Infectious diseases causing vasculitis

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Varicella zoster virus vasculopathy

Varicella zoster virus (VZV) can lead to stroke due to viral infection of the cerebral artery walls (for review see Nagel et al. [25]). Two different types of infection can be differentiated depending on the immune status of the patient. Immunocompromised individuals, e.g. organ transplant or AIDS patients, show a diffuse inflammation of cerebral blood vessels of all sizes. Immunocompetent patients may develop herpes zoster associated cerebral angiitis, a granulomatous angiitis that usually affects larger arteries. In both cases, histopathological features include multinu-cleated giant cells, Cowdry A inclusion bodies, and VZV particles.

Diagnosis of VZV vasculopathy can be difficult, and is based on patient history, imaging studies, and analysis of the cerebrospinal fluid (CSF). It should be suspected in patients with ischemic lesions in MRI or CT, combined with a positive VZV PCR or serological detection of VZV IgG. Patient history often reveals a typical herpetiform rash. The rash can precede the manifestation of stroke by up to several months. When cerebral angiography is performed, unifocal or multifocal vascular lesions with corresponding lesions in CT or MRI imaging studies can be found.

Randomized clinical trials for standard treatment are lacking. Based on expert opinion, current treatment includes intravenous acyclovir in combination with steroids. A vaccination for VZV is available and has significantly diminished VZV-related morbidity and mortality in children. Prevention of herpes zoster by this vaccine has so far not been demonstrated [26].

HIV-associated vasculopathy and vasculitis

Several cohort studies around the world have shown that stroke in patients with acquired immunodeficiency syndrome (AIDS) is more frequent than in an age-adjusted HIV-negative population. However, a firm causal relationship between HIV infection and stroke has yet to be proven. A recent cohort study on young patients with stroke in South Africa suggests that the mechanisms leading to stroke in HIVpositive patients are largely similar to those in HIVnegative controls [27]. In this study, frequent causes were opportunistic infections (tuberculosis, neurosyphilis, varicella zoster vasculopathy, cryptococcal meningitis), coagulopathy, and cardioembolism. In 10-20% of the cases, HIV-associated vasculitis was suspected as a cause of stroke.

In the early stages of HIV infection an intracranial vasculopathy of small arteries can be found [28]. Histological features are thickening of the vessel wall, perivascular space dilatation, rarefaction, pigment deposition, and occasional perivascular inflammatory cell infiltrates. This condition is associated with asymptomatic microinfarcts and may predispose to ischemic stroke.

In later stages of AIDS, HIV-associated vasculitis can be found, a poorly characterized entity that involves large or medium sized intra- or extracranial arteries. It results in fusiform aneurysms, stenosis or thrombosis and can lead to ischemic or hemorrhagic stroke. Whether HIV-associated vasculitis is directly caused by HIV infection or is due to an undetected opportunistic infection is still under debate [29].

Vasculitis from infectious diseases, e.g. varicella zoster virus and HIV, can result in ischemic stroke.

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