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Diagnosis of invasive aspergillus tracheobronchitis facilitated by endobronchial ultrasound-guided transbronchial needle aspiration: a case report
© Casal et al; licensee BioMed Central Ltd. 2009
Received: 27 October 2009
Accepted: 23 November 2009
Published: 23 November 2009
Invasive pulmonary aspergillosis is the most common form of infection by Aspergillus species among immunocompromised patients. Although this infection frequently involves the lung parenchyma, it is unusual to find it limited to the tracheobronchial tree, a condition known as invasive aspergillus tracheobronchitis.
A 65 year-old Hispanic man from Bolivia with a history of chronic lymphocytic leukemia developed cough and malaise eight months after having an allogenic stem cell transplant. A computed tomography of the chest revealed an area of diffuse soft tissue thickening around the left main stem bronchus, which was intensely fluorodeoxyglucose-avid on positron emission tomography scanning. An initial bronchoscopic exam revealed circumferential narrowing of the entire left main stem bronchus with necrotic and friable material on the medial wall. Neither aspirates from this necrotic area nor bronchial washing were diagnostic. A second bronchoscopy with endobronchial ultrasound evidenced a soft tissue thickening on the medial aspect of the left main stem bronchus underlying the area of necrosis visible endoluminally. Endobronchial ultrasound-guided transbronchial needle aspiration performed in this area revealed multiple fungal elements suggestive of Aspergillus species.
We describe the first case of invasive aspergillus tracheobronchitis in which the diagnosis was facilitated by the use of endobronchial ultrasound guided trans-bronchial needle aspiration. To the best of our knowledge, we are also presenting the first positron emission tomography scan images of this condition in the literature. We cautiously suggest that endobronchial ultrasound imaging may be a useful tool to evaluate the degree of invasion and the involvement of vascular structures in these patients prior to bronchoscopic manipulation of the affected areas in an effort to avoid potentially fatal hemorrhage.
Invasive aspergillosis is one of the most common fungal infections in immunocompromised hosts, involving the respiratory tract in 90% of cases . This disease occurs almost exclusively in immunosuppressed and especially myelosuppressed patients, although there have been rare patients without any grossly apparent immune defect. The most common form of aspergillus species infection in immunocompromised patients is invasive pulmonary aspergillosis, which mainly involves the lung parenchyma and, rarely, the trachebronchial tree . Infection confined only to the tracheobronchial tree is known as invasive aspergillus tracheobronchitis (IATB), and it generally carries an ominous prognosis. The diagnosis of this condition is usually delayed due to its non-specific presentation. We are presenting a case of IATB in which the diagnosis was obtained by endobronchial ultrasound (EBUS)-guided fine needle aspiration (FNA) after initially failing to reach the diagnosis through flexible bronchoscopy. Additionally, although lesions caused by aspergillus in the lungs have already been shown to have increased fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) scanning [3, 4], we are presenting the first PET scan images of IATB in the literature.
His medical history was remarkable for adult-onset asthma, two episodes of pneumonia several years ago, actinic keratosis and squamous cell carcinoma of the skin. He was a lifelong non-smoker and was on immunosuppression with prednisone and tacrolimus, and routine prophylaxis with atovaquone, valacyclovir and voriconazole. His vital signs were stable and his respiratory exam was unremarkable. He was thrombocytopenic (21,000/mm3), but not neutropenic (absolute neutrophil count 3,960/mm3).
Human aspergillosis can be classically divided as invasive, saprophytic or allergic. Aspergillus fumigatus is the species most commonly responsible for invasive aspergillosis, followed by Aspergillus flavus, Aspergillus niger and Aspergillus terreus . These fungi can use the lower respiratory tract, sinuses or skin as entry portals to cause invasive infections. Inhalation of airborne aspergillus spores results in colonization of the respiratory mucosal surfaces. The progression from colonization to tissue invasion and the type of disease that patients develop depend mainly on their immune status and on local defense mechanisms [6, 7]. The most common form of invasive aspergillosis in immunocompromised patients is invasive pulmonary aspergillosis. IATB is a rare manifestation defined as localized invasion of the bronchial wall by aspergillus. Young et al. reviewed the postmortem findings in 98 cases of aspergillosis and found that the infection was limited to the tracheobronchial tree in only five patients .
Three morpholgical variants of IATB have been described: obstructive tracheobronchitis, ulcerative tracheobronchitis and pseudomembranous necrotizing bronchial aspergillosis (PNBA) [6, 8, 9]. The obstructive form is characterized by massive intraluminal growth of aspergillus species associated with thick mucus plugs that generally produce atelectasis. Ulcerative lesions like the one we found in our patient penetrate through the tracheo-bronchial wall, and can create bronchoesophageal or bronchoarterial fistulas that may produce fatal hemorrhage [9, 10]. In fact, Putnam et al.  reported a case of IATB localized to the right main stem bronchus and invading the right pulmonary artery in which the patient had a fatal hemorrhage after bronchoscopic manipulation. PNBA is characterized by extensive formation of whitish pseudomembranes composed of hyphae, fibrin and necrotic debris. Rather than three distinct entities, these morphologic variants may just represent different stages in the development of IATB [6, 8].
The clinical mainfestations of IATB are entirely different from those of invasive pulmonary aspergillosis. The insidious presentation with non-specific symptoms and the paucity of findings in chest roentgenograms often delay the diagnosis, giving this disease an ominous prognosis [10–12]. Airway-related symptoms such as cough, dyspnea, wheezing and hemoptysis are cardinal features. There is little documentation of the radiologic features of IATB in the literature. As previously mentioned, lesions caused by aspergillus in the lungs and other organs are known to have increased FDG activity on PET scanning [3, 4]. Nevertheless, to the best of our knowledge, we are presenting the first PET/CT scan images of IATB in the literature (Figure 2).
The diagnosis of IATB is almost always confirmed by bronchoscopic examination and sampling. Although thrombocytopenia is commonly a limiting factor for acquiring endobronchial biopsies, bronchoscopic aspiration of debris and bronchial washings allow diagnosis in the majority of cases by showing the presence of Aspergillus hyphae in special stains or by recovering the organism in fungal cultures. The samples obtained during the first bronchoscopic examination of our patient, however, were negative. As the patient's thrombocytopenia was refractory to platelet transfusions, we opted for EBUS-guided TBNA in order to achieve diagnosis with the lowest risk of bleeding. This is the first case of IATB in which diagnosis was facilitated by EBUS that we could find in the medical literature. It is our opinion that real-time EBUS might also be useful in delineating the relationships during fungal invasion into adjacent tissues and the involvement of major vascular structures, potentially preventing lethal hemorrhage. This type of infection can progress very rapidly, leading to invasion of major vessels in the time between CT imaging and bronchoscopy, making routine bronchoscopic manipulation and sampling of debris extremely dangerous and even fatal .
In conclusion, IATB is a rare form of invasive aspergillosis affecting mainly immunocompromised patients. The non-specific clinical presentation often leads to late diagnosis and poor prognosis. We report the first case of IATB diagnosed by EBUS-guided TBNA. We also cautiously suggest that EBUS imaging may be a useful tool to evaluate the depth of fungal invasion into adjacent tissues and the involvement of vascular structures in these patients prior to bronchoscopic manipulation of the affected areas in an effort to avoid fatal hemorrhage.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the journal's Editor-in-Chief.
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