Only a Train Can Mask Another Train

A 36-year-old man presented with fever, abdominal pain and diarrhea reportedly lasting for the past three months. Originally an immigrant from Mexico, he had been living in California for the past four years and made a recent trip back to Guerrero, Mexico.

On admission, the patient was febrile (41°C), hypotensive (94/54 mmHg), tachycardic (118 beats/min) and tachypneic (36 breaths/min). Multiple bilateral cervical and axillary lymph nodes were palpated. Other findings included crackles in the bases of both lungs and a large mass in the left hypochondrium.

Initial laboratory tests were significant, showing a partial pressure of O₂ of 36 mmHg in arterial blood while breathing room air, a total leukocyte count of 3.8×10⁹/L (neutrophils 79%, bands 5%, lymphocytes 14% and monocytes 1%), a hemoglobin level of 102 g/L, hematocrit of 32%, a mean corpuscular volume of 78.7 fL and a platelet count of 273×10⁹/L. A lumbar puncture was normal, with no organisms seen on smear, and India ink was negative with negative bacterial cultures. A tuberculin skin test was also negative. Serology (both ELISA and Western blot assays) was negative for HIV. The initial chest x-ray was abnormal with a wide mediastinum, but without infiltrates. Further work-up included an abdominal ultrasound, which revealed a hypoechogenic mass adjacent to the tail of the pancreas.

Pancytopenia developed during the admission. A computed tomography scan of the chest showed the presence of mediastinal and peribronchial lymph nodes, bilateral pleural effusions and consolidation in both lung bases. A computed tomography scan of the abdomen showed an irregular large mass near the pancreatic tail encasing the splenic vein and multiple ill-defined densities in the periaortic area.

What diagnostic procedure was performed, and what was the diagnosis?

Diagnosis

A bone marrow biopsy revealed Histoplasma capsulatum inclusions in monocytes (Figure 1), and a bone marrow culture confirmed the diagnosis of histoplasmosis. After an initial full recovery following amphotericin B therapy and then oral itraconazole and monthly follow-up, he was readmitted five months later with a recurrence of histoplasmosis. Repeat HIV serology was positive, indicating recent HIV seroconversion.

Figure 1.

Bone marrow biopsy demonstrating the presence of a monocyte (centre) containing intracytoplasmic inclusions, each with a halo, characteristic of Histoplasma capsulatum. A few plasmacytes and lymphocytes are visible (hematoxylin and eosin stain, original magnification ×40)

Discussion

This patient had fever of unknown origin, and his final diagnosis of disseminated histoplasmosis is considered unusual without an established state of immunosuppression. He was HIV-negative in both the ELISA and Western blot assays at initial hospital admission; however, he was HIV-positive five months later. At the time of the symptomatic histoplasmic infection, the patient most likely had a very early HIV infection but was still antibody-negative. His initial two-month flu-like illness, consisting of fever, chills, fatigue and decreased appetite, could have represented early acute HIV viral syndrome. A literature review failed to disclose other reports of acute HIV seroconversion coincident with the onset of histoplasmosis as an opportunistic infection. The usual time from HIV viral inoculation to seroconversion is between two weeks and six months (1). It took us five months to establish the diagnosis of HIV seroconversion in our patient. However, the patient became symptomatic with an H capsulatum infection during the seroconversion period, which, in retrospect, could have been a combination of symptoms arising from the simultaneous infections. If we had obtained plasma for HIV RNA viral load at the time of his initial presentation, we could have confirmed the HIV seroconversion despite an initial negative serology.