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Original Report |
1 Department of Diagnostic Radiology, Chang Gung Memorial Hospital at Linkou,
School of Medicine, Chang Gung University, 5 Fu-Hsing Rd., Kweishan, Taoyuan
Hsien 333, Taiwan.
2 Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou,
School of Medicine, Chang Gung University, Kweishan, Taoyuan Hsien 333,
Taiwan.
3 Department of Diagnostic Radiology, Chang Gung Memorial Hospital at Kaohsiung,
School of Medicine, Chang Gung University, 123 Ta-Pei Rd., Kaohsiung Hsieng
833, Taiwan.
Received September 29, 2003; accepted after revision November 20, 2003.
Address correspondence to Y.-L. Wan
(ylw0518{at}adm.cgmh.org.tw).
OBJECTIVE. The purpose of this study was to describe the radiographic findings and evolution of round pneumonia found in eight patients with confirmed severe acute respiratory syndrome (SARS).
CONCLUSION. SARS may present as round pneumonia on chest radiographs initially or during the treatment course. It may remain unchanged for up to 9 days before evolution to ill-defined air-space opacities. Radiologists and physicians should consider the possibility of "SARS pneumonia" when spherical air-space opacities are noted on chest radiographs of febrile patients.
An outbreak of severe acute respiratory syndrome (SARS) occurred in one of the hospitals in Taipei on April 22, 2003 [1]. Subsequently, the disease spread rapidly throughout the island and was primarily associated with hospital settings. The number of infected individuals soared, and the patients included health care workers, inpatients, hospital visitors, and hospital patients' relatives [1]. The infectious disease was gradually brought under control by early June 2003. On July 5, 2003, the World Health Organization (WHO) removed Taiwan from the list of areas with recent local transmission of SARS [2].
Although WHO has announced that the human-to-human chain of transmission of this new disease has been broken globally, vigilant measures against SARS are still advocated because a resurgence of the disease is possible when the climate or seasons change [2].
The most common radiographic findings of SARS are focal, unilateral multifocal, or bilateral multifocal air-space opacities that may progress during treatment [3–7]. However, during the epidemic period from March to July 2003, we encountered some cases of probable SARS that presented as round opacities. Because a resurgence of SARS is possible and rapid detection of the disease is critical in halting any outbreaks, the purpose of our study was to describe the clinical course and radiographic evolution of round pneumonia in patients with SARS. To our knowledge, our study is the largest series dealing with round pneumonia, and this article is the first to describe its manifestations in patients with SARS.
Materials and Methods
Inclusion Criteria for Patients
Round pneumonia is a form of pneumonia or lung infection that appears as a
round or oval opacity on chest radiography
[8–10].
It usually evolves to ill-defined air-space opacities
[8–10].
During the epidemic period of SARS from March to July 2003 in Taiwan, 28
patients with a confirmed diagnosis of SARS were treated at our northern
hospital. Every radiograph of the 28 patients was assessed retrospectively and
independently by two radiologists who knew the diagnosis of SARS had been
confirmed. In addition to interstitial infiltration and focal or multifocal
air-space opacities, findings consistent with round pneumonia were seen with a
consensus interpretation on chest radiographs in eight of 28 patients. These
eight cases form the basis of this study. All eight patients were women (age
range, 18–47 years; mean age, 32.5 years) who fulfilled the WHO criteria
for probable SARS
[9–11].
All patients experienced fevers exceeding 38°C. They lived in an area in
which community transmission of SARS was documented (n = 5), had
traveled to such an area (n = 2), or had come in close contact with a
person known to have SARS (n = 1). Four of the eight patients were
nurses.
Clinical and Laboratory Data
The clinical manifestations, disease course, outcomes, and laboratory data
of the eight patients were reviewed. Of the eight patients, two required
endotracheal intubation because of respiratory failure, including one who died
after 9 days of hospitalization. The chief complaints other than fever, cough,
and chest discomfort were diarrhea (n = 3), headaches (n =
1), chills (n = 3), general soreness (n = 2), general
malaise (n = 1), rhinorrhea (n = 1), sore throat (n
= 2), bilateral flank pain (n = 1), abdominal pain (n = 1),
and lower back pain (n = 1).
