A Novel Presentation of Mycobacterium Avium Complex in a Recipient of a Lung Transplant

A Case Report

Leah Cohen; Jeannette Guarner; William R. Hunt

Disclosures

J Med Case Reports. 2017;11(240) 

In This Article

Case Presentation

A 66-year-old African-American woman, a recipient of a bilateral lung transplant with distant history of breast cancer, presented to our clinic with progressive shortness of breath, wheezing, and cough of 2 months' duration. Approximately 20 years prior to undergoing lung transplantation, she developed infiltrating ductal carcinoma of her right breast with metastases to her right axilla. She underwent mastectomy and right axillary lymph node dissection and subsequent adjunct chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil along with radiation therapy. She responded well to therapy and remained in remission. However, she also developed an aggressive form of pulmonary fibrosis and ultimately required bilateral lung transplantation secondary to end-stage lung disease 4 years prior to her current presentation.

Her subsequent medical course following transplantation had been complicated by pancytopenia requiring monthly filgrastim injections, chronic gastroparesis, hypertension, stage IV chronic kidney disease, and diabetes. Our center's typical immunosuppression protocol utilizes a combination therapy of a calcineurin inhibitor, a cell-cycle inhibitor, and oral steroids. However, this patient's immunosuppression regimen comprised only a calcineurin inhibitor (tacrolimus) and low-dose prednisone. She had not been on a cell-cycle inhibitor, such as azathioprine, for several years due to her significant pancytopenia.

Upon presentation she was independently mobile, but had developed a significant decrease in her exercise tolerance. She also had developed an associated cough over the preceding 4 weeks that she reported was intermittently productive of scant blood-tinged sputum. She denied any unintentional weight loss or objective fevers, but she did endorse consistent night sweats for nearly 6 months prior to admission. She had developed persistent wheezing, only minimally responsive to bronchodilators, and chest tightness. Her nephrologist had recently discontinued her ramipril (1.25 mg daily) due to increasing serum creatinine levels. She denied any improvement in her cough with the discontinuation of the angiotensin-converting-enzyme (ACE) inhibitor. In terms of her active medications, she was on a modified immunosuppression regimen as previously described with tacrolimus 5 mg every 12 hours (goal tacrolimus trough level was between 8 and 10 ηg/mL), and prednisone 5 mg daily. The remainder of her medications consisted of aspirin 162 mg daily, atorvastatin 10 mg nightly, filgrastim 300 mcg by subcutaneous injection once weekly, pentamidine 300 mg inhaled once monthly for Pneumocystis jirovecii prophylaxis, and insulin therapy with Levemir (insulin detemir) 12 units subcutaneously every morning and aspart 4 units subcutaneously with meals. She was a lifelong non-tobacco smoker and had discontinued alcohol consumption prior to her lung transplantation. She held a master's degree in education and worked as a school counselor for 30 years, but unfortunately had to take early retirement approximately a year before her lung transplantation due to her worsening lung disease. Since undergoing lung transplantation she had not traveled outside the southeastern United States of America (USA). She denied any recent sick contacts or other exposures. Her initial chest computed tomography (CT) scan is shown in Figure 1 and demonstrated a new endobronchial lesion in the left mainstem near the anatomic anastomosis.

Figure 1.

Representative computed tomography axial a and coronal b mediastinal windows which demonstrate a 2.2×1.1×0.9 cm polypoid soft tissue lesion projecting from the roof of the left mainstem bronchus (red arrow) adjacent to the bronchial anastomotic site. There is severe narrowing of the left mainstem bronchus with the residual lumen measuring approximately 3 mm. Computed tomography axial c and coronal d lung windows demonstrate diffusely decreased attenuation of the left lung parenchyma, compatible with diffuse air trapping secondary to obstructive endobronchial lesion. There is lower lobe predominant tree-in-bud nodularity (black arrows)

Physical Examination

On physical examination she was afebrile (35.9 °C) with a heart rate of 80 beats/minute, blood pressure (BP) of 137/86 mmHg, respiratory rate of 22 breaths/minute, and oxygen saturation of 97% on room air. There was no palpable cervical lymphadenopathy. A chest examination revealed a well-healed clamshell incision from her previous lung transplant surgery. There were surgical changes associated with her previous right-sided mastectomy and flap repair. There were focal end-expiratory wheezes noted over her left lung-field on auscultation. Her neuro examination was non-focal. The rest of the physical examination was unremarkable.

