Vaskulitische Neuropathien

D. Heuss; B. Schlotter-Weigel; C. Sommer

doi:10.1055/s-0038-1624382

Nervenheilkunde, Table of Contents

Nervenheilkunde 2003; 22(03): 122-130
DOI: 10.1055/s-0038-1624382

Original- und Übersichtsarbeiten/Original and Review Articles

Schattauer GmbH

Vaskulitische Neuropathien

Diagnosis and therapy of vasculitic neuropathy

Authors

D. Heuss

¹Neurologische Klinik der Friedrich-Alexander-Universität Erlangen-Nürnberg
B. Schlotter-Weigel

²Friedrich-Baur-Institut an der Neurologischen Klinik der Ludwig-Maximilians-Universität München
C. Sommer

³Neurologische Klinik der Julius-Maximilians-Universität Würzburg

Abstract

Zusammenfassung

Unter vaskulitischen Neuropathien versteht man immunvermittelte Erkrankungen des peripheren Nervensystems, bei denen die Schädigung der Nerven durch eine Entzündung der Blutgefäße bedingt ist. Unterschieden werden vaskulitische Neuropathien bei primären und sekundären systemischen Vaskulitiden, bei entzündlichrheumatischer Systemerkrankung, bei malignen Erkrankungen, medikamenteninduzierten Vaskulitiden und die nicht-systemische vaskulitische Neuropathie (NSVN). Das typische klinische Erscheinungsbild einer vaskulitischen Neuropathie ist eine asymmetrische oder multifokale schmerzhafte sensomotorische Neuropathie mit akutem/subakutem oder chronischem Verlauf mit schubförmigen Verschlechterungen. Charakteristisch sind weiterhin der elektrophysiologische Nachweis einer aktiven asymmetrischen axonalen sensomotorischen Neuropathie und die Besserung durch immunsuppressive Therapie. Eine gesicherte Vaskulitis liegt vor, wird ein positiver Biopsiebefund erhoben; das Fehlen eindeutiger morphologischer Befunde schließt sie jedoch nicht aus. Es gibt keinen Labortest, der eine Vaskulitis definitiv nachweist oder ausschließt, so ist auch bei ausschließlich unauffälligen Ergebnissen von durchaus umfangreichen Blutuntersuchungen das Vorliegen einer NSVN möglich. Systemische Vaskulitiden treten mit einer Inzidenz von mindestens 4/100000 jährlich auf und haben unbehandelt eine schlechte Prognose, die durch immunsuppressive Therapie entscheidend verbessert wird. Bei der NSVN ist die Prognose deutlich besser, eine längerfristige immunsuppressive Therapie ist auch hier häufig erforderlich.

Summary

Vasculitic neuropathies are immune mediated diseases of the peripheral nervous system, in which inflammation of the blood vessels causes damage to the nerves. We distinguish neuropathies associated with primary and secondary systemic vasculitis, with rheumatic diseases, with malignant disorders, drug-induced vasculitis and the non-systemic vasculitic neuropathies (NSVN). The typical clinical picture consists in an asymmetric or multifocal, painful sensorimotor neuropathy with an acute, subacute or chronic course and acute relapses. Neurophysiology reveals an active, asymmetric, axonal sensorimotor neuropathy. The disorders usually respond to immunosuppressive treatment. A diagnosis of definite vasculitis can be made with evidence of vasculitis in a biopsy specimen. The absence of positive morphological evidence, however, does not exclude the diagnosis. There is no single laboratory test that can prove or exclude vasculitis, in NSVN even an elaborate panel of blood tests can show normal findings. Systemic vasculitis has an incidence of 4/100 000 per year and, untreated, has a poor prognosis, which is greatly improved by the use of immunosuppressive treatment. The prognosis of NSVN is generally better, although many patients need long term immunosuppression. Current treatment recommendations for vasculitic neuropathies are presented.

