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.