Laboratory Findings

Laboratory findings noted pancytopenia: white blood count of 0.9 10[3]/mL, hemoglobin 10.4 g/dL, and platelet count of 134 10[3]/mL. Serum chemistry was normal except for an elevated creatinine of 2.37 mg/dL and blood urea nitrogen (BUN) of 35 mg/dL. Blood levels of CMV and Epstein–Barr virus (EBV) were undetectable by polymerase chain reaction (PCR). Her tacrolimus level was 9.7 mg/dL (her goal target was 8 to 10 mg/dL). Her C-reactive protein was mildly elevated to 9.43 mg/L (normal range 0.3 to 8.0 mg/L).

It is protocol at our center that patients undergo serial surveillance bronchoscopies post lung transplant to evaluate for occult rejection. However, surveillance bronchoscopies are only performed routinely through the first 12 months following transplantation, with subsequent bronchoscopies performed only for clinical suspicion of underlying pathology. As such, this patient had not undergone bronchoscopy within the preceding 4 years. Her last bronchoscopy demonstrated no evidence of an endobronchial lesion, stenosis, or rejection. However, with her new symptoms and radiographic findings, there was a high concern for endobronchial squamous cell carcinoma and so she underwent rigid bronchoscopy.

Diagnostic bronchoscopy demonstrated a fibrinous mass protruding into the left mainstem proximal to the anastomosis. Multiple biopsies were obtained from the mass and samples were sent for both histopathologic as well as microbiologic evaluation. The mass was further cored out during rigid bronchoscopy and when patency of her left-sided airway was secured, a flexible bronchoscope was inserted and a bronchial wash was performed in the lower lobe of her left lung. The bronchial wash was sent for microbiologic evaluation including bacterial, fungal, and acid-fast bacilli (AFB) culture per center policy. Histopathology demonstrated fragments of partially necrotic granulation tissue with extensive inflammation. There were also scant fragments of focally ulcerated bronchial mucosa as seen in Figure 2. Given the pathologic findings, special stains including Gram stain, Grocott-Gomori methenamine silver stain (GMS), and AFB stain were employed on the tissue specimen. GMS staining demonstrated intracellular bacilli. The AFB stain also highlighted numerous intracellular AFB. The ill-formed granulomas and presence of little necrosis aroused suspicion that the infection was probably not tuberculosis. However, it is not possible to define the species of mycobacteria from the histopathological perspective. Therefore, a rapid Mycobacterium tuberculosis deoxyribonucleic acid (DNA) probe was performed on the bronchial wash, which was negative. Both the tissue culture and bronchial wash grew MAC.

Figure 2.

a Hematoxylin and eosin stain (original magnification 40×) of biopsy specimen showing granulation tissue (vessels observed to the left, black arrows) with inflammation composed of mostly macrophages with few neutrophils (circled). The macrophages have abundant cytoplasm with blue staining material inside them. Also present intermingled with the inflammatory infiltrate are areas of necrosis. b Acid-fast bacilli stain (original magnification 400×) showing abundant bacilli (all red stained material) inside macrophages

Therapeutic Course

Given her immunosuppressed state and unusual presentation of infection, she was considered to have severe disease. She was started on therapy with azithromycin 250 mg daily, ethambutol 15 mg/kg per day, and rifampin 600 mg daily. However, out of concern for possible significant interaction with rifampin and her calcineurin inhibitor, the rifampin was exchanged for moxifloxacin 400 mg daily nearly immediately. Her immunosuppression regimen was maintained throughout her MAC therapy as she was already on a modified regimen due to her pre-existing chronic pancytopenia. As such, she remained on tacrolimus with a goal trough level of 8 to 10 ηg/mL and low-dose prednisone at 5 mg daily. She continued on triple therapy with azithromycin, ethambutol, and moxifloxacin for the first 2 months, although she tolerated the regimen very poorly. She experienced significant nausea and anorexia, losing approximately 6.8 kg (15 lbs) since just prior to her initial presentation. She also developed visual disturbances with bilateral optic neuritis approximately 2 months after initiation of therapy and ethambutol was promptly discontinued. She remained on dual therapy with azithromycin and moxifloxacin for the remainder of her antibiotic course, although she continued to have intermittent nausea, diarrhea, and poor appetite. After several negative sputum cultures, her therapy was discontinued approximately 12 months following initiation. Subsequent chest CT imaging demonstrated resolution of the nodular infiltrates in the lower lobe of her left lung and a patent left mainstem bronchus. Following discontinuation of her therapy, her visual disturbances nearly resolved as did her diarrhea. Her pulmonary function test over the 12 months following therapy discontinuation remained relatively stable and she did not develop recurrent respiratory symptoms. Unfortunately, her long-standing chronic kidney disease secondary to calcineurin inhibitor use and diabetes did progress over time. Approximately 7 months following completion of her MAC therapy she developed the need for hemodialysis. She died from complications of end-stage renal disease and hemodialysis 6 months later.

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