The abnormal laboratory results included leukopenia (range, 1,900–3,100/µL; mean ± standard deviation [SD], 2,580 ± 486.83/µL; normal, 3,500–11,000/µL for women), lymphocytopenia (range, 300–680/µL; mean ± SD, 549.60 ± 196.92/µL; normal, < 1,000/µL), and thrombocytopenia (range, 82,000–120,000/µL; mean ± SD, 98,800 ± 14,620/µL; normal, 150,000–400,000/µL). Elevated levels of lactate dehydrogenase (range, 147–568 U/L; mean ± SD, 315.60 ± 166.87 U/L; normal, 47–140 U/L), aspartate aminotransferase (range, 55–131 U/L; mean ± SD, 105.80 ± 31.01 U/L; normal, 0–34 U/L), and alanine aminotransferase (range, 63–226 U/L; mean ± SD, 136.00 ± 70.77 U/L; normal, 0–36 U/L) were seen in five cases each. An elevated level of creatine kinase was noted in two patients with 319 and 725 U/L, respectively (normal, 15–130 U/L). All eight patients had significant seroconversion of the SARS-associated coronavirus antibody, indicating recent infection by the SARS-associated coronavirus. The treatment protocol of SARS included empiric antibiotics, ribavirin, and IV injection of immunoglobulin and corticosteroid.
Imaging Studies
In total, 122 chest radiographs were obtained for evaluation of the disease
process during a total of 123 hospitalization days for the eight patients. The
122 radiographs included 85 obtained in the anteroposterior view; 34, in the
posteroanterior view; and three, in the lateral view. The studies were
obtained using either conventional radiography (70 examinations, AMX-4,
General Electric Medical Systems) or computed radiography (52 studies, FCR
5000 plus, Fuji Medical System). The technique for portable radiography was
72–80 kVp at 1.25–1.5 mAs. The number of chest radiographs
obtained for each patient ranged from seven to 26 radiographs, with a mean of
15.3. The number of days of hospitalization for each patient ranged from 9 to
24 days, with a mean of 15.4. On average, a radiograph was obtained for each
patient every day while the patients were hospitalized.
Image Analysis
Radiographic data were collected with respect to the following findings:
round or oval opacities despite ill-defined air-space opacities and
interstitial infiltration at other areas of lung; mediastinal changes, pleural
effusion, and cavitation in parenchymal lesions; and the diameter, outline,
and interval changes of the round or oval opacities. On the basis of the
location of the center of the round opacity, the location of a lesion was
described as upper, middle, or lower lung zones and as central (inner two
thirds of the lung) or peripheral (outer one third of the lung) areas. Lesions
were measured using a radiopaque scale on a conventional radiograph that was
obtained using the same parameters for chest radiographs, including
tube-to-film distance.
Results
In eight patients, the locations of the opacities were right lower central in three and right upper central, right middle central, right lower peripheral, right upper central, and left lower central in one each. The outline was well defined in six and appeared slightly fluffy in two. Four cases of round pneumonia were found initially (Fig. 1A, 1B), and four were diagnosed during the treatment course (Figs. 2A, 2B, 2C and 3A, 3B, 3C). In the latter four, two evolved from air-space opacities and two from reticular infiltrations. The round opacities lasted for 1–9 days (mean, 2.5 days), whereas the lung lesions other than round opacities or suspicious fibrosis persisted for 8–24 days (mean, 13 days). The diameters of the round opacities ranged from 3 to 5.4 cm (mean, 3.9 cm), and all remained unchanged before regression or evolution into ill-defined air-space opacities. None of our eight patients had mediastinal abnormality, pleural effusion, or lung cavitation. Of the eight cases of round pneumonia, seven progressed to become ill-defined air-space opacities, and one completely regressed within 1 day. Of the seven cases of round pneumonia that became ill-defined air-space opacities, the lesions remained unifocal in one and progressed to become unilateral multifocal in three and bilateral multifocal in three.
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Discussion
The most common and characteristic radiographic findings of SARS are focal, unilateral multifocal, or bilateral multifocal ill-defined air-space opacities [3–7]. The lesions may progress or regress during treatment. The initial lung lesions were unifocal in 50–55% of the cases and multifocal or bilateral in 45–50% of the cases; the right lung was involved in 76% of the multifocal cases [3, 4]. Seven of the eight cases of round pneumonia were located in the right lung, four of which were in the lower lung. During the appearance of findings consistent with round pneumonia in our eight patients, concurrent ill-defined air-space opacities in other areas were found in only one patient. To our knowledge, this study is the largest series with respect to round pneumonia and the first report to describe its appearance in patients with SARS.
