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Plate 6-5 Integumentary System
India ink preparation
CRYPTOCOCCOSIS showing C. neoformans.
No hyphae are seen.
Cryptococcosis is an opportunistic fungal infection A. Budding organism
caused by Cryptococcus neoformans or, less frequently, by with thick capsule
Cryptococcus gattii. It is seen primarily in immunosup- B B. Nonbudding organisms
pressed patients such as patients taking chronic immu- A
nosuppressive medications and those with the acquired C. Unencapsulated
immunodeficiency syndrome (AIDS). A diagnosis of form (budding)
cryptococcosis in a patient with human immunodefi-
ciency virus (HIV) infection is considered to be an C
AIDS-defining illness. B
It is primarily a lung disease, but dissemination to the
skin and to the central nervous system (CNS) are well
described. Cryptococcosis has a higher tendency to
affect the CNS than the other opportunistic fungi do.
Primary cutaneous cryptococcosis is a rarely seen con-
dition that is caused by direct inoculation of the yeast
into the skin.
Clinical Findings: A variety of infectious outcomes
can occur after exposure to this encapsulated yeast.
Immunocompetent hosts typically do not show any
signs or symptoms. On occasion, the fungus can be
found colonizing the oropharynx and upper airway; this
has been shown to be transient and appears to cause no
harm. Most of the population in North America show
serological evidence of exposure. If a colonized patient
subsequently becomes immunosuppressed, the dormant
fungus may cause disease. Cryptococcosis is ubiquitous
in North America, and patients routinely come in
contact with the fungus. Immunosuppressed patients Skin lesions on foot and ankle.
who contact the fungus during routine outdoor envi- Above, Molluscum-like lesion.
ronmental exposure may become infected. The fungus Right, Diffuse lesion involving
can be found in soil and is frequently found in bird lateral aspect of limb mimicking
droppings, especially those of pigeons. The fungus cellulitis.
gains entry via inhalation. Once in the lung tissue, it is
able to grow and reproduce. The host may develop
signs of lung inflammation including cough, hemopty-
sis, pain, pleurisy, and pneumonia. The fungus eventu-
ally disseminates through the bloodstream to infect
various tissues.
The skin is affected in up to 25% of patients with
disseminated disease, especially those patients with
AIDS. The lesions can appear as small white papules
with a central dell that mimic molluscum contagio-
sum. The most commonly described morphology of
cutaneous cryptococcosis is that of a red macule that
can be large and can imitate cellulitis. Many other
cutaneous morphologies have been described in the
literature. Cutaneous nodules with underlying abscess
formation and overlying ulcerations are not uncom-
mon. Clinical suspicion should lead the physician to
perform an incisional or punch biopsy for histological Infection is by respiratory route. India ink preparation Accumulation of encapsulated
evaluation and microbiological culture to ascertain the Pigeon dung and air conditioners showing budding and cryptococci in subarachnoid space
diagnosis. may be factors in dissemination. capsule (PAS or methenamine-silver stain)
Pathogenesis: C. neoformans and C. gattii are oppor-
tunistic yeasts that are encapsulated. The capsule is
critical in that it helps the fungus avoid host defenses. Immunocompetent patients are more likely to have a study and differentiate this organism from other fungi
Various serotypes of the species exist. The host inhales granulomatous infiltrate with few yeast organisms and and from other cryptococcal species.
the organism or accidentally becomes inoculated a vigorous host granulomatous response. The yeast Treatment: Patients with a diagnosis of cutaneous
through a penetrating skin wound. The yeast can over- capsule can be stained with Alcian blue, India ink, or cryptococcosis need to be evaluated for CNS involve-
come the host’s cell-mediated immunity if the immune mucicarmine. Periodic acid–Schiff stain can be used to ment, because the therapy is very different. If a spinal
system is compromised. This can lead to fungal abscess demarcate the central portion of the yeast. fluid analysis shows evidence of fungal involvement, the
and hematogenous spread of the fungus. Cryptococcus is Cultures of the fungus reveal fast-growing, off-white, treatment of choice is amphotericin B with or without
a unique fungus that has a neurotrophic behavior and mucoid colonies. The fungus is unique in that it can flucytosine. If no nervous system involvement is present,
often causes CNS disease. grow at varying temperatures, including the routine long-term use of itraconazole or fluconazole can be
Histology: The histological features are somewhat culture temperature of 24°C to 25°C and body tem- prescribed. Cutaneous abscesses should be incised and
dependent on the immune status of the patient. In perature of 37°C. Microscopic examination reveals drained to decrease the fungal load. Treatment consid-
severely immunosuppressed patients, the biopsy speci- round, budding, encapsulated yeasts without hyphae. erations should also include the immune status of the
men often shows a gelatinous appearance with numer- C. neoformans has unique biochemical features, such as patient and appropriate screening and testing for HIV
ous yeast cells and a mixed inflammatory infiltrate. its inability to ferment sugars, that allow mycologists to infection.
166 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

