Coccidioidomycosis
is caused by Coccidioides immitis and
occurs predominantly in the
Southwestern United
States
where the disease is endemic. However, sporadic cases might be diagnosed in
areas where the disease is not endemic as a result of reactivation of previous
infection. The incidence of disease in endemic areas was from 2%--5% in the
pre-ART era. Increased risk is associated with extensive exposure to disturbed
soil.
Both
localized pneumonia and disseminated infection are usually observed in those
with CD4+ T lymphocyte counts <250 cells/µL.
The use of ART appears to have reduced the incidence in this patient
population.
Clinical
Manifestations
The
two most common clinical presentations of coccidioidomycosis are disseminated
disease and meningitis. Disseminated disease is associated with generalized
lymphadenopathy, skin nodules or ulcers, peritonitis, liver abnormalities, and
bone and joint involvement. Localized meningeal disease results in symptoms of
lethargy, fever, headache, nausea or vomiting, or confusion and occurs in
approximately 10% of patients. Among those with meningeal involvement, CSF
analysis typically demonstrates a lymphocytic pleocytosis with CSF glucose
levels <50 mg/dL. CSF protein might be normal or mildly elevated.
Diagnosis
The
diagnosis of coccidioidomycosis is confirmed by culture of the organism from
clinical specimens or by demonstration of the typical spherule on
histopathological examination of involved tissue. Blood cultures are positive
in a minority of patients. C. immitis
serology is frequently positive among HIV-1--infected patients with
coccidioidomycosis and is useful in diagnosis. Complement fixation serology
(IgG) is generally positive in the CSF in coccidioidal meningitis.
Treatment
Recommendations
For
nonmeningeal pulmonary or disseminated disease, amphotericin B is the preferred
initial therapy (AII).
Data evaluating lipid formulations of amphotericin B are limited such that
appropriate dosing recommendations cannot be made.
Therapy
with amphotericin B should continue until clinical improvement is observed,
which usually occurs after administration of 500--1,000 mg. Certain specialists
would use an azole antifungal concurrently with amphotericin B (BIII).
Fluconazole or itraconazole might be appropriate alternatives for patients with
mild disease (BIII).
Coccidioidal
meningitis should be treated with fluconazole, which has been reported to be
successful in approximately 80% of patients with
C. immitis meningitis (AII).
Treatment for patients with meningeal disease requires consultation with a
specialist. Intrathecal amphotericin B is the most accepted alternative but is
toxic (CIII).
Prevention
of Recurrence
Patients
who complete initial therapy for coccidioidomycosis should be administered
lifelong suppressive therapy (i.e., secondary prophylaxis or chronic
maintenance therapy) using either fluconazole 400 mg daily or itraconazole 200
mg twice daily (AII). Although
patients might be at low risk for recurrence of systemic mycosis when their CD4+
T lymphocyte counts increase to >100 cells/µL
in response to ART, the numbers of patients who have been evaluated are
insufficient to warrant a recommendation to discontinue secondary prophylaxis
in this setting.
Special
Considerations During Pregnancy
Coccidioides
infections appear to be more likely to disseminate if acquired during pregnancy
among HIV-uninfected women, with the risk increasing with increasing
gestational age . This increased risk might be related to the agonistic effect
of estradiol and progesterone, both found at high levels during pregnancy, on
the growth of C. immitis . The risk
for dissemination among HIV-1--infected pregnant women has not been evaluated.
Invasive fungal infections should be treated the same in pregnancy as in the
nonpregnant woman, with the exception that amphotericin B is the preferred
agent in the first trimester because of the potential teratogenic risks of the
azoles if efficacy is expected to be superior or similar to that of the azoles
(BIII).