16% of subjects positive to a 'Monotest' (MT) or a Mantoux (MX) 10 IU and the thin TT failed to detect 5% (p less than 0.05); at a greater than or equal to 5 mm limit the figures were 77% and 59% (p less than 0.01) respectively. In moderately sensitized populations, thick coated TT could lead to an excess of false negative results. The TT is of limited value as a screening test unless thin and uniform coating of tuberculin can be guaranteed.

Evaluation of a third sequential tuberculin skin test in a chronic care population.

To evaluate factors that might influence the accuracy of tuberculin tests in identifying elderly persons recently infected with Mycobacterium tuberculosis, we performed as many as 3 sequential administrations of 5 tuberculin units of purified protein derivative in 1,726 persons residing in chronic care facilities. Significant reactions (greater than or equal to 10 mm of induration) to 1 of 3 tests were found in 702 (40.7%) persons. Of these, 68% were found with Test 1, 22.5% with Test 2, and 9.5% with Test 3. Of 1,146 persons with nonsignificant reactions to Test 1, 13.8% had significant reactions on Test 2, and of 769 persons with nonsignificant reactions to Tests 1 and 2, 8.7% had significant reactions on Test 3. Males, nonwhites, and persons between 50 and 79 yr of age had a greater proportion of significant reactions for each of the first 2 tests but not for the third test. These data indicate that continued boosting of the tuberculin reaction occurs in a substantial number of persons who receive a third sequential test. Marked increases in the size of reactions caused by boosting may explain high apparent conversion rates found in facilities where the third test is delayed for one year.

Heaf test

The reading of the Heaf test was defined by a scale: Negative - No induration, maybe six minute puncture scars Grade 1 - four to six papules (also considered negative) Grade 2 - Confluent papules form indurated ring (positive) Grade 3 - Central filling to form disc (positive) Grade 4 - Disc >10 mm with or without blistering (strongly positive) Grades 1 and 2 could result from previous BCG or avian tuberculosis, rather than human TB infection. Children who were found to have a grade 3 or 4 reaction were referred for X-ray and follow-up. For interpretation of the test, see Tuberculosis diagnosis. Other tests The equivalent Mantoux test positive levels done with 10 TU (0.1 mL 100 TU/mL, 1:1000) are 0–4 mm induration (Heaf 0-1) 5–14 mm induration (Heaf 2) >15 mm induration (Heaf 3-4) The Mantoux test is preferred in the United States for the diagnosis of tuberculosis; multiple puncture tests, such as the Heaf test and Tine test, are not recommended. References

[The booster phenomenon in two-step tuberculin testing of employees in a community hospital].

A study was made to clarify to what degree the booster phenomenon was present when the employees in a community hospital in Japan received two-step tuberculin testing (PPD). Of the seventy-five employees, most of all BCG-vaccinated subjects, twenty-three showed strongly positive of more than 30 mm of induration at the first test (PPD/T1), and the remaining fifty-two subjects received a second (PPD/T2) after 2 weeks. The second PPD showed a marked increase in reactivity, sixteen subjects newly became strongly positive and six of eight who were initially PPD negative (< 10 mm) were converted positive, and the mean reaction size changed from 14.7 +/- 5.6 mm (PPD/T1) to 31.5 +/- 15.5 mm (PPD/T2). The degree of boosting, measured by the change in millimeters induration size between PPD/T1 and PPD/T2 (PPD/T2-PPD/T1), was correlated with neither the size of PPD/T1 nor the age of the study participants, and was not associated with the difference of the position in the hospital. Thus, we could not explain the factor why such a marked boosting was observed in this study. However, these results indicated that the two-step tuberculin testing is an essential means of distinguishing new tuberculous infection from booster phenomenon. We agree with the current recommendation for routine two-step testing of new employees in the hospital.

Investigation into typical and atypical tuberculin sensitivity in the Royal Netherlands Army, resulting in a more rational indication for isoniazid prophylaxis.