Schlüsselwörter

Vaskulitische Neuropathie - Klinik - Diagnostik - Therapie

Keywords

Vasculitic neuropathy - diagnosis - therapy

Full Text

References

Literatur
1 Moore PM. Vasculitic neuropathies. J Neurol Neurosurg Psychiatry 2000; 68 (03) 271-4.
2 Said G, Lacroix-Ciaudo C, Fujimura H, Blas C, Faux N. The peripheral neuropathy of necrotizing arteritis: a clinicopathological study. Ann Neurol 1988; 23 (05) 461-5.
3 Kissel JT, Slivka AP, Warmolts JR, Mendell JR. The clinical spectrum of necrotizing angiopathy of the peripheral nervous system. Ann Neurol 1985; 18: 251-7.
4 Kissel J. Vasculitic neuropathies. In: Gilman S. (ed). Med-Link Neurology. San Diego: MedLink Corporation; 2001.
5 Collins MP, Mendell JR, Periquet MI, Sahenk Z, Amato AA, Gronseth GS. et al. Superficial peroneal nerve/peroneus brevis muscle biopsy in vasculitic neuropathy. Neurology 2000; 55 (05) 636-43.
6 Griffith ME, Gaskin G, Pusey CD. Classification, pathogenesis, and treatment of systemic vasculitis. Ren Fail 1996; 18 (05) 785-802.
7 Fauci AS, Haynes B, Katz P. The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations. Ann Intern Med 1978; 89 (5 Pt 1): 660-76.
8 McCluskey RT, Fienberg R. Vasculitis in primary vasculitides, granulomatoses, and connective tissue diseases. Hum Pathol 1983; 14 (04) 305-15.
9 Lie JT. Systemic and isolated vasculitis. A rational approach to classification and pathologic diagnosis. Pathol Annu 1989; 24 (Pt 1): 25-114.
10 Churg J, Churg A. Idiopathic and secondary vasculitis: a review. Mod Pathol 1989; 02 (02) 144-60.
11 Waldherr R, Eberlein-Gonska M, Noronha IL. Histopathological differentiation of systemic necrotizing vasculitides. APMIS Suppl 1990; 19: 17-8.
12 Hunder GG, Arend WP, Bloch DA, Calabrese LH, Fauci AS, Fries JF. et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Introduction. Arthritis Rheum 1990; 33 (08) 1065-7.
13 Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL. et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37 (02) 187-92.
14 Hunder GG, Arend WP, Bloch DA, Calabrese LH, Fauci AS, Fries JF. et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Arthritis Rheum 1990; 33 (08) 1065-7.
15 Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH. et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33 (08) 1122-8.
16 Bruce IN, Bell AL. A comparison of two nomenclature systems for primary systemic vasculitis. Br J Rheumatol 1997; 36 (04) 453-8.
17 Dyck PJ, Benstead TJ, Conn DL, Stevens LC, Windebank AJ, Low PA. Nonsystemic vasculitic neuropathy. Brain 1987; 110: 843-54.
18 Diaz-Perez JL, Winkelmann RK. Cutaneous periarteritis nodosa. Arch Dermatol 1974; 110 (03) 407-14.
19 Goldberg JW, Lee ML, Sajjad SM. Giant cell arteritis of the skin simulating erythema nodosum. Ann Rheum Dis 1987; 46 (09) 706-8.
20 Kissel JT, Mendell JR. Vasculitic neuropathy. Neurol Clin 1992; 10 (03) 761-81.
21 Harati Y, Niakan E. The clinical spectrum of inflammatory – angiopathic neuropathy. J Neurol Neurosurg Psychiat 1986; 49: 1313-6.
22 Schröder JM. Pathologie peripherer Nerven. Berlin: Springer-Verlag; 1999.
23 Davies L, Spies JM, Pollard JD, McLeod JG. Vasculitis confined to peripheral nerves. Brain 1996; 119 (Pt 5): 1441-8.
24 Olney RK. AAEM minimonograph #38: Neuropathies in connective tissue disease. Muscle Nerve 1992; 15 (05) 531-42.
25 Olney RK. Neuropathies associated with connective tissue disease. Semin Neurol 1998; 18 (01) 63-72.
26 Rosenbaum R. Neuromuscular complications of connective tissue diseases. Muscle Nerve 2001; 24 (02) 154-69.
27 Said G. Vasculitic neuropathy. Baillieres Clin Neurol 1995; 04 (03) 489-503.
28 Said G. Necrotizing peripheral nerve vasculitis. Neurol Clin 1997; 15 (04) 835-48.
29 Hunder GG. Vasculitis: clinical and laboratory features. In: Schumacher HR, Klippel JH, Koopman WJ. (eds). Primer on the Theumatic Diseases. 10 ed. Atlanta: Arthritis Foundation; 1993: 14-47.
