Objectives: The aim of this study was to assess initial and follow-up computed tomography findings of invasive pulmonary aspergillosis in solid-organ transplant recipients and to examine the most common computed tomography patterns during hospitalization.
Materials and Methods: From January 2011 to September 2016, the total number of solid-organ transplant patients at our institution was 784. These patients consisted of 550 kidney, 164 liver, and 67 heart transplant recipients. Of these, 15 patients had a proven diagnosis of invasive pulmonary aspergillosis according to clinical and radiologic features with culture evidence of aspergillosis from bronchoalveolar lavage or lung biopsy. Computed tomography examinations were performed at initial diagnosis and at follow-up for evaluation of treatment. Computed tomography patterns were retrospectively evaluated by 2 experienced radiologists. Configurations and types of the largest lesions in each of the 15 patients were evaluated, and changes to lesions during treatment were recorded. Invasive pulmonary aspergillosis patterns were categorized into 6 main groups: ground-glass opacity, nodules, irregular nodules, patchy consolidation, cavity, and tree-in-bud patterns.
Results: The most common patterns were ground-glass opacity and irregular nodules, which were observed in 12 of 15 patients (80%), followed by regular nodules (73%), patchy consolidation and cavity (26%), and tree-in-bud pattern (20%). Long-term follow-up computed tomography studies showed that the regular nodules, tree-in-bud patterns, and ground-glass opacity areas gradually reduced by 50% in 4 weeks. However, patchy consolidations and irregular nodules showed less regression than the other lesions over the 4-week period.
Conclusions: Irregular nodules and ground-glass opacity were the most common computed tomo-graphy patterns in our solid-organ transplant recipients. Computed tomography patterns without irregular nodules and patchy consolidations may be associated with better prognosis due to their relatively rapid healing.
Key words : Ground-glass opacity, Irregular nodules, Pulmonary infections
Pulmonary infections are a source of high morbidity and mortality in immunocompromised transplant recipients during the posttransplant course.1 The infective agent generally reaches the lung via inhalation of airborne droplets or direct dissemination from the nasopharynx. Hematogenous contamination from an infected site outside the chest is another origin of infection.
The lungs are the leading place of infections, especially in lung and heart transplant recipients, followed by liver transplant recipients.2 The incidence of pneumonia is lowest among kidney transplant recipients. Solid-organ transplant recipients present with infective complications due to lymphocyte deficiency. Risk of infection during the first month posttransplant is generally related to surgery and hospitalization but is also related to immunosup-pressive agents. Recipients receive maximal immunosuppression within the first 6 months and are at the greatest risk of opportunistic infections.
Invasive pulmonary aspergillosis (IPA) is the most common cause of opportunistic fungal pneumonia in solid-organ transplant recipients.2 The incidence of IPA is approximately 5% in liver and heart transplant recipients. It is less common after kidney transplant.
The main imaging modalities for diagnosis of suspected pulmonary infections are chest radiography and computed tomography (CT). Although CT imaging is not recommended as the first step, it is much more sensitive and diagnostic than plain chest radiography.3 A CT scan can depict the exact location and form of consolidation for pneumonia. Furthermore, CT scans can also confirm whether there are associated pathologies, such as pleural effusion or empyema and lymphadenopathy and whether any cavities are occurring.
The characteristic CT signs of IPA in immuno-compromised patients such as transplant recipients are solitary or multiple lung nodules with poorly defined or irregular margins. Generally, lung nodules are surrounded by ground-glass opacity (GGO), which are called “halo sign.” These mostly specific signs are best defined with CT imaging.4 CT findings may be helpful for exact and rapid diagnosis of pulmonary aspergillosis and may ensure prompt treatment.
In this study, our aim was to evaluate and analyze the CT patterns of IPA in solid-organ transplant recipients at our institution.
