Routine chest radiography for the evaluation of febrile neutropenic patients after autologous stem cell transplantation

Chest radiographs are routinely obtained for diagnostic evaluation of neutropenic febrile patients. We investigated the frequency of chest radiographic abnormalities during febrile episodes after autologous PBSC transplants and assessed the relationship of these abnormalities to past history of pulmonary disease, pre-transplant chest radiographic abnormalities, and pulmonary signs or symptoms at time of fever. We also studied the impact of chest radiographic findings on patient management. Sixty-one consecutive adult autologous PBSC transplant recipients were studied. Fifty-two (85%) developed fever, and 20 (38%) of these showed new chest radiographic abnormalities suggestive of pulmonary infection. Patients with pre-transplant chest radiographic abnormalities were more likely to develop additional abnormalities with fever post-transplant. Pulmonary symptoms or signs had low sensitivity or specificity for predicting radiographic abnormalities. Only 40% of patients with pulmonary symptoms or signs had an abnormal chest radiograph. Twenty-six percent of patients with abnormal chest radiographs had no clinical findings suggestive of pulmonary infection. The identification of chest radiographic abnormality did not change empiric antibiotic treatment in any patient. The role of routine chest radiography for diagnostic evaluation of febrile autologous PBSC transplant patients should be re-evaluated.     

High-resolution ultrafast chest CT in the clinical management of febrile bone marrow transplant patients with normal or nonspecific chest roentgenograms

Plain chest roentgenograms may be normal or show nonspecific abnormalities during the frequent febrile episodes that occur in patients after bone marrow transplantation. In this group, ultrafast 10-mm and 3-mm high-resolution CT scans were prospectively performed in 33 patients to determine if useful information was provided that either changed the patient's clinical management or added confidence to the clinical diagnosis. The 36 symptomatic episodes that occurred in 33 patients included fever in 20 episodes and fever combined with cough, dyspnea, chest pain, or rales in 16. Fourteen chest roentgenograms were interpreted as normal, and 22 were interpreted as demonstrating nonspecific changes; however, none of the roentgenograms was considered helpful in that they did not provide sufficient information for further management. In 2 of 14 episodes in patients with normal chest roentgenograms and in 9 of 22 episodes in patients with nonspecific chest roentgenograms, CT scanning resulted in a change in clinical management that included performing bronchoscopy, increasing or changing antibiotic coverage, starting white blood cell transfusions, requesting surgical biopsy, or a combination of these. In 1 of 14 episodes in patients with normal chest roentgenograms and in 8 of 22 episodes in patients with nonspecific roentgenograms, CT added confidence to the diagnosis. In the remaining 16 episodes, CT scans provided no additional information. We conclude that in many instances, noncontrast ultrafast chest CT scans can provide information that may either change a patient's clinical management or more clearly establish the extent of pulmonary disease.     

Occult dental infection as a cause of fever of obscure origin.

Three patients with prolonged unexplained fevers were ultimately found to have deep-seated dental infection. After initial examination failed to elicit symptoms or signs of dental infection, and extensive in-hospital evaluation was nonproductive, dental consultation with roentgenograms provided the diagnosis. All three patients underwent dental extractions with periapical or peridontal debridement; following a brief postoperative febrile period, all three responded with defervescence, without subsequent recurrence of fever. These cases emphasize the importance of periapical and peridontal infection as causes of fever of obscure origin. The pathogenesis, characteristics and bacteriology of periapical abscess are discussed.     

Bronchoscopy guided by high-resolution computed tomography for the diagnosis of pulmonary infections in patients with hematologic malignancies and normal plain chest X-ray

BACKGROUND AND OBJECTIVES: High-resolution computed tomography (HRCT) of the chest is able to demonstrate the presence of pulmonary infiltrates in febrile neutropenic patients with normal chest X-rays. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is a safe procedure for the etiological diagnosis of pulmonary infiltrates in oncohematologic patients. The objective of this study was to determine the diagnostic yield and subsequent therapeutic changes of a protected BAL (p-BAL) guided by HRCT in febrile oncohematologic patients unresponsive to broad-spectrum antibiotics with a normal chest X-ray. DESIGN AND METHODS: Twenty-two episodes from 20 oncohematologic patients were included: group A, 9 episodes (8 patients) with no respiratory symptoms and group B, 13 episodes (12 patients) with signs or symptoms of pulmonary infection. HRCT and p-BAL were performed in all episodes within the first 24 hours. RESULTS: HRCT showed abnormalities in all 22 episodes (bilateral abnormalities in 14 of the 22 episodes [64%]) and the most frequent pattern was ground-glass infiltrate (7 out of 22 episodes). An infectious agent was isolated in 12 of the 22 episodes, 5 in group A and 7 in group B with a diagnostic yield of 54%. Antimicrobial therapy was modified in 12 of the 22 episodes (54%): 5 in group A and 7 in group B. In 6 episodes, treatment was changed according to HRCT results and in the remaining 6 due to positive microbiologic results. Modifications in empirical therapy were associated with a favorable response in 44% episodes of group A and in 31% of group B. INTERPRETATION AND CONCLUSIONS: Oncohematologic patients with fever of unknown origin unresponsive to empirical antibiotics and with a normal chest X-ray can be candidates to undergo a HRCT. This subgroup of high-risk patients can benefit from a combined strategy consisting of BAL guided by a previous HRCT.     

