A79-year-old Haitian man with a three-year history of painful oral ulcerations, progressive dysphagia, and weight loss who presented to our medical center directly after arrival from Haiti. On evaluation, the patient complained of acute worsening of oral pain, odynophagia, dysphagia and a two-week history of hoarseness. He also described weight loss, generalized weakness, and an intermittent non-pruritic, non-vesicular rash. The patient's past medical history was significant for hospitalization three years prior for diffuse oral ulcerations, dysphagia, and a wide-spread non-pruritic, keloid-like rash present on his torso and bilateral upper extremities. Nonspecific gastritis and a hiatal hernia were found on endoscopy; no further evaluation was performed and the patient was lost to follow-up. The patient traveled frequently between Haiti and New Jersey and had been a plantation farmer in Haiti since childhood. He worked primarily with vegetable crops, but had exposure to chickens, cows, and pigs. His sexual history was significant for multiple female sexual partners with only occasional condom use. He denied prior history of sexually transmitted diseases. He denied tobacco, alcohol, or illicit drug use.
On initial examination the patient was cachectic and appeared chronically ill. Vital signs included a temperature of 37.3  C, heart rate of 84 beats per minute, respiratory rate of 16, and blood pressure of 221/105 mmHg. Oxygen saturation was 100% on room air. His weight was 42.9 kg with a body mass index of 14.8. He had pronounced bitemporal wasting, bilateral erythema of the forehead and cheeks and diffuse left-sided facial swelling. Multiple 3-5 mm ulcerations were present throughout the oral cavity, including on the hard and soft palates, tongue, and buccal mucosa. There was diffuse oropharyngeal edema and mucosal pallor and dryness. He was breathing comfortably with no stridor or wheezing. Additional findings included bilateral anterior cervical chain lymphadenopathy and hypopigmented and hyperpigmented areas of skin on the thorax, abdomen and extremities, including the soles of both feet.
Significant laboratory findings included hyperkalemia (potassium 5.2 mg/dL), anemia (hemoglobin 11.6 g/dL) and hypoalbuminemia (albumin 3.3 mg/dL). Chest radiographs demonstrated pronounced airway narrowing and neck radiographs severe oropharyngeal and hypopharyngeal airway narrowing with subepiglottic stenosis. Computed tomography of the neck was performed and revealed diffuse thickening of the mucosal oropharynx, supraglottic larynx, aryepiglottic folds, piriform sinuses, and true/false vocal cords (Fig. 1, Fig. 2). Subsequent evaluation by otolaryngology with laryngoscopy revealed a granular edematous epiglottis, right aryepiglottic fold, and nasal vestibules without evidence of any distinct masses.
Malignancy, autoimmune, and infectious etiologies were considered and further diagnostic studies were obtained. HIV antigen/antibody testing, HTLV, HSV, CMV, and RPR antibody tests were negative. His CD4 count was 345 cells/muL (normal 300-1400 cells/muL) with a decreased CD4 percentage of 21.3% (normal 28-57%) and an inverted CD4/CD8 ratio of 0.35 (normal 1.0-3.6). Histoplasma urine antigen and serum complement fixation antibody were negative. Interferon-gamma release assay (QuantiFERON -TB Gold) was negative. Epstein-Barr virus IgM and IgG were both positive. ANA was positive at a low titer (1:160) with a non-specific pattern. C3 and C4 values were within normal limits. Anti-smith, anti-RNP, anti-SSA/SSB, and C1 esterase inhibitor antibodies were negative. Serum protein electrophoresis was notable for an elevated IgG level of 1964 nmg/dL, of which 30.7% was composed of gamma globulin. His sedimentation rate was 59 mm/h and C-reactive protein was 10 mg/L. Blood cultures, including fungal blood cultures, were negative. Throat cultures grew Klebsiella pneumoniae and Serratia marcescens.
Oral pharyngeal squamous cell carcinoma was considered the leading diagnosis and a biopsy of a labial mucosal ulcer was performed. Histologic examination of the biopsy revealed granulomatous mucositis with multinucleated giant cells containing multiple budding yeast forms (Fig. 3) that stained with Grocott's methenamine silver (Fig. 4) and were consistent with histoplasma species. Staining for acid-fast organisms was negative. Histoplasma was not recovered from tissue fungal cultures.
On histologic identification of yeast consistent with Histoplasma, therapy with daily intravenous liposomal amphotericin B (5 mg/kg daily) was initiated. Despite aggressive intravenous saline hydration, acute kidney injury developed after only three doses of amphotericin, necessitating a change in antifungal therapy to itraconazole suspension. Due to the patient's extensive oropharyngeal inflammation and failed fiberoptic endoscopic swallow evaluations, a percutaneous endoscopic gastrostomy was placed for nutrition and administration of itraconazole. Computed tomography of the chest, abdomen and pelvis obtained to evaluate for disseminated histoplasmosis were unremarkable. The patient had rapid clinical improvement in his symptoms with initiation of antifungal therapy. His serum itraconazole levels were measured and were therapeutic. He was discharged home with a planned 12-month course of itraconazole.