A 52-year-old male presented to the emergency department with four days of sore throat, odynophagia, and productive cough with clear-white, blood-tinged sputum. He also noted unintentional weight loss of approximately 10 pounds over the past three months but denied dyspnea, night sweats, fever, chills, or prior pulmonary complaints. Additional complaints included nausea, vomiting, polydipsia, and polyuria for the past few days after he stopped taking his long-acting insulin to adjust for decreased oral intake. He was sent to the emergency department by his primary care physician for abnormalities on chest X-ray taken the previous day, at which time he had been prescribed cephalexin empirically for suspected community acquired pneumonia.
His past medical history was significant for type 2 diabetes mellitus controlled with metformin and long-acting insulin without previous hospitalizations. He immigrated to the United States approximately 40 years ago from Central America and had never left the United States since. He works as short-distance truck driver and previously smoked heavily for a decade before quitting 20 years ago.
Upon arrival to the emergency department, his vital signs included blood pressure 123/90 mmHg, heart rate 134 beats per minute, respiratory rate 40 breaths per minute, temperature 97.8 F, and oxygen saturation 98% on room air. His physical exam revealed a cachectic man in mild distress with tachypnea, without nasal flaring or retractions, with dry mucous membranes, and hoarse voice. Lung auscultation revealed diffuse bilateral crackles. Cardiac exam revealed tachycardia with regular rhythm. Abdominal exam did not demonstrate hepatosplenomegaly or tenderness. There were no other significant physical findings on examination.
His chest X-ray revealed diffuse bilateral reticulonodular opacities and airspace disease with a possible lingular cavitary lesion (Figure 1). A thoracic CT without contrast was obtained which revealed numerous, bilateral tiny nodular densities, most prominently in the upper lobes, and confirmed the lingular cavitary lesion (Figure 2). A few scattered mediastinal lymph nodes were also noted. Serum chemistry was remarkable for an anion gap of 35, beta-hydroxybutyrate of 8.09 mmol/L, and blood glucose of 532 mg/dL. Hematology showed a white blood cell count of 13 000/muL with 0% eosinophils. Venous blood gas analysis revealed a pH of 7.13, pCO2 of 32, and lactic acid of 5.46 mmol/L. Urinalysis was positive for 4+ glucose and 3+ acetone. Later, HIV antigen testing for types 1 and 2 was negative and CD4 count was 343 cells/muL. Vancomycin 1 g and piperacillin/tazobactam 3.375 g were given intravenously in the emergency department. Intravenous insulin was started with dose adjustment according to an in-house nursing algorithm alongside vigorous hydration.
He was admitted to the ICU on airborne isolation with differential diagnoses including coccidioidomycosis, tuberculosis, and lymphangitic carcinomatosis, complicated by diabetic ketoacidosis. In the ICU, empiric antifungal therapy with fluconazole 800 mg/day was started intravenously for suspected pulmonary Coccidioides infection. Although serum anion gap and bicarbonate normalized on day two, he remained tachycardic and tachypneic and required supplemental oxygen. He also continued to have odynophagia that necessitated enteral tube feeding until hospital day five, when he was finally able to tolerate an oral diet. At this point, he developed a mild elevation of transaminases and fluconazole was changed to itraconazole 200 mg twice daily due to concern for hepatotoxicity, and abdominal ultrasound and computed tomography (CT) were obtained to rule out hepatic involvement from the suspected fungal infection. Both of these studies were negative for ascites, focal hypoattenuation within the liver, or hepatic or splenic enlargement. The CT additionally did not demonstrate abdominal adenopathy. Aminotransferases trended from their peak on hospital day three to normal on day eight.
A week after admission, he remained tachypneic, hypoxic, and hoarse. Three sputum samples were negative for acid-fast bacilli but Coccidioides antibody titer and complement fixation had not yet resulted; thus, bronchoscopy was performed, revealing irregular-appearing borders of false and true vocal cords with erythema and edema, two vocal cord polyps, inflamed upper trachea in the subglottic space, and several flesh-colored endobronchial lesions bilaterally. Forceps biopsies and brushings were performed on the endobronchial lesions, true and false cords, and posterior trachea just below the larynx. Bronchoalveolar lavage (BAL) was performed in the right middle lobe and lingula. BAL fluid cell count and differential showed a neutrophilic predominance with spherules and endospores, consistent with Coccidioides immitis or Rhinosporidium seeberi. The biopsy specimens demonstrated the same pathogen in the laryngeal tissue. The culture of the BAL fluid eventually grew Coccidioides immitis on the day prior to discharge (day 14), but the laryngeal tissue was not cultured.
Otolaryngology consultant recommended outpatient follow-up with consideration for laryngoscopy after resolution of his acute illness. Two days after bronchoscopy, Coccidioides antibody titer returned positive at 1 : 16. The infectious disease consultant recommended continuing itraconazole for a minimum of 12 months with serial monitoring of Coccidioides titer, transaminases, and itraconazole level every three months. He continually improved on antifungal therapy until successfully weaning from supplemental oxygen and discharge after two weeks of hospitalization.
Coccidioides complement fixation returned strongly positive at 1 : 1024 nine days after discharge. Histoplasma urine antigen was positive but below the limit of quantification. At his follow-up appointments two and twelve weeks after discharge, his productive cough was present but improved and his hoarseness, dyspnea, and odynophagia had resolved. His liver enzymes remain within normal limits. At time of writing, the patient had not yet returned to have his Coccidioides titer or itraconazole level measured.