Treatment of Vasculitis

Introduction

Vasculitis, in general, is the inflammation of blood vessels. However, not all cases of vasculitis are identical. Vasculitis can vary based on a number of characteristics such as size of blood vessel involved, target organs, etiology, and the underlying pathogenesis which can range from infectious, malignant to connective tissue disease. When involving the central nervous or peripheral nervous system, diagnosis and treatment can be difficult due to variable presentations, lack of highly sensitive and specific diagnostic tests, and vasculitis mimics. A prompt diagnosis with treatment is essential for the prevention of morbidity and mortality ( Table 148.1 ). We use categories from the 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides to subgroup a number of vasculitides that can affect the central and peripheral nervous system, with focus on treatments .

Large-Vessel Vasculitis

Giant cell arteritis (GCA) is an immune-mediated vasculitis of medium- to large-sized arteries, which commonly involves cranial arteries, but may affect the aorta as well . Clinical manifestations include headaches, fever, visual loss, limb claudication, fatigue, weight loss, and polymyalgia rheumatica symptoms. Inflammatory markers including ESR and CRP should be elevated. Before a diagnosis of GCA is confirmed with a temporal artery biopsy, treatment with high-dose corticosteroids should be initiated once clinical suspicion is present that the patient has this disease . Typical starting doses are 60–80 mg/day until symptoms disappear and inflammatory markers normalize, typically 2–4 weeks after initiation. Typical tapers involve reducing the dose of prednisone by a maximum of 10% of the total daily dose every 1–2 weeks after reaching 40 mg/day. Flares, indicated by a return of symptoms or elevation of inflammatory markers, may require a lengthened taper. Patients generally will be on corticosteroid therapy for 1–2 years. Differing results have been seen in randomized controlled trials utilizing IV and oral steroids, but there has been no consensus that IV steroids have shown greater efficacy.

Given the average length of time utilizing corticosteroid treatment, various steroid-sparing agents have been investigated. Methotrexate (MTX) has been evaluated in three randomized controlled trials of GCA with divergent results. The trials suggest that MTX is, at best, a moderately effective steroid-sparing agent. Recently, case reports have suggested that the use of tocilizumab may be effective in patients with GCA in whom it has been difficult to taper glucocorticoids. There is evidence that IL-6 may be important in the pathogenesis of GCA. In one of these studies, 22 GCA patients with refractory disease were treated with tocilizumab (8 mg/kg once monthly) . After a median follow-up of 9 months, 17 patients achieved remission, and the median prednisone dose was tapered from 19 mg to 5 mg daily. Tocilizumab remains a promising steroid-sparing agent, but more studies need to be performed.

Takayasu arteritis is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation . Acute inflammation can destroy the arterial media and lead to aneurysm formation. A two-stage process has been suggested with a “prepulseless” phase characterized by nonspecific inflammatory features, followed by a chronic phase with development of vascular insufficiency. The disease commonly presents in the second or third decade of life. Symptoms consist of fever, malaise, weight loss, arthralgias, myalgias, diminished or absent pulses, limb claudication, and vascular bruits. Neurological features secondary to hypertension and ischemia include postural dizziness, seizures, headaches, and amaurosis. Treatments should aim to control disease activity and preserve vascular competence, while minimizing long-term side effects. Steroids remain the mainstay or treatment for Takayasu arteritis, but response may be related to the stage of disease at which this treatment is introduced. Glucocorticoid-sparing agents such as azathioprine, mycophenolate, MTX, tocilizmab, leflunomide, anti-TNF alpha inhibitors, and cyclophosphamide have been tried, but studies have not shown one medication to be clearly superior to others. Providers may initiate one medication for 4–6 months, and switch immunosuppressants if there is lack of efficacy.