Vasculitic Neuropathy Clinical Presentation

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.

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. ^[23]

• 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.

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 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.