Disseminated Coccidioidomycosis: Sites, Demographics, and Prognosis
Most Common Sites of Dissemination
The skin, skeletal system, and meninges are the most frequent destinations of disseminated coccidioidomycosis, with skin and soft-tissue involvement occurring in 15-67% of disseminated cases. 1, 2
- Skin manifestations occur in up to 67% of patients with disseminated disease, and importantly, 90% of persons with skin dissemination have concurrent infection at other extrapulmonary sites 2
- Skeletal involvement (bones and joints) represents another major site of extrapulmonary spread 1
- Central nervous system infection, particularly meningitis, is the most life-threatening form of dissemination 1, 3
- Lymph nodes are commonly involved in extrapulmonary disease 4, 2
Demographics and Risk Factors
Disseminated coccidioidomycosis occurs in only 0.5-2% of all infections, but risk varies dramatically by race and immune status. 5
Racial/Ethnic Disparities:
- African Americans and Filipinos face several-fold higher risk of dissemination compared to Caucasians 1, 5
- Persons of Asian, Hispanic, and Native American ancestry also have elevated risk compared to Caucasians 1
- For Caucasians, extrapulmonary complications occur in approximately 0.5% of infections 1
Immunocompromised Populations at Highest Risk:
- Solid organ transplant recipients: 4-9% infection rate in endemic areas, with majority occurring within 1 year post-transplant and frequent dissemination 1
- HIV/AIDS patients with CD4+ counts <250 cells/mL 1
- Patients on high-dose corticosteroids (≥20 mg prednisone daily for ≥2 weeks) 1
- Patients receiving TNF inhibitors or other immunosuppressive therapy 1
- Pregnant women, especially in third trimester 1
Other High-Risk Groups:
Prognosis
Central Nervous System Disease (Worst Prognosis):
- CNS coccidioidomycosis is nearly always fatal if untreated 3
- Even with treatment, 23% mortality rate has been documented in contemporary cohorts, with death occurring on average 22 months after diagnosis 6
- The most common life-threatening complication in the modern era is CNS vasculitis leading to cerebral ischemia, infarction, and hemorrhage 1
- Encephalopathy at presentation is associated with significantly higher risk of death 6
- Hydrocephalus develops in the majority of meningitis cases and nearly always requires shunt placement 1
- Shunt failure requiring revision surgery occurs in 52.5% of patients 6
- Rehospitalization due to CM-related complications occurs in 59% of patients 6
- Lifelong antifungal therapy is required for all patients with coccidioidal meningitis 1, 3
Disseminated Non-CNS Disease:
- Solid organ transplant recipients treated with amphotericin B followed by azoles have 83% survival 1
- Transplant recipients treated with azoles alone demonstrate 87% survival 1
- Concurrent amphotericin B and azole therapy (used for severe disease) shows only 34% survival, likely reflecting selection bias toward more critically ill patients 1
General Disseminated Disease:
- Because infection in transplant patients frequently disseminates and carries a high risk of mortality, prophylactic strategies are increasingly employed 1
- Treatment duration is typically prolonged—potentially lifelong—especially in patients with overt immunocompromising conditions 1
Key Clinical Pitfalls
- Do not rely solely on serology for diagnosis of disseminated disease—tissue diagnosis via histopathology or culture from extrapulmonary sites is essential, as CF antibody titers can be misleadingly low or high regardless of dissemination status 1
- Immunosuppressed patients may have negative serology despite active disseminated infection 1
- Medication nonadherence is documented in 43% of patients with coccidioidal meningitis, contributing to poor outcomes 6
- Patients in endemic areas are often rural agricultural workers with barriers to care including poverty and low health literacy 6