A male in his forties with past medical history significant for rheumatoid arthritis-related interstitial lung disease on significant immunosuppressive medications including mycophenolate mofetil, infliximab, and daily prednisone presented to an outside hospital with syncope and gastrointestinal bleeding. He arrived at our institution approximately five days later secondary to worsening acute hypoxic respiratory failure and worsening abdominal pain. He underwent an emergent exploratory laparoscopy with small bowel resection secondary to a duodenal perforation. The infectious diseases team evaluated the patient due to incidentally discovered cavitary nodules in the setting of an elevated serum galactomannan. There was concern for pulmonary aspergillosis. Further history revealed that the patient had been experiencing subjective fevers, chills, weight loss, night sweats, fatigue, dyspnea, productive cough with white sputum, and a slowly enlarging painful tongue ulcer over the past 4-6 months.

Medications included mycophenolate mofetil 1500 milligrams by mouth every 12 hours, prednisone 20 milligrams by mouth once daily, and infliximab 100 milligrams intravenously every 6 weeks. His last dose of infliximab was 6 weeks prior to presentation. He was also taking trimethoprim-sulfamethoxazole 160-800 milligrams and azithromycin 500 milligrams by mouth on Mondays, Wednesdays, and Fridays as primary prophylaxis.

The patient appeared critically ill and was in mild distress. The blood pressure was 168/89 mm Hg, pulse 91 beats per minute, temperature 100.3° Fahrenheit (37.9° Celsius), respirations 30 breaths per minute, and oxygen saturation of 100% on 40 liters of high flow nasal cannula. The examination was notable for a 2 cm ulcerated lesion on the right lateral tongue (Figure 1). He had coarse rhonchi bilaterally with accessory muscle use. The rest of the examination was otherwise normal.

Figure 1. Physical exam finding of the right lateral tongue ulcer.

Figure 2a.High resolution CT Chest without contrast. Axial view with multifocal nodules and opacities with surrounding ground glass halo.

Figure 2b. High resolution CT Chest without contrast. Partial cavitation in the right upper lobe with multifocal nodules.

The urine histoplasma antigen was elevated at >19 nanograms/milliliter (reference range 0.4-19). Fungal isolator blood cultures initially revealed mold, which was ultimately identified as Histoplasma capsulatum 12 days after the cultures were obtained. He underwent a biopsy of his tongue ulcer which revealed numerous Grocott's methenamine silver (GMS) stain positive yeast forms compatible with Histoplasma species (Figure 3). Furthermore, the pathology report from the proximal jejunum (taken at the time of the surgical exploration for small bowel perforation) revealed non-necrotizing granulomas with numerous microorganisms consistent with Histoplasma and negative acid-fast bacilli stains (Figure 4).

Figure 3. GMS stain of tongue biopsy showing yeast forms consistent with Histoplasma capsulatum. Photo courtesy of Todd Stevens, MD

Figure 4. Hematoxylin and eosin (H&E) stain and GMS stain of the proximal jejunum. A) Submucosal inflammation and granulomas B) Granuloma C) Higher magnification of the granuloma to show histoplasmosis microorganisms D) GMS special stain for fungi, low magnification E) GMS special stain for fungi, high magnification. Photo courtesy of Sameer Al Diffalha, MD

Histoplasmosis is a fungal infection caused by a dimorphic fungus Histoplasma capsulatum predominantly found in the soil and endemic to the midwestern and southeastern US, central Canada, and parts of Central and South America. Infection with H. capsulatum can manifest broadly, ranging from asymptomatic self-limited disease to a potentially fatal disseminated presentation. Disseminated histoplasmosis occurs in about 1 in 2000 patients with acute infection. Risk factors for disseminated disease include acquired immunodeficiency syndrome, solid organ transplantation, tumor necrosis factor-alpha inhibitor use, and prolonged steroid use. Diagnosis of histoplasmosis include antigen detection as well as histopathology and cultures of the affected tissues. False positive Aspergillus galactomannan assays have been described in the literature in solid organ transplant patients with histoplasmosis and can cloud the diagnosis.

This case highlights a rare complication of disseminated histoplasmosis presenting as a small bowel perforation. One study showed that approximately 70% of patients with disseminated histoplasmosis were found to have gastrointestinal involvement although only less than 10% of those patients had gastrointestinal symptoms. A high index of suspicion is needed in order to diagnose disseminated histoplasmosis. Recognizing common and uncommon presentations of histoplasmosis, identifying patients at highest risk, and understanding diagnostic tests can aid in the correct diagnosis.

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ID week Fellows' Day 2021 - oral presentation

This case was contributed by: Pia Cumagun, MD

University of Alabama at Birmingham

The case was originally presented at ID Week 2021, a joint effort of Infectious Diseases Society of America (IDSA), HIV Medical Association, Pediatric Infectious Diseases Society (PIDS), and the Society for Healthcare Epidemiology of America (SHEA), during an interactive session on Fellows' Day. Copyright Infectious Disease Society of America (IDSA), 2021. Used with permission.

Case #21001: A Male in His Forties with Syncope and Gastrointestinal Bleeding [Internet]. Partners Infectious Disease Images. Available from: http://www.idimages.org/idreview/case/caseid=589

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