A 77-year-old female, an immigrant from Peru 20 years earlier, with interferon-gamma release assay positivity for M. tuberculosis, presented with fevers and decreased oral intake due to poor appetite for the previous 3 weeks. Her review of systems on admission was otherwise negative, and she reported no recent travel. She had been diagnosed with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis approximately 1 year earlier and, after completing a 6-month course of cyclophosphamide, was taking 10 mg of prednisone and 100 mg of azathioprine (AZA) at the time of admission. Even prior to the diagnosis of vasculitis, her chest imaging had revealed fibrocystic and bronchiectatic changes.
Physical examination revealed a comfortable but undernourished woman with a temperature of 101.3  F and dry crackles on lung auscultation. There were no other pertinent findings. Laboratory values were significant for serum sodium of 126 meq/L and normocytic anemia with a hemoglobin level of 11 gm/dL. Her admission chest radiograph (CXR) was unchanged from previous radiographs.
She was started on ceftriaxone and azithromycin for possible pneumonia. Her immunosuppressants were continued. Fevers persisted despite broadening of her antibiotic regimen first to cefepime and then to imipenem. Her subsequent CXR revealed subtle diffuse reticulonodular densities (Fig. 3A). Chest CT demonstrated a miliary pattern of involvement superimposed on chronic changes (Fig. 3B).
Due to concurrent worsening pancytopenia, AZA was discontinued, but the dose of prednisone was not changed. Despite the initiation of empiric anti-tuberculous therapy, she became progressively more hypoxemic and somnolent with a worsening CXR (Fig. 3C). Two sputum mycobacterial smears returned negative. Continued deterioration and pancytopenia prompted a bone marrow biopsy, which revealed rare aggregates of histiocytes (Fig. 4). Stains for acid-fast bacilli and fungi were negative. The patient expired just as she was about to receive the first dose of L-AmB for presumed DH. Post-mortem, her urine and serum Histoplasma antigen titers were reported as above the limit of quantification (>19 ng/ml, Quest Diagnostics, Inc., Teterboro, NJ, USA). Sputum and blood cultures ultimately revealed no growth. The family declined autopsy.