Need for developing case definition and guidelines for data collection, analysis, and presentation
Background to vasculitic peripheral neuropathy
The vasculitides are a heterogeneous group of disorders associated with organ dysfunction caused by inflammatory disease of blood vessels. The various clinical manifestations of different vasculitides depend on local immunologic environments, tissue vulnerabilities, and blood flow territorial distributions [1]. Systemic vasculitides involve multiple organs and tissues, whereas in some patients vasculitis is restricted to a single organ or tissue [2]. Vasculitic peripheral neuropathy (VPN) typically manifests as an asymmetric neuropathy resulting from ischaemic axonal injury. Clinically, vasculitic neuropathies are usually painful and asymmetric, with sensory, motor, and autonomic involvement; less commonly, they exhibit exclusively sensory involvement [3], [4]. Electrodiagnostic studies in vasculitic neuropathy typically show asymmetric or non-length dependent patterns of axonal neuropathy [5]. Histopathological confirmation is the gold standard for diagnosis of vasculitic neuropathy even though there are no universally accepted criteria [6]. There are no population-based studies describing the incidence and prevalence of systemic and non-systemic vasculitic neuropathies. The frequency of occurrence of neuropathy in systemic vasculitides varies and may be as high as 65% in patients with polyarteritis nodosa (PAN), eosinophilic granulomatosis with polyangiitis (EGPA; Churg–Strauss), and cryoglobulinemic vasculitis [3].
Pathophysiology
The vasculitides may be triggered by immune reaction to certain antigens, including infectious agents, possibly explaining the aetiology of post-immunisation vasculitis. Due to the relative lack of collateral blood flow and high metabolic demand, nerves are particularly susceptible to vasculitic injury. Depending on the size of involved vessels, vasculitic neuropathies can be divided into (a) vasculitis of large arterioles and small arteries of nerve and (b) microvasculitis of nerve [7]. Vasculitic nerve injury is usually related to T-cell cytotoxicity and chronic delayed type hypersensitivity. The spectrum of nerve injury and underlying pathophysiological mechanisms vary in different vasculitic syndromes [3].
Subtypes of vasculitis
VPN may occur in the context of systemic vasculitis (SV), i.e., systemic vasculitic neuropathy (SVN), or as a single-organ non-systemic vasculitic neuropathy (NSVN). Vasculitic neuropathies can be also classified based on histopathological features. SVN associated with different types of systemic vasculitides may herald the onset of multisystem vasculitis [8] or follow clinical involvement of other organs or tissues. Systemic vasculitides are further divided into primary vasculitides and secondary vasculitides associated with connective tissue disorders, malignancies, infections, drugs, and toxin exposures [2]. If untreated, multisystem vasculitis has a very high mortality rate. In contrast to SVN, NSVN is confined to nerves and occasionally muscles, usually causes less morbidity, and is typically not fatal. Patients with well-defined NSVN who are treated with immunosuppressive agents almost never develop multisystem vasculitis [9], [10]. Clinical presentation of SVN also includes systemic symptoms and involvement of other organs which depend on the type of underlying systemic vasculitis. Vasculitic neuropathies typically manifest with subacute stepwise progression or progressive worsening, although some patients exhibit more insidious chronic progression over many years.