30 de Groot K, Schmidt DK, Arlt AC, Gross WL, Reinhold-Keller E. Standardized neurologic evaluations of 128 patients with Wegener granulomatosis. Arch Neurol 2001; 58 (08) 1 215-21.
31 Nadeau SE, Watson RT. Neurologic manifestations of systemic vasculitis and collagen vascular syndromes. In: Baker AB, Joynt RA. (eds). Clinical Neurology. Philadelphia: Harper & Row; 1983: 29-34.
32 Cavaletti G, Petruccioli MG, Crespi V, Pioltelli P, Marmiroli P, Tredici G. A clinico-pathological and follow up study of 10 cases of essential type II cryoglobulinaemic neuropathy. J Neurol Neurosurg Psychiatry 1990; 53 (10) 886-9.
33 Gemignani F, Pavesi G, Fiocchi A, Manganelli P, Ferraccioli G, Marbini A. Peripheral neuropathy in essential mixed cryoglobulinaemia. J Neurol Neurosurg Psychiatry 1992; 55 (02) 116-20.
34 Chalk CH, Homburger HA, Dyck PJ. Anti-neutrophil cytoplasmic antibodies in vasculitis peripheral neuropathy. Neurology 1993; 43 (09) 1826-7.
35 Cruickshank B. The arteritis of rheumatoid arthritis. Ann Rheum Dis 1954; 13: 136.
36 Omdal R, Mellgren SI, Husby G, Salvesen R, Henriksen OA, Torbergsen T. A controlled study of peripheral neuropathy in systemic lupus erythematosus. Acta Neurol Scand 1993; 88 (01) 41-6.
37 Enevoldson TP, Wiles CM. Severe vasculitic neuropathy in systemic lupus erythematosus and response to cyclophosphamide. J Neurol Neurosurg Psychiatry 1991; 54 (05) 468-9.
38 Mauch E, Volk C, Kratzsch G, Krapf H, Kornhuber HH, Laufen H. et al. Neurological and neuropsychiatric dysfunction in primary Sjogren’s syndrome. Acta Neurol Scand 1994; 89 (01) 31-5.
39 Nitta Y, Sobue G. Progressive systemic sclerosis associated with multiple mononeuropathy. Dermatology 1996; 193 (01) 22-6.
40 Hietaharju A, Jaaskelainen S, Kalimo H, Hietarinta M. Peripheral neuromuscular manifestations in systemic sclerosis (scleroderma). Muscle Nerve 1993; 16 (11) 1204-12.
41 Fuller GN, Jacobs JM, Guiloff RJ. Nature and incidence of peripheral nerve syndromes in HIV infection. J Neurol Neurosurg Psychiatry 1993; 56 (04) 372-81.
42 Schäfers M, Neukirchen S, Toyka KV, Sommer C. Borrelia neuropathy: histologic and immunohistochemical characterization. J Peripher Nerv Syst 2001; 06: 175.
43 Said G, Lacroix C, Plante-Bordeneuve V, Le Page L, Pico F, Presles O. et al. Nerve granulomas and vasculitis in sarcoid peripheral neuropathy: a clinicopathological study of 11 patients. Brain 2002; 125 (Pt 2): 264-75.
44 Sanchez J, Coll JCanti, Ariza A, Olive A, Cuixart A, Teixido J. Neuropathy due to necrotizing vasculitis: a study of the anatomo clinical and neurophysiological characteristics, and those of the clinical course, of the disorder in 27 patients. Rev Neurol 2001; 33 (11) 1033-6.
45 Charles LA, Caldas ML, Falk RJ, Terrell RS, Jennette JC. Antibodies against granule proteins activate neutrophils in vitro. J Leukoc Biol 1991; 50 (06) 539-46.
46 Ewert BH, Jennette JC, Falk RJ. The pathogenic role of antineutrophil cytoplasmic autoantibodies. Am J Kidney Dis 1991; 18 (02) 188-95.
47 Dolman KM, Gans RO, Vervaat TJ, Zevenbergen G, Maingay D, Nikkels RE. et al. Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy. Lancet 1993; 342 (8872): 651-2.
48 Vogt BA, Kim Y, Jennette JC, Falk RJ, Burke BA, Sinaiko A. Antineutrophil cytoplasmic autoantibody-positive crescentic glomerulonephritis as a complication of treatment with propylthiouracil in children. J Pediatr 1994; 124 (06) 986-8.
49 Lamprecht P, Moosig F, Gause A, Herlyn K, Csernok E, Hansen H. et al. Immunological and clinical follow up of hepatitis C virus associated cryoglobulinaemic vasculitis. Ann Rheum Dis 2001; 60 (04) 385-90.
