HRCT of pulmonary infections in patients post solid organ transplantation

Transcription

1 HRCT of pulmonary infections in patients post solid organ transplantation Poster No.: C-2100 Congress: ECR 2012 Type: Educational Exhibit Authors: K. Sulkowska, P. D. Palczewski, M. Golebiowski, K. Mucha, B. Foroncewicz, M. Ciszek, L. Paczek; Warsaw/PL Keywords: Transplantation, Infection, elearning, CT-High Resolution, Conventional radiography, Thorax DOI: /ecr2012/C-2100 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 41

2 Learning objectives To know HRCT findings suggestive of a particular causative microorganism. To understand how clinical data can be integrated to narrow the differential diagnosis. Page 2 of 41

3 Background The growing number of transplantations provides a valuable therapeutic option for those suffering from the end-stage organ failure, but at the same time increases the population of immunocompromised patients [1]. Pneumonia remains an important source of morbidity and mortality in transplant recipients [2]. Since cultures may be timeconsuming, imaging plays an important role in establishing the probable etiology of pneumonia. Plain films are used as an initial study in transplant recipients with symptoms of infection, however they have a limited capacity in differentiating the causative factors. Clinical data can help in interpreting the radiological images, especially the type of immunosuppressive treatment (affecting mainly humoral or cell-mediated immunity) and the time from transplantation to the onset of pneumonia (Table 1 on page 4, Table 2 on page 4) [2-6]. HRCT is used as a problem-solving tool in patients with unclear plain film findings and/or no response to treatment. The main advantage of HRCT is a very detailed depiction of the lung parenchyma. When there is no contraindication to contrast injection, mediastinal structures can also be assessed. Even though HRCT findings are not always specific, there are several sings that are more common in certain types of pneumonia. The aim of the article is to present radiological findings suggestive of a particular causative microorganism and show how they can narrow the differential diagnosis when coupled with clinical data. Page 3 of 41

4 Images for this section: Table 1: Table 1. Influence of immunosuppressive drugs on patients' immunity and susceptibility to different microorganisms. Extracellular organisms are mainly bacteria (such as: Pseudomonas, Klebsiella, and Hemofilus), intracellular organisms are mainly viruses and fungi (such as: Cytomegalovirus, Candida, Mycobacterium, Legionella, and Pneumocystis). Page 4 of 41

5 Table 2: Table 2. Etiology of pneumonia depending on the time from the transplantation to the onset of symptoms. Page 5 of 41

6 Imaging findings OR Procedure details Imaging findings or procedure details: Bacterial pneumonia: Bacterial pneumonia is very common in transplant recipients and is usually caused by gram negative organisms, which in liver and kidney recipients may be responsible for more than 90% and 50% of the bacterial pneumonia, respectively[7,8]. The most common pathogens are Pseudomonas aeruginosa and Klebisella pneumoniae. Pseudomonas pneumonia is most often secondary to the aspiration of infectious material from the upper respiratory tract and less frequently to bacteremia, therefore it usually takes the form of bronchopneumonia [9,10]. Early radiological findings include nodular peribronchial opacities that are usually bilateral and have predilection to the lower lobes [10] (Fig. 1 on page 10). The nodules may progress to larger areas of consolidation with air-bronchogram. Tissue necrosis with abscess formation is common and usually some pleural thickening with mild effusion may be observed [10]. Gram negative organisms may also cause lobar pneumonia, similar to pneumococcal pneumonia (Fig. 2 on page 13) [11]. This pattern is common in Klebsiella pneumoniae infection, which sometimes can be distinguished by increased volume of the involved lung with a displacement of fissures (a so called "bulging fissure" sign) [11] (Fig. 3 on page 10, Fig. 4 on page 11). Also, there is a higher tendency to abscess formation and the pleural effusion is more pronounced than in pneumococcal pneumonia [12]( Fig. 5 on page 12). Mycobacterium tuberculosis (MTB) is responsible for approximately 20% of pneumonia cases in patients after renal transplantation and from 2 to 5% of cases in lung and heart-lung recipients [8,12,13]. Patients under long term immunosupperssion are at increased risk of reactivation of pulmonary tuberculosis but are also vulnerable to primary infection. There is a broad spectrum of radiological abnormalities associated with MTB infection, which is related to the severity of immunosuppression and includes: single / multiple nodules, disseminated heterogeneous opacities with nodular and linear components, lobar consolidations, parenchymal opacities with cavitation, lymphadenopathy, and pleural effusion [14]. In patients with low-dose immunosupperssion, the radiological appearance of MTB may be similar to postprimary disease in immunocompetent population - parenchymal opacities, most often with cavitation, can be seen in the apical and posterior segments of the upper lobes or in the superior segments of the lower lobes [15](Fig. 6 on page 16). In more severely immunosuppressed patients, MTB can produce a lobar pneumonia indistinguishable from gram negative pneumonia (Fig. 7 on page 17). The tree-in-bud pattern is statistically more often encountered in MTB pneumonia than in other bacterial pneumonias [16]. Page 6 of 41