Materials and Methods
From January 2011 to September 2016, the total number of solid-organ transplant patients at our institution was 784. These patients consisted of 550 kidney, 164 liver, and 67 heart transplant recipients. Of these, 15 patients (11 males, 4 females) had a proven diagnosis of IPA according to clinical and radiologic features, with culture evidence of aspergillosis from bronchoalveolar lavage or lung biopsy. All patients with IPA had chest CT scans performed at our institution. The CT scans had been obtained using 16-section multidetector row CT (Sensation 16, Siemens Medical Solutions, Erlangen, Germany). Intravenous contrast-media were administered during CT scans.
All CT images were evaluated by 2 radiologists with over 5 years of experience in interpreting multidetector CT imaging of the chest in their daily clinical practice. The analyses of the images were based on reviews of patient records, which were available on the workstation (Leonardo, Siemens Medical Solutions). The radiologists interpreted the studies using multiplanar reconstruction sections.
Computed tomography scans had been per-formed for initial diagnosis and during follow-up for treatment evaluation. The configurations and types of lesions in each of the 15 patients were categorized into 6 main groups: ground-glass opacity (GGO), nodules, irregular nodules, patchy consolidation, cavity, and tree-in-bud patterns. The multidetector CT patterns of IPA lesions were recorded separately. Long-term evaluations had been done with second and third control multidetector CT scans of patients. These findings also allowed detection of which type of infiltration was more resistant.
Our study group included 15 transplant recipients with confirmed IPA diagnosis. The most common patterns were GGO and irregular nodules, which were observed in 12 of 15 patients (Figure 1), followed by regular nodules in 11 patients, patchy consolidation and cavity in 4 patients (Figures 2 and 3), and tree-in-bud patterns in 3 patients. The GGO areas aroundthe nodules (halo signs) were seen in 10 patientswith regular or irregular nodule form infiltrations (Figure 4). Twelve patients developed IPA within the early posttransplant period (31-100 days post-transplant), and 3 patients developed IPA in the late posttransplant period (101 days and beyond).
Long-term follow-up CT studies showed that the regular nodules, tree-in-bud patterns, and GGO areas gradually reduced by 50% in 4 weeks. However, patchy consolidations and irregular nodules showed less regression than the other lesions in this period (Figure 4). Pleural effusion was seen in 3 patients (20%). Interlobular septal thickening sign was not seen in our patients.
Pulmonary infections are the most commonly encountered in immunocompromised transplant recipients, with the lung being the most frequently affected organ.2 Due to the high risk of morbidity and mortality, these pulmonary infections require exact diagnosis and treatment. Specific radiologic signs of CT may be very helpful in expediting differential diagnosis with almost specific patterns.
Chest radiography has an important role in the detection of pulmonary pathologies as a first-step radiologic modality. Due to the depressed inflam-matory reaction, it could be difficult to evaluate chest radiography scans in immunosuppressed patients. Most infiltrations look similar to each other, and a diagnosis is difficult in many cases. Roentgenogram also has a lower sensitivity for detection of specific infections, such as IPA.
Heussel and associates concluded that CT scans are 20% more accurate in detection of pneumonia in patients with pulmonary infections, occurring 5 days earlier than use of chest radiography.5 Computed tomography plays a key role in detection of pul-monary infections when chest radiography alone lacks specificity.6 It must be carried out when there is a strong suspicion of pulmonary infection that is generally accompanied by ambiguous or nonspecific radiography, especially in immunocompromised patients. Computed tomography imaging can also confirm whether there are associated issues, such as pleural effusion, empyema, cavity formation, or pathologic lymphadenopathies. Furthermore, CT is also helpful for IPA follow-up during treatment.7
Invasive pulmonary aspergillosis is a mycotic disease caused by Aspergillus species, usually Aspergillus fumigatus. Pulmonary aspergillosis can be divided into 5 subtypes: aspergilloma, allergic bronchopulmonary aspergillosis, semi-invasive aspergillosis, airway-invasive aspergillosis, and IPA.
