eMedicine Specialties > Neurology > Neuromuscular Diseases

Vasculitic Neuropathy

Author: Abbas Mehdi, MD, Director, MDA Center of Central California; Consulting Staff, Department of Neurology, California Neurological Center, Inc
Coauthor(s): Said R Beydoun, MD, Chief, Professor, Department of Neurology, University Hospital, University of Southern California
Contributor Information and Disclosures

Updated: Jan 19, 2010

Introduction

Background

Peripheral neuropathy is common in many vasculitic syndromes and may be the only manifestation of the underlying vasculitic disease.

Vasculitic neuropathy can be a part of systemic vasculitis. It also can present as a nonsystemic vasculitic neuropathy, without any constitutional symptoms or serologic abnormalities. The clinical and pathologic features are those of an ischemic neuropathy caused by a necrotizing vasculitis of small arterioles.

Patients with vasculitic neuropathy may present with either mononeuritis multiplex or asymmetric sensorimotor neuropathy. Symmetric neuropathy is rare. It can present as acute/subacute relapsing, progressive, or relapsing progressive neuropathy.

Asymmetric or multifocal painful sensorimotor neuropathy is the most common presentation.

Asymmetry and length-independent involvement are the hallmarks of mononeuritis multiplex, which is the most common presenting feature of vasculitic neuropathy.

Pathophysiology

Wallerian degeneration of nerves results from ischemic infarction caused by inflammatory occlusion of the blood vessels. Segmental fibrinoid necrosis of a vessel wall and transmural inflammatory cell infiltration are the main pathologic features of vasculitis. Leukocytoclastic reaction traditionally has been considered the primary mechanism of vessel injury in these diseases, although more recent evidence suggests that cellular-mediated mechanisms may be more important in the peripheral nerve.

Immune complexes are formed as a result of antibodies reacting with antigen found within the blood vessel walls. These immune complexes within the circulation activate the complement cascade, generating chemotactic factors responsible for recruitment of polymorphonuclear leukocytes at the local site of deposition of the complex. Degranulation of the polymorphonuclear leukocytes releases proteolytic enzymes, which, along with free radicals, disrupt cell membranes and damage blood vessels. T cell–mediated processes against epineurial and endoneurial vessels likely are also important in the pathogenesis of vasculitic neuropathies.

Necrotizing vasculitis causes neuropathy through ischemic injury to the vessels supplying the nerve. Poor collateral circulation in the nerves makes them susceptible to ischemic injuries. Commonly involved nerves with these features tend to be in the mid upper arm and mid thigh in the "watershed zone."

Vasculitic neuropathy most often presents as mononeuropathy multiplex (ie, in more than 60% of patients), with the peroneal nerve most commonly affected (89% of patients), followed by the sural nerve (84%), tibial nerve (68%), ulnar nerve (42%), and median nerve (26%).

Distal symmetric polyneuropathy is the second most common presentation, seen in less than one third of patients. The nerves most often affected clinically are a diffuse mix of distal more than proximal lower limb nerves, arising either from the lumbosacral plexus or from widespread multifocal nerve involvement (ie, summation of existing patchy lesions).

Cranial nerve involvement also has been reported in systemic vasculitis. Facial nerve neuropathy is observed most commonly, occasionally accompanied by abnormalities in cranial nerve III, VI, or X.

Diagnostic classification of peripheral vasculitic neuropathy (see image below)

• Systemic vasculitic neuropathy (85%)¹⁰
  • Primary systemic vasculitis (60%)¹⁰
    • Medium vessel
      • Polyarteritis nodosa (17.9%)
    • Small vessel
      • Churg-Strauss syndrome (20.8%), most common
      • Wegener granulomatosis (13.2%)
      • Microscopic polyangiitis (7.5%)
      • Essential cryoglobulinemia (1.9%)
      • Henoch-Schönlein purpura (0.9%)
  • Secondary vasculitis (22%)¹⁰
    • Connective tissue disease (15%)
      • Rheumatoid arthritis
      • Systemic lupus erythematosus
    • Infection-related (3%)
      • Hepatitis C – associated cryoglobulinemia
      • Meningitis
      • HIV infection
    • Paraneoplastic (3.5%)
      • Non-Hodgkin lymphoma
      • Small-cell lung carcinoma
      • GI malignancy
  • Unclassified (5%)¹⁰
• Nonsystemic vasculitic neuropathy 10-15%¹⁰

Frequency

United States

Peripheral neuropathy occurs in 60-70% of patients with some systemic vasculitic syndromes. Several reports have noted that approximately 34% of patients with vasculitis have disease restricted to the peripheral nervous system, termed nonsystemic vasculitic neuropathy.^{1,11,2,3,9,12}

Relapse rates observed in systemic vasculitides range from 11-60%¹³ when all manifestations are included (neurologic and systemic). Relapse occurred almost exclusively in patients treated with prednisolone alone. Aggressive early treatment with cyclophosphamide may prevent relapse. 