Chest roentgenographic abnormalities in IL-2 recipients. Incidence and correlation with clinical parameters.

The chest roentgenograms of 54 patients receiving high dose interleukin-2 with or without lymphokine-activated killer cell therapy for advanced cancer were retrospectively reviewed. Thirty-nine patients (72 percent) developed chest roentgenographic abnormalities consisting of pleural effusions, 28 (52 percent); diffuse infiltrates (pulmonary edema), 22 (41 percent); and focal infiltrates, 12 (22 percent). These abnormalities resolved in 30 of 39 (77 percent) patients by four weeks after therapy. Simple pleural effusions were the only residual roentgenographic abnormalities seen and were present primarily in patients receiving IL-2 by bolus intravenous injection (8 of 28) (29 percent) as compared to continuous intravenous infusion (1 of 24) (4 percent) (p = 0.03). Only roentgenographic evidence of pulmonary edema appeared to correlate with the degree of clinical pulmonary toxicity (p = 0.001). The development of chest roentgenographic abnormalities correlated with the administration of IL-2 solely by bolus intravenous injection (p = 0.04), a pretreatment FEV1 of less than 3 L (p = 0.04), and treatment associated bacteremia (p = 0.09), but not with prior therapy, the presence of pulmonary metastases or the degree of systemic capillary leak as measured by percentage of weight gain during therapy. Although the roentgenographic abnormalities did not relate to the number of LAK cells received, two patients developed sudden onset of dyspnea and chest roentgenographic evidence of pulmonary edema shortly after the first LAK cell administration, implying that a direct cause-and-effect relationship exists in some patients. Possible mechanisms for these IL-2 related chest roentgenographic abnormalities and pulmonary toxicity in general are discussed.     

Clinical predictors of malaria and other febrile illnesses in children under five on Pemba Island, Tanzania

Under the current guidelines of presumptive treatment of all children with reported fever, the risk of over-prescribing antimalarial drugs and missing other important causes of fever, like acute respiratory tract infection (ARI), is substantial. Clinical algorithms have been shown to be useful in diagnosing malaria, but often with differing results, due to regional variations. We set out to explore the clinical features associated with malaria compared with other febrile illnesses and specifically severe malaria with ARI in children under five in Pemba. Two hundred and seven children aged six months to five years presenting to a hospital clinic with fever were studied in Pemba. Clinical findings were related to the presence of malaria parasitaemia. Malaria accounted for 67.7% of the febrile episodes investigated. Five symptoms and signs, including pallor, drowsiness, splenomegaly, fever duration and no chest crackles, could accurately predict a case of malaria with a sensitivity of 91.3% and specificity of 53% and positive predictive value of 80.3%. Several clinical features were found to differentiate severe malaria from ARI. These results confirm that clinical algorithms can increase the diagnostic accuracy of malaria, although not sufficiently to replace microscopy, and by promoting the use of clinical skills other treatable causes of febrile illnesses may be identified.These findings could have implications in optimizing treatment and malaria control in children on Pemba.     

Chest roentgenogram in pulmonary tuberculosis. New data on an old test

The utility of routine admission chest roentgenograms (CXRs) was evaluated in detecting pulmonary tuberculosis and the relationship between roentgenographic patterns and the likelihood of finding acid-fast bacilli (AFB) on sputum smear. Of 58 patients whose chief complaints were unrelated to pulmonary tuberculosis, the CXR suggested tuberculosis in 52 cases (90 percent). In 45 cases, the emergency room physician failed to elicit the patient's respiratory symptoms and did not consider tuberculosis as a diagnostic possibility. In 18 individuals, the diagnosis was missed in the emergency room because of failure to obtain a CXR. Among patients whose roentgenograms showed cavitation or extensive alveolar infiltrate, sputum smears showed AFB in 98 percent of cases. If alveolar infiltrate was absent, or if the roentgenographic pattern was not that of adult reactivation disease, sputum smears revealed AFB in only one half of the cases. We conclude that routine admission CXRs are useful in hospitals serving populations where tuberculosis is still common, and the probability of detecting AFB on sputum smear is greatly influenced by the roentgenographic findings.     

