Case Presentation: A 68 year old Ohioan male with history of chronic renal failure and prior evaluation for monoclonal gammopathy of undetermined significance (MGUS) presents with weakness and unintentional weight loss. Previous work up identified Bence Jones proteinuria, normal K/L ratio, serum immunofixation (IF) and serum protein electrophoresis (SPEP) with two IgG lambda bands and two monoclonal protein bands respectively. Additional findings included urine IF identifying monoclonal free kappa light chains, a right tibial lytic lesion, hypercalcemia, coagulopathy, pancytopenia, and splenic infarcts, although the myeloma FISH panel was normal. CT chest revealed ground glass opacities concerning for viral pneumonia. Given clinical deterioration and upon recommendation of oncology, a bone marrow biopsy was pursued which subsequently identified the absence of plasma cell disorder but raised concerns for disseminated histoplasmosis (DH). Patient had no prior history of immune compromise, denied recent travel, and was noted to be HIV negative. Bronchoscopy was without evidence of a bacterial, viral, or fungal infection. Serologic studies however revealed a positive fungitell, histoplasma antibodies mycelial (1:4096), yeast antibody (1:512), and immunodiffusion with H and M bands. Patient underwent lumbar puncture which was negative for histoplasma antibodies. Following consultation with infectious disease, he was started on liposomal amphotericin B followed by a prolonged course of posaconazole.
Discussion: Histoplasma capsulatum is the most prevalent endemic mycosis in the United States, specifically in the Midwestern states. Infection usually manifests when inhaled microbes transform into yeast in the lungs. In dissemination, macrophages are engorged with yeast which accelerate disease proliferation. DH in immunocompetent individuals is rare and usually occurs in older adults. Manifestations usually include pancytopenia, hepatosplenomegaly, and lymphadenopathy and follow a protracted course. Generally, the diagnosis of DH should be suspected in patients with known exposures, immunocompromised state, extremes of age, and presenting signs/symptoms that include fever, fatigue and weight loss.In this case, DH was identified by way of bone marrow biopsy in an immunocompetent patient without any obvious risk factors. Interestingly, in a recent retrospective study, 42% of patients diagnosed with histoplasmosis were immunocompetent, many of whom were from Central America or Western India. In this case, patient presentation was initially attributed to concern for MGUS which was ultimately determined to be related to DH instead.
Conclusions: Though less common, this case highlights the importance of having an index of suspicion for DH in an immunocompetent host. Presenting signs and symptoms can easily be mistaken for malignancy, like a plasma cell disorder. Prompt diagnosis of DH can lead to earlier initiation of targeted therapy and better outcomes. Further studies are needed to better understand presentation, manifestations, and early treatment initiation in immunocompetent patients with DH.