Page 55 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 31

Johnson and colleagues [117] attributed the vasculitic nature of this process
histopathologically to cerebral vasculitis mediated by acute inflammation and necrosis.
Younger and colleagues [123] reported large named cerebral vessel occlusion attributed to
circulating anticardiolipin antibodies in a young man in whom a vasculitic mechanism was
not evoked. A number of fluorescent antibody tests provide serological support of SLE. The
antinuclear antibody (ANA) screen produces a homogenous pattern in the majority of
patients, with antibodies to native double-stranded DNA (anti-dsDNA) and reactivity to the
smith (Sm) and ribonucleoprotein (RNP) antigens, the combination of which constitutes the
extractable nuclear antigen (ENA). Circulating IgG and IgM antibodies with an affinity for
charged phospholipids, antiphospholipid antibodies (APA), some of which have procoagulant
activity such as the lupus anticoagulant (LAC) and the generic anticardiolipin (aCL) antibody
assay using cardiolipin as the antigen probe for APA are all important determinants of
prothrombotic events, especially in the CNS wherein there is a propensity for occlusive
microangiopathy. Circulating SLE-related antibodies can impact the CNS by affecting both
vascular mechanisms and brain tissue directly. Immune complex mediated vasculitis probably
affecting small vessels is thought to account for much of the damage in CNS lupus in light of
spite of the paucity of cerebral vasculitis evident in the form of inflammatory infiltrates in
vessel walls at postmortem examination. In those with discrete vascular infarcts, there is a
known association with the presence of circulating pathogenic antibodies which predisposes
some individuals to a high risk of stroke due to both small and large vessel occlusion [123,
124]. Lupus cerebritis and meningoencephalitis are two neurological disturbances that can be
associated with preceding headache. So noted in up to 75% of patients with SLE depending
upon criteria [125], an etiopathogenesis related to antibody-mediated neuronal dysfunction is
likely given the lack of correlation of symptoms of NPSLE and CNS lesions at postmortem
examination, together with the transient nature of the disturbance. Patients with SLE are also
predisposed to infectious episodes including those yet treated due to impaired B-cell function
and humoral immunity, in addition to others receiving immunosuppressant medication
rendered impaired in T-cell function and cell mediated immunity [125]. The treatment of
CNS Lupus should be guided by the tempo of the presenting neurological features, duration
of disease activity, results of serological studies, comorbid disorders, and the presence of true
vasculitis, with most patients receiving corticosteroids and those with true vasculitis of the
brain considered for concomitant immunosuppressant therapy. Despite less major organ
involvement and decreased incidence of neurological complications overall, late-onset SLE
has a poor prognosis because of the higher frequency of comorbid conditions, longer
exposure to classical vascular risk factors, both the less likelihood of treatment with higher
doses of corticosteroids and the concomitantly higher rate of complications to
cyclophosphamide when administered [116].

Rheumatoid Arthritis Vasculitis

A joint working group from the ACR and the European League Against Rheumatism
(EULAR) published the 2010 classification criteria for RA [126]. Extra-articular RA (ExRA)
occurrence is associated with increased comorbidity and mortality [127]. Criteria for severe
ExRA were proposed in 2004 [128]. Active RA with high disease activity is associated with

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