The Department of Military Health Services (DMGZ) vaccination clinic, Utrecht, The Netherlands. To improve upon PPD skin testing procedure by introducing a double Mantoux test. During the first part of the study, from 1986-1988, army recruits were double-tested simultaneously with PPD and Mycobacterium scrofulacaeum sensitin. During the second part of the study, from 1989 to 1993, recruits reacting to PPD, with an induration in the range of 10-15 mm, underwent a second skin test with M. scrofulaceum sensitin. The total study population consisted of 237,692 non-BCG-vaccinated recruits. From 1986-1993 and average of 0.45% persons reacted with indurations > or = 10 mm to PPD. An average of 7.76% if army recruits reacted with indurations > or = 10 mm to M. scrofulaceum sensitin during the first part of the study. Using a modified ITSC (International Tuberculosis Surveillance Centre) model, 48% of the persons reacting to PPD with indurations in the range 10 mm and 15 mm were classified as false-positive. A total of 16% with indurations > or = 10 mm to PPD were classified as false positive. False-positive persons were then excluded from INH chemoprophlaxis. In areas with a high prevalence of non-tuberculous mycobacteria infection the use of double skin testing might be useful in differentiating between indurations due to tubercle bacilli and those due to infection with non-tuberculous mycobacteria.

Mantoux test

A tuberculin test conversion is defined as an increase of 10 mm or more within a two-year period, regardless of age. Alternative criteria include increases of 6, 12, 15 or 18 mm. False positive result TST (tuberculin skin test) positive is measured by size of induration. The size of the induration considered to be a positive result depends on risk factors. For example, a low-risk patient must have a larger induration for a positive result than a high-risk patient. High-risk groups include recent contacts, those with HIV, those with chest radiograph with fibrotic changes, organ transplant recipients, and those with immunosuppression.

Lepromin

By contrast, two forms of positive reactions are seen when tuberculoid or borderline cases of HD are assessed by the lepromin test. (There are three borderline diagnoses possible as well as the tuberculoid and lepromatous diagnoses in the Ridley-Jopling classification system. The severity of disease and thus assignment to one of the five diagnoses is related to the strength of the cell mediated immune response.) The Fernandez (early) reaction appears within two days and is roughly equivalent in nature and underlying mechanism to the response seen in tuberculosis patients reacting positively to the tuberculin test. Induration of 5mm or more with erythema (redness), or 10mm without, 48 hours post-injection are positive Fernandez reactions. Unlike the tuberculin test, however, another reaction occurs in lepromatous patients at the injection site 21 days post-injection, also appearing as induration and possible ulceration. This late positive reaction is known as the Mitsuda reaction.

[Two-step tuberculin testing and BCG vaccination in the personnel of a medical and pharmaceutical university].

In an attempt to cope with recent nosocomial spread of tuberculosis, the tuberculin test with a 0.05 microgram of 0.1 ml intradermal dose of purified protein derivative was performed by a two-step procedure on the personnel of a medical and pharmaceutical university, followed by BCG vaccination for non-reactors in the second test. The second test was repeated after two weeks in all but those with erythema of 10 mm or more in diameter associated with double erythema, vesicle formation, and/or necrosis on the initial testing. The first test was done in a total of 935 participants (73% of all personnel) with a median age of 37 (range, 21-67) years. The rate of participation, by occupation, in the hospital personnel ranged from 63% (183/289) for doctors to 98% (351/358) for nurses. The size of erythema showed a unimodal distribution with a peak in the range of 10-19 mm, with a median of 20 mm (range, 0-102). Reactions below 9 mm, which are interpreted as negative, were found in 16% of all participants, and those above 30 mm in 35%. Among participants aged 20-49 years, especially among nurses, reactions tended to be larger with increasing age. Among 539 participants undergoing repeated testing, reactions between the first and second tests correlated well, showing a median increase in size of 10 mm (range, -43-(+)70) on retesting. Reactions above 30 mm associated with an increase in size larger than 20 mm, among those initially below 29 mm in diameter, were observed in 28% of those retested. Adverse reactions such as vesicle formation with or without hemorrhage, or lymphangitis occurred in 2.5% of all participants on the initial testing and in 1.5% on the retesting, with the highest frequency seen in those aged 30-39 years. BCG was administered to 26 of the 49 participants with a negative reaction on the second test. All vaccinees with a median age of 30 (range, 21-46) years showed tuberculin conversion after two months without developing Koch's phenomenon soon after the vaccination. Incidentally, it is desirable that two-step tuberculin testing such as that in the present study should also be performed using the diameter of induration, particularly that measured transversely, since erythema is not used in any other country than Japan.

[Results of two-step tuberculin skin test against medical and nursing school students and treatment according to the results of the test].

