Systemic Diseases and Drug-Induced Vasculitis

Inflammatory diseases of the CNS blood vessels are a large heterogeneous group with multiple causes sharing certain pathological features, particularly intramural inflammation and necrotic changes within the vascular wall. Unlike infectious vasculitides secondary to direct infection of blood vessels by organisms, non-infectious CNS vasculitides appear to result from immunological injury. Noninfectious cerebral vasculitides are challenging to clinicians because of the variable clinical symptoms, the difficulties establishing a correct diagnosis, the need for specific therapy, and the poor outcome. They are also difficult for the pathologist; their etiology and pathogenesis are controversial and the histopathological features are variable and non-specific. Classification of CNS vasculitides is essential since they require different treatments and have varying prognoses. To date, there is no generally accepted classification of vasculitides. The American College of Rheumatology consensus conference for the nomenclature of systemic vasculitides proposed a classification based on clinical criteria (26). The 1993 Chapel Hill Classification is based on the caliber of involved vessels (31) (Table 1) and other classifications rely on pathogenetic mechanisms (32) (Table 2). Recently, many of the effector mechanisms that mediate inflammatory vascular damage have been defined (11, 67). Cytokine-mediated changes in the expression and function of adhesion molecules, in combination with activation of leukocytes and endothelial cells, are the primary factors involved in vessel damage. There are several potential mechanisms of vessel damage in vasculitis (Table 2). Pathogenic circulating antigen-antibody immune complexes containing activated complement are deposited in vessels at sites of increased permeability leading to endothelial damage, production of chemotactic factors, infiltration of neutrophils and monocytes, stimulation of clotting and kinin pathways, and release of cytokines, oxygen radicals, and proteolytic enzymes. This mechanism plays an important role in Henoch-Schönlein purpura, drug-related cutaneous vasculitis, hepatitis B-associated polyarteritis nodosa (PAN) and essential mixed cryoglobulinemia (related to hepatitis C). Other potential pathogenetic mechanisms include anti-endothelial cell antibody-mediated vessel damage (in Takayashu arteritis, PAN and Kawasaki disease) and direct damage to the vessel by infectious agents or tumor cells. Abnormal production of ANCA can lead to neutrophil-mediated vascular injury in ANCAassociated vasculitis. In some type of vasculitis (giant cell, Takayasu, Wegener, Churg-Strauss), there is a granulomatous reaction initiated by a T-cell mediated immune response directed against an antigen (probably an infection-related supra antigen). On a practical level, CNS vasculitis may be divided into primary or secondary. Primary cranial or cerebral vasculitides include Takayasu arteritis (chapter 18), giant cell arteritis (chapter 17), and primary or granulomatous angiitis of the CNS (chapter 19), it usually requires a biopsy for diagnosis, and the outcome is often poor. Secondary inflammation of CNS blood vessels includes manifestations of systemic diseases, malignancy-related vasSystemic Diseases and Drug-Induced Vasculitis Céline Bazille Catherine Keohane Françoise Gray