A Rare Presentation of Pulmonary Aspergillosis

To the Editor: Clinical manifestations of Aspergillus species range from allergic reactions to aspergilloma, and semi-invasive and invasive aspergillosis, depending on immune status of the host. Most types of Aspergillus infections affect the lung parenchyma of immuncompromised patients or those with underlying cavitary pulmonary disease such as cystic fibrosis or tuberculosis.1,2 Endobronchial Aspergillus infections called tracheobronchial aspergillosis (TBA) are relatively rare conditions. Bronchial stump aspergillosis (BSA) is infection of the granulation tissue surrounding sutures of lung resection. Herein, we report a case of BSA who was previously operated for bronchial carcinoid. CASE A 46-year-old nonsmoker female patient presented with expectoration of a brownish slimy material 4 times during the last 3 months. She had undergone right middle and lower lobectomy for an endobronchial lesion diagnosed as typical carcinoid tumor in the bronchus intermedius 3 years ago. There was no tumor at surgical margins, and the resected lymph nodes were reactive. She received no further therapy, and the follow-up period was uneventful. She never reported hemoptysis. She was treated for hyperparathyroidism 1 year ago. Her physical examination was unremarkable except for a thoracotomy scar and diminished basal breath sounds on the right. Computed tomography of the thorax revealed usual changes due to bilobectomy inferior. Fiberoptic bronchoscopy (FOB) to rule out recurrence showed necrotic and fragile lesions on the stump extending toward the lumen (Fig. 1). Mucosal biopsies revealed necrosis, fungal hyphae, and spores suggesting Aspergillus infection. Voriconazole was administered 200 mg bid.FIGURE 1: Necrotic material on stump.Four months later, she presented with bullous rashes on her lower extremities, which were exacerbated by exposure to sunlight. Voriconazole was discontinued, and her skin manifestations resolved. She had no symptoms otherwise. One month later, the patient reported coughing up mucoid brownish material again (Fig. 2). Repeat FOB revealed the bronchial stump covered with white necrotic material (Fig. 3). Besides biopsies, visible parts of the sutures were cauterized and extracted via forceps during FOB. Pathologic examination of biopsy samples was compatible with Aspergillus infection (Fig. 4). Septate hyphae, vesicle formation, phialides, and conidia were observed. The culture of the biopsy sample yielded Aspergillus flavus complex identified by conventional methods.3 An Aspergillus strain that could not be identified by species level by morphologic examination was also isolated. Antifungal susceptibility tests were performed using EUCAST reference microdilution method.4 Minimum inhibitory concentration (µg/mL) values for amphotericin B, itraconazole, voriconazole, and posaconazole were 2, 0.5, 0.5, and 0.5 µg/mL, respectively, for the A. flavus complex strain. The minimum inhibitory concentrations obtained for the other strain of Aspergillus were 2, 1, 0.5, and 1 µg/mL, respectively, for the denoted drugs. As per the available clinical breakpoint for A. flavus complex strains, the isolate was susceptible to itraconazole (www.eucast.org). Oral posaconazole was administered 300 mg/d for 6 months. She was asymptomatic, and there were a few white and brown plaques on the sutures at the bronchial stump, which were removed with forceps on control bronchoscopy (Fig. 5). Biopsies and bronchial washing cultures were negative for Aspergillus, and posaconazole was discontinued. Her course was uneventful for BSA during the follow-up for 12 months.FIGURE 2: Necrotic material expectorated by patient.FIGURE 3: Recurrent white necrotic material on bronchial stump seen on repeat fiberoptic bronchoscopy.FIGURE 4: Histopathologic examination of the biopsy sample, hematoxylin and eosin. Septate hypha (black arrow), vesicle, phialides, and conidia (red arrow).FIGURE 5: Appereance of stump during last bronchoscopy.DISCUSSION Aspergillus species are ubiquitous in the environment. The inhalation of conidia is a frequent but not threatening for immunocompetent individuals. TBA refers to infection involving the large airways, which encompasses simple colonization, obstructing tracheobronchitis, and pseudomembranous or ulcerative tracheobronchitis.5 BSA, an unusual form of TBA, is an infection of bronchial granulation tissue surrounding sutures after pulmonary resection, which usually develops in nonimmunocompromised patients. Although it seems limited to the airways, concurrent aspergilloma6 and aspergillus empyema7 cases have also been published. BSA was first described by Sawasaki et al8 in 1969 in a clinical and experimental study, which concluded that silk sutures used in pulmonary resection were responsible for BSA (Table 1). They claimed that silk sutures permitted progression of infection with their high capillarity in contrast to nylon sutures. Local inflammation and BSA were observed in 24% and 1.5% of patients with silk sutures, but it was observed only in 