7 This pattern is comprised of well-defined centrilobular nodules connected by branching linear opacities and reflects thickening and filling of small bronchioles caused by an endobronchial spread of bacteria (Fig. 8 on page 15,Fig. 9 on page 15,Fig. 10 on page 14). The miliary pattern refers to innumerable small (1-2 mm) nodules diffusely distributed throughout the lungs and reflects a hematogenous dissemination of mycobacteria. Lymphadenopathy is not very common, however necrotic nodules are suggestive of tuberculosis. Involved lymph nodes, usually hilar and mediastinal, typically have a central area of low attenuation (central necrosis) surrounded with enhancing rim that reflects inflammatory capsular reaction [14, 15] (Fig. 11 on page 18). A radiologist may be faced with a question of activity of tuberculosis. There are several features that indicate either an active (nodules in miliary or tree-in-bud pattern, conosolidation, cavities) or inactive (calcified nodules, linear opacities, bronchiectases) process (Table 3 on page 27), however a confident evaluation is best made on the basis of follow up studies showing no change in lesions morphology for longer than 6 months. Viral pneumonia: Cytomegalovirus (CMV) is a common cause of pneumonia in patients after lung (56% of cases) and liver (47%) transplantation and only occasionally affects kidney transplant recipients (2% of cases) [7,8,12]. The most common HRCT abnormalities in CMV pneumonia are scattered areas of ground-glass opacities that can progress into air-space consolidations and diffuse, small, centrilobular nodules [17](Fig. 12 on page 19,Fig. 13 on page 20,Fig. 14 on page 21). The tree-in-bud sign, reticular pattern of opacities, and bronchiolar wall thickening are infrequent. Small pleural effusions may be present in less than half of patients. Horger et al. observed that large areas of ground-glass opacities are an unfavourable prognostic factor and may be associated with a fatal outcome [17]. Influenza virus is responsible for upper and lower respiratory tract infections in immunocompetent population, however in immunocompromised patients, it can also lead to pneumonia. The number of published cases with radiological assessment of pneumonia caused exclusively by influenza virus in immunocompromised patients is limited: Leung et al. described one patient after bone marrow transplantation and Oikonomou et al. four patients with hematological malignancies [19,20]. According to the study of Oikonomou et al., the chest radiography of all the patients showed bilateral, patchy areas of consolidations and in 50% of cases small nodules with ill-defined margins [20]. The HRCT of those patients showed predominantly areas of patchy groundglass opacities, 2 to 9 mm centrilobular nodules, as well as small areas of alveolar consolidations and tree-in-bud pattern [20](Fig. 15 on page 23). It is useful to remember, that influenza virus is seldom the only pathogen responsible for pneumonia. Usually a superinfection occurs and the radiographic picture consists of overlapping abnormalities due to influenza virus and other microorganism. In lung recipients, CMV Page 7 of 41

