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Antineutrophil Cytoplasmic Antibodies in Nonsystemic Vasculitic Neuropathy

To the Editor:

It was recently brought to my attention that my editorial on nonsystemic vasculitic neuropathy (NSVN)1 received comment by Peer Aries and Wolfgang Gross2. I thank them for their interest and appreciate this opportunity to address their concerns.

Aries and Gross were "amazed" that the importance of antineutrophil cytoplasmic autoantibody (ANCA) testing in NSVN and, for that matter, any "undefined neuropathy" was not emphasized. However, NSVN is not an ANCA-associated vasculitis (AAV), which is why I elected to discuss more pertinent issues in my editorial.

For the record, in our own series of 48 patients with NSVN encountered at Ohio State University3, only one of 14 patients assessed for ANCA was positive [anti-myeloperoxidase (MPO) pANCA]. For a 2004 review article, I combined this data with the available literature to obtain an 11% (3/28) prevalence of ANCA in NSVN4. In the intervening 2 years, an additional 40 patients with NSVN tested for ANCA have appeared, all with negative results2,5-7. Therefore, the current cumulative percentage of published NSVN cases positive for ANCA is 4% (3/68), implying that NSVN is not an AAV.

I agree with Aries and Gross that peripheral nerve involvement is common in Churg-Strauss syndrome8, but ANCA occur in less than 40% of patients with this condition9-11, an observation that has prompted some experts to doubt their pathogenic significance9. The "classic example" of an AAV, Wegener's granulomatosis, is rare in series dedicated to pathologically proven vasculitic neuropathy12-15. I also agree that every patient diagnosed with a vasculitic neuropathy should undergo surveillance for additional vasculitic manifestations, but this is true irrespective of ANCA status.

Patients who develop an unexplained multifocal or asymmetric neuropathy suspicious for vasculitis deserve to undergo ANCA testing as part of their "systemic" workup. However, Aries and Gross go further and recommend similar testing for all patients with an unexplained neuropathy, irrespective of tempo or pattern. I disagree. For the type of neuropathy most commonly encountered by practicing neurologists and primary care physicians — a late-onset, indolent, slowly progressive, distal, symmetric polyneuropathy — the diagnostic specificity of ANCA testing is quite low. In the only study of its kind, Chalk, et al obtained ANCA in 166 consecutive patients referred to a peripheral neuropathy center16. Although 4/6 patients with a vasculitic neuropathy (none of them nonsystemic) did, in fact, have pANCA or MPO-ANCA, MPO-ANCA were also identified in 5/44 patients with other types of inflammatory neuropathy, 1/8 with motor neuron disease, 13/69 with other types of noninflammatory neuropathy, 5/22 with central nervous system or muscle diseases, and 7/17 with symptoms but no signs or laboratory abnormalities. None of the patients had cANCA or PR3-ANCA. The authors concluded that "in patients being evaluated for peripheral neuropathy, the utility of ANCA as a simple serologic test for vasculitic neuropathy is limited by nonspecificity"16. By inference, if every patient with an unexplained neuropathy is tested for ANCA, false positives will outnumber true positives, engendering many unnecessary nerve biopsies. A more cost-effective approach is to tailor ANCA testing and nerve biopsy to the neuropathic profile.

MICHAEL P. COLLINS, MD, Department of Neurology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, Wisconsin 53226-3596, USA. E-mail:


Search PubMed for:

1. Collins MP. Localized vasculitis and the peripheral nervous system [editorial]. J Rheumatol 2005;32:769-72.

2. Aries PM, Gross WL. Nonsystemic vasculitic neuropathy: a clinicopathological study of 22 cases [letter]. Kararizou E [reply]. J Rheumatol 2006;33:636-7.

3. Collins MP, Periquet MI, Mendell JR, Sahenk Z, Nagaraja HN, Kissel JT. Nonsystemic vasculitic neuropathy: Insights from a clinical cohort. Neurology 2003;61:623-30.

4. Collins MP, Periquet MI. Non-systemic vasculitic neuropathy. Curr Opin Neurol 2004;17:587-98.

5. Lee SS, Lee SH, Kim SW. Combined hereditary neuropathy with liability to pressure palsies and non-systemic vasculitic neuropathy [letter]. J Peripher Nerv Syst 2005;10:215-6.

6. Sugiura M, Koike H, Iijima M, et al. Clinicopathologic features of nonsystemic vasculitic neuropathy and microscopic polyangiitis-associated neuropathy: a comparative study. J Neurol Sci 2006;241:31-7.

7. Yamanaka Y, Hiraga A, Arai K, et al. Leukocytoclastic vasculitic neuropathy diagnosed by biopsy of normal appearing skin [letter]. J Neurol Neurosurg Psychiatry 2006;77:706-7.

8. Hattori N, Ichimura M, Nagamatsu M, et al. Clinicopathological features of Churg-Strauss syndrome-associated neuropathy. Brain 1999;122:427-39.

9. Hellmich B, Ehlers S, Csernok E, Gross WL. Update on the pathogenesis of Churg-Strauss syndrome. Clin Exp Rheumatol 2001;21 Suppl 32:S69-S77.

10. Sable-Fourtassou R, Cohen P, Mahr A, et al. Antineutrophil cytoplasmic antibodies and the Churg-Strauss syndrome. Ann Intern Med 2005;143:632-8.

11. Sinico RA, Di Toma L, Maggiore U, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum 2005;52:2926-35.

12. Collins MP, Kissel JT. Neuropathies with systemic vasculitis. In: Dyck PJ, Thomas PK, editors. Peripheral neuropathy. 4th ed. Philadelphia: Elsevier; 2005:2335-404.

13. Hawke SH, Davies L, Pamphlett R, Guo YP, Pollard JD, McLeod JG. Vasculitic neuropathy. A clinical and pathological study. Brain 1991;114:2175-90.

14. Said G, Lacroix-Ciaudo C, Fujimura H, Blas C, Faux N. The peripheral neuropathy of necrotizing arteritis: a clinicopathological study. Ann Neurol 1988;23:461-5.

15. Vital C, Vital A, Canron MH, et al. Combined nerve and muscle biopsy in the diagnosis of vasculitic neuropathy. A 16-year retrospective study of 202 cases. J Peripher Nerv Syst 2006;11:20-9.

16. Chalk CH, Homburger HA, Dyck PJ. Anti-neutrophil cytoplasmic antibodies in vasculitic peripheral neuropathy. Neurology 1993;43:1826-7.

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