Blastomycosis Pneumonia as an Unusual Cause of Horner Syndrome: Case Report and Review
We describe an immunocompetent patient with Horner syndrome secondary to invasive Blastomyces pneumonia and provide a review of the rare infectious etiologies of this syndrome. To our knowledge, this is the first published human case report of Horner syndrome secondary to Blastomyces pneumonia.
Horner syndrome is typically associated with apical lung malignancy. Blastomyces pneumonia is a commonly diagnosed infection in several parts of the United States. However, to our knowledge, this is the first published human case of Horner syndrome secondary to Blastomyces pneumonia.
This patient case presents the rarely encountered infectious Horner syndrome in an immunocompetent patient secondary to Blastomyces pneumonia and reviews the infectious causes of the syndrome.
An 81-year-old man presented to the emergency department after he developed a cough, subjective fever, and shortness of breath. He was initially treated with azithromycin for bronchitis. His symptoms progressed and a chest radiograph performed at his primary care physician's office showed a right upper lobe (RUL) infiltrate, and he was prescribed levofloxacin. After 4 doses of antibiotic and no improvement, he presented to the emergency department with a temperature of 38.6°C, pulse 130 beats/min, blood pressure 114/61 mm Hg, respiratory rate 22 breaths/min, and oxygen saturation 82% that improved to greater than 90% with 5 L/min of oxygen. Lung sounds were diminished in the RUL, with diffuse crackles in the right lung base. No clubbing or cyanosis was detected. Cardiac examination was significant for a tachycardic irregularly irregular rhythm, a systolic ejection murmur (chronic), and mild pitting edema to the knee bilaterally. No cervical or axillary lymphadenopathy was palpated. Neurologic and skin examinations were normal.
His medical history included coronary artery disease with coronary artery bypass two years prior, atrial fibrillation on rivaroxaban, heart failure with reduced ejection fraction, stage 3 chronic kidney disease, and type 2 diabetes mellitus (hemoglobin A1c of 8.1%). Purified protein derivative skin testing for tuberculosis was previously negative. The patient reported no animal contact, sick contacts, or travel outside Minnesota within the past year. He had spent many years as a missionary in the South American jungles of Columbia but his last trip there was 2 years before admission. More recently, he had spent his summer at a Northern Minnesota cabin, but initially reported no time in the woods and hardly any time outdoors other than boating. The patient had never smoked and rarely consumed alcohol.
Chest radiograph on admission demonstrated dense consolidation of the RUL consistent with pneumonia, no endobronchial obstruction, patchy nodular infiltrates of the left upper lobe, and a 5-mm noncalcified rounded infiltrate in the posterolateral left lower lobe, which were new findings compared with one year prior (Figure 1, A, B) . Laboratory studies were significant for a leukocytosis to 15 000/mm3 and procalcitonin of 0.77 ng/mL. He was treated with piperacillin-tazobactam for community-acquired pneumonia and hospitalized.
He progressed to acute hypoxic and hypercarbic respiratory failure requiring urgent intubation and transfer to the intensive care unit. Bronchoscopy performed after intubation revealed moderate clear secretions with erythematous and edematous bronchial mucosa. Bronchoalveolar lavage of the right upper lobe was obtained, and cytology demonstrated spherical broadly based budding yeast on Grocott-Gomori methenamine silver stain (Figure 1, D) and cultures grew Blastomyces dermatitidis. Samples were negative for Mycobacterium tuberculosis, and cytology was negative for malignancy.
Shortly after admission, blood antigens for Histoplasma and Cryptococcus; urine antigens for Blastomyces, Histoplasma, and Legionella; and nasal antigen for influenza had been collected. These slowly returned over the course of his hospitalization and were all negative except for a positive Blastomyces urine antigen and Histoplasmosis blood antigen. The histoplasmosis blood antigen was felt to be cross-reactive with his clinical, cytologic, and culture diagnosis of blastomycosis. Tuberculosis interferon-γ release assay testing was indeterminate, but 3 expectorated smears for acid-fast bacilli were negative. Considering his past travel to South America, testing for Paracoccidioides serum antibody was done and returned negative.
He was treated with liposomal amphotericin B (LAB) (3 mg/kg/d) for septic shock and severe acute hypoxic respiratory failure secondary to Blastomyces pneumonia. He had acute kidney injury on chronic kidney disease (glomerular filtrate rate 26 mL/min/1.73 m2) secondary to sepsis-related acute tubular necrosis before initiation of his LAB, but renal function worsened (18 mL/min/1.73 m2) after 7 days on LAB and he received enteral itraconazole (200 mg enteral 3 times a day for 9 doses, then twice daily). Several days after starting antifungal therapy, the patient developed right- sided ptosis, anisocoria with an asymmetrically miotic right pupil, more evident in a dark environment with dilation of the contralateral pupil, and generalized weakness. In the setting of therapeutic heparin for atrial fibrillation, concern for an intracranial bleed resulted in an emergent computed tomography scan of the head that was normal. Subsequent magnetic resonance imaging of the brain also demonstrated no acute process.