50 Dahlberg PJ, Lockhart JM, Overholt EL. Diagnostic studies for systemic necrotizing vasculitis. Sensitivity, specificity, and predictive value in patients with multisystem disease. Arch Intern Med 1989; 149 (01) 161-5.
51 Siva A. Vasculitis of the nervous system. J Neurol 2001; 248 (06) 451-68.
52 Gilden DH, Kleinschmidt-DeMasters BK, LaGuardia JJ, Mahalingam R, Cohrs RJ. Neurologic complications of the reactivation of varicella-zoster virus. N Engl J Med 2000; 342 (09) 635-45.
53 Heckmann JG, Kayser C, Heuss D, Manger B, Blum HE, Neundörfer B. Neurological manifestations of chronic hepatitis C. J Neurol 1999; 246: 486-91.
54 Ferri C, Marzo E, Longombardo G, Lombardini F, La Civita L, Vanacore R. et al. Interferonalpha in mixed cryoglobulinemia patients: a randomized, crossover-controlled trial. Blood 1993; 81 (05) 1132-6.
55 Hawke SH, Davies L, Pamphlett R, Guo YP, Pollard JD, McLeod JG. Vasculitic neuropathy. A clinical and pathological study. Brain 1991; 114 (Pt 5): 2175-90.
56 Antoine JC. Immunological mechanisms in paraneoplastic peripheral neuropathy. Clin Rev Allergy Immunol 2000; 19 (01) 61-72.
57 Guillevin L, Durand-Gasselin B, Cevallos R, Gayraud M, Lhote F, Callard P. et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum 1999; 42 (03) 421-30.
58 Bouche P, Léger JM, Travers MA, Cathala HP, Castaigne P. Peripheral neuropathy in systemic vasculitis: clinical and electrophysiologic study of 22 patients. Neurology 1986; 36: 1598-602.
59 Cornblath DR, Sumner AJ. Conduction block in neuropathies with necrotizing vasculitis. Muscle Nerve (letter) 1991; 14: 185.
60 Low PA. Laboratory evaluation of autonomic function. Philadelphia: Lippincott-Raven Publishers; 1997.
61 Leuschner T, Neundörfer B, Heuss D. Reliability of morphological methods in vasculitic neuropathy. J Peripher Nerv Syst 2001; 06: 156.
62 Said G. Value of nerve biopsy?. Lancet 2001; 357: 1220-1.
63 Schröder JM. Recommendations for the examination of peripheral nerve biopsies. Virchows Arch 1998; 432: 199-205.
64 Wees SJ, Sunwoo IN, Oh SJ. Sural nerve biopsy in systemic necrotizing vasculitis. Am J Med 1981; 71 (04) 525-32.
65 Dyck PJB, Norell BS, Dyck PJ. Microvasculitis and ischemia in diabetic lumbosacral radiculoplexus neuropathy. Neurology 1999; 53: 2113-21.
66 Kelkar P, Masood M, Parry GJ. Distinctive pathologic findings in proximal diabetic neuropathy (diabetic amyotrophy). Neurology 2000; 55 (01) 83-8.
67 King R. Atlas of peripheral nerve pathology. London: Arnold; 1999.
68 Heuss D, Hecht M. Ätiologische Abklärung einer Polyneuropathie. Klin Neurophysiol 2001; 32: 1-9.
69 Said G, Goulon-Goeau C, Lacroix C, Moulonguet A. Nerve biopsy findings in different patterns of proximal diabetic neuropathy. Ann Neurol 1994; 35: 559-69.
70 Said G, Elgrably F, Lacroix C. Painful proximal diabetic neuropathy: inflammatory nerve lesions and spontaneous favorable outcome. Ann Neurol 1997; 41: 762-70.
71 Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983; 98 (01) 76-85.
72 Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD. et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116 (06) 488-98.
73 Adu D, Pall A, Luqmani RA, Richards NT, Howie AJ, Emery P. et al. Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. Qjm 1997; 90 (06) 401-9.
74 Luqmani RA, Jayne D. European Vasculitis Study Group. A multi-centre randomised controlled trial of cyclophosphamide versus azathioprine during remission in ANCA-associated systemic vasculitis (CYCAZAREM). Arthritis Rheum 1999; 42 (Suppl): S225.
75 Stone JH, Tun W, Hellman DB. Treatment of non-life threatening Wegener’s granulomatosis with methotrexate and daily prednisone as the initial therapy of choice. J Rheumatol 1999; 26 (05) 1134-9.
76 Gold R, Toyka KV. (eds). Immuntherapie neurologischer Erkrankungen. Bremen: Uni-Med Verlag AG; 2001.
77 Jayne DR, Esnault VL, Lockwood CM. ANCA anti-idiotype antibodies and the treatment of systemic vasculitis with intravenous immunoglobulin. J Autoimmun 1993; 06 (02) 207-19.
