CRYPTOCOCCOSIS
Cryptococcosis is an opportunistic fungal infection caused by Cryptococcus neoformans or, less frequently, by Cryptococcus gattii. It is seen primarily in immunosuppressed patients such as patients taking chronic immunosuppressive medications and those with the acquired immunodeficiency syndrome (AIDS). A diagnosis of cryptococcosis in a patient with human immunodeficiency virus (HIV) infection is considered to be an AIDS-defining illness.
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 condition 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
who contact the fungus during routine outdoor environmental exposure may become
infected. The fungus can be found in soil and is frequently found in bird
droppings, especially those of pigeons. The fungus 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, hemoptysis, pain, pleurisy, and
pneumonia. The fungus eventually 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 contagiosum. 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 uncommon. Clinical suspicion should
lead the physician to perform an incisional or punch biopsy for histological
evaluation and microbiological culture to ascertain the diagnosis.
Pathogenesis:
C.
neoformans and C. gattii are opportunistic yeasts that are encapsulated. The
capsule is critical in that it helps the fungus avoid host defenses. Various
serotypes of the species exist. The host inhales the organism or accidentally
becomes inoculated through a penetrating skin wound. The yeast can over- come
the host’s cell-mediated immunity if the immune system is compromised. This can
lead to fungal abscess and hematogenous spread of the fungus. Cryptococcus is
a unique fungus that has a neurotrophic behavior and often causes CNS disease.
Histology:
The
histological features are somewhat dependent on the immune status of the
patient. In severely immunosuppressed patients, the biopsy specimen often shows
a gelatinous appearance with numerous yeast cells and a mixed inflammatory
infiltrate.
Immunocompetent
patients are more likely to have a granulomatous infiltrate with few yeast
organisms and a vigorous host granulomatous response. The yeast capsule can be
stained with Alcian blue, India ink, or mucicarmine. Periodic acid–Schiff stain
can be used to demarcate the central portion of the yeast.
Cultures of
the fungus reveal fast-growing, off-white, mucoid colonies. The fungus is
unique in that it can grow at varying temperatures, including the routine
culture temperature of 24°C to 25°C and body temperature of 37°C. Microscopic
examination reveals round, budding, encapsulated yeasts without hyphae.
C.
neoformans has unique biochemical features, such as its inability to ferment
sugars, that allow mycologists to study and differentiate this organism from other fungi and from other
cryptococcal species.
Treatment:
Patients
with a diagnosis of cutaneous cryptococcosis need to be evaluated for CNS
involvement, because the therapy is very different. If a spinal fluid analysis
shows evidence of fungal involvement, the treatment of choice is amphotericin B
with or without flucytosine. If no nervous system involvement is present,
long-term use of itraconazole or fluconazole can be prescribed. Cutaneous
abscesses should be incised and drained to decrease the fungal load. Treatment
considerations should also include the immune status of the patient and
appropriate screening and testing for HIV infection.