The neurology department consulted, and his generalized weakness was attributed to critical illness myopathy. In the setting of a normal brain magnetic resonance imaging scan, his anisocoria (more prominently seen with darkness) and ptosis was consistent with a right Horner syndrome secondary to his right apical lung process visualized on repeat computed tomography (Figure 1, C).
The patient required prolonged vasopressor and ventilator support and eventual tracheostomy. He was discharged to a long-term acute care hospital for ongoing medical care and rehabilitation. Within 3 months, the patient was weaned from the ventilator. His Horner syndrome resolved during this same period. He regained ability to ambulate and had no residual neurologic deficits. However, the patient's acute kidney injury worsened, likely because of receiving amphotericin B and having septic shock and required ongoing intermittent hemodialysis. The patient received 1 year of itraconazole therapy with radiographic improvement of his lung infiltrate.
In 1932, Dr. Henry Pancoast first described a series of 7 patients with “superior pulmonary sulcus tumors” who developed Horner syndrome often had progression to rib destruction, wasting of the muscles of the hand, and eventual vertebral body erosion (1). Since his initial paper, suspicion for an apical pulmonary malignancy in a patient with Horner syndrome has been embedded in medical teaching, but the relatively uncommon cause of Horner syndrome from an infectious source is often overlooked. Pancoast's original 1924 article discusses Mycobacterium tuberculosis as a potential pathogen causing this syndrome, for which there are now several case reports demonstrating pulmonary tuberculosis as the pathogen responsible for Horner syndrome (2–3).
Infectious causes of Horner syndrome still appear to be relatively rare. A recent publication identified 31 case reports of infectious causes ranging in pathogens from atypical pulmonary bacterial infections such as Staphylococcus aureus and Pseudomonas aeruginosa, fungal infections such as mucormycosis and aspergillosis, and 7 cases of the parasite Echinococcus causing infectious Horner syndrome (4). Infectious causes of Horner syndrome have even been mistaken for malignancy leading to lobectomy (5). Blastomyces has been described as a cause of Horner syndrome in only 1 other case of a soft-tissue mass with thoracic erosion and compression of the spinal cord and anterior mediastinal structures (6). We are not aware of any prior cases of blastomycosis pneumonia causing Horner syndrome in humans.
It was highly unusual that our patient did not have an underlying pulmonary malignancy, his bronchial culture did not grow mycobacterium, and that his anisocoria improved with resolution of the Blastomyces pneumonia. There was also no underlying malignancy in the lung. Why did this patient contract Blastomyces dermatitidis? On the day before discharge, his wife told us about picking blueberries at their cabin in Northern Minnesota 1 month before admission, which was his only known soil or decaying wood exposure just before becoming ill. The patient was successfully treated based on current Infectious Disease Society of America recommendations for severe pulmonary Blastomyces infection with liposomal amphotericin B (3–5 mg/kg) for 2 weeks or until stable, followed by oral itraconazole 200 mg 3 times daily for 3 days, then twice daily for 6 to 12 months (7).
The mechanism of this Horner syndrome patient case was likely from cervicothoracic sympathetic chain irritation secondary to diffuse apical and posterior involvement of lung tissue and pleural inflammation. The patient demonstrated anisocoria and ptosis on the side ipsilateral to the pneumonia. No anhidrosis was appreciated but not fully evaluated for.
Dr. Pancoast has convinced us to evaluate for superior pulmonary sulcus malignancy in the setting of Horner syndrome. However, almost a century later when a patient presents with new-onset ptosis, miosis with anisocoria, and unilateral anhidrosis, one must also consider infectious etiologies in both immunocompetent and immunocompromised individuals where endemic fungal infections, tuberculosis, and other opportunistic infections may invade or cause inflammation of the cervicothoracic sympathetic chain in the thoracic cavity and cause Horner syndrome. In patients in Blastomyces-endemic areas who fail appropriate treatment of community-acquired pneumonia, one should consider Blastomyces as a cause of community acquired pneumonia regardless of their immune status.
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Author, Article, and Disclosure Information
1Brent A. Schotl,
1Department of Medical Education, Abbott Northwestern Hospital, Minneapolis, Minnesota
2Department of Neurology, Abbott Northwestern Hospital, Minneapolis, Minnesota
3Department of Infectious Disease, Abbott Northwestern Hospital, Minneapolis, Minnesota
Brent A. Schotl, MD; Abbott Northwestern Hospital, 800 E. 28th St, Minneapolis, MN 55407; e-mail, [email protected]; and David Tierney, MD; Abbott Northwestern Hospital, 800 E. 28th St, Minneapolis, MN 55407; e-mail, [email protected].