The typical appearance of new-onset pulmonary aspergillosis is a single ground-glass area or dens alveolar consolidation with blurred margins, which is restricted to the area next to the lung fissures. Aspergillus species infection is generally associated with GGO and ill-defined nodules.5,8
An area of GGO is defined as focal high attenuation of the lung parenchyma in CT imaging due to partially filled exudates into alveoli and decreased air content. This sign is not specific for infection and could be seen in other conditions, including congestion and vasculitis. Accompanying nodules should be demonstrated in the lung to accept GGO as a diagnostic criteria for IPA9 In our experience, GGO infiltration was the most common findings, observed in 80% of the patients in our study.
In addition, IPA is characterized as having nodular lesions with peripheral GGO, which is known as the halo sign. The halo sign is due to the angioinvasive effect of aspergillosis and represents focal hemorrhage around the nodule as a result of microvascular involvement. This sign is highly suggestive of fungal infections in immunocom-promised patients, including transplant recipients.10,11 In general, it is accompanied by irregular or wedge-shaped consolidations.1 In our study, GGO infiltration and irregular nodules were the most common findings, observed in 80% of our patients.
In our study, regular nodules (73%) were the second most common sign and the halo sign was seen around the regular or irregular nodules in about 66% of patients with IPA. However, the halo sign is neither sensitive nor specific for IPA; this sign has been reported in 50% of cases in the literature.6,8,10,12 The halo sign may be found in some other patients, especially those with fungal infections, those with bronchoalveolar carcinoma, and elderly patients with Wegener granulomatosis disease.4
Cavitation is not a common complication in IPA recipients after solid-organ transplant. Semi-invasive aspergillosis is an uncommon manifestation of Aspergillus species infection, which is most commonly seen in patients who are mildly immunocompromised, such as those who are on chronic corticosteroid therapy.2 We found cavity formation in 4 patients (26%) with IPA in our study. Necrotizing pneumonia with community-acquired causes such as Staphylococcus aureus may also create cavitation. Therefore, bacterial pneumonia should be considered a differential diagnosis in IPA.1
Another specific CT sign that we found in IPA patients was the tree-in-bud sign. Three patients showed this sign (20%). However, the tree-in-bud sign is a well-appreciated sign in various conditions, including forms of bronchiolitis and many infective pathologies. Therefore, this could not be accepted as a specific sign of IPA.12
It is important that differential diagnoses be done carefully before the diagnosis of IPA is confirmed. Some other lung parenchymas may mimic lung infection and IPA. These are caused by various conditions, including cardiogenic edema, cryptogenic organizing pneumonia, cancer with lymphangitis, and chemotherapy-associated lung changes. Hence, recognizing the relevant clinical and laboratory findings can provide optimal differential diagnoses and play an important role in patient care.
Our study has some limitations. First, because of the relatively short research period, we have a limited number of patients. Second, patients were primarily given chest radiographic scans at follow-up. In our center, CT imaging occurs when symp-toms become more serious.
Invasive pulmonary aspergillosis can be predicted in febrile immunocompromised posttransplant reci-pients with high accuracy if the patient has nodules on CT imaging. We demonstrated that irregular nodules and GGO are the most common CT patterns in solid-organ transplant recipients with IPA.
Volume : 17
Issue : 1
Pages : 216 - 219
DOI : 10.6002/ect.MESOT2018.P73
From the 1Department of Radiology, the 2Department of Pulmonary Diseases, and
the 3Department of Surgery, Baskent University, School of Medicine, Ankara,
Acknowledgements: The authors received no financial support for this study. The authors declare they have no conflicts of interest.
Corresponding author: Koray Hekimoglu, Baskent Universitesi Hastanesi, Radyoloji ABD, Fevzi Cakmak Cad. 10. sok. No: 45, Bahcelievler, Ankara 06490, Turkey
Phone: +90 312 203 68 68 ext.1866
Figure 1. Computed Tomography Image From a 52-Year-Old Male Patient 2 Weeks After Liver Transplant
Figure 2. Computed Tomography Image From a 55-Year-Old Male Liver Transplant Recipient
Figure 3. Computed Tomography Image From a 43-Year-Old Male Liver Transplant Recipient
Figure 4. Computed Tomography Signs in Invasive Pulmonary Aspergillosis