28 December 2020: Articles
Invasive Pulmonary Aspergillosis with Hydropneumothorax in a Patient Taking High-Dose Glucocorticoids
Unusual clinical course, Diagnostic / therapeutic accidents
Devika Dixit1BEF*, Nelson T. Kuete1EF, Philip Bene1EF, Imran Khan1F, Gabriela Oprea-Ilies2BE, Eric Flenaugh3EDOI: 10.12659/AJCR.928499
Am J Case Rep 2020; 21:e928499
Abstract
BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a severe form of the fungal infection with relatively high mortality rates. Risk factors that lead to IPA include immunosuppression through corticosteroid use. IPA complicated by hydropneumothorax is rare and its mechanism of formation is unknown.
CASE REPORT: A 72-year-old woman recently diagnosed with a right frontal meningioma that was managed with dexamethasone presented with a new 3-day history of nonproductive cough, chest pain, and dyspnea and was managed for pneumonia. The patient failed to improve, prompting a follow-up computed tomography scan, which revealed a right middle lobe cavitary lesion. During the workup of this lesion, the patient’s hospital course was complicated by hemoptysis and development of a large right hydropneumothorax that was successfully managed with a chest tube. Despite initial resolution of hydropneumothorax, the patient developed a right apical pneumothorax that gradually worsened. Bronchoscopy culture revealed Aspergillus fumigatus, leading to the diagnosis of IPA, which was managed with intravenous voriconazole.
CONCLUSIONS: Corticosteroid use with subsequent immunosuppression is a risk factor for developing IPA. Clinicians should include IPA in their differential diagnosis for respiratory infections in patients receiving corticosteroids. Although overall prognosis of IPA is poor, outcomes can be improved with early diagnosis, early empiric initiation of antifungals, and withdrawal of immunosuppressive therapy. IPA complicated by hydropneumothorax is a rare phenomenon with a poorly understood mechanism of formation. Based on our case, we propose a mechanism of hydropneumothorax formation from IPA.
Keywords: Glucocorticoids, Hydropneumothorax, invasive pulmonary aspergillosis, Antifungal Agents, voriconazole
Background
Because aspergillosis is not a reportable infection in the United States, its incidence is difficult to determine. The epidemiology of invasive
Immunosuppression is the most important risk factor for IPA. Prolonged neutropenia (for more than 3 weeks) or neutrophil dysfunction (chronic granulomatous disease) impart a significant risk for IPA. Other risk factors for IPA include prolonged, high-dose corticosteroid therapy; lung and bone marrow transplantation; hematologic malignancy (higher risk with leukemia); cytotoxic therapy; and AIDS [3]. Risk factors associated with poor prognosis with aspergilloma include chronic underlying diseases such as sarcoidosis and HIV infection, increasing size and number of lesions on chest radiographs, immunosuppression (including corticosteroid treatment), increasing
Patients with IPA present with respiratory symptoms similar to bronchopneumonia, such as fever, cough, sputum production, and dyspnea. Other symptoms include pleuritic chest pain and mild to massive hemoptysis. IPA is the most common cause of hemoptysis in neutropenic patients. Other pulmonary symptoms that have been reported include tracheobronchitis and secondary atelectasis [3]. More rare respiratory complications such as a hydropneumothorax can occur, as demonstrated by the current case. Multiple cases of aspergillosis complicated by pneumothorax have previously been reported [4–7]. The purpose of this case report is to present an unusual case of IPA complicated with hydropneumothorax and to propose effective diagnostic methods and management of IPA.
Case Report
A 72-year-old woman with a medical history of urinary incontinence initially presented for a ground-level fall and was diagnosed with a right frontal meningioma. Neurosurgery deferred surgical intervention at that admission given that the tumor was benign and indolent but scheduled outpatient surgery for brain mass resection. The meningioma was managed with dexamethasone (4 mg orally every 6 h for 20 days) and outpatient surveillance. The patient returned to the hospital following a second ground-level fall and with a new 3-day history of dyspnea, nonproductive cough, chest pain, and generalized weakness. The initial physical examination revealed crackles in the right lung base, and a chest X-ray demonstrated consolidation in the right lung base suggestive of pneumonia. Laboratory test results displayed elevated white blood cell counts, elevated neutrophils, thrombocytopenia, and normal renal function. The patient was admitted for suspected community-acquired pneumonia and further management of meningioma. Pneumonia was managed with intravenous (IV) ceftriaxone and azithromycin. The patient was also noted to have abruptly discontinued a month-long course of 4 mg dexamethasone 3 days before admission. She was restarted on dexamethasone 4 mg IV every 6 h and tapered up to 6 mg IV every 6 h in the next 20 days for concerns about acquired adrenal insufficiency.