To assess the risk of tuberculosis infection in medical and nursing school students, tuberculin skin tests were carried out in the two-step manner. The second tuberculin skin test was repeated two weeks later excluding those who were strongly positive in the first test. BCG vaccination was done with the consent of students who showed negative reaction twice. Medical interview and revaluation of prior routine chest radiogram were made on students who were strongly positive. Prophylactic INH medication was considered to those who are at high risk of tuberculosis. Eight hundred thirty eight students underwent the two-step tuberculin skin test, and among them, 771 students showed the positive reaction on the first test (92.0%) which included 58 weakly positive (6.9%), 347 intermediately positive (41.4%) and 366 strongly positive (43.7%) and 2 not-measurable (0.2%), and 65 students were negative (7.8%). The average size of the erythema was 30.9 +/- 18.8 mm on the first test and 37.9 +/- 20.6 mm on the second test. Twenty one students were negative on the second tuberculin skin test, and among them, 15 received BCG vaccination. Out of eight students who were vaccinated with BCG in 1999 and were followed up in the next year, 6 (75.0%) converted to positive. Strongly positive reaction was seen in 28 students (3.3%) and one of them underwent prophylactic medication of INH according to her family history of exposure to tuberculosis.

A comparative study of the old tuberculin tine test and the PPD-tine test.

Forty-one children suspected of having tuberculosis were simultaneously given an intermediate strength Mantoux test, an old tuberculin tine test (OT), and a purified protein derivative (PPD) tine test. Each test was read at 48 hours, and the largest diameter of induration was recorded. Twenty-nine patients had a positive reaction to the Mantoux test, 20 patients had a positive reaction to the OT tine test, and 16 patients had a positive reaction to the PPD-tine test. There were seven instances of a doubtful reaction to the OT tine test and nine to the PPD-tine test. Two children with positive Mantoux tests had negative OT tine tests, and four with positive Mantoux tests had negative PPD-tine test reactions. There was a significant difference between the number of positive reactors to the Mantoux test and both tine tests. If all tine test reactions of 2 mm or more were considered positive (doubtful plus positive reactors), there was no significant difference between any of the tuberculin tests. All suggestively positive tine reactors should, therefore, be retested with a Mantoux test to avoid false-negative interpretation of the tines.

Mantoux test

the bacteria is expected to mount an immune response in the skin containing the bacterial proteins. The response is a classical example of delayed-type hypersensitivity reaction (DTH), a type IV of hypersensitivities. T cells and myeloid cells are attracted to the site of reaction in the timeframe of 1–3 days and generate local inflammation. The reaction is read by measuring the diameter of induration (palpable raised, hardened area) across the forearm (perpendicular to the long axis) in millimeters. If there is no induration, the result should be recorded as "0 mm". Erythema (redness) should not be measured. In the Pirquet version of the test tuberculin is applied to the skin via scarification.

Interpretation of a serial Mantoux test taking into account the annual risk of tuberculous infection.

Interpretation of tuberculin tests (TSTs) can be difficult. However, it is even more difficult to classify an individual as infected or non-infected if he or she has undergone a prior TST, as the difference between the booster effect and true conversion is not always clear. To determine the size of the induration that is indicative of true infection after a second Mantoux test, based on the fact that the annual risk of tuberculous infection (ARTI) is equivalent, regardless of whether it is calculated directly or indirectly. We performed two TSTs in the same population (aged 6 years at the first examination) with a 1-year interval. We calculated the prevalence of infection the first year (1.16%, 95%CI 0.67-1.65) and the ARTI using the indirect method (0.18%, 95%CI 0.00-0.37). For the second year, we considered different induration sizes and finally accepted a diameter of >10 mm as the criterion according to which the ARTI, calculated directly, corresponded to the value of the previous year (0.18%). Although they served as an aid in the interpretation of the TST, calculations of this type will probably be unnecessary in the future, when in vitro diagnostic tests for tuberculosis are made available in every health centre, thus enabling the classification of those individuals with indurations of intermediate size in the TST.

Two-step tuberculin skin test and booster phenomenon prevalence among Brazilian medical students.

