Non-resolving Community Acquired Pneumonia (CAP) due to Blastomyces dermatitidis (Pulmonary Blastomycosis): Case Report and Review of Literature

Abstract

In this case report, we describe a case of progressive acute pulmonary blastomycosis in a healthy adult living in Kentucky, initially presenting with flu like illness with a left sided consolidation, who did not respond to antibiotic therapy. Patient’s clinical condition deteriorated with development of necrotizing bronchopneumonia, mediastinal lymphadenopathy, tree-in-bud reticulonodularity and pleural effusion. A diagnosis of progressive pulmonary blastomycosis was established by radiological findings as well as transbronchial needle aspiration cytology and bronchoalveolar lavage culture demonstrating Blastomyces dermatitidis. Patient showed significant clinical improvement with resolution of pulmonary lesions on antifungal treatment. Since symptoms of blastomycosis are often similar to the symptoms of flu or other lung infections, our case highlights the importance of maintaining a high index of suspicion and appropriate microbiologic and histologic evaluation especially in patients who live in or have traveled to areas endemic for blastomycosis and are not responding to antibiotic therapy. Early diagnosis coupled with prompt initiation of antifungal treatment may lead to favorable outcomes. DOI: 10.18297/jri/vol2/iss1/9 Received Date: February 12, 2018 Accepted Date: March 26, 2018 Website: https://ir.library.louisville.edu/jri Affiliations: 1St. Elizabeth Physicians, Infectious Disease, Crestview Hills, KY, USA ©2018, The Author(s). 39 ULJRI Vol 2, (1) 2018 REVIEW ARTICLE *Correspondence To: Johnson Britto, MD, MPH Work Address: St. Elizabeth Physicians, Infectious Disease, Crestview Hills, KY, USA Work Email: johnsypb@gmail.com Due to a lack of clinical improvement after three days of antimicrobial treatment, chest computed tomographic (CT) scan was obtained that showed a dense consolidation involving the majority of the left lower lobe, and a trace left pleural effusion (Figure 2). Bronchoscopy was performed. Bronchoscopy did not show any endobronchial lesions, Gram’s stain of bronchoalveolar lavage (BAL) of left lower lobe showed many white blood cells and rare Gram-positive bacilli, culture grew 10,000-100,000 CFU/mL of normal respiratory flora, KOH Prep was negative for fungal elements, acid-fast bacilli was negative, as was legionella PCR. BAL sample was not sent for cytological analysis. She was hospitalized for five days during which there was no significant change in her clinical status and she remained without clinical improvement or deterioration. She completed a five day course of oral oseltamivir. Intravenous antimicrobials were switched to oral levofloxacin to complete a course of seven days and she was discharged home with outpatient follow up. Figure 1. Initial Chest X-ray (CXR) showing ovoid superior segment left lower lobe consolidation. Figure 2. Chest computed tomographic (CT) scan showing dense consolidation involving the majority of the left lower lobe and trace left pleural effusion. After discharge from hospital, she reported worsening of her symptoms and complained of fevers and chills, productive cough with hemoptysis, dyspnea, pleuritic left sided chest pain and worsening fatigue. She presented to our hospital for evaluation of these symptoms about four days after discharge from an outside hospital. Vital signs at the time of initial evaluation in our emergency department were as follows: temperature 102.0oF, heart rate 115 beats per minute, respiratory rate 20 per minute, blood pressure 126/66 mm Hg, and oxygen saturation 95% on room air. On physical exam, she had no respiratory distress, no lymphadenopathy, examination of the respiratory system revealed diminished breath sounds, whisper pectoriloquy, egophony and crackles at the left lower lobe, examination of the cardiovascular system, abdomen, central nervous system and skin were unremarkable. Pertinent initial diagnostic laboratory work up showed leucocyte count of 33.3 x 103 cells/mm3 (83% segmented neutrophils, 12% lymphocytes and 4% monocytes). Hemoglobin 11.5 g/ dl, hematocrit 34% and platelet count 539,000/mm3. Serum electrolytes revealed serum sodium 139 mmol/L, potassium of 3.1 mmol/L, renal function revealed blood urea nitrogen and serum creatinine of 6.0 mg/dL and 0.46 mg/dL respectively, liver function tests revealed alkaline phosphatase 255 U/L, AST 145 U/L, ALT 110 U/L, albumin 3.1 g/dL, and total bilirubin 1.0 mg/dL. Chest X-ray (CXR) showed progression of the radiological changes, in the intervening 10 days from the initial imaging, with a new development of worsening left lower lobe consolidation with cavitary changes consistent with necrotizing pneumonia (Figure 3). Chest computed tomography (CT) scan was obtained that showed dense necrotizing bronchopneumonia throughout left lower lobe, with left hilar, central mediastinal lymphadenopathy, and “tree-in-bud” reticulonodularity identified throughout the remainder of the lungs with scattered areas of noncavitary satellite nodularity, these findings likely representing manifestations of endobronchial spread of infection throughout the lungs (Figure 4). Figure 3. Chest X-ray (CXR) showing left lower lobe consolidation with cavitary changes consistent with necrotizing pneumonia. 