Toxoplasma gondii pneumonitis in patients infected with the human immunodeficiency virus.

Pulmonary toxoplasmosis is a rarely recognized opportunistic infection in immunocompromised patients. A few case reports have described pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in association with Toxoplasma gondii central nervous system disease. We encountered six cases of pulmonary toxoplasmosis in human immunodeficiency virus-infected patients who presented with a protracted febrile illness, respiratory symptoms, and an abnormal chest roentgenogram in the absence of neurologic findings. No clinical or roentgenographic features distinguished T gondii pneumonitis from more common opportunistic pulmonary infections. As the acquired immunodeficiency syndrome epidemic progresses, the presenting illnesses have evolved. Toxoplasma gondii must be considered a potential cause of pulmonary disease during the evaluation of human immunodeficiency virus-infected patients with respiratory symptoms.     

Consecutive epidemics of Q fever in a residential facility for drug abusers: impact on persons with human immunodeficiency virus infection.

Two large outbreaks of Q fever occurred in 1987 and 1988 in an agricultural community for the rehabilitation of drug users. Approximately 40% of the residents were human immunodeficiency virus (HIV)-positive. Two hundred thirty-five residents presented with clinical evidence of a flulike syndrome that was confirmed to be Q fever; moreover, a large proportion of residents developed an asymptomatic infection. Clinical signs and symptoms were rather nonspecific: fever, malaise, and muscle pain that were often associated with pulmonary symptoms. Single or multiple opacities were detected, with mild interstitial inflammation evident on chest roentgenograms. The source of infection was the sheepfold, which is part of the stock-farming activity of the community. Both outbreaks occurred just after lambing had begun. Residents who were exposed during the first epidemic were protected in the second one. The attack rate among HIV-positive residents was significantly higher than that among HIV-negative residents in the first outbreak, whereas only a slight, marginally significant difference was observed in the second outbreak. The clinical features of Q fever did not differ between HIV-positive and HIV-negative individuals. No cases of relapse or chronic disease were observed.     

The clinical feature of febrile episodes

Institutionalized elderly patients are at risk of nosocomial infection because of their compromised status by aging. To clarify the relationship between fever and disease in elderly patients, we analyzed 1,105 febrile episodes, the etiology of which were already diagnosed, of 443 patients (136 men, 307 women). All patients who were 65 years of age or older and who had been admitted to the hospital for more than 7 days had fevers above 37.5 degrees C recorded. The etiologies of the 1,105 febrille episodes were respiratory tract infection in 381 (34.5%), urinary tract infection in 263 (23.8%), other diseases in 164 (14.8%) and in 297 (26.9%) unknown. The episodes were categorized into two groups by the degree of initial fever: group A, 559 episodes (50.6%) of 37.5-38.0 degrees C and group B, 546 episodes (49.4%) of above 38.0 degrees C. Of the episodes, 41.0% were one-day fevers, 21.4% two-day fevers, and 14.0% three-day fevers. The frequency of two-or-more-day fevers was significantly higher in group B (69.0%) than in group A (49.2%) (p < 0.001). In group B, respiratory tract infection (44.3%) was more frequent than urinary tract infection (16.1%) (p < 0.001). Of the respiratory tract infections, 63.5% were in group B and, in contrast, 66.5% of the urinary tract infections were in group A. The white blood cell count and C-reacting protein levels were significantly higher in group B than in group A (p < 0.001). The degree of initial fever is an important predictive marker of severity of disease in elderly patients.     

Noncaseating pulmonary granulomas associated with small cell carcinoma of the lung

Noncaseating pulmonary granulomas are rarely associated with primary carcinoma of the lung. The patient described herein presented with constitutional symptoms and nodular pulmonary infiltrates associated with noncaseating granulomas without evident neoplasm in both transbronchial and open lung biopsy specimens. Despite corticosteroid therapy for presumed sarcoidosis, chest roentgenographic findings worsened and repeated transbronchial biopsy 12 months after the onset of initial symptoms revealed small cell carcinoma of the lung. Twenty-two months after initiation of chemotherapy, the patient is well with no evidence for carcinoma.     

