Page 162 - The Vasculitides Volumes 2

138 Patricia K. Coyle

It typically causes disease in immunocompromised hosts, although CNS vasculitis and
stroke occur in immunocompetent patients [73, 74]. The major human pathogens are from the
Aspergillus fumigatus, niger and flavus species. Patients with hematologic malignancies and a
history of bone marrow transplantation can have fulminant CNS courses with mortality rates
of 85% to 99% [4].

The Aspergillus organisms invade blood vessels with resultant production of proteases
that weaken the vessel wall leading to aneurysm formation [75]. The course can be more
chronic and insidious in those with lesser degrees of immune compromise, such as due to
diabetes mellitus. Spread to the CNS occurs via hematogenous routes from the lung, or by
direct extension through the paranasal sinuses and orbits. CNS involvement which occurs in
10% to 50% of systemic infections includes meningoencephalitis and intracerebral
hemorrhage, as well as, vasculopathy, and mycotic aneurysm formation leading respectively
to stroke and potentially fatal subarachnoid hemorrhage with greater involvement of
penetrating than larger named vessels.

Aspergillus infection should be considered in immunocompromised hosts with
pulmonary disease and either ischemic or hemorrhagic stroke. The diagnosis can be difficult
since CSF cultures are positive in less than 50% of cases, and PCR is investigational. Two
antigen assays, each for biomarkers including galactomannan and beta-D-glucan, have not
been standardized in the CSF. Tissue biopsy can be confirmatory. Brain neuroimaging may
demonstrate ring-enhancing lesions, meningeal enhancement, and ischemic or hemorrhagic
stroke. Therapy involves oral voriconazole and surgical resection of focal cerebral and
extraneural sites of involvement.

Candida

Candida species are part of normal human flora and thus typically are not pathogenic
unless there is mitigating systemic immune compromise. Neutropenia is a major risk factor
for invasive disease. Candida is considered a yeast infection with Candida albicans the most
common agent in humans. It invades small blood vessels and can be associated with
thrombosis and infarction. Neurologic involvement most often takes the form of meningitis
that may predispose to basilar artery thrombosis [76]. One affected patient with HIV/acquired
immune deficiency virus syndrome (AIDS) and subacute meningitis who was treated
empirically for tuberculosis and initiated on HAART therapy developed fatal worsening due
to postmortem-proven basilar Candida meningitis and cerebral vasculitis characterized by
CD8+ T-cell infiltration and microinfarcts, consistent with IRIS [77]. The diagnosis of
Candida infection is based on a positive culture and informative PCR, and suggestive findings
on antigen assays to mannan and beta-D glucan albeit not routinely performed. Effective
treatment depends upon the age and severity of infection with lipid formulations of
amphotericin, fluconazole, or echinocandin.

Coccidioides Immitis
Coccidioides immitis is a soil based fungus endemic to the arid Southwest and Latin

America. Infection may be asymptomatic or the cause of mild pulmonary issues such as
occurs in valley fever. About one-half of disseminating cases involve the CNS resulting in
basilar meningitis with a local vasculitis of small and medium arteries, and occasionally

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