Case Twenty Two: A Disseminated Infection

Article excerpt

Case Follow up

The organism was identified as presumptive Histoplasma capsulatum. The identification was confirmed by Quest Diagnostics Laboratories using DNA probes.

During treatment with liposomal amphotericin B, the patient's condition significantly improved. Her head computed tomography (CT) showed no sign of central nervous system (CNS) involvement. Lumbar puncture (LP) revealed elevated white blood cells with low glucose and high protein. CNS involvement is a concern. She will continue on amphotericin B for total of 4 weeks followed by a repeat LP on June 18. This will be followed by one year of itraconazole. The patient was discharged from the hospital on June 9 after remaining afebrile for several days.


Histoplasmosis is an endemic mycosis caused by the dimorphic fungus, Histoplasma capsulatum. Three subspecies have been described in the literature. Two of them, H. capsulatum var. duboisii, and H. capsulatum var. capsulatum, are human pathogens. H. capsulatum var. duboisii are found mainly in Africa. H. capsulatum var. capsulatum are distributed worldwide, and are endemic to the Mississippi and Ohio River valleys and to Central and South America. When infected, most people remain asymptomatic, or the infection is self-limited. However, some people develop acute pulmonary infections or severe and progressive disseminated infection. Progressive disseminated histoplasmosis often occurs in immunocompromised patients.

H. capsulatum is a thermally dimorphic fungus, growing as a mold form in the environment and as a yeast form at 37[degrees]C. Infection develops when H. capsulatum microconidia are inhaled into the lungs, where they change into the yeast form. Many cells including neutrophils, macrophages, lymphocytes, and natural killer cells respond to the infection. In patients with progressive disseminated infection, macrophages are typically engorged with yeast. Most organisms are confined to macrophages and rarely are seen growing freely outside the cells; although in this case, most of the organisms in the bone marrow appeared to be mainly outside of the cells. In patients with disseminated infection, the organisms can occasionally be seen in peripheral white blood cells. T-cell immunity plays the important role in recovery from histoplasmosis. Once cellular immunity to H capsulatum develops, macrophages become activated to kill the organism. Cytokines such as interleukin (IL)-12 and interferon-gamma (IFN-gamma) help macrophages kill the fungus and prevent progression of disease. In patients with progressive disseminated histoplasmosis, sufficient macrophage fungicidal capacity appears to be the missing component in immunity to H. capsulatum. Most patients with disseminated histoplasmosis have underlying conditions that impair their ability to kill the intracellular pathogen. Many conditions have been found to predispose an individual to disseminated histoplasmosis. They include AIDS, primary immunodeficiency or other immunosuppressive disorders, immunosuppressive medications such as methotrexate and corticosteroids, and advanced age. The status of our patient was post liver transplant. She was immunocompromised due to ongoing therapy with tacrolimus and mycophenolate mofetil (CellCept).

The exact incidence of histoplasmosis is unknown since most studies were done in areas affected by outbreaks of histoplasmosis. H. capsulatum was first isolated from soil contaminated with chicken excreta in 1948. The natural habitat of H. capsulatum is soil, especially soil contaminated by bat or bird droppings. It can live in contaminated soil for many years. Transmission occurs through inhalation of H. capsulatum spores from contaminated soil. Following inhalation of the infecting particles, most patients remain asymptomatic, and only a minority of patients becomes symptomatic. The incubation period varies from a few days to a few weeks.

Clinical presentation

The clinical manifestations of disseminated histoplasmosis vary based on host immune status and the degree of exposure to the fungus. …