Clinicopathologic features of nonsystemic vasculitic neuropathy and microscopic polyangiitis-associated neuropathy: A comparative study

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Abstract

Objective

To compare clinicopathologic findings in nonsystemic vasculitic neuropathy (NSVN) and microscopic polyangiitis-associated neuropathy (MPAN).

Methods

Patients clinicopathologically confirmed to have NSVN (n = 23) or MPAN (n = 40) were compared with respect to clinical, electrophysiologic, and histopathologic features.

Results

Clinical features of neuropathy such as initial symptoms, progression, and distribution of sensory and motor deficits were similar in both groups, while functional compromise was greater in MPAN than NSVN. Abnormalities of laboratory data including those reflecting severity and extent of inflammation such as C-reactive protein were more conspicuous in MPAN than NSVN. Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were positive in two-thirds of patients with MPAN but negative in all NSVN. Electrophysiologic and histopathologic findings indicated axonal neuropathy in both groups, whereas the reduction of compound muscle action potentials in the tibial nerve and sensory nerve action potentials in the median nerve was significantly more profound in MPAN than NSVN. As for the epineurial perivascular infiltration, frequencies of cell-specific markers for T lymphocytes, macrophages, and B lymphocytes among cells infiltrating the vasculitic lesions were essentially similar between groups.

Conclusions

Clinicopathologic profiles and vascular pathology were similar between NSVN and MPAN but the age at onset, severity, and presence of p-ANCA were clearly different. Further study is needed to clarify the pathogenesis of NSVN and its place in the vasculitic spectrum of diseases.

Introduction

Vasculitic neuropathy occurs in association with various diseases including systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, infection, malignant neoplasia, and cryogloblinemia [1]. In addition to vasculitic neuropathies secondarily to these diseases, primary systemic vasculitides including microscopic polyangiitis (MPA), Churg-Strauss syndrome, and Wegener's granulomatosis are known to involve the peripheral nervous system. Finally, vasculitis confined to the peripheral nervous system without systemic manifestations has been reported [2], [3]. Subsequently, Dyck et al. described 20 patients with vasculitic neuropathy in the absence of other organ involvement [4]. These patients showed few laboratory abnormalities suggesting either systemic inflammation or collagen diseases, lacked nonspecific constitutional symptoms such as fever or weight loss, and had a favorable prognosis [4]. Since then, such vasculitic neuropathy has been known as nonsystemic vasculitic neuropathy (NSVN) and has attracted attention mainly among neurologists. Although NSVN possesses distinctive clinical features, involving only the peripheral nervous system, pathogenesis has remained unknown. In addition, vasculitis in this neuropathy has not been proven pathologically to be confined to the peripheral nervous system, so it might subclinically involve other organs. A related question is whether NSVN has a pathogenesis distinct from that of systemic vasculitides, especially MPA. MPA, a vasculitis involving small vessels including arterioles, venules, or capillaries [5], originally was considered a subtype of polyarteritis nodosa with rapidly progressive necrotizing glomerulonephritis and sometimes lung hemorrhage [6]; because of frequent renal involvement [5], this disorder has been studied by nephrologists as well as rheumatologists, with far less attention given to its neurologic aspects [5], [7]. Since diagnostic criteria for primary vasculitis, such as those of Chapel Hill Consensus Conference [7], have been established mainly by rheumatologists, the nosologic relationship of systemic vasculitides to NSVN has remained obscure.

In this study we compared clinicopathologic features of neuropathy without and with systemic involvement (so-called NSVN and MPA-associated neuropathy: MPAN) to clarify the relationship of NSVN to systemic vasculitic neuropathy.

Section snippets

Patients

Clinicopathologic findings in consecutive patients with pathologically confirmed NSVN and MPA-associated neuropathy (MPAN) with systemic involvement who were referred to Nagoya University Graduate School of Medicine and performed sural nerve biopsy from 1990 to 2003 were retrospectively compared. In the NSVN group symptoms of vasculitis were confined solely to the peripheral nerves, with no clinical or laboratory evidence of other organ involvement [4]. Laboratory data in this group were normal

General symptoms

Age at onset was significantly younger in the NSVN group than the MPAN group (58.4 ± 15.3 versus 67.2 ± 8.0 years; p < 0.05; Table 1). The male to female ratio was 1.6:1 in NSVN and 1.9:1 in MPAN. Nonspecific symptoms, specifically fever, weight loss, skin eruption, arthralgia, and myalgia, respectively were seen in 83%, 43%, 30%, 13% and 13% of MPAN patients; these symptoms were absent in NSVN patients. In the MPAN group, renal involvement was present in 38% of patients, and pulmonary involvement in

Discussion

Although NSVN is clinically distinctive from other systemic vasculitides such as MPA in that clinically apparent vasculitis is confined to the peripheral nervous system, uncertainty prevails as to whether NSVN is likely to have a distinct etiology and pathogenesis and to represent an independent disease entity. The nosologic relationship between NSVN and MPA-associated neuropathy (MPAN) therefore remains in question. Although MPA frequently involves lung and kidney, the Chapel Hill consensus

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