First Author: Nainesh Shah, MD
Second Author: Kartik Rajagopalan, PhD
A 34-year-old Liberian woman with a history of HIV and AIDS diagnosed 10 years prior had not been taking anti-retroviral therapy for the past four years when she presented with two weeks of fever, frontal headache, vomiting, right upper quadrant abdominal pain, and non-productive cough. When she arrived, she had a temperature of 40 degrees Celsius, tachycardia to 110 beats per minute, and a normal respiratory rate and oxygen saturation. She was in mild discomfort and diaphoretic. Her physical examination demonstrated mild epigastric tenderness without rebound or guarding but was otherwise unremarkable.
Her laboratory workup revealed a CD4 count of less than ten, elevated transaminases and alkaline phosphatase (AST=189, ALT=39, Alkaline Phosphatase = 164), and normal bilirubin levels. She had a white blood count of 1650/microliter with a normal differential, hemoglobin of 10.5 g/dL, and platelet count of 28,000/microliter. Abdominal ultrasound and computed tomography (CT) showed diffusely enlarged abdominal lymph nodes. Chest CT showed evidence of healed calcified granulomas and non-specific mildly enlarged mediastinal lymphadenopathy. MRI of her brain was unremarkable. Lumbar puncture was performed and CSF analysis showed less than 1 nucleated cell/microliter with normal glucose and normal protein. Toxoplasma IgG was negative and serum analysis for CMV showed 2,460 DNA copies/mL. She was started on Vancomycin and Zosyn.
She continued to have high fevers intermittently to 40 degrees Celsius. Her ferritin level and lactate dehydrogenase were both elevated to greater than 100,000 ng/milliliter and greater than 2133 units/liter respectively. Her blood smear was referred to the pathologist who noted intracellular yeast. A presumptive diagnosis of disseminated histoplasmosis was made and she was started on AmBisome. Urine Histoplasma antigen later detected greater than 20 ng/mL and fungal blood culture eventually grew Histoplasma capsulatum.
Disseminated histoplasmosis occurs when spores are inhaled into the lungs and transform to yeast which are able to travel through the blood stream. It is a common opportunistic infection in the AIDS population, but the diagnosis is often delayed because the urine antigen test is a send-out study that takes several days to return. In this case, the patient’s blood smear aided in the diagnosis and initiation of appropriate therapy.
The incidence of Histoplasma detection on peripheral blood smear is not well quantified and is likely under-reported. A blood smear is relatively inexpensive and results can be obtained immediately. This low cost and high yield test would assist in a quicker diagnosis and prompt initiation of therapy sooner. Internists should consider routinely engaging the pathologist in reviewing the blood smear when disseminated histoplasmosis is in the differential.