Discussion
Coccidioidomycosis manifests a heterogeneous clinical spectrum depending
on the immune status of the host. The true number of cases is 6 to 14
times greater than the number reported since only 40% of
coccidioidomycosis infections are symptomatic; among them, some do not
seek medical care, others are misdiagnosed, and some identified cases
are not reported [4]. Males are reported to have a greater risk for
dissemination, suggesting a hormonal or genetic component. However, dust
exposure within endemic regions due to occupation is considered the
primary risk factor for infection [3].
Primary pulmonary coccidioidal infection is the most common disease
presentation in immunocompetent patients, with symptoms manifesting 7-21
days after exposure. Pulmonary symptoms are typically associated with
systemic complaints such as fever, headache, night sweats, weight loss,
and fatigue [1,2]. Patients with primary pulmonary disease may also
develop symmetric arthralgia and cutaneous manifestations. Radiographic
findings in primary pulmonary disease include dense pulmonary
infiltration, hilar adenopathy, and pulmonary nodules or cavities.
Conversely, disseminated coccidioidomycosis infection often involves the
skin, bones, joints, and central nervous system. Progression to
disseminated disease through hematogenous or lymphatic spread occurs in
less than 0.2% of coccidioidal infections, with immunocompromised
patients being at the highest risk [1,2].
Skin involvement is one of the most common extrapulmonary manifestations
of coccidioidal infection. It can be categorized as reactive lesions and
organism-specific lesions. Reactive manifestations that do not contain
visible microorganisms include erythema nodosum, erythema multiforme,
acute generalized exanthema, and Sweet’s syndrome. These manifestations
occur during acute primary pulmonary infection in up to 50% of cases
due to host immunological response [3]. Organism-specific
manifestations contain microorganisms within lesions and can be
classified as primary cutaneous disease from direct inoculation or
secondary cutaneous disease from hematogenous spreading [3].
Sweet’s syndrome has been observed as one of the reactive skin
manifestations of coccidioidomycosis. Few cases have been reported, with
most patients presenting with erythematous plaques commonly involving
the trunk, neck, and upper extremities [5,6]. Skin biopsy specimens
in Sweet’s syndrome typically show a diffuse inflammatory infiltrate in
the dermis, with neutrophils and leukocytoclastic debris. The treatment
for Sweet’s syndrome should focus on the underlying cause. When no
specific cause is evident, systemic corticosteroids are the mainstay of
therapy; however, they are not recommended in the setting of
coccidioidal infection.
Our patient did not have dominant respiratory symptoms associated with
primary coccidioidal infection, but instead presented with
extrapulmonary non-specific systemic symptoms such as fever, night
sweats, and weight loss. While these symptoms were suspicious of
malignancy, the patient’s arthralgia and cutaneous manifestations were
suggestive of an underlying inflammatory process. The initial CT chest
showed a spiculated lung mass with hilar lymphadenopathy, also
suggestive of malignancy. Initial radiographic findings in primary
coccidioidal infection may resemble malignancy. Additionally, cutaneous
manifestations associated with Sweet’s syndrome can be associated with
pregnancy, drugs, infection, and malignancy; As such, a biopsy of the
lung mass should be considered for definitive diagnosis. In this case,
the lung biopsy specimen showed granuloma formation with scattered
eosinophils and no malignant cells. An immunohistochemical marker CK7, a
marker for primary lung cancer, was also negative. These results,
correlated with clinical findings and positive coccidioidal serology
studies, allowed for the correct diagnosis of coccidioidomycosis to be
established.
Diagnosis of suspected primary coccidioidal infection is confirmed with
serology testing. Enzyme-linked immunoassay (EIA) is performed to detect
coccidioidal IgM and IgG antibodies. Immunodiffusion testing is
typically performed after an initial positive EIA test to quantify
coccidioidal antibody concentration and support the diagnosis.
Definitive diagnostic testing may be performed with histopathology of
biopsy specimens, revealing granulomatous inflammation and spherules of
endospores upon cytological staining [7,8]. Finally, fungal culture
from patient respiratory samples may be used for definitive diagnosis,
since Coccidioides spp. are not part of the normal human
microbiota.
Treatment of coccidioidomycosis is based on the severity of pulmonary
infection, the presence or absence of dissemination, and host immunity
status. Asymptomatic or mild disease may not require antifungal therapy
because the disease is commonly self-limiting in normal hosts. However,
it is important to classify between primary pulmonary and disseminated
infection to decide on the duration of treatment [7]. Several
studies indicated that CF titers of 1:32 were considered a specific
indication of heightened activity and possible dissemination [7,8].
Our patient showed no clinical evidence of disseminated infection, but
with a high yeast phase Ab titer (1:32), which is infectious, the
infectious disease consultant decided to pursue the treatment for
disseminated coccidioidomycosis with Fluconazole 800 mg for at least 3
months.