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Pseudomembranous Tracheobronchitis Caused by Rhizopus sp. After Allogeneic Stem Cell Transplantation

Williams, Kathryn E. MB, BCh, BAO*; Parish, James M. MD; Lyng, Philip J. MD; Viggiano, Robert W. MD; Wesselius, Lewis J. MD; Ocal, Idris T. MD; Vikram, Holenarasipur R. MD§

Journal of Bronchology & Interventional Pulmonology: April 2014 - Volume 21 - Issue 2 - p 166–169
doi: 10.1097/LBR.0000000000000058
Brief Reports

Invasive fungal infections are a major cause of morbidity and mortality in allogeneic stem cell transplant recipients. They can occasionally involve the tracheobronchial tree with serious clinical consequences. Tracheobronchial involvement is often an unexpected finding during diagnostic bronchoscopy. Herein, we report a case of pseudomembranous tracheobronchitis caused by Rhizopus sp. in an allogeneic stem cell transplant recipient.

*Department of Medicine

Divisions of Pulmonary, Critical Care, and Sleep Medicine


§Infectious Diseases, Mayo Clinic, Scottsdale, AZ

Disclosure: There is no conflict of interest or other disclosures.

Reprints: Kathryn E. Williams, MB, BCh, BAO, 13400 E. Shea Blvd, Scottsdale, AZ 85259 (e-mails:;

Received May 19, 2013

Accepted February 17, 2014

Invasive fungal infections are frequently encountered in the setting of ongoing immunosuppression, particularly in allogeneic stem cell transplant recipients. Although pulmonary parenchymal involvement is the most common manifestation of invasive mold infections, endobronchial lesions are rare. Endobronchial fungal infections can manifest as mass lesions, gray-white fibrinous obstructive plugs, stenosis, ulceration, and pseudomembranes.1,2 Implicated fungal pathogens in pseudomembranous tracheobronchitis include Aspergillus sp., Mucorales (formally Zygomycota), Candida sp., and Cryptococcus sp.1

Herein, we report of a case of Rhizopus pseudomembranous endobronchial lesions leading to respiratory failure and death.

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A 59-year-old male with a history of type 2 diabetes mellitus and high-risk chronic lymphocytic leukemia underwent allogeneic stem cell transplantation. He was hospitalized 92 days after transplant for intractable nausea and emesis. Before hospitalization, he had been receiving prophylactic voriconazole.

Initial laboratory results on admission revealed pancytopenia with an absolute neutrophil count of 700 cells/µL. Endoscopic evaluation for his intractable nausea revealed grade 4 graft-versus-host disease of his stomach requiring high doses of steroids and alemtuzumab. He subsequently developed a progressive cough on hospital day 10. A CT scan of his chest (Fig. 1) showed a new left upper lobe infiltrate and a bronchoscopy was requested.



During bronchoscopy, irregular erythematous endobronchial mucosa creating the appearance of an endobronchial mass was noted in the distal left main stem bronchus and left upper lobe, particularly in the lingula (Fig. 2). Biopsies were obtained from the lesion. Washings from the left lingula demonstrated filamentous fungal organisms and eventually grew Rhizopus sp. The patient was initiated on intravenous liposomal amphotericin B, inhaled amphotericin B and intravenous caspofungin. Unfortunately, he developed worsening shortness of breath followed by hypoxic respiratory failure and was intubated approximately 7 days after antifungal therapy was commenced. A repeat CT chest showed significant progression of the consolidation.



A second bronchoscopy was performed after mechanical ventilation was initiated and revealed denuded and desquamated appearing mucosa separating from the submucosal layer in the distal left main stem and proximal left upper and lower lobes with the appearance of a pseudomembrane (Fig. 3). Bloody secretions were emanating from the left lobes. Bronchoalveolar lavage of both upper and lower lobes returned blood tinged fluid that did not clear with repeated aliquots suggesting diffuse pulmonary hemorrhage. Endobronchial biopsy was obtained from the pseudomembrane.



Two days after the second bronchoscopy, the patient’s respiratory condition continued to decline and the patient eventually expired.

