Vasculitic neuropathies

Vasculitic neuropathies, part of systemic vasculitis affecting various organs, present with acute, painful neuropathy and sensory deficits. Treatment targets the underlying condition with immunosuppressants like glucocorticoids or cyclophosphamide and symptom management. Pain is managed with drugs like pregabalin. Rehabilitation and monitoring through neurological exams are crucial for detecting and managing relapses.

Vasculitic Neuropathies Overview

Vasculitic neuropathies are a heterogeneous group of peripheral nerve disorders. Vasculitic neuropathy is usually only one feature of a systemic vasculitis which could involve the skin, lungs, and/ or kidneys. Although many systemic vasculitides can cause neuropathy, those that affect either small- or medium- sized arteries are the most commonly implicated. They include microscopic polyangiitis, polyarteritis nodosa, granulomatosis with polyangiitis, antineutrophil cytoplasmic autoantibodies, eosinophilic granulomatosis with polyangiitis [Churg-Strauss], and mixed cryoglobulinemia. In a minority of patients, the peripheral nervous system is the only site of involvement (nonsystemic vasculitic neuropahy [NSVN]). Vasculitic neuropathy typically presents acutely as a focal, painful neuropathy which worsens over weeks to involve other regions of the body with objective sensory or sensorimotor deficits. (1, 2)

Treatment Goals and Strategies

When vasculitic neuropathy is associated with an identifiable systemic vasculitis, immunosuppressive therapy is directed at the underlying disease with symptom management and non-pharmacological measures. The goals of therapy for NSVN are to minimise ongoing nerve injury and prevent involvement of additional nerves through symptom management and non-pharmacological measures. Because the regeneration of nerves can take months to years and functional recovery may be incomplete, monitoring the response to therapy could be challenging. (3, 4)

Pharmacological Treatment for Vasculitic Neuropathy

For patients with mild vasculitic neuropathy, initial treatment usually with either glucocorticoids (for mild cases; prednisolone 60-80 mg, for severe cases; methylprednisolone 1gm IV for 3 days) or, in NSVN only, alternative to glucocorticoids, steroid sparing agents could be considered, only in NSVN; including azathioprine (50 mg/day) and methotrexate (initiated at 15 mg/week, with increases in dose every week of 5 mg/week up to 25 mg/week). For severe case, or in steroid unresponsive patients; combination therapy might be considered and it consists of glucocorticoid plus oral cyclophosphamide (a regimen recommended by Peripheral Nerve Society guidelines is pulse intravenous cyclophosphamide at 0.6 g/m2 every two weeks for three doses followed by 0.7 g/m2 every three weeks for three to six doses), or rituximab (1g. initially followed 14 days later by another 1g. dose). (5, 6)

Pain Management in Vasculitic Neuropathy

The pain associated with vasculitic neuropathy may be severe. A number of pain modifying agents may be considered, including pregabalin (50mg daily), duloxetine 60 mg, amitriptyline (10- 25 mg once daily). (7)

Non-Pharmacological Measures and Rehabilitation

Non pharmacological measures include rehabilitation programs, physical and occupational therapy which should begin as early as possible. An ankle foot orthosis or wrist splint may be helpful in allowing patients to reestablish useful function in an affected extremity. (8)

Monitoring and Management of Relapses

One of the more challenging aspects is monitoring the response to therapy as new nerve infarctions could happen in distributions of extensive vascular compromise up to several weeks after the institution of therapy. Vasculitic neuropathy is primarily monitored clinically at a monthly interval by serial neurological examinations to monitor for relapses which present clinically as new areas of weakness and numbness. Treatment depends on the severity of relapses. Mild relapses, such as involvement of one new nerve during initial glucocorticoid taper, are treated by increasing the glucocorticoid dose and prolonging the taper. On the other hand, repeated relapses or severe relapses are handled by substitution of the initial treatment. Available agents include cyclophosphamide, rituximab, methotrexate, intravenous immune globulin (IVIG). (9, 10)

References

1- Basu, N., Watts, R., Bajema, I., Baslund, B., Bley, T., Boers, M. et al. EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis. Ann Rheum Dis. 2010; 69: 1744–1750.

2-Agard, C., Mouthon, L., Mahr, A. and Guillevin, L. Microscopic polyangiitis and polyarteritis nodosa: how and when do they start? Arthritis Rheum. 2003; 49: 709–715.

3- Ransohoff R, Beneviste E, Cadavid D. Vascultis and vasculopathies of the nervous system. In: Continiuum neuroimmunology, First Edition, Mancall EL, Cascino TL, Devereaux MW, Lambert AL (Eds), Lippincott Williams & Wilkins, Philadelphia 2001. p.146.

4-Mathew L, Talbot K, Love S, et al. Treatment of vasculitic peripheral neuropathy: A retrospective analysis of outcome. QJM 2007; 100:41.

5-Collins MP, Dyck PJ, Gronseth GS, et al. Peripheral Nerve Society Guideline on the classification, diagnosis, investigation, and immunosuppressive therapy of non-systemic vasculitic neuropathy: Executive summary. J Peripher Nerv Syst 2010; 15:176.

6-Cacoub, P., Delluc, A., Saadoun, D., Landau, D. and Sene, D. Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemic vasculitis: where do we stand? Ann Rheum Dis, 2008; 67: 283–287.

7-Yamamoto, M., Ito, Y., Mitsuma, N., Hattori, N. and Sobue, G. Pain-related differential expression of NGF, GDNF, IL-6, and their receptors in human vasculitic neuropathies. Intern Med. 2003: 42: 1100–1103.

8-Said, G. and Lacroix, C. Primary and secondary vasculitic neuropathy. J Neurol; 2005: 252: 633–641.

9-Guillevin, L., Pagnoux, C., Seror, R., Mahr, A., Mouthon, L. and Le Toumelin, P. The fivefactor score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine (Baltimore); 2011: 90: 19–27.

10-Levy Y, Uziel Y, Zandman G, et al. Response of vasculitic peripheral neuropathy to intravenous immunoglobulin. Ann N Y Acad Sci 2005; 1051:779.