Coccidioidomycosis is infection by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. Coccidioides spp. are endemic to the deserts of the southwestern United States and parts of Mexico and Central and South America. Clinical disease ranges from self-limited pneumonia (valley fever) to disseminated disease, especially in immunosuppressed patients.
Coccidioides spp. grow in the mycelial phase a few inches below the surface of the desert soil. With dry conditions, the mycelia fracture into highly infectious single-cell spores (arthroconidia), 3 to 5 in size, that can remain suspended in the air for prolonged periods. On inhalation, an arthroconidium greatly enlarges into a yeastlike spherule, in which endospores evolve. Rupture of mature spherules releases endospores into the infected tissue; each endospore is potentially capable of producing another spherule.
Among persons living in endemic areas, the risk of
exposure to Coccidioides spp. is approximately 3% per year, with
a seasonal pattern, typically highest in dry periods after a rainy season.
Infections may also occur in individuals simply passing through an endemic
area. Southern Arizona and California account for 90% of the infections seen in
the United States. The increase in population in these areas has resulted in
increased rates of new infections to 150,000 per year. Infections are subclinical
in more than half with only later development of delayed cutaneous
hypersensitivity to coccidioidin.
Clinically signiﬁcant illness can present subacutely,
known as valley fever, with respiratory and systemic symptoms often lasting for
weeks to months. The most frequent clinical manifestation is community-acquired
pneumonia with an incubation period of 1 to 3 weeks. The most common presenting
symptoms are chest pain, cough, fever, and fatigue. Arthralgias, erythema
nodosum, and erythema multiforme occur occasionally, and hemoptysis suggests
the development of cavitary disease.
Chest radiographs may be unremarkable in up to 50% of
all patients, even in those with respiratory complaints. Common abnormalities
include unilateral or bilateral inﬁltrates and ipsilateral hilar adenopathy.
Less frequently, mediastinal adenopathy and pleural effusion are seen. The
primary pneumonitis usually clears spontaneously, leaving a residual nodule or
a peripheral thin-walled cavity in about 5% of cases. Dissemination is seen in
about 1% of patients to any organ but most commonly skin, bones and joints, and
the central nervous system. Risk factors for complicated pulmonary disease and
dissemination include defects in cellular immunity, as in HIV infection, organ
transplantation, or with high-dose glucocorticoids. Pregnant women, especially
during the third trimester, and individuals of African or Philippine descent
are at increased risk of dissemination. Diabetes mellitus has been associated
with slowly resolving pulmonary infection and residual cavitation.
The diagnosis of coccidioidomycosis is often missed
because of the nonspeciﬁc clinical presentation and because the diagnosis is
not considered. Early speciﬁc diagnosis is important because it reduces
unnecessary diagnostic testing, inappropriate antibiotic use, and morbidity
from progressive pulmonary or disseminated disease. An absolute diagnosis
requires isolation of Coccidioides spp. in culture from respiratory
samples; however, growth may take several days to weeks. The propagation of Coccidioides
spp. in the clinical laboratory represents a signiﬁcant health risk to
personnel, who should be notiﬁed when a sample with
suspected Coccidioides spp. is sent for processing. Serologic tests are
reliable for the diagnosis of coccidioidomycosis except sometimes early in the
disease and in immunocompromised hosts. An immunodiffusion assay that detects
serum IgG and IgM antibodies to Coccidioides spp. is the most commonly
used test, although complement ﬁxation assays are used for testing other body
ﬂuids such as cerebrospinal ﬂuid. Most patients lose serologic reactivity
within months of an infection, so sustained reactivity indicates residual
lesions or active infection. Serial serologic testing is therefore useful to
Most patients with uncomplicated pulmonary
coccidioidomycosis resolve their infection without speciﬁc antifungal
treatment. However, such treatment might beneﬁt some patients, either by
shortening the course or by preventing
complications. Because of lack of adequate trial data, clinical judgment is
used in identifying these patients. Commonly used indicators for treatment
include symptoms persisting for more than 2 months, more than 10% loss of body
weight, night sweats persisting for more than 3 weeks, inability to work,
extensive unilateral or bilateral lung inﬁltrates, prominent or persistent
hilar adenopathy, and complement ﬁxing antibody titers above 1 : 16. Treatment
is also indicated in patients at risk for or manifesting complicated pulmonary
or disseminated disease.
Azole therapy with ketoconazole, ﬂuconazole, or
itraconazole for 3 to 6 months is the usual regimen. The latter two agents are
better tolerated. Posaconazole and voriconazole may have a role in refractory
cases. Intravenous amphotericin B is reserved for rapidly progressive cases or
with infection at vital sites such as the spine. After discontinuation of
treatment, close follow-up is necessary because of a substantial rate of
relapse in up to one-third of patients.