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Routine H&E sections showed a necrotic background and abundant fungal microorganisms with broad, irregular hyphae consistent with pseudomembranous tracheobronchitis with several branching organisms (Fig. 4). Rhizopus sp. was again grown from the bronchial lavage specimen. A silver stain (GMS-Grocott methenamine silver) highlighted the fungal hyphae.



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A pseudomembrane is a layer of fibrin, leukocytes, and possibly bacteria overlying a damaged mucous membrane, giving the appearance of viable tissue.3,4 The deadly physiology of pseudomembrane formation stems from the ball-and-valve mechanism when the membrane dislodges. The tissue is freed from the tracheal wall and is pulled into the lumen by the negative pressure of inspiration. This is the cause of unilateral wheeze or intermittent stridor leading to rapid progression of dyspnea and respiratory decompensation.5 Before the dislodging of tissue from the bronchial wall, the patient generally has cough and fever consistent with pneumonia. This leads to an average of a 5-day lag period before an established diagnosis of pseudomembranous tracheobronchitis.6

The order Mucorales consists of several common environmental molds; invasive infection in an immunocompetent individual is uncommon. Rhizopus, Rhizomucor, Mucor, Absidia, and Chlamydoconidia are the most common genera pathogenic to humans. The most common risk factors for Mucorales infection include uncontrolled diabetes mellitus, hematopoietic stem cell transplantation, neutropenia, and increased serum iron levels.7 Patients receiving augmented immunosuppression for graft-versus-host disease are also at a higher risk for mucormycosis.8 Case reports of invasive Mucorales also have implicated hospital building construction as a risk factor.9 In addition breakthrough mucormycosis have been reported on prophylactic voriconazole therapy.10

Pseudomembranous lesions constitute a small category of endobronchial fungal infections. Diagnosis of pseudomembranous tracheobronchitis is made by direct visualization of the pseudomembranes on bronchoscopy. Mucormycosis of the tracheobronchial tree can present as a mass-like lesion, fibrinous plug, or ulceration.1 In contrast, Aspergillus is more likely to cause ulcerative disease in solid organ transplant recipients, whereas neutropenic patients tend to develop the pseudomembranous form.11

The diagnosis of pulmonary mucormycosis is based on bronchoscopic examination, tissue biopsy, and culture. Unfortunately, only one third of biopsy proven mucormycosis is culture positive.12 Early diagnosis may be critical to survival. Chamilos et al13 found that delays in treatment with amphotericin B-based regimes by >5 days resulted in doubling of mortality at 12 weeks.

Spellberg et al14 conducted review of current available therapies for mucormycosis. A step-wise approach to the management begins with efforts to reverse the risk factors (diabetic ketoacidosis, neutropenia, immunocompromise). If possible, consideration should be given to surgical lobectomy.15,16 However, these are very high-risk patients and the risks of surgery often outweighs expected benefits. Al-Majed et al17 described a rigid bronchoscope approach with biopsy forceps and successfully removed a Mucorales mass-like lesion. However, Di Carlo et al18 reported a mass-like lesion that when removed ultimately resulted in fatal pulmonary hemorrhage.

The angioinvasive Mucorales can lead to vascular thrombosis thereby limiting the delivery of antifungal therapy to the site of active infection. Amphotericin B formulations are the first-line antifungal agents for the treatment of mucormycosis. Lipid formulations of amphotericin B are preferred given the safety profile and a modest survival benefit as compared with conventional amphotericin B (67% vs. 39%).19 Posaconazole has been utilized for salvage therapy. Zaizen and Ohtsu20 have reported success with bronchoscopic administration of amphotericin B in addition to treatment with an aerosolized and IV formulation.

To the best of our knowledge, this is the second report of Rhizopus pseudomembranous tracheobronchitis in the English language literature. Consideration of this unique complication of invasive mold infection in heavily immunocompromised patients in the appropriate clinical setting can lead to early diagnosis and prompt initiation of antifungal therapy.

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pseudomembranous; tracheobronchitis; mucormycosis; Rhizopus; allogeneic stem cell transplant

© 2014 by Lippincott Williams & Wilkins.