A week after admission, the patient reported continued chest pain and developed a productive cough with hemoptysis. Repeat chest X-ray demonstrated a possible cavitary lesion, and a subsequent computer tomography scan confirmed the presence of a cavitary mass in the right middle lobe measuring 6×3.5 cm (Figure 1). The cavitary lesion prompted collection of 2 sputum samples for acid fast bacilli (AFB) stain and culture, and the results were negative. An initial serum QuantiFERON gold test (interferon gamma release assay) was indeterminate, and a repeat test was negative. The serum
Despite the antibiotics, the patient developed a large right-sided hydropneumothorax, requiring a chest tube placement, which resolved the pneumothorax (Figure 2). Owing to the worsening of the patient’s condition, a pulmonary consult was requested for diagnostic bronchoscopy for tissue sampling. The patient underwent bronchoscopy with bronchoalveolar lavage. The AFB stain and culture were again negative, but the BAL culture grew
Her hospital course was complicated by prolonged ileus and worsening renal function
Discussion
Corticosteroids are a recognized risk factor for developing IPA. Patients receiving steroids constitute a far broader population than those considered classically or most severely immunocompromised, such as HIV/AIDS patients and hematopoietic stem cell transplant patients. The current case involved a patient taking high-dose dexamethasone, with no underlying lung disease, malignancy, or other immunosuppression, who developed severe IPA with drastic complications. In patients taking high-dose steroids, IPA should be included in the differential diagnosis for pulmonary infections; failure to respond appropriately to empiric pneumonia therapy should provoke further diagnostic workup and initiation of early antifungal therapy when warranted.
The overall prognosis of patients with IPA is poor. Data on mortality are the most robust for hematopoietic stem cell transplant patients. One older retrospective case study of 89 hematopoietic stem cell transplant patients with IPA showed a 51% overall 2-year mortality attributed to IPA [8]. A recent retrospective database review of 412 patients with IPA in the Intensive Care Unit, excluding transplant, cancer, AIDS, and neutropenic patients, found an overall hospital mortality rate of 46% (although this is not IPA-attributable mortality) [9]. Out of the 412 patients that were studied, 315 (76.5%) received acute high-dose corticosteroid therapy, which included corticosteroids such as dexamethasone, methylprednisolone, prednisolone, and prednisone during their hospital stay [9].
The cornerstone of IPA management consists of early initiation of antifungals. Typically, voriconazole or isavuconazole can be used as first-line agents, requiring an extended duration (6–12 weeks) of therapy, and tapering and removal of immunosuppressive therapy to allow for immune system reconstitution [10,11]. Our patient was initially managed for community-acquired pneumonia, and was she was diagnosed with IPA and initiated on antifungals only after 24 days had passed. Her risk factor for acquiring IPA was her treatment with high-dose corticosteroids. Her symptoms of pleuritic chest pain and hemoptysis, while nonspecific, could have raised the clinical suspicion for IPA. While the prognosis for IPA remains poor, early initiation of antifungals has been shown to improve outcomes. One study indicated that a delay in antifungal treatment increased the length of stay and hospital costs; for example, a 1-day delay resulted in an extra 1.28-day stay and a 4% increase in cost [9]. Among patients that fail to respond to initial therapy, some may respond to different antifungal agents, while select cases may require surgery [10].
Unfortunately, during this patient’s diagnostic workup prior to her diagnosis of IPA, she experienced the complication of hydropneumothorax, which eventually led to respiratory failure. Hydropneumothorax is formed by free fluid and air entering the pleural space. Hydropneumothorax is commonly associated with malignancy, chest trauma (including chest tube placement or after thoracentesis), rheumatologic diseases that affect lung parenchyma, and pulmonary infections [12]. In this case, hydropneumothorax developed due to IPA, an infectious process. There is little to no literature around the mechanism of hydropneumothorax formation from IPA. However, there has been some research on hydropneumothorax formation from other infections such as
In the case of IPA, the fungal hyphae can proliferate in the pulmonary parenchyma and invade the pulmonary bronchi and blood vessels, resulting in thrombosis, hemorrhagic infarction, and a necrotizing pneumonitis. However, 1 study showed that nonneutropenic patients, similar to the patient in the current case, tend to not show angioinvasion [15]. Little is known about the way in which this fungal disease influences pulmonary function and general physiology. We propose a mechanism of hydropneumothorax formation from IPA that is similar to what occurs with tuberculosis. Specifically, we suggest that the fungus breaks down the lung parenchyma, creating an inflammatory reaction that results in edema and eventual air flowing from the lungs into the pleural space. Further investigation in the development of hydropneumothorax in IPA patients is needed.
Conclusions
Development of IPA in patients on high-dose corticosteroid should be considered. If clinicians have a high suspicion of IPA, then initiation of antifungal treatment and withdrawal of immunosuppressive agents, such as corticosteroids, should occur as early as possible. Additionally, the current case had a unique presentation of IPA complicated with hydropneumothorax, and further studies are needed to understand the underlying pathophysiology.
