We report four cases of posttraumatic pleural effusion associated with blood hypereosinophilia. Three men and one woman were examined at our institution for pleural effusion between 21 and 50 days after a minor thoracic trauma. At their initial examination, the pleural fluid analysis showed, for each subject, a high eosinophilic count (54, 45, 25, and 45 percent, respectively). Blood analysis taken at that time revealed a concomitant increase in the number of peripheral eosinophils (1,078, 3,894, 900, and 2,128 eosinophils per cubic millimeter, respectively). For each subject, there was no evidence of past or current allergy or of systemic disease that could be associated with hypereosinophilia. We observed a parallel regression of the pleural effusion and of the number of blood eosinophils in each case. Only when the pleural effusion completely cleared did the blood eosinophilia return to normal. We conclude that posttraumatic pleural effusion may cause a striking blood eosinophilia and that a persistently elevated number of blood eosinophils suggests the nonresolution of the pleural effusion.
Pleural fluid eosinophilia associated with blood hypereosinophilia has been reported in numerous systemic diseases, including Hodgkins' disease, Loffler's syndrome, polyarteritis, tropical eosinophilia, and hydatid disease. Localized pleural diseases, such as posttraumatic pleural effusion or pneumothorax, are frequently associated with pleural fluid eosinophilia. Although the presence of blood hypereosinophilia (>450 eosinophils per cubic millimeter) with these disorders has been reported,[3-5] only two case reports describe the outcome of the blood eosinophilia in relation to that of the pleural effusion.[3,4] Posttraumatic effusion is usually not recognized as a cause of marked blood hypereosinophilia.[2,3,4,6]
The purpose of this report is to describe four well-documented cases of posttraumatic eosinophilic pleural effusion associated with blood hypereosinophilia . The number of blood eosinophils was particularly high in two patients. We also show that in all cases the resolution of the pleural effusion parallels that of the blood eosinophilia.
A 24-year-old machinist fell on his left side at work. Three weeks later, he was given benzonatate for persistent cough and thoracic pain. On the 30th day after his accident, he was referred to us for a left-sided pleural effusion. His history was unremarkable and he had no known allergy. On hospital admission, blood analysis revealed a hematocrit of 41.9 percent and a white blood cell count of 7,700/cu mm with 14 percent eosinophils. Chest roentgenogram showed a left-sided pleural effusion. On the same day, 350 ml of strawcolored pleural fluid containing 12,000 red blood cells and 7,210 white blood cells per cubic millimeter was removed. Differential cell count was as follows: neutrophils, 1 percent; eosinophils, 54 percent; lymphocytes, 40 percent; and mesothelial cells, 5 percent. Pleural biopsy specimen disclosed an eosinophilic infiltrate. Fluid culture was negative. A second pleural aspiration of 1,150 ml done on the next day showed 77 percent eosinophils. Five days later fluid of a third aspiration, of 400 ml, had 58 percent eosinophils. Stool examination was negative for ova and parasites. A 5-TU PPD test was negative. On the 70th day, the number of blood eosinophils and chest roentgenogram had returned to normal.
A 49-year-old construction worker suffered chest trauma with fracture of the posterior arc of his seventh left rib. Twenty-one days after trauma, he was started on a one-week trial of amoxicillin for dyspnea associated with thoracic pain. On the 30th day, chest roentgenogram revealed a left-sided pleural effusion and he was referred to our institution. His medical history was unremarkable. He had no known allergy. On hospital admission, his hematocrit was 41 percent, and his white blood cell count was 11,800/cu mm with 33 percent eosinophils. A first thoracentesis yielded 200 ml of bloody exudate containing 46,800 red blood cells and 5,500 white blood cells per cubic millimeter. Differential cell count was as follows: neutrophils, 3 percent; eosinophils, 45 percent; lymphocytes, 48 percent; and unidentified, 4 percent. Pleural biopsy specimen disclosed an eosinophilic infiltrate and fibrinohemorrhagic pleuritis. Culture of the fluid was negative. A second thoracentesis of 180 ml was done five days later; the fluid was not analyzed. Sixty days after trauma, the number of blood eosinophils and the chest roentgenogram had returned to normal.
A 21-year-old man suffered right-sided trauma with fracture of the eighth, ninth, tenth, 11th, and 12th ribs. On the 41st day after trauma, he was referred for the investigation of progressive dyspnea associated with low-grade fever. His history was unremarkable and he had no known allergy. A chest roentgenogram disclosed a large right-sided pleural effusion, and 1,600 ml of straw-colored pleural fluid was withdrawn on the day of admission. The fluid contained 6,600 red blood cells and 8,750 white blood cells per cubic millimeter. Differential cell count was as follows: neutrophils, 22 percent; eosinophils, 25 percent; and lymphocytes, 53 percent. Pleural biopsy specimen showed nonspecific pleuritis. Culture of the fluid was negative. The day following the thoracentesis, the hematocrit was 38.8 percent and the white blood cell count was 7,500/cu mm; 12 percent of these cells were eosinophils. Stool examination was negative for ova and parasites. Four days after admission, a second thoracentesis of 650 ml showed 32 percent eosinophils. On the 90th day, the number of blood eosinophils and the chest roentgenogram had returned to normal.