8 and Pseudomonas aeruginosa were the most frequent co-infection factors [20] (Fig. 1 on page 10). Fungal pneumonia: Aspergillus fumigatus is responsible for approximately 3 to 13% of pneumonia incidents in transplant recipients [7,8,12,13]. Aspergillus is associated with several lung disease entities that evolve depending on patient's immune status [21]. In immunocompetent population it can induce allergic bronchopulmonary aspergillosis or a saprophytic aspergillosis without tissue invasion - aspergilloma [21]. Semi-invasive (chronic necrotizing) aspergillosis occurs in patients with a mild immune deficiency (malnutrition, alcoholism, chronic illness). Angioinvasive and airway-invasive aspergillosis is seen almost exclusively in severely immunocompromised patients [21, 22]. Most common HRCT features of airway-invasive form of Aspergillus are: patchy distributed centrilobular nodules and tree-in bud pattern. If the lung parenchyma is affected, the air-space consolidations have a peribrionchal distribution [22]. In angioinvasive aspergillosis two characteristic signs have been described. The first one - the CT halo sign - is associated with an early stage of the disease and has a high frequency (up to 96%) of occurrence during first days of infection [23]. It consists of nodules or masses surrounded by a rim of hazy ground-glass opacity (Fig. 16 on page 22). The CT appearance of the halo sign correlates with the ischemic necrosis seen on pathology examination - the nodule represents the focus of infarction and the ground-glass attenuation reflects the surrounding alveolar hemorrhage [24](Fig. 17 on page 24). Occasionally, the halo sign is associated with nonhemorrahagic nodules, where the ground-glass opacity is a result of tumor or infection infiltrates in lung parenchyma. Although the CT halo sign can be observed in a number of other diseases (Table 4 on page 26), in an appropriate clinical setting it is highly suggestive of angioinvasive aspergillosis [23]. The second radiological sign that also indicates angioinvasive aspergillosis is the air-crescent sign [25]. It consists of a crescent shape hyperlucency within a preexisting parenchymal opacity and develops when an infarcted lung tissue begins to separate from a healthy lung (Fig. 18 on page 25). The aircrescent sign appears during the resolution phase of the disease, when the patient's immunological status improves (e.g. the immunosuppressive treatment is reduced), usually after two weeks from the onset of infection [25]. Pneumocystosis (Pneumocystis jirovieci [carini] pneumonia, PCP) occurs in 13% of lung recipients [12], 6% of liver recipients [7], and 4% of kidney recipients [8]. The conventional radiography appearance of pneumocystosis typically consists of bilateral, perihilar, reticular interstitial infiltrations that can progress into air-space consolidation within few days [26]. In some patients the chest radiography remains normal and in 5% of them an atypical pattern of abnormalities is observed [26]. Atypical manifestations include: lung nodules and masses or interstitial fibrosis. In HRCT, the most characteristic Page 8 of 41

9 findings for PCP are extensive areas of ground-glass attenuation with geographic distribution (Fig. 19 on page 28,Fig. 20 on page 29). Subpleural lung regions are often spared. In up to one third of patients, a cystic lung disease may be present (Fig. 21 on page 30). Cysts (pneumatoceles) may differ in size, wall thickness, and localization, however upper lobe predilection has been observed. Subpleural cysts can rapture and lead to spontaneous pneumothorax [27](Fig. 22 on page 31). Mediastinal lymphadenopathy and pleural effusion is uncommon in pneumocystosis and the presence of those two abnormalities virtualy excludes PCP from differential diagnosis [26]. Pneumonia due to Candida albicans occurs mainly in patients after lung transplantation, where the fungi colonize a necrotic lung parenchyma. In other recipients pulmonary candidiasis is infrequent [22]. HRCT in most patients is dominated by bilateral nodules with predilection to the lower lung zones [22] (Fig. 23 on page 34, Fig. 24 on page 32). Nodules are often accompanied by areas of ground-glass opacities, randomly distributed air-space consolidation or tree-in-bud pattern [22] (Fig. 25 on page 33). Occasionally, nodules can have a rim of ground-glass attenuation (the halo sign). Page 9 of 41

10 Images for this section: Fig. 1: 1. Influenza virus pneumonia with Pseudomonas superinfection. There are bilateral geographic areas of ground-glass opacities accompanied by linear opacities. In the right middle lobe, lingua, and right lower lobe, there are irregular, confluent peribronchial nodular consolidations corresponding to bronchopneumonia. Page 10 of 41

11 Fig. 3: 3. Klebsiella pneumoniae infection. There is an air-space pneumonia affecting the entire left lower lobe. Page 11 of 41

12 Fig. 4: 4. Klebsiella pneumoniae infection. The involved lobe shows an increased volume with the left interlobar fissure bulging anteriorly (arrows). Page 12 of 41

13 Fig. 5: 5. Klebsiella pneumoniae infection.a large pneumo-pyothorax is present on the left. Page 13 of 41

14 Fig. 2: 2. Lobar (or "air-space") gram negative pneumonia. There are peripheral, homogenous consolidations in the right upper lobe showing tendency to fuse into larger areas with air-bronchogram. Fig. 10: 10. Mycobacterium tuberculosis.a diagram superimposed on the magnification of Figure 9 shows a tree-in-bud pattern produced by small well-defined centrilobular nodules connected by linear opacities. Page 14 of 41

15 Fig. 9: 9. Mycobacterium tubeculosis. MIP reconstruction showing a tree-in-bud pattern. Page 15 of 41

16 Fig. 8: 8. Mycobacterium tuberculosis. There are multiple, small peribronchial nodules in the right upper lobe reflecting the endobronchial spread of the disease. Page 16 of 41

