Clinical Features of Biopsy-Proven Large-Arteriole and Microvasculitis in Peripheral Nerves

By Jennifer Langsdorf, MD

Synopsis: In this retrospective, an observational cohort study undertaken to characterize the clinical features of nerve vasculitis based on vessel size, large-arterial vasculitis (≥ 75 microns) in comparison to microvasculitis (< 75 microns) was demonstrated. Large arteriole vasculitis usually was a distal symmetrical polyneuropathy and associated with a systemic vasculitis illness. Microvasculitis most often presented with radiculopathy and/or plexopathy and was not associated with systemic illness.

Source: Soontrapa P, Pinto MV, Shouman K, et al. Distinctive clinical features in biopsy-proven nerve large-arