Case Presentation: A 50yo Pacific Islander male with history of ESRD due to DM s/p DDRT (2018) on immunosuppression (tacrolimus, MMF, prednisone), HTN, and type II DM presented with 10 days of fever of undetermined etiology, headache, neck stiffness, nausea, and vomiting. Patient had several ER visits prior to admission, where he was started on Amoxicillin, then Bactrim, for possible sinusitis but did not complete either course due worsening GI symptoms. Patient endorsed recent travel by automobile through California, Wisconsin, Iowa, and Nebraska. Patient reported high compliance with immunosuppressants, and denied sick contacts and tick or mosquito bites.On admission, patient was febrile to 38.1C (100.6F) with mild diffuse abdominal tenderness. Labs were remarkable for leukopenia (3.7 K/uL) and thrombocytopenia (138 K/uL). Head, abdominal, and pelvic CT, urinalysis, and LP cell count were unremarkable for acute infectious etiology. Patient was started on Cefepime, Ampicillin, Doxycycline, and Vancomycin per Infectious Disease recommendation for suspected CNS infection. Blood cultures were unremarkable. After 2 days without resolution, chest CT was performed, showing multifocal bilateral airspace opacities, possibly indicating atypical pneumonia. Urine antigen testing for Histoplasma and Blastomyces were performed. Patient later developed a transaminitis, oral ulceration, and acute hypoxic respiratory failure, requiring 4L O2 via NC to maintain saturation >92%. Repeat CXR revealed worsening diffuse interstitial opacities with trace pleural effusion, prompting referral for bronchoscopy. Two days later, transbronchial biopsy results and a positive urine antigen test returned, which were consistent with histoplasmosis, presumed disseminated. Antibiotics were discontinued; Amphotericin B and Itraconazole were initiated. Patient showed progressive improvement and was discharged 6 days later on Itraconazole.
Discussion: Histoplasma capsulatum is a dimorphic fungus found throughout the United States, though is classically known for its Ohio and Mississippi River Valley distribution . Transmission occurs via inhalation of aerosolized microconidia, causing pulmonary infection. Immunocompetent hosts who develop clinical infection typically experience a self-limited course of nonspecific fevers and malaise with mild pulmonary symptoms. Immunocompromised individuals, however, are susceptible to disseminated infection and treatment may be delayed due to nonspecific presentation. Here we highlight an unusual case of histoplasmosis, where the lack of pulmonary symptoms on presentation resulted in treatment delays. The presenting symptoms led multiple ER visits, as well as our initial intervention, to focus on CNS infection. After expanding our scope, we detected Histoplasma as the responsible etiology. In addition to the absence of pulmonary symptoms at presentation, other rare presentations include oral ulcerations  and GI involvement (nausea, vomiting) , which have previously been reported with disseminated histoplasmosis infections, underscoring its broad nature.
Conclusions: Early diagnosis of histoplasmosis and proper treatment is crucial, particularly in the immunocompromised population. Unfortunately, this can be challenging due to its vague presentation. For immunocompromised patients with fever of undetermined etiology, especially those with travel history to endemic areas, histoplasmosis should always be considered a possible etiology.