Abstract
Sural nerve biopsy is considered mandatory for diagnosing non-systemic vasculitic neuropathy (NSVN). This invasive technique may be associated with unpleasant sequelae and cannot easily be repeated. Skin punch biopsy from an affected area may be a less invasive and repeatable diagnostic method. Here we assessed the potential diagnostic value of skin punch biopsies in NSVN by analyzing skin biopsies in 20 patients with sural nerve biopsy-proven NSVN and in 11 patients with non-inflammatory axonal neuropathy. As further controls, skin biopsies were studied in nine healthy volunteers. Five millimeter skin punch biopsies were taken under local anesthesia from the distal lateral calf and T cells and macrophages were quantified after immunostaining. The diagnostic sensitivity and specificity compared to sural nerve biopsy was determined using receiver operating characteristic (ROC) analysis. ROC analysis revealed that the highest sensitivity (94%) and specificity (79%) for NSVN was obtained when perivascular macrophages were quantified. Quantification of scattered T cells yielded a sensitivity and specificity of 65%. Inflammatory cells were very rare in controls. Quantification of inflammatory cells in skin biopsies may thus be a sensitive and specific additional tool for diagnosing NSVN.
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Chao CC, Hsieh ST, Shun CT et al (2007) Skin denervation and cutaneous vasculitis in eosinophilia-associated neuropathy. Arch Neurol 64:959–965
Collins MP, Mendell JR, Periquet MI et al (2000) Superficial peroneal nerve/peroneus brevis muscle biopsy in vasculitic neuropathy. Neurology 55:636–643
Collins MP, Periquet MI, Mendell JR et al (2003) Nonsystemic vasculitic neuropathy: insights from a clinical cohort. Neurology 61:623–630
Davies L, Spies JM, Pollard JD et al (1996) Vasculitis confined to peripheral nerves. Brain 119(Pt 5):1441–1448
Dyck PJ, Benstead TJ, Conn DL et al (1987) Nonsystemic vasculitic neuropathy. Brain 110(Pt 4):843–853
Kennedy WR, Wendelschafer-Crabb G, Polydefkis M (2005) Pathology and quantitation of cutaneous nerves. In: Dyck PJ, Thomas PK et al (eds) Peripheral neuropathy. Elsevier Saunders, Philadelphia, pp 869–896
Kissel JT, Slivka AP, Warmolts JR et al (1985) The clinical spectrum of necrotizing angiopathy of the peripheral nervous system. Ann Neurol 18:251–257
Lauria G, Cornblath DR, Johansson O et al (2005) EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol 12:747–758
Lee JE, Shun CT, Hsieh SC et al (2005) Skin denervation in vasculitic neuropathy. Arch Neurol 62:1570–1573
Lombardi R, Erne B, Lauria G et al (2005) IgM deposits on skin nerves in anti-myelin-associated glycoprotein neuropathy. Ann Neurol 57:180–187
Said G, Lacroix-Ciaudo C, Fujimura H et al (1988) The peripheral neuropathy of necrotizing arteritis: a clinicopathological study. Ann Neurol 23:461–465
Satoh J, Yamamoto T, Kuroda Y (1999) Vasculitis confined to the peripheral nerve and skin: a variant of non-systemic vasculitic neuropathy. Eur J Neurol 6:241–244
Schmidt B, Toyka KV, Kiefer R et al (1996) Inflammatory infiltrates in sural nerve biopsies in Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy. Muscle Nerve 19:474–487
Sommer C (2008) Skin biopsy as a diagnostic tool. Curr Opin Neurol 21:563–568
Sommer C, Koch S, Lammens M et al (2005) Macrophage clustering as a diagnostic marker in sural nerve biopsies of patients with CIDP. Neurology 65:1924–1929
Sugiura M, Koike H, Iijima M et al (2006) Clinicopathologic features of nonsystemic vasculitic neuropathy and microscopic polyangiitis-associated neuropathy: a comparative study. J Neurol Sci 241:31–37
Tseng MT, Hsieh SC, Shun CT et al (2006) Skin denervation and cutaneous vasculitis in systemic lupus erythematosus. Brain 129:977–985
Vlckova-Moravcova E, Bednarik J, Dusek L et al (2008) Diagnostic validity of epidermal nerve fiber densities in painful sensory neuropathies. Muscle Nerve 37:50–60
Vrancken AF, Hughes RA, Said G et al (2007) Immunosuppressive treatment for non-systemic vasculitic neuropathy. Cochrane Database Syst Rev CD006050
Vrancken AF, Notermans NC, Jansen GH et al (2004) Progressive idiopathic axonal neuropathy—a comparative clinical and histopathological study with vasculitic neuropathy. J Neurol 251:269–278
Yamanaka Y, Hiraga A, Arai K et al (2006) Leucocytoclastic vasculitic neuropathy diagnosed by biopsy of normal appearing skin. J Neurol Neurosurg Psychiatry 77:706–707
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We thank H. Klüpfel and K. Stahl for technical assistance. This work was supported by intramural funds of the University of Würzburg.
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Üçeyler, N., Devigili, G., Toyka, K.V. et al. Skin biopsy as an additional diagnostic tool in non-systemic vasculitic neuropathy. Acta Neuropathol 120, 109–116 (2010). https://doi.org/10.1007/s00401-010-0662-5
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DOI: https://doi.org/10.1007/s00401-010-0662-5