Familiarity with the unusual radiographic manifestations of SARS shown in our patients is crucial because of the high infectivity and morbidity associated with the disease. The pathology of lung biopsy specimens obtained at autopsy showed diffuse alveolar damage in different parts of the lung that was characterized by pulmonary congestion, edema, and the formation of hyaline membranes, suggestive of the early phase of adult respiratory distress syndrome [12]. In addition, lymphocytic inflammatory infiltrate and multinucleated pneumocytes were noted [12].
Pneumonia caused by viruses can be either interstitial or alveolar due to different pathologic reactions, depending on the virulence of the organism and the immune status of the host [13]. A chronic or indolent course featuring interstitial disease mainly results from lymphatic infiltration of the interstitium or interlobular septa. A more virulent disease, as was evident in patients with SARS, results in diffuse alveolar damage that affects the interstitium and the alveolar space and is related to the alveolar–capillary membrane [12, 13].
Round pneumonia is an acute infective pneumonia that may occur in both children and adults [8–10, 13]. It was first reported in the radiology literature in 1954 [10]. The pathogenesis of round pneumonia is unknown. Round pneumonia is hypothesized to be an early manifestation of the disease resulting from an infectious focus that has spread centrifugally, either by traveling through the pores of Kohn and Lambert canals or by destroying the walls of the surrounding acini [8, 9].
Discovering round pneumonia is considered to be serendipitous [13]; most affected patients are conservatively treated without ever undergoing chest radiography [8]. The frequency with which round pneumonia is seen depends on how early and how frequently a radiograph is obtained during the course of the illness. Because of the high virulence and infectivity of the SARS coronavirus, our patients were closely followed up with radiography; the availability of many radiographs may partially explain the high prevalence of round pneumonia (29% [8/28 cases]) in our patients with SARS.
A number of entities may feature a round opacity in the lung: bacterial pneumonia, septic emboli, granulomatous infections, malformations, neoplasms, vascular abnormalities, round atelectasis, focal organizing pneumonia, immune system–related disorders such as rheumatoid nodules, and Wegener's granulomatosis [11, 14]. Most patients with focal organizing pneumonia or atelectasis are asymptomatic, and the lesions require weeks to months for resolution in cases of remission [8, 13]. In contrast, all our patients with round pneumonia had contact with someone infected by the SARS coronavirus [2]; they had been suffering from an acute onset of symptoms or fever, and seven of the eight lesions progressed to become an ill-defined air-space opacity after 1–9 days. Round pneumonia has been reported to persist for 8 hr–3 days before progressing to become an ill-defined air-space opacity [9].
Our study has several limitations. First, the lesions could not be anatomically localized to a lobe or segment because of the unavailability of lateral radiographs or CT images. Because most of the patients were quite ill, radiographs were obtained at bedside in the frontal projection. Second, this study describes only the unusual radiographic manifestations of SARS pneumonia; the pathophysiology of those features could not be correlated with histopathology or an animal model. Third, this study is retrospective with a limited number of cases.
Nevertheless, several clinically important findings were uncovered in this study. First, a patient with SARS may present initially with round pneumonia on radiography, which occurred for four of our eight patients. Second, the causative organisms of round pneumonia apparently include coronaviruses in addition to Streptococcus pneumoniae, Klebsiella pneumoniae, Hemophilus influenzae, Coxiella burnetii, and Mycobacterium tuberculosis [9]. Third, the round opacities in our patients did not grow centrifugally, which contradicts a previous pathologic hypothesis [8, 9]. Our experience suggests that its growth probably reflects immune response of the host for confining the infectious process. Fourth, the literature frequently emphasizes that round pneumonia is characteristically mild with viral syndromes, but two of our eight patients had to be intubated because of respiratory failure, and one patient died. These results suggest that this entity does not absolutely imply a mild disease. Instead, the outcome of round pneumonia primarily depends on the virulence of the infective organism and host immunity.
In conclusion, round pneumonia may be found initially or during the treatment course in patients with SARS. In cases of pulmonary nodule, radiologists and physicians should list SARS in the differential diagnoses.
Acknowledgments
We thank Ping-Cherng Chiang, Tzou-Yien Lin, Hsieh-Shong Leu, Cheng-Huei Lee, and Kuo-Chien Tsao for their contributions to daily expert meetings for preventing an outbreak of SARS in the hospital during the epidemic period.
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