Fever in renal transplant recipients: causes, prognostic significance and changing patterns at the University of Minnesota Hospital

During a three year period in which 433 renal transplants were performed, 194 episodes of fever were documented in allograft recipients hospitalized at the University of Minnesota. Viral infections were responsible for over half of the febrile episodes, and 98 (51 percent) of the fevers were associated with cytomegalovirus (CMV), either occurring alone or in conjunction with allograft rejection or another systemic infection. Bacterial infections, fungal infections and rejection were other important causes of fever, accounting for 14 percent, 5 percent and 13 percent of the febrile episodes, respectively. Most fevers occurred in the first four months after transplantation; although about two thirds of these fevers were due to CMV, only 17 percent of fevers that occurred more than one year after the renal transplant were due to CMV. Bacterial and fungal infections and malignancy were important causes of these fevers. Of the febrile illnesses associated with transplant nephrectomy or death, a majority occurred in patients with CMV disease. Secondary bacterial and/or fungal infections were observed in a large majority of patients with lethal CMV disease. During the third year of this study there was a significant decrease in the proportion of febrile episodes due to CMV.     

Multiple pulmonary arterial aneurysms in Behçet's disease: clinical and radiologic remission after cyclophosphamide and corticosteroid therapy

Beh?et's disease (BD) with pulmonary arterial aneurysm is rare and often associated with a poor prognosis. But there is also a chance that the aneurysm may completely resolve with medical therapy. A 39-year-old man presented with fever, malaise, bilateral chest pain, recurrent oral ulcers, and hemoptysis. The chest radiograph showed a round opacity in the right hilum. Computed tomography and magnetic resonance angiography (MRA) further revealed multiple, bilateral pulmonary arterial aneurysms consistent with the diagnosis of BD. The patient was started on a course of cyclophosphamide and corticosteroid therapy that resulted in cessation of his symptoms and complete resolution of radiologic findings. The chest radiograph and MRA reverted to normal on long-term follow-up. He is still alive and symptom-free 20 months after diagnosis.     

Initial roentgenographic manifestations of bacteriologically proven Mycobacterium tuberculosis. Typical or atypical?

Admission chest roentgenograms were reviewed of all patients diagnosed with pulmonary and extrapulmonary tuberculosis (TB) at the Medical College of Georgia--Eugene Talmadge Memorial Hospital (MCG-ETMH) during a five-year period from 1979 to 1983. Of 75 patients included, 51 had pulmonary TB, whereas 24 had extrapulmonary infection. Cavitary disease was common (28 of 51 patients with pulmonary TB). Forty-four of 51 patients with pulmonary TB had involvement of apical and/or posterior segments of the upper lobes with cavitation or infiltrates. Pleural effusion, parenchymal nodules, lymphadenopathy, and lower lung field disease were uncommon. Thirteen of 24 patients with extrapulmonary TB had abnormal admission chest roentgenograms, suggesting the possibility of Mycobacterium tuberculosis infection. Despite recent studies suggesting that TB presents with atypical roentgenographic features more commonly than reported in the past, the roentgenographic manifestations of TB in our series were typical of those previously described as pathognomonic for the disease.     

Patterns of infection in patients with aplastic anemia and the emergence of Aspergillus as a major cause of death.

Patterns of infection were studied in 150 patients with aplastic anemia who were admitted to the Clinical Hematology Branch, National Institutes of Health, between January 1978 and December 1989 for immunosuppressive therapy. Sixty percent of the patients were males, 71% were white, their mean age was 33.6 years (median, 27.5; range, 1-75), and 83% had severe aplastic anemia. One hundred three patients developed 1 or more febrile episodes during the study period. The risk factors for developing a febrile episode included a low Absolute Neutrophil Count (ANC) and Absolute Monocyte Count (AMC) at admission and the presence of an indwelling central venous catheter (Hickman-Broviack or Port-A-Cath). A total of 289 febrile events were studied, including unexplained fever (FUO) in 89 (31%), microbiologically documented infection (MBDI) in 137 (47%), and clinically documented infection (CDI) in 63 patients (22%). Compared to documented infections (MBDI) or CDI), FUO events were associated with a higher frequency of rigors, signs and symptoms of serum sickness, and treatment regimens known to cause fevers. None of the FUO events had a fatal outcome, even if the antibiotic therapy was discontinued before day 7. Among CDI events, bacteria were the most commonly defined etiologic agent (67%), followed by fungi (23%), viruses (7%), and parasites (3%). The patterns of bacterial infections in patients with aplastic anemia were similar to those observed in patients with cancer-related neutropenia. Twenty-one patients (15%) developed invasive fungal infections (aspergillus, 11; candida, 7; and both, 3), which were fatal in 19 (90%). Fungal infections accounted for 30% of the secondary infectious events and for 55% of fatal infectious events. The only identifiable risk factors for developing a fungal infection were the degree of neutropenia and monocytopenia at initial admission or final evaluation. Invasive pulmonary aspergillosis developed despite empirical amphotericin B therapy and was associated with a high incidence of fatal pulmonary hemorrhage (10 of 13 patients [77%]). Infection was responsible for 36 (62%) of the deaths observed during the study period and hemorrhage alone for 4 (7%). However, 20 of the patients who died of infection had concomitant hemorrhage. No significant drop in ANC, AMC, or platelet count could be demonstrated during a fatal infectious event as compared to a nonfatal infectious event. Invasive fungal infections, predominantly with aspergillus and candida, emerged in our study as the major causes of mortality in patients with aplastic anemia. Without bone marrow recovery the prognosis associated with invasive mycoses was grave.     

