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inflammatory response. The yeasts of H capsulatum are difficult to see with routine
hematoxylin-eosin staining, appearing only as small faint bluish dots or circles.
Special stains should be used to identify the presence of H capsulatum in tissue biopsies
or cytologic material. Methenamine silver staining provides the best contrast and is the easiest to
screen, but the yeasts may be confused with the slightly larger budding cells of Candida when
pseudohyphae are lacking in the latter. In regions with prevalent Leishmania infections, there
may be difficulty in distinguishing H capsulatum by hematoxylin-eosin staining alone.
A PAS stain helps to define the thin cell membrane or "capsule" of H capsulatum and the
central dot-like cell contents that form with artefactual shrinkage during fixation. Clusters of
such organisms are quite characteristic of H capsulatum. However, immunoglobulin inclusions
(Russell bodies) within plasma cells (Mott cells) must be distinguished from yeasts on PAS
staining by the homogeneity of staining, greater pleomorphism, and lack of a capsule in the
former. Immunohistochemical staining for H capsulatum will aid in diagnosing difficult cases.
Microbiologic culture will provide a definitive--though delayed--answer.[479]
Prophylaxis for H capsulatum using antifungal agents has not been shown to prevent
histoplasmosis. Treatment resulting in prolonged survival may include induction with
amphotericin B followed by long-term maintenance on itraconazole or fluconazole.
Histoplasmosis responds well to therapy, but relapses in the absence of chronic suppressive
antifungal therapy. When death occurs from histoplasmosis, organ involvement is frequently so
widespread that it is difficult to determine a specific organ failure as a cause of
death.[208,479,481]
H duboisii infection has some similarities to that caused by H capsulatum. The portal of
entry is probably the respiratory tract, and less likely direct inoculation. H duboisii exists in
soils. It can cause disseminated infection involving any organ, but classically is associated with
nodular and ulcerative skin lesions and osteolytic bone lesions, particularly affecting the skull,
ribs, and vertebrae. Microscopic examination shows granuloma formation with necrosis and
suppuration. The yeasts of H duboisii are large, 7–15 μm in size, and appear globose to ovoid,
thick-walled, and typically lemon-shaped with a narrow budding. They are often seen in the
cytoplasm of giant cells. There is serologic cross-reactivity between H capsulatum and H
duboisii. The treatment for H duboisii is similar to that for H capsulatum.[478]