Pharmacotherapy of vasculitis

Abstract

The systemic vasculitides are characterized by inflammatory lesions in blood vessels. Therapeutic approaches should be based on the aetiology or pathophysiology of disease. Unfortunately, for many of these disorders neither is fully understood and empirical treatment based on clinical presentation and the pattern of organ involvement is used. This approach is effective in improving survival in the most serious forms. We undertook a systematic literature review to assess the evidence for using drug therapies in vasculitis. Glucocorticoids remain essential for many forms of vasculitis; indeed, in giant-cell arteritis, they may be the only therapy necessary. However, additional immunosuppressive agents are required for other forms of vasculitis: methotrexate in Takayasu's arteritis and non-renal small-vessel vasculitis and cyclophosphamide for classic Wegener's granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome with poor prognostic features. Subsequent disease control is with low-dose glucocorticoid and azathioprine or methotrexate. Biologic therapy is being used in resistant cases. Patients experience significant short- to medium-term toxicity, especially infection and steroid side effects. Late sequelae due to high cumulative doses of cyclophosphamide include infertility and malignancy. Such risks are being reduced due to more judicious use of short courses of cyclophosphamide followed by substitution by safer agents.

Assessment of Risks of Pulmonary Infection During 12 Months Following Immunosuppressive Treatment for Active Connective Tissue Diseases: A Large-scale Prospective Cohort Study

“…Treatment of connective tissue diseases (CTD) has advanced with the introduction of molecular-targeted therapies, such as biologics and new classes of immunosuppressants 1,2,3,4 . Corticosteroids, still indispensable for the treatment of CTD, as well as most of the new treatments have the potential to increase susceptibility to infection, and risk of infection should be compared across these medications within a single cohort.…”

Immune Mediated Diseases and Immune Modulation in the Neurocritical Care Unit

“…Once diagnosed, induction therapy for treatment of WG usually consists of parenteral corticosteroids and cyclophosphamide [146]. In a recent study in which all patients were treated with highdose corticosteroids to induce remission, rituximab was shown to be as good as cyclophosphamide for treating ANCA-associated vasculitides and better than cyclophosphamide for patients with relapsing-remitting disease [147,148].…”

“…For active disease, induction therapy with corticosteroids and cyclophosphamide is standard care, although methotrexate and azathioprine are reasonable alternatives for long-term maintenance therapy [146,150]. In a recent study in which all patients were treated with high-dose corticosteroids to induce remission, rituximab was shown to be as good as cyclophosphamide for treating AAVs and better than cyclophosphamide for patients with relapsingremitting disease [147,148].…”

“…CNS involvement is seen in approximately 6 to 8% of patients with CSS and cerebral infarction, as well as intracerebral and subarachnoid hemorrhage being reported [160][161][162]. Patients with active disease, especially with neurological involvement, should undergo induction therapy with corticosteroids and cyclophosphamide [146]. Rituximab has also been reported to improve outcome in both patients with and without CNS involvement [163,164].…”

Molecular dissection of Porphyromonas gingivalis-related arteriosclerosis: a novel mechanism of vascular disease

“…Of the arterioscleroses, atherosclerosis and arteriosclerotic aneurysm are relatively common diseases (38,54,59,85,86,92,99). In contrast, inflammatory arterial diseases, which are characterized by inflammatory lesions with infiltration of inflammatory cells, and include BuergerÕs disease, KawasakiÕs disease, TakayasuÕs arteritis and vasculo-Behçet syndrome, occur only with low prevalence (8,12,61,64,78,79,84). The immune system is also activated in arteriosclerosis, and thus vasculitis in various forms is a common feature of all major vascular diseases.…”