40 ULJRI Vol 2, (1) 2018 The patient was admitted to the hospital with a diagnosis of nonresolving pneumonia. She was started on empiric intravenous vancomycin and piperacillin/tazobactam. Sputum Gram’s stain showed Gram-positive cocci in pairs and sputum culture grew 2+ indigenous oral flora. Sputum for acid-fast bacilli was negative, as was MRSA nasal PCR, viral respiratory panel, serum interferon gamma release assay, human immunodeficiency virus serology, urine streptococcal and legionella antigens, and blood cultures. Procalcitonin level was 0.3 ng/mL. Bronchoscopy was performed, it did not show any endobronchial lesions. A large amount of purulent secretions were seen at the superior segment of left lower lobe which were suctioned out without difficulty. Bronchoalveolar lavage (BAL) and transbronchial lung biopsies were obtained from left lower lobe segments. Despite being on intravenous antibiotics for four days, she developed worsening of her clinical status. Repeat chest X-ray (CXR) and chest computed tomographic (CT) scan were obtained that showed worsening pneumonia with complete consolidation of the left lower lobe and new patchy consolidation and nodules in the right lung as shown in Figure 5 and Figure 6 respectively. Additional laboratory work up including fungal 41 ULJRI Vol 2, (1) 2018 Figure 4. Chest computed tomographic (CT) scan showing dense necrotizing bronchopneumonia seen throughout left lower lobe with left hilar, central mediastinal lymphadenopathy, and “tree-in-bud” reticulonodularity identified throughout the remainder of lungs with scattered areas of non-cavitary satellite nodularity. Figure 5. Chest X-ray (CXR) showing persistent diffuse bilateral pneumonia, left greater than right, with a moderate left-sided pleural effusion. Figure 6. Chest computed tomographic (CT) scan showing worsening diffuse pneumonia with complete consolidation of the left lower lobe, new patchy consolidation in the left upper lobe/lingula and right lower lobe and new/enlarging nodules in the right lung. New small left pleural effusion with fluid in the fissure and layering over the apex. blood cultures, urine Histoplasma antigen, serum Aspergillus Galactomannan antigen by EIA, serum (1-3)-Beta-D-Glucan, serum Coccidioides immitis antibodies were ordered. Fungal blood cultures, Aspergillus Galactomannan antigen, serum Coccidioides immitis antibodies were negative. Urine Histoplasma antigen was detected and (1-3)-Beta-D-Glucan was strongly positive at >500 pg/mL. (Less than 60 pg/mL are interpreted as negative. 60 to 79 pg/mL are interpreted as indeterminate). Patient was empirically started on IV amphotericin B. The transbronchial lung biopsy results from the left lower lobe returned and showed numerous lymphocytes, histiocytes, many multinucleated giant cells, forming ill-defined granulomas. The biopsy also revealed the presence of thick-walled single yeast forms of approximately 8–15 μm in size as shown in Figure 7a. The organisms stained positively with Gomori methenamine silver (GMS) stain as shown in Figure 7b. Some of these yeast forms showed eccentric broad-based budding, overall morphology was consistent with blastomycosis. Bronchial biopsy and BAL cultures using Sabouraud Dextrose Agar (SDA) showed growth of fungus as shown in Figures 8a, 8b and 8c. The patient showed significant clinical improvement on antifungal treatment. She was treated with amphotericin for 2 weeks followed by oral itraconazole. She tolerated the treatment well without any side effects. Follow-up imaging of the lungs showed resolution of the pulmonary lesions. Figure 7a. Hematoxylin-and-eosin-stained section of left lower lobe lung biopsy, low-power (Bottom) and high-power (Top) magnification, shows numerous lymphocytes, histiocytes, many multinucleated giant cells, forming ill-defined granulomas and presence of thick-walled single yeast forms of approximately 8–15 μm in size with eccentric broad-based budding overall morphology consistent with blastomycosis. Figure 7b. Gomori methenamine silver (GMS) (1000X magnification) stain shows a budding yeast of Blastomyces dermatitidis with the characteristic broad-based bud. Figure 8a. Phase-contrast microscopy: (1000X magnification): Shows the typical appearance of Blastomyces dermatitidis. Round to oval shape, thick, doubly refractile cell wall, and single broad-based bud.