Case Presentation: A 69-year-old immunocompetent man presented with progressive dyspnea, weight loss, and low-grade fever for one month. Physical exam revealed mild rhonchi at the lung bases and cachexia. Complete blood count with differential was normal. CT chest revealed calcified mediastinal granulomas, parenchymal ground-glass opacity, and bilateral adrenal masses (4cm in right, 3cm in left). There was no evidence of excess hormone production or adrenal insufficiency. Beta D glucan was >500pg/mL. Despite high clinical suspicion, Histoplasma serum and urine antigen were negative, complicating diagnosis. HIV testing was negative. Blastomyces antibody testing was positive with negative immunodiffusion; infectious disease consultant deemed this likely a false positive. Pneumocystis jirovecii pneumonia was also considered unlikely.Biopsy of right adrenal gland revealed budding intracellular yeasts in the background of extensive necrosis. Adrenal tissue culture grew Histoplasma capsulatum. Patient received two weeks of Amphotericin for presumed disseminated histoplasmosis. Patient’s symptoms improved and he was discharged on a twelve-month course of Itraconazole.
Discussion: This case illustrates the diagnostic complexity of disseminated Histoplasma capsulatum. Disseminated disease typically occurs in immunocompromised individuals (1), but this patient had multiorgan involvement despite being immunocompetent. This suggests variability in presentation of disseminated histoplasmosisFor disseminated disease, enzyme immunoassays have high sensitivity (2). This patient tested negative for Histoplasma antigen and antibody in both urine and serum, complicating the diagnosis. This led to the pursuit of more invasive diagnostic methods. In cases with high clinical suspicion for H. capsulatum, biopsy should be considered.Furthermore, this case also highlights the challenge of post-treatment monitoring. Standard monitoring practices rely on serial antigen or antibody testing (3). For this case, with negative antibody and antigen assays, symptom monitoring takes precedence over serum assays. Here, we show limitations of serologic testing for disease monitoring, emphasizing the need for close clinical follow-up.
Conclusions: This case highlights the importance of maintaining a high index of suspicion for disseminated histoplasmosis, even in the setting of negative antigen and antibody testing. Hospitalists should maintain a high index of suspicion for disseminated histoplasmosis in patients with compatible clinical findings, even in the presence of negative serology, and consider early biopsy for definitive diagnosis. These patients may also require individualized strategies for long-term monitoring.