Five medical schools in three cities in Rio de Janeiro State, Brazil, with different tuberculosis (TB) incidence rates. To evaluate the prevalence of the booster phenomenon and its associated factors in a young universally BCG-vaccinated TB-exposed population. A two-step tuberculin skin test (TST) was performed among undergraduate medical students. Boosting was defined as an induration > or =10 mm in the second TST (TST2), with an increase of at least 6 mm over the first TST (TST1). The association of boosting with independent variables was evaluated using multivariate analysis. Of the 764 participants (mean age 21.9 +/- 2.7 years), 672 (87.9%) had a BCG scar. The overall booster phenomenon prevalence was 8.4% (95%CI 6.5-10.6). Boosting was associated with TST1 reactions of 1-9 mm (aOR 2.5, 95%CI 1.04-5.9) and with BCG vaccination, mostly after infancy, i.e., after age two years (aOR 9.1, 95%CI 1.2-70.7). The prevalence of the booster phenomenon was high. A two-step TST in young BCG-vaccinated populations, especially in those with TST1 reactions of 1-9 mm, can avoid misdiagnosis as a false conversion and potentially reduce unnecessary treatment for latent TB infection.

High rate of negative results of tuberculin and QuantiFERON tests among individuals with a history of positive skin test results.

To evaluate individuals at high risk for tuberculosis exposure who had a history of a positive tuberculin skin test (TST) result in order to determine the prevalence of unsuspected negative TST results. To confirm these findings with the QuantiFERON-TB test (QFT), an in vitro whole-blood assay that measures tuberculin-induced secretion of interferon-gamma. This survey was conducted from November 2001 through December 2003 at 3 sites where TST screening is regularly done. Detailed histories and reviews of medical records were performed. TSTs were placed and read by 2 experienced healthcare workers, and blood was drawn for QFT. Any subject with a negative result of an initial TST during the study (induration diameter, <10 mm) underwent a second TST and a second QFT. The TST-negative group comprised individuals for whom both TSTs had an induration diameter of <10 mm. The confirmed-negative group comprised individuals for whom both TSTs yielded no detectable induration and results of both QFTs were negative. A total of 67 immunocompetent subjects with positive results of a previous TST were enrolled in the study. Of 56 subjects who completed the TST protocol, 25 (44.6%; 95% confidence interval [CI], 31.6%-57.6%) were TST negative (P<.001). Of 31 subjects who completed the TST protocol and the QFT protocol, 8 (25.8%; 95% CI, 10.4%-41.2%) were confirmed negative (P<.005). A significant proportion of subjects with positive results of a previous TST were TST negative in this study, and a subset of these were confirmed negative. These individuals' TST status may have reverted or may never have been positive. It will be important in future studies to determine whether such individuals lack immunity to tuberculosis and whether they should be considered for reentry into tuberculosis screening programs.

The use of repeat skin tests to eliminate the booster phenomenon in serial tuberculin testing.

During the early years of our annual tuberculosis skin testing program for hospital employees, we experienced conversion rates that were inordinately high. In an effort to eliminate the booster phenomenon in serial tuberculin testing as a contributing factor, a program of repeat skin testing performed within 7 to 28 days in new employees with less than 10-mm induration on initial skin testing was begun in 1978. Employees demonstrating a 6-mm increase in reaction size to a total induration of 10 mm or greater on repeat testing were classified as boosters. The booster rate for 1978 was 8.3%, and elimination of these employees from subsequent annual testing resulted in a decrease in the conversion rate from 8.7% in 1978 to 2.9% in 1979 (p less than 0.01). The rate of conversion was age-dependent in 1978, but this effect was absent in 1979 when the boosters were eliminated. On the basis of the results for the first 2 yr of our program, we concluded that repeat tuberculin skin testing is a practical approach to reduce falsely elevated conversion rates and can potentially reduce the number of persons exposed to the risk of isoniazid toxicity.

[Two-step tuberculin skin test in nurse students and hospital employees].