Peripheral nervous system involvement is an American College of Rheumatology (ACR) diagnostic criterion for polyarteritis nodosa and Churg-Strauss syndrome; it occurs in 50-78% of patients.^14,15,16,17 The reported incidence of vasculitic peripheral neuropathy in primary vasculitides has varied from 20-80%¹⁸ , reflecting the clinicopathological overlap between individual syndromes and associated nosological uncertainty.

Mortality/Morbidity

No controlled studies document mortality rate, but death generally is secondary to systemic complications of the vasculitis. Chance of recovery is better in nonsystemic vasculitic neuropathy, with good recovery for most patients.

Mathew et al found that 1-year survival was 90.3%, with death occurring predominantly in older patients with severe multisystem disease.¹⁰

Studies have shown that morbidity and mortality rates tend to be very high if the condition is untreated and systemic or if the condition is misdiagnosed.

• In one study, final disability in those who survived more than 24 month was no sign or symptoms in 17%, mild-to-moderate disability in 65%, moderately severe disability in 13%, and severe disability in 4%. Chronic pain was persistent in more than 60% of patient in this study.
• One cohort study showed a 5-year survival rate of 87%.

Race

The racial distribution of vasculitic neuropathy is unknown.

Sex

Both genders are represented equally.

Age

Mean age at presentation is 62 years.

Clinical

History

Vasculitic neuropathy can present as acute/subacute relapsing, progressive, or relapsing progressive neuropathy.

• Asymmetric or multifocal painful sensorimotor neuropathy is the most common presentation.
• Duration of neuropathy symptoms before biopsy or diagnosis ranges from 3 weeks to 5 years (mean 8 ± 11 mo).
• Constitutional symptoms, including weight loss, anorexia, fatigue, arthralgias, myalgias, and fevers, occur in about two thirds of patients.
• Neuropathies are painful in more than 80% of patients.
• About 75% of patients experience at least one acute attack, but about 25% have an indolent slowly progressive course from onset. In about half of all patients, the neuropathy follows an acute relapsing course.
• Typically, the initial symptom of vasculitic neuropathy is acute pain poorly localized in the affected area or limb. Deep aching and burning pain or tingling in the affected nerve distribution appears a few days later. This is followed by weakness in the distribution of the involved nerve.

Physical

A thorough neurologic examination can assist in localizing the involved nerve(s). In general, the patient presents with asymmetric neurological symptoms involving the peripheral nerve(s), with pain and dysesthesias as initial symptoms followed by weakness.

• Weakness in vasculitic neuropathy is mostly focal and presents acutely. On examination, about three quarters of patients have an asymmetric polyneuropathy, either as a multiple mononeuropathy or, less commonly, as an asymmetric polyneuropathy (ie, overlapping multiple mononeuropathies).
  • Legs are more commonly involved than arms. Distal involvement is more frequent than proximal involvement.
  • Cranial nerve involvement occurs in 8% of patients, typically involving cranial nerve VII. Asymmetrical lumbosacral plexopathy occurs in 8%. In a small percentage of patients, pure dermatomal sensory loss can also be involved.
  • A proximal symmetric polyneuropathy is the least frequent presentation.
  • Pure motor neuropathy is almost unheard of.
  • Vasculitic neuropathy is unlikely in patients with no asymmetries, pure motor involvement, no pain, and entirely proximal findings.
  • Peroneal nerve: Patient has weakness of foot dorsiflexion and usually presents with foot drop or slapping gait.
  • Tibial nerve: Patient has weakness of foot plantar flexion and inversion. Patient may present with unstable gait.
  • Ulnar nerve: Patient is unable to spread fingers and flex the distal phalanx of the fourth and fifth digits. Weakness of other ulnar-innervated intrinsic hand muscles also is noted.
  • Median nerve: Patient displays weakness of finger and wrist as well as weakness of other median-innervated intrinsic hand muscles.
  • Radial nerve: Wrist drop is the most striking clinical presentation of radial nerve palsy. Elbow extension weakness also may be present.
• Sensory findings are frequent and usually are the initial presentation of vasculitic neuropathy. Whereas most patients exhibit mixed sensorimotor findings on examination, about 10% have a pure or predominant sensory neuropathy. Both large-fiber and small-fiber sensory modalities are affected in about 90%, with predominant large-fiber loss in the rest.
  • Burning dysesthetic pain over the distribution of involved nerve is associated with altered or decreased sensation. Large sensory fiber involvement is seen frequently, presenting as decreased vibration sensation and proprioception in affected limbs.
  • Patients with a previous misdiagnosis or those presenting after the acute inflammatory phase has subsided can present with neuropathic pain. This can be mild tingling or numbness to severe dull or burning pain with or without sensory loss.
• Reflexes: Hyporeflexia or areflexia, which can be asymmetric, is observed.
• Findings inconsistent with a diagnosis of vasculitic neuropathy include the following:
  • Acute onset of symmetric motor weakness
  • Sharp sensory level
  • Bowel and bladder dysfunction
  • Spontaneous remission