78 Jayne DR, Chapel H, Adu D, Misbah S, O’Donoghue D, Scott D. et al. Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. Qjm 2000; 93 (07) 433-9.
79 Mazzaro C, Lacchin T, Moretti M, Tulissi P, Manazzone O, Colle R. et al. Effects of two different alpha-interferon regimens on clinical and virological findings in mixed cryoglobulinemia. Clin Exp Rheumatol 1995; 13 (Suppl): S181-5.
80 Donada C, Crucitti A, Donadon V, Chemello L, Alberti A. Interferon and ribavirin combination therapy in patients with chronic hepatitis C and mixed cryoglobulinemia. Blood 1998; 92 (08) 2983-4.
81 Barbaro G, Di Lorenzo G, Soldini M, Giancaspro G, Pellicelli A, Grisorio B. et al. Intravenous recombinant interferon-beta versus interferon-alpha-2b and ribavirin in combination for short-term treatment of chronic hepatitis C patients not responding to interferon-alpha. Multicenter Interferon Beta Italian Group Investigators. Scand J Gastroenterol 1999; 34 (09) 928-33.
82 Lamprecht P, Schnabel A, Gross WL. Hepatitis C virus-associated cryoglobulinemic vasculitis. Dtsch Med Wochenschr 1998; 123: 637-42.
83 Misiani R, Bellavita P. Mixed cryoglobulinemia. A guide to drug treatment. Clin Immunother 1996; 05: 115-21.
84 Lockwood CM. Refractory Wegener’s granulomatosis: a model for shorter immunotherapy of autoimmune diseases. J R Coll Physicians Lond 1998; 32 (05) 473-8.
85 Thomas-Golbanov C, Sridharan S. Novel therapies in vasculitis. Expert Opin Investig Drugs 2001; 10 (07) 1279-89.
86 Gause A, Manger B, Kalden JR, Burmester GR. [Therapy of inflammatory rheumatic diseases: from current practice standards to future]. Internist 2001; 42 (02) 223-32 234-6.
87 Metzler C, Low-Friedrich I, Reinhold-Keller E, Schmitt WH, Gross WL. Leflunomide, a new promising agent in maintenance and remission in Wegener’s granulomatosis. Clin Exp Immunol 1998; 112: 56.
88 Nowack R, Birck R, van der Woude FJ. Mycophenolate mofetil for systemic vasculitis and IgA nephropathy. Lancet 1997; 349 (9054) 774.
89 Salama AD. Pathogenesis and treatment of ANCA-associated systemic vasculitis. J R Soc Med 1999; 92 (09) 456-61.
90 Waiser J, Budde K, Braasch E, Neumayer HH. Treatment of acute c-ANCA-positive vasculitis with mycophenolate mofetil. Am J Kidney Dis 1999; 34 (03) e9.
91 Richter C, Wanke L, Steinmetz J, Reinhold-Keller E, Gross WL. Mononeuritis secondary to rheumatoid arthritis responds to etanercept. Rheumatology (Oxford) 2000; 39 (12) 1436-7.
92 Luqmani RA. Is it possible to offer evidencebased treatment for systemic vasculitis?. Scand J Rheumatol 2000; 29 (04) 211-5.
93 Pedersen RS, Bistrup C. Etoposide: more effective and less bone-marrow toxic than standard immunosuppressive therapy in systemic vasculitis?. Nephrol Dial Transplant 1996; 11 (06) 1121-3.
94 Papo T, Le Thi Huong D, Wiederkehr JL, Woehl-Kremer B, Bletry O, Wechsler B. et al. Etoposide in Wegener’s granulomatosis. Rheumatology (Oxford) 1999; 38 (05) 473-5.
95 Tatsis E, Schnabel A, Gross WL. Interferon-alpha treatment of four patients with the Churg-Strauss syndrome. Ann Intern Med 1998; 129 (05) 370-4.
96 Stegmayr BG, Almroth G, Berlin G, Fehrman I, Kurkus J, Norda R. et al. Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis. A Swedish multi-center study. Int J Artif Organs 1999; 22 (02) 81-7.
97 Tyndall A, Fassas A, Passweg J, Ruiz de Elvira C, Attal M, Brooks P. et al. Autologous haematopoietic stem cell transplants for autoimmune disease – feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and the International Stem Cell Project for Autoimmune Disease. Bone Marrow Transplant 1999; 24 (07) 729-34.
98 Sommer C. Symptomatic treatment of painful neuropathies. In: Sommer C. (ed). Pain in peripheral Nerve Disease. Basel: Karger; 2001: 171-95.