Pseudomembranous tracheitis caused by Aspergillus fumigatus in the setting of high grade T-cell lymphoma.

Pseudomembranous tracheitis (PMT) is a rare condition most commonly caused by fungal or bacterial infection that is characterized by a pseudomembrane that partially or completely covers the tracheobronchial tree. PMT is most commonly found in immunocompromised patient populations, such as post-chemotherapy, AIDS, post-transplant and hematological malignancies. Due to its rarity, PMT is often not included in the differential diagnosis. This case describes a 65 year old male with persistent fever and refractory cough despite high dose empiric antibiotics. Subsequent bronchoscopy with biopsy revealed pseudomembranous tracheitis due to Aspergillus fumigatus in the setting of T-cell lymphoma. PMT should be considered in the differential diagnosis of refractory cough in the immunocompromised population. However, it has been described in patients with nonspecific respiratory symptoms such as dyspnea, cough, and other airway issues.

Introduction

Pseudomembranous tracheitis (PMT) is a rare condition most commonly caused by fungal or bacterial infection that is characterized by a pseudomembrane that partially or completely covers the tracheobronchial tree. PMT is most often found in immunocompromised patient populations, such as post-chemotherapy, AIDS, post-transplant, and hematological malignancies [1], [2]. Fungal infections of the trachea can cause this rare phenomenon which may potentially lead to necrosis [3]. The pathogens known to cause this pseudomembranous infection are: Aspergillus, Candida, Cryptococcus, Rhizopus, and Mucorales [4], [5]. In more rare cases, pseudomembranous tracheitis may be caused by invasive bacterial pathogens such as Bacillus cereus [6]. PMT should be considered in the differential diagnosis of refractory cough in the immunocompromised population. However, it has been described in patients with nonspecific respiratory symptoms such as dyspnea, cough, and other airway issues [7]. Herein, we present a case of pseudomembrane tracheitis in the setting of high grade T-cell lymphoma.

Case report

A 65 year old male with a past medical history of non-obstructive coronary artery disease, urothelial cancer (status post resection), abdominal aortic aneurysm (status post repair), hypothyroidism, and 50 pack-year history of smoking, was admitted presenting with recurring fevers and a 30-pound weight loss over the past several months. A Chest x-ray (CXR) revealed a right mid-lung consolidation. Computer tomography (CT) showed a left supraclavicular/lower cervical mass, hilar lymphadenopathy as well as enlargement of the subcarinal and mediastinal lymph nodes. Subsequent lymph node biopsy revealed high grade T-cell lymphoma.

The patient was started up on empiric antibiotic therapy but continued to be febrile. He subsequently underwent bronchoscopy which revealed a pseudomembrane extending from the bronchus intermedius down to the right lower lobe (Fig. 1). Bronchoscopy was negative for any masses, abscesses, erosions or areas of bleeding.

Fig. 1

Bronchoscopy shows mucous-like layer in the bronchotrachial tree. A) Right upper lobe apico-posterior B) Bronchus intermedius C) Secondary carina right side.

Both an endobronchial biopsy as well as culture of the bronchioalveolar lavage revealed Aspergillus fumigatus (Fig. 2).

Fig. 2

Microscopic view of biopsy shows strains of Aspergillus fumigatus with characteristic hyphae.

Patient was initiated on Voriconazole. Repeat bone marrow biopsy was negative for Aspergillus. The patient was discharged on Voriconazole and oxygen. Despite treatment the patient died of progressive pulmonary infiltrates and respiratory failure.

Discussion

Pseudomembranous tracheitis (PMT) is commonly caused by fungal or bacterial infection that is characterized by pseudomembrane formation in the large airways [1], [2]. Here we described a case of a 65-year-old male with undiagnosed malignancy that had developed Aspergillus-related PMT. PMT is a rare condition that manifests with different symptoms and etiologic microorganisms. Previously reported cases of PMT have been outlined in Table 1.

Table 1

Cases of PMT.