1.5% and none of the patients with nylon sutures, respectively.8 Although 13 (68.4%) of the 19 reported cases were associated with use of silk threads, BSA also occurred with nylon sutures or stapler in 2 cases each (Table 1). In the specific case, bronchial resection was performed ahead of pulmonary arterial and venous dissection due to excessive bronchial secretion causing intraoperative hypoxemia. Polyester monofilament surgical suture (Ethibond Excel) was used instead of stapler, which was technically inappropriate.TABLE 1: Cases of Bronchial Stump Aspergillosis in the LiteratureAlthough they may be completely asymptomatic, most patients present with 1 or more symptoms. The most common symptoms are hemoptysis, expectoration of a fungus mass, necrotic material or suture thread, cough, putrid sputum, asthma exacerbation, and acute dyspnea. Only 2 patients were asymptomatic, and infection in 1 of them was detected during control bronchoscopy.10,11 The period between operation and the diagnosis of BSA ranges from 1 month to 7 years, but the majority present within the first year of pulmonary resection.6,8,9,12 The symptom-free period until the expectoration of tumor-like material in the current case was ∼3 years. Bronchoscopic findings of BSA may imitate endobronchial tumor or recurrence because of its white and necrotic appearance. It may also obstruct the airways.12 Fungal hyphae can be shown between necrotic areas, and cultures can be positive in tissue or bronchial lavage as well. Fungal hyphae were shown microscopically in tissue, and the culture of bronchial lavage grew A. flavus complex as well in this patient. In addition to septate hyphae, vesicle, phialides, and conidia were also observed in histopathologic examination. While septate hyphae may be visualized in tissue samples only, vesicle, phialides, and conidia are, virtually, the structures observed when the fungus is grown in culture and the wet mount preparation of the colony is examined microscopically. However, if the site of the infection is one that is directly exposed to air, as in this case, these structures may be observed in tissue samples as well. Although there was no study comparing the treatment modalities of BSA, antifungal therapy and total removal of the suture threads is recommended for both treatment and avoidance of recurrence in previous reports.6,8,9 In Table 1, oral itraconazole was administered to 6 patients and was successful in 4 patients (66%).6,11,13 Of the 19 patients in Table 1, removal of sutures was accomplished in 10 patients (52%).6,8–10,13 Le Rochais et al10 used inhalation of liposomal amphotericin B in 2 patients, but it failed, and bronchoscopic removal of sutures with forceps and Nd:YAG was required. Oral voriconazole was combined with amphotericin B inhalation in 1 patient and used in addition to forceps excision of sutures in another and was successful in both.12 Sawasaki et al8 noted that mycostatin inhalation, phenylacetic quicksilver, and iodine tincture were added to the excision of the sutures, and treatment was successful in all patients. Treatment ranged from 1 to 20 months. A successful outcome in invasive aspergillosis requires early and appropriate antifungal treatment. Voriconazole has excellent in vitro activity against Aspergillus species. Primary treatment with voriconazole led to higher response rates and improved survival when compared with amphotericin B-deoxycholate.14 Currently, voriconazole is recommended as the drug of choice by several guidelines as primary treatment.2,15,16 While liposomal amphotericin B is always a viable alternative to treatment, the need for intravenous administration may be difficult once the patient is discharged from the hospital. Posaconazole, with its similar spectrum of activity against Aspergillus species and the availability of an oral formulation, provides an excellent choice for outpatient treatment, and has been used successfully as salvage treatment.17,18 Our patient was started on voriconazole but switched to posaconazole when she developed photosensitivity related to the drug. To best of our knowledge, this is the first case wherein posaconazole was used successfully in the treatment of BSA. Although itraconazole, amphotericin B, and voriconazole have been successful in the literature, there are no definite recommendations with regard to the choice and duration of treatment due to the small number of cases. BSA is a rare but important complication after pulmonary resection. Bronchoscopists should keep BSA in mind in patients who present with hemoptysis or tissue expectoration after pulmonary resection. Oguz Karcioglu, MD* Riza Dogan, MD† Omrum Uzun, MD‡ Fatma Tokat, MD§ Dolunay Gülmez, MD∥ Sevtap Arikan-Akdagli, MD∥ Ziya T. Selcuk, MD¶*Department of Chest Diseases Çubuk Halil Şivgin State Hospital, Çubuk Departments of†Thoracic Surgery‡Infectious Diseases and Clinical Microbiology∥Medical Microbiology¶Chest Diseases, Hacettepe University Faculty of Medicine Ankara§Department of Pathology, Acibadem Mehmet Ali Aydinlar University İstanbul Turkey