Figures
Figure 1.. High-resolution computed tomography scan of a new cavitary mass in the right middle lobe measuring 6×3.5 cm, indicating formation of invasive pulmonary aspergillosis. Figure 2.. Chest X-ray with large right-sided pneumothorax with a minimal right to left mediastinal shift that initially resolved with a chest tube but then reformed. Figure 3.. Three microphotographs of Aspergillus organisms and a background photo of heavy mixed, neutrophilic, and lymphocytic infiltrate with numerous macrophages. The 3 microphotographs show dichotomous hyphae of 2.5–4.5 μm in diameter with frequent septations and branching at 45°. Counterclockwise from the upper left corner are different histological stains with internal scales: hematoxylin eosin (HE) ×40, Grocott-Gömöri methenamine silver (GMS) ×40, periodic acid Schiff (PAS) ×40. The background photo used a Romanowsky-type stain called Diff-Quik (DQ) with an internal scale of ×10.References:
1.. Naaraayan A, Kavian R, Lederman J, Invasive pulmonary aspergillosis – case report and review of literature: J Community Hosp Intern Med Perspect, 2015; 5(1); 26322
2.. , Aspergillosis statistics, 2019 https://www.cdc.gov/fungal/diseases/aspergillosis/statistics.html
3.. Soubani AO, Chandrasekar PH, The clinical spectrum of pulmonary aspergillosis: Chest, 2002; 121(6); 1988-99
4.. Zhang W, Hu Y, Chen L, Pleural aspergillosis complicated by recurrent pneumothorax: A case report: J Med Case Rep, 2010; 4; 180
5.. Suri T, Makkar N, Ray A, Sood R, A unique case of hydropneumothorax in allergic bronchopulmonary aspergillosis: Med Mycol Case Rep, 2019; 25; 29-31
6.. Ricketti AJ, Greenberger PA, Glassroth J, Spontaneous pneumothorax in allergic bronchopulmonary aspergillosis: Arch Intern Med, 1984; 144; 151-52
7.. Kant S, Saheer S, Singh A, Hassan G, Pyopneumothorax secondary to Aspergillus infection: A case report: Oman Med J, 2012; 27(6); 494-96
8.. Yeghen T, Kibbler CC, Prentice HG, Management of invasive pulmonary aspergillosis in hematology patients: A review of 87 consecutive cases at a single institution: Clin Infect Dis, 2000; 31(4); 859-68
9.. Baddley JW, Stephens JM, Ji X, Aspergillosis in Intensive Care Unit (ICU) patients: Epidemiology and economic outcomes: BMC Infect Dis, 2013; 13; 29
10.. Patterson TF, Thompson GR, Denning DW, Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America: Clin Infect Dis, 2016; 63(4); e1-60
11.. Ullmann AJ, Aguado JM, Arikan-Akdagli S, Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMMERS guideline: Clin Microbiol Infect, 2018; 24; e1-38
12.. Miller JC, Boyce TG, Hydropneumothorax as a complication of necrotizing pneumonia in a young girl: Clin Case Rep, 2019; 7(8); 1559-61
13.. Suri T, Makkar N, Ray A, Sood R, A unique case of hydropneumothorax in allergic bronchopulmonary aspergillosis: Med Mycol Case Rep, 2019; 25; 29-31
14.. Kates DE, Pollack CV, Hydropneumothorax due to tuberculosis: J Emerg Med, 1995; 13(1); 27-30
15.. Kosmidis C, Denning DW, The clinical spectrum of pulmonary aspergillosis: Thorax, 2015; 70(3); 270-77
Figures
In Press
Case report
Invasive Hydatidiform Mole Mimicking Ectopic Pregnancy: A Case Report and Literature AnalysisAm J Case Rep In Press; DOI: 10.12659/AJCR.946388
Case report
Managing Chyle Leakage Following Right Retroperitoneoscopic Adrenalectomy: A Case StudyAm J Case Rep In Press; DOI: 10.12659/AJCR.945469
Case report
Cervical Neuroendocrine Carcinoma Presenting as Isolated Large Ovarian Metastasis: A Case ReportAm J Case Rep In Press; DOI: 10.12659/AJCR.945078
Case report
Acalculous Cholecystitis as an Atypical Presentation of Viral Pericarditis: A Case ReportAm J Case Rep In Press; DOI: 10.12659/AJCR.946029
Most Viewed Current Articles
21 Jun 2024 : Case report 81,734
Intracranial Parasitic Fetus in a Living Infant: A Case Study with Surgical Intervention and Prognosis Anal...DOI :10.12659/AJCR.944371
Am J Case Rep 2024; 25:e944371
07 Mar 2024 : Case report 48,471
Neurocysticercosis Presenting as Migraine in the United StatesDOI :10.12659/AJCR.943133
Am J Case Rep 2024; 25:e943133
20 Nov 2023 : Case report 22,406
Azithromycin Treatment for Acne Vulgaris: A Case Report on the Risk of Clostridioides difficile InfectionDOI :10.12659/AJCR.941424
Am J Case Rep 2023; 24:e941424
07 Jul 2023 : Case report 19,447
A Classical Case of Cesarean Scar Endometriosis in a 35-Year-Old Woman Presenting with Cyclical Abdominal P...DOI :10.12659/AJCR.940200
Am J Case Rep 2023; 24:e940200