Author	Primary disease	Causes	Organism	Signs/Symptoms	Treatment	Outcomes
Williams et al. [5]	Leukemia	Stem cell transplantation secondary to pancytopenia	Aspergillus	Progressive cough, nausea	Amphotericin B (IV), Amphotericin B (inhaled), caspofungin (IV)	Deceased
Strauss et al. [6]	Unknown	Aplastic Anemia	Bacillus cereus	Petechiae, weakness, dyspnea	Broad-spectrum antibiotic, anti-viral, antifungal therapy	Deceased (multiple organ failure)
Chang et al. [8]	Pt. 1: Diabetes mellitusPt. 2: Diabetes	Diabetic ketoacidosisDiabetic ketoacidosis	AspergillusAspergillus	Chest pain, cough, dyspnea, wheezeNon-productive cough, right side chest pain, fever	Parental amphotericin Bamphotericin B	Deceased (septic shock)Improved
Tait et al. [7]	Pt. 1:Non-Hodgkin's lymphomaPt. 2: Systemic lupus erythematosus-like disorder	NeurtopeniaNeurtopenia	AspergillusAspergillus	Weight loss, anorexia, non-productive cough, and pyrexiaWeight loss, polyarthralgia, night sweats, pyrexia	amphotericin Bintravenous amphotericin B (1 mg/kg/day), flucytosine (120 mg/kg/day), and oral itraconazole (600 mg/day) commenced,	DeceasedDeceased (respiratory failure)
Hines et al. [9]	Pt.1: COPDPt.2: Hodgkin's lymphomaPt. 3 Myelodysplastic syndromePt. 4 Hepatic lesions	Respiratory arrestNeutropeniaBone marrow transplantNeutropenia	AspergillusAspergillusAspergillusAspergillus	Fever, wheezingFeverFever, hypotensionEpigastric and lower back pain	Vancomycin, Clindamycin, AmikacinAmphotericin BAmphotericin BBroad spectrum antibiotics	DeceasedDeceased (respiratory failure)Deceased (progressive respiratory insufficiency)Deceased
Pornsuriyasak et al. [10]	Tuberculous	Tuberculous tracheal stenosis	Aspergillus	Fever, Dyspnea, Chest pain	Oral voriconazole Nebulized amphotericin B	Cured
Huang et al. [11]	16 cases:56.3% (9/16) Pulmonary malignancies31.3% (5/16)Bronchial involvement secondary to non-pulmonary tumor12.5% (2/16)Lung transplant	62.5% (10/16)Radiotherapy43.8% (7/16) Repeated chemotherapy25.0% (4/16)Recurrent intervention therapy by bronchoscope	Aspergillus	87.5% (14/16)Progressive dyspnea75.0% (12/16)Irritable cough	100% Amphotericin B (inhalation and infusion)	68.8% (11/16)Deceased
Putnam et al. [3]	Leukemia	Bone marrow transplantation secondary to aplastic anemia	Aspergillus	Weakness, fatigue, dyspnea	Amphotericin B (IV)	Deceased
Patel et al. [12]	Leukemia	Pancytopenia	Aspergillus	Shortness of breath, cough, pleuritic chest pain	Amphotericin B (IV)	Deceased (progressive leukemia and sepsis)
Williams et al. [5]	Type 2 Diabetes and leukemia	allogeneic stem cell trans- plantation.	Rhizopus sp.	Progressive cough, dyspnea, nausea and emesis	intravenous liposomal amphotericin B, inhaled amphotericin B, intravenous caspofungin	Deceased (respiratory failure)
Le et al. [13]	Acute lymphoblastic leukemia.	chemotherapy	Aspergillus.	Cough, fever, and hoarseness.	Intravenous voriconazoleG-CSF	Improved
Argüder et al. [14]	Diabetes mellitus	Inconsistent use of insulin	Aspergillus	Cough, chest pain, hoarseness, fever, dyspnea	liposomal amphotericin B	Deceased
Ramos et al. [15]	Cardiac amyloidosis	Heart transplant	Aspergillus	Fever, dyspnea, wheezing, and a cough	IV voriconazoleIV caspofungin	Improved
Shah et al. [16]	Stillbirth	Pulmonary edema	Aspergillus	Dyspnea, stridor	Voriconazole	Improved, then lost to follow up