Booster phenomenon (recall effect) of tuberculin skin test, which disturbs diagnosis of tuberculous infection, is prevalent among BCG vaccinated population. We retested 34 nurse students whose initial tuberculin reaction was smaller than 30 mm by erythema (Group A) and 53 hospital employees whose initial reaction was smaller than 20 mm by erythema (Group B). Among the people whose diameter of erythema was less than 10 mm by the first test, 88 percent (8/9) of group A and 43% (6/14) of group B showed reaction 10 mm < or = by erythema and among those whose induration was < 10 mm, 54% (6/11) of group A and 48% (12/25) of group B showed reaction 10 mm < or = in the second testing. Mean and standard deviation of [the difference between the diameter of the 2nd and the 1st testing] was +7.3 +/- 11.8 mm in group A, +9.8 +/- 11.1 mm in group B by erythema and +2.6 +/- 5.9 mm in group A, +2.9 +/- 5.1 mm in group B by induration. These results indicate that booster phenomenon is highly prevalent among the tested group and there can be no appropriate criteria to distinguish new infection and booster phenomenon. Though two-step tuberculin skin test is recommended to get rid of booster phenomenon. Only a little is known about the value of this test to diagnose new infection in Japanese population, majority of whom being BCG vaccinated. Further investigations are required to apply two-step tuberculin skin test for diagnosis of new infection among hospital employees and health care workers in Japan.

Mantoux test

T-SPOT.TB is another IGRA; it uses the ELISPOT method. Heaf test The Heaf tuberculin skin test was used in the United Kingdom, but discontinued in 2005. The equivalent Mantoux test positive levels done with 10 TU (0.1 ml at 100 TU/ml, 1:1000) are <5 mm induration (Heaf 0–1) 5–15 mm induration (Heaf 2) >15 mm induration (Heaf 3–4) See also Tuberculosis Latent tuberculosis QuantiFERON Tine test References Immunologic tests Tuberculosis Dermatologic procedures

Mantoux test

Classification of tuberculin reaction The results of this test must be interpreted carefully. The person's medical risk factors determine at which increment (5 mm, 10 mm, or 15 mm) of induration the result is considered positive. A positive result indicates TB exposure. 5 mm or more is positive in An HIV-positive person Persons with recent contacts with a TB patient Persons with nodular or fibrotic changes on chest X-ray consistent with old healed TB Patients with organ transplants, and other immunosuppressed patients 10 mm or more is positive in Recent arrivals (less than five years) from high-prevalence countries Injection drug users Residents and employees of high-risk congregate settings (e.g., prisons, nursing homes, hospitals, homeless shelters, etc.) Mycobacteriology lab personnel

Tuberculin reactivity in Bacillus Calmette-Guérin vaccinated subjects.

The Centre for Prevention and Control of Tuberculosis in Barcelona, Spain, where the staff appointed to Training Centers are examined. To check for tuberculin sensitivity due to Bacillus Calmette-Guérin (BCG) vaccine and ascertain its duration. We compared the results of a tuberculin test (TT) on vaccinated and non-vaccinated subjects. The induration diameter and the time elapsed between BCG vaccination and the TT were determined. Of the 2424 vaccinated subjects, 1489 (61.4%) reacted to TT (> or = 5 mm) and of the 3135 non-vaccinated, 905 (28.9%) reacted, a significant difference. Of 1978 subjects vaccinated between 6 and 14 years of age, 63.3% were TT reactors, compared to 23.9% of the 1948 non-vaccinated. Induration diameters > or = 15 mm amounted to 11% for vaccinated subjects and 8% for those not vaccinated, a significant difference. The time from vaccination to TT was 13-25 years. Of the 446 subjects vaccinated at birth, 237 were reactors (53.1%); of the 887 non-vaccinated subjects of the same age, 154 (17.4%) reacted. Reactors > or = 15 mm amounted to 40 (9%) for vaccinated subjects and 46 for non-vaccinated (5.2%), a significant difference. The time elapsed between vaccination and TT was 20-25 years. For 124 vaccinated subjects with a previous negative TT, a second test was positive for 87 (70.2%), and for 257 non-vaccinated it was positive for 64 (24.9%). The difference is due to a booster effect. BCG vaccination at birth and for school age children causes a reactivity to tuberculin which persists for 20 to 25 years. An induration diameter of > or = 15 mm does not exclude a vaccinal origin. For vaccinated subjects with a previous negative TT, it is necessary to exclude the booster effect.

PPD Skin Test -- Interfering Factors -- Two-step Testing and Boosted Reaction

In some individuals, the reaction to tuberculin antigen wanes over time, which results in a false-negative reaction. In individuals with a prior TB infection from years earlier, sensitization to tuberculin may be weak, and there may be a false-negative PPD test. However, if a subsequent test is administered, the tuberculin PPD may stimulate the immune system. A boosted reaction is seen on subsequent testing due to "recalling" of the immune response.