The vasculitides are a group of heterogeneous disorders that present with a variable and complex clinical picture. Debates over clinical versus pathological approaches to classification abound in the literature, with recognized limitations given the variable clinical presentations and the overlap between the recognized diagnostic entities. Peripheral neuropathy is an important, and often the presenting, clinical feature of the vasculitides. Its recognition can be critical to attain an early diagnosis in these disorders where the ultimate outcome can be greatly influenced by early therapeutic intervention.
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• Neuropathy related to vasculitis can occur as either a primary condition (in the setting of systemic vasculitis) or secondary to a range of diseases including infection and connective tissue disorders. Localized nonsystemic vasculitic neuropathies include diabetic lumbosacral radiculoplexus neuropathy (DLRPN) and nondiabetic lumbosacral radiculoplexus neuropathy (LRPN).
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• Vasculitic neuropathies can be classified according to clinical features or histopathologically based on the size of involved vessels.
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• Diagnostic tests include electrodiagnostic studies demonstrating an asymmetric non-length dependent axonal neuropathy and nerve biopsy when necessary.
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• Management involves institution of immunosuppressive therapy and removal of the inciting agent when present.
Historical note and terminology
Peripheral neuropathy figured prominently in the first complete description of a systemic necrotizing vasculitis (polyarteritis nodosa) by Kussmaul and Maier in 1866. For the next 80 years, essentially all vasculitic diseases, irrespective of clinical features, were called polyarteritis nodosa. Scattered descriptions of patients with peripheral neuropathy appeared in many of these early reports. Neuropathy occurring in the setting of rheumatoid arthritis was also described in the late 19th century, and one report described in detail the vascular histopathology (04).
In the 1950s, hypersensitivity vasculitis, Churg-Strauss syndrome, and Wegener granulomatosis were all described in the English language literature as entities distinct from polyarteritis nodosa, and Zeek first proposed a classification scheme for the vasculitic syndromes based on the size of involved blood vessels (01). Over the next 20 years, numerous reports appeared detailing the clinical features, histopathology, response to treatment, and prognosis of the various vasculitic syndromes; peripheral neuropathy was an important finding in many of these reports. During this time several different, and often conflicting, classification schemes for the vasculitides were proposed based on the size of involved vessels, type of vascular pathology, clinical features, or immunopathologic mechanisms. Despite several multicenter studies that have attempted to standardize the nomenclature, diagnostic criteria, and classification of the vasculitic syndromes, some confusion over these issues persists (31; 33; 01). The International Chapel Hill Consensus Conference updated their classification system in 2012, now organized primarily by vessel size and etiology (34). Additionally, in 2010, the Peripheral Nerve Society published new guidelines on the classification of vasculitic neuropathies, subdividing them into primary systemic, secondary systemic, and nonsystemic or localized vasculitides. This scheme included the entities of nondiabetic lumbar radiculoplexus neuropathy (LRPN) and diabetic lumbosacral radiculoplexus neuropathy (DLRPN), which had not been included in prior classification systems (08). In 2015, the Brighton criteria revised the diagnostic criteria for vasculitic neuropathies using the same histopathological criteria as the Peripheral Nerve society but also included several clinical features in addition (25).
In 1972, Dyck and colleagues published a seminal work detailing the sural nerve histopathology in 14 patients with various vasculitic syndromes (14). This study correlated the three-dimensional morphology of nerve fiber degeneration and vascular pathology, and provided strong support for the concept that ischemia probably accounts for the nerve damage in these syndromes. Several large series of patients with vasculitic neuropathy have defined the clinical spectrum, laboratory features, electrophysiologic findings, and immunopathology of these syndromes. An important concept to emerge from these studies is that neuropathy can be the sole manifestation of an underlying vasculitis (40; 03; 26; 13; 60; 55; 29; 52; 11). Several studies have documented a true necrotizing vasculitis associated with the syndrome of proximal diabetic neuropathy (diabetic amyotrophy/lumbosacral radiculoplexus neuropathy) (41; 15; 20; 59). A similar vasculopathy has also been found in nondiabetics presenting with lumbosacral radiculoplexopathy (16).