Invasive pulmonary aspergillosis (IPA) is the most common form of disease caused by Aspergillus species infection. In addition, a rare form of IPA is an infection of the tracheobronchial tree, called Aspergillus Tracheobronchitis (AT) [17]. Four types of AT: ulcerative tracheobronchitis, obstructive bronchial aspergillosis, aspergillus bronchitis, and pseudomembranous necrotizing bronchial aspergillosis, or PMT have been described [1], [2]. The pseudomembrane is thought to be derived from fibrin, hyphae, and necrotic tissue [12]. Other fungi such as Rhizopus, Cryptococcus and Candida can also form a pseudomembrane via similar mechanisms [4], [5]. Rarely viruses may be implicated in PMT. Known causes of PMT have been outlined in Table 2.

Table 2

Causes of Psuedomembranous tracheitis.

Infectious Causes

Noninfectious Causes

Fungal• Aspergillus species • Candida • Cryptococcus • Rhizopus • Mucorales Bacterial• Pseudomonas aeruginosa • Haemophilus influenza • Corynebacterium diphtheriae • Staphylococcal infections • a-hemolytic Streptococcus species • Moraxella catarrhalis • Bacillus cereus • Chlamydia species • Mycoplasma bovis • Pseudomembranous croup Viral• Bovine herpes virus1 • Adenovirus • Influenza (co-infection)

Smoke inhalationEndotracheal intubationCrohn diseaseStevens-Johnson syndromeAgents of bioterrorismLigneous conjunctivitisParaquat ingestion

Patients with pseudomembranous tracheitis typically present symptoms of dyspnea, fever, non-resolving cough, and chest pain. Dyspnea, as one of the presenting symptoms, is usually caused by the pseudomembrane obstructing the airways to the lungs [11]. Colonies of fungi create plaques that line the bronchi which leads to a necrotizing bronchitis. Most common signs and symptoms of PMT are outlined in Table 3.

Table 3

Common symptoms of PMT.

Fever

Dyspnea

Cough

Chest pain

Fatigue

Unilateral wheeze

PMT is a rare condition, therefore a strong clinical suspicion is needed to diagnose this condition. Bronchoscopy is essential to discover pseudomembrane in the airways. A pseudomembrane has the potential to form and constrict the airways, thus causing the symptoms that are associated with PMT [7]. Based on pathological tissue, brush smear, and fluid from bronchial that are obtained by a bronchoscopy, the results can lead to a diagnosis of airway aspergillus infection and the type of Aspergillus as well [11]. In our case non resolution of infiltrates despite adequate antibiotic therapy prompted us to perform a bronchoscopy.

Since pseudomembranous tracheitis is mostly caused by fungal infection, a range of antifungal treatments would deem most effective towards the condition. Table 1 suggests that amongst health care providers intravenous Amphotericin B is the initial treatment of choice [11]. Other treatments such as voriconazole, itraconazole, and echinocandins (caspofungin) [5], [12] However recently, Voriconazole has been administered to patients with PMT due to its better prognosis, as shown in Table 1.

PMT has a high morbidity and mortality in immunosuppressed patients. This in itself lends to a high morbidity and mortality that is associated with opportunistic infections. It has been reported that death usually ensues between 1 and 6 weeks after diagnosis [18]. Majority of cases of PMT have resulted in demise as demonstrated in Table 1. Some causes for death include respiratory failure, septic shock, or other organ failure. Respiratory failure in PMT may result from the pseudomembrane constricting the airways and can even dislodge thus creating a ball valve that leads to obstruction [6], [12].

Conclusion

PMT is a rare condition that is mostly caused by fungal, and sometimes, bacterial infection. It usually requires a high index of suspicion for diagnosis. The prognosis depends on timely diagnosis and initiation of antifungal therapy.

Funding source

The author(s) received no financial support for the research, authorship and/or publication of this article.

Financial disclosure

The authors have no financial relationships relevant to this case report to disclose.

Conflict of interest

The authors have no potential conflicts of interest to disclose.