A 44-year-old woman fell on her left side at home and she immediately complained of chest pain and dyspnea. Right-sided pneumothorax was demonstrated on the chest roentgenogram. It was drained with a chest tube that was removed three days later. She left the hospital on the fourth day. At that time, the chest roentgenogram was normal and blood analysis revealed a white blood cell count of 11,300/cu mm but no eosinophils. Six weeks later (day 50) she still had chest pain and dyspnea and was referred to our institution for further evaluation. Her history was unremarkable and she had no known allergy. She was taking codeine and flurbiprofen for the pain. These medications were maintained until the pleural effusion resolved. At that first visit to our institution blood analysis revealed a hematocrit of 39 percent and a white blood cell count of 15,200/cu mm with 14 percent eosinophils. Chest roentgenogram showed a right-sided pleural effusion. A pleural thoracentesis of 60 ml was performed. The removed fluid contained 164,000 red blood cells and 6,930 white blood cells per cubic millimeter. Differential cell count was as follows: neutrophils, 6 percent; eosinophils, 45 percent; lymphocytes, 15 percent; and monocytes, 15 percent. On the 134th day, the number of blood eosinophils and chest roentgenogram had returned to normal.
A graphic summary of pertinent data for our four patients is presented in Figure 1. This figure shows the number of blood eosinophils for our four patients over the time course of their follow-up. Figure 2 demonstrates the parallel outcome of the blood eosinophilia and the pleural effusion for patient 1. This pattern was similar for the other patients.
These four patients had no evidence of past or current allergy and had no systemic disease. Patients 1 and 3 had negative result of stool examination for ova and parasites.
Patients 1 and 2 had taken medications before the investigation; benzonatate and amoxicillin, respectively. Although an allergic reaction with hypereosinophilia is possible with these drugs, we consider this improbable because of the parallel regression of the pleural effusion and blood hypereosinophilia and the absence of other manifestations of drug allergy. Patient 4 took codeine and flurbiprofen throughout the observation and still was taking these medications when the blood eosinophilia returned to normal.
Patient 4 had two localized pleural diseases that can be accompanied by eosinophilic effusion: pneumothorax was treated six weeks prior to her first visit at our institution when blood hypereosinophilia was documented, it is much more likely that the hemothorax was responsible for her hypereosinophilia.
The fact that localized pleural disease can lead to systemic manifestations such as blood hypereosinophilia is intriguing. Chapman and coworkers[7,8] demonstrated that the injection of washed red blood cells into the peritoneal cavity of mice produces a striking systemic and peritoneal eosinophilic response. Changes in peripheral blood seem to precede those in the peritoneal cavity by about 24 hours.[7,8] This response was not reproduced by the injection of hemoglobin and plasma. The authors concluded that the membrane of the red blood cell could contain an eosinophilic chemotactic factor responsible for this phenomenon.
On the other hand, an eosinophilic chemotactic factor could be released by other cells; Versess et all suggested that lymphocytes may be the cells responsible for this secretion. Although we can only speculate on the mechanism of the blood eosinophilia, we believe that after an eosinophil chemotactic factor has been released in the pleural space, many eosinophils enter both the pleural space and the systemic circulation.
In a recent review of the literature, Adelman et al mentioned that most eosinophilic pleural effusions are not associated with striking blood eosinophilia. Most reports on this subject provide little or no hematologic data. Brocard et al reported three cases of posttraumatic pleural effusion with 5, 13, and 19 percent eosinophils from their data. In two other case reports, the peripheral eosinophil count was 1,020 and 850 per cubic millimeter.[3,4] We found a marked increase in the number of blood eosinophils in two of our patients (3,893/cu mm and 2,128/cu mm). This shows that posttraumatic pleural effusion can cause higher blood hypereosinophilia than what was previously believed.
The overall frequency of blood hypereosinophilia in pleural eosinophilic effusions of any cause is reported to vary between 25 percent and 50 percent.[10,11] Considering the few case reports that specifically address the association of blood hypereosinophilia and posttraumatic pleural effusion, we cannot evaluate the frequency of this association from the literature.
The clinical courses of these four patients are interesting. The blood eosinophilia persisted until the chest roentgenogram returned to normal; only when the pleural effusion completely cleared did the blood eosinophilia return to normal. As mentioned earlier, there seems to be a factor that attracts the eosinophils both in the pleural cavity and the peripheral blood and this continues for as long as there is fluid in the pleura. The parallel regression of pleural and peripheral eosinophils was so consistent that a persisting elevated peripheral eosinophil count suggested the nonresolution of the pleural effusion.
The exact role of the eosinophils in pleural diseases and particularly in posttraumatic pleural effusion is not known, and previous reports on this subject have focused on the diagnostic significance of this finding. Activated blood eosinophils can secrete cytotoxic products, including the major basic protein, proteases, and toxic oxygen radicals. It is also known that pleural eosinophils can be activated and thus can also have a cytotoxic activity. We can only speculate that the presence of these cytotoxic products in the pleural fluid could accelerate the destruction of intrapleural cells and therefore enhance the rapidity of the pleural fluid resorption.
Another point of interest is the prognostic significance of pleural eosinophilia in posttraumatic effusion. For each of our subjects, the pleural effusion resolved without leaving a fibrothorax. This is especially significant for the two patients with a hemothorax. A large number patients with posttraumatic pleural effusion will have to be studied before we can reach a conclusion on this interesting observation.
From our four patients, we conclude that posttraumatic pleural effusion may be a cause of striking blood eosinophilia and that blood hypereosinophilia may be more frequently found with this disorder if it is specifically looked for. Also, the persistence of blood hypereosinophilia may be a clue suggesting the nonresolution of the posttraumatic pleural effusion. This report should stimulate further studies of pleural eosinophilia in posttraumatic pleural effusion.
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 Adelman, M, Albelda S, Gottlieb J, Hoponik EF. Diagnostic utility of pleural fluid eosinophilia. Am J Med 1984; 77:915-20
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