The management of allergic bronchopulmonary aspergillosis.

Twenty-five patients with allergic bronchopulmonary aspergillosis (ABPA) were observed for periods of 12 months to 10 years (average duration, 2.6 years) after initial therapy with prednisone, which was then tapered and discontinued unless maintained at minimal doses as required for control of asthma. Thirteen patients have had no recurrence, 4 patients did not comply with the initial regimen and could not be considered to be controlled, and 8 patients had 12 recurrent episodes of ABPA characterized by pulmonary infiltrates with no explanation other than ABPA. The exacerbations were closely correlated with sharp increases in total serum IgE, which subsequently decreased after resumption of prednisone therapy. The increase of IgE preceded the pulmonary infiltrates in 7 or 12 exacerbations. The exacerbations, characterized by increased serum IgE and pulmonary infiltrates, may be associated with minimal symptoms. Acute asthma without pulmonary infiltrates was not associated with increased IgE. Four exacerbations occurred during administration of beclomethasone diproprionate used for control of asthma, and therefore, this agent does not appear to prevent or reverse exacerbations of ABPA. Twelve exacerbations occurred in 8 persons, with 2 patients having 4 and 2 recurrences, respectively. This suggests that exacerbations are more likely to occur in certain patients. Serial measurements of total serum IgE appears to be a useful index of disease activity in ABPA. In the 4 patients who did not comply with the prednisone therapy regimen or regular physician visits, patterns of IgE changes, clinical evaluations, and chest roentgenograms were not of use in evaluation of the clinical state or progress of the patient. A treatment regimen is suggested for initial therapy and recurrences of ABPA on the basis of these observations.     

Severe hypoxemia in farmer's lung disease with normal findings on chest roentgenogram

A 33-year-old woman farmer developed an acute episode of fever, cough, and shaking chills with persistent shortness of breath. Her PaO2 was 51 with a restrictive pattern on pulmonary function. Her diffusion capacity was 36 percent of predicted. In spite of these abnormalities, she always had normal chest roentgenographic findings. Further studies, including a lung biopsy, led to the diagnosis of farmer's lung disease.     

Hydrocarbon aerosol pneumonitis in an adult

A 20-year-old woman was exposed to a kerosene mist for five days at an insecticide manufacturing facility. She had shortness of breath, fever, severe hypoxemia, bilateral pulmonary infiltrates, and a notable reduction of diffusion capacity/total lung capacity ratio. Her symptoms and roentgenographic findings resolved rapidly after cessation of exposure and corticosteroid therapy. Whether her roentgenographic findings resulted from a pulmonary injury similar to that seen with aspirate hydrocarbons is unclear. Industrial exposure to hydrocarbon aerosols is a potential health hazard that may result in short-term and long-term pulmonary disability.     

Pulmonary empyema 48 years after Lucite-ball Plomb implantation for tuberculosis]

A 68-year-old woman was diagnosed as having empyema on the left side. She had a history of pulmonary tuberculosis and tuberculous pleurisy in 1949. She was treated with artificial pneumothorax and implantation of 7 Lucite-ball plombs in the left upper thorax. A chest radiograph taken 14 years after initial operation, revealed an increase in density inside some of the Lucite-ball plombs. She was again admitted after experiencing fever and dyspnea 48 years after initial operation. The chest radiograph then showed a large mass on the left side, which compressed the mediastinum to the right. Inside the mass, Lucite-ball plombs were detected. The fever and inflammatory findings were improved with antibiotic therapy, but the dyspnea was persistent. The Lucite-ball Plombs and coagulating tissue were removed successfully. The patient's symptoms and respiratory function improved after the second operation.