Causes

Causes of vasculitic neuropathy can be classified on the basis of size of the vessels or primary versus secondary vasculitis. A simple classification is based on systemic vasculitis, causing vasculitic neuropathy with other constitutional symptoms or serologic abnormalities, versus nonsystemic vasculitis, which presents as neuropathy only.

• Systemic vasculitis
  • Systemic necrotizing vasculitis: These vasculitides classically involve small and medium-sized arteries affecting multiple organ systems, including the peripheral and central nervous systems. Polyarteritis nodosa is the most common necrotizing vasculitis, with greater than 50% involvement of peripheral nerves. The necrotizing vasculitides include the following:
    • Polyarteritis nodosa
    • Churg-Strauss syndrome
    • Wegener granulomatosis
    • Overlap syndrome
    • Cryoglobulinemia
  • Hypersensitivity vasculitis: These vasculitides classically involve small vessels, including capillaries, arterioles, and venules. They rarely cause irreversible dysfunction of vital organs and have better prognosis than systemic necrotizing vasculitides. Trigger is usually endogenous or exogenous antigen exposure. Cutaneous manifestations dominate the clinical picture but involvement of other organs and the peripheral nervous system also is noted. The hypersensitivity vasculitides include the following:
    • Henoch-Schönlein purpura
    • Serum sickness
    • Infectious vasculitis (eg, HIV, hepatitis B)
    • Drug-induced vasculitis (eg, cocaine, heroin)
    • Neoplasm (eg, chronic lymphocytic leukemia)
    • Cryoglobulinemia
    • Behçet syndrome
  • Giant cell arteritides: These vasculitides classically involve large and medium-sized vessels. Giant cell formation with mononuclear cell infiltrates is seen frequently. Peripheral neuropathy is rare and is seen in less than 15% of patients with temporal arteritis. The giant cell arteritides include the following:
    • Temporal arteritis
    • Takayasu arteritis
  • Connective tissue disease: Patients with connective tissue disease can present with systemic necrotizing vasculitis or hypersensitivity vasculitis. Rheumatoid arteritis (RA) is the connective tissue disease that most often causes vasculitis. Vasculitis develops in 8-25% of patients with RA, usually 10-15 years after onset of RA. Overall, vasculitic neuropathy occurs in 40-50% of patients with systemic vasculitis. Systemic lupus erythematous presents as polyneuropathy in 6-21% of patients. Connective tissue diseases most often associated with vasculitis include the following:
    • Rheumatoid arteritis
    • Systemic lupus erythematous
    • Sjögren syndrome
    • Systemic sclerosis
• Nonsystemic vasculitic neuropathy
  • Localized vasculitis affects either the central nervous system (primary central nervous system angiitis) or the peripheral nervous system. Nonsystemic vasculitic neuropathy involves small and medium-sized arteries.
  • Clinical and histologic presentation is similar to that of neuropathy observed in systemic vasculitis but without any other organ involvement.
  • Nonsystemic vasculitic neuropathy represents one third of all vasculitic neuropathies. Prognosis is better than that of systemic vasculitic neuropathy.
  • Paraneoplastic vasculitic neuropathy: Paraneoplastic vasculitic neuropathy is a rare paraneoplastic syndrome characterized by nonsystemic subacute vasculitic neuropathy. The cancers most commonly associated with paraneoplastic vasculitic neuropathy are small cell lung cancer and lymphomas.

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