17 Fig. 6: 6. Postprimary tuberculosis. A nodular area of consolidation with a small area of central cavitation is visible in the superior segment of the left lower lobe. Page 17 of 41

18 Fig. 7: 7. Lobar pneumonia in Mycobacterium tuberculosis infection. There is an extensive consolidation involving the right upper lobe with large areas of cavitation. Page 18 of 41

19 Fig. 11: 11. Necrotic lymphadenopathy in tuberculosis. There is an enlarged right paratracheal lymph node with a central hypodense necrotic area and a hyperdense rim of capsular enhancement. Page 19 of 41

20 Fig. 12: 12. CMV pneumonia. There are diffuse, bilateral, centrilobular, hazy ground glass opacities quite evenly distributed throughout the lungs, accompanied by numerous, tiny, ill-defined centrilobular nodules. Page 20 of 41

21 Fig. 13: 13. CMV pneumonia. There are diffuse, bilateral, centrilobular, hazy ground glass quite evenly distributed throughout the lungs, accompanied by numerous, tiny, ill-defined centrilobular nodules. Page 21 of 41

22 Fig. 14: 14. CMV pneumonia.a diagram superimposed on the magnification of Figure 13 shows a classic appearance of centrilobular nodules that are equally spaced and separated from the pleura. The white hexagon represents the shape of pulmonary lobule. Page 22 of 41

23 Fig. 16: 16. Angioinvasive aspergillosis. In the left segment 10, there is a large, nodular area of consolidation sourrounded by ground-glass opacities - the CT halo sign. Page 23 of 41

24 Fig. 15: 15. Influenza virus pneumonia with Pseudomonas superinfection. There are bilateral geographic areas of ground-glass opacities accompanied by linear opacities. Page 24 of 41

25 Fig. 17: 17. Angioinvasive aspergillosis. Peripherally to the lesion presented on Figure 16, an area of ground-glass opacities in segmental distribution is visible, most probably corresponding to pulmonary hemorrhage secondary to the obstruction of the segmental artery. Page 25 of 41

26 Fig. 18: 18. Angioinvasive aspergillosis during treatment. The lesions show cavitation, in the small lesion in the right upper lobe there is the air crescent sign (arrow). Page 26 of 41

27 Table 4: Table 4. Diseases manifesting with a halo sign. Page 27 of 41

28 Table 3: Table 3. HRCT features suggesting active vs inactive tuberculosis. Page 28 of 41

29 Fig. 19: 19. Pneumocystis jirovecii pneumonia (PCP). There are extensive bilateral areas of ground-glass opacity with a sparing of subleural regions. Page 29 of 41

30 Fig. 20: 20. Pneumocystis jirovecii pneumonia (PCP). There are extensive bilateral areas of ground-glass opacity with a sparing of subleural regions. Page 30 of 41

31 Fig. 21: 21. Pneumocystis jirovecii pneumonia (PCP). Areas of consolidation and peripheral pneumatoceles (arrows) in the right upper lobe. Page 31 of 41

32 Fig. 22: 22. Pneumocystis jirovecii pneumonia (PCP). Spontaneous right-sided pneumothorax secondary to the rupture of pneumatocele. The subcutaneous emphysema is secondary to the chest tube placement. Page 32 of 41

33 Fig. 24: 24. Candidasis. There are numerous nodules of different size in both lungs. Page 33 of 41

34 Fig. 25: 25. Candidasis. A diagram superimposed on the magnification of Figure 25 shows random distribution of nodules suggesting the hematogenous spread of the disease. Page 34 of 41

35 Fig. 23: 23. Candidasis. There are numerous nodules of different size in both lungs. Nodules show a predilection to the lower lung zones. Page 35 of 41

36 Conclusion The most characteristic HRCT features of pneumonia in patients after transplantation are listed in Table 5 on page 37 and Table 6 on page 37. The radiological pattern is sufficiently specific to suggest a particular pathogen only in selected cases (mainly in angioinvasive aspergillosis and pneumocystosis). However, the knowledge of important clinical data can further increase the specificity of radiological findings. Thus, it may be possible to narrow the differential diagnosis and introduce empiric treatment, even before the diagnosis is confirmed by microbiology. Page 36 of 41

37 Images for this section: Table 5: Table 5. HRCT features of bacterial and viral pneumonia. Page 37 of 41

38 Table 6: Table 6. HRCT features of fungal pneumonia. Page 38 of 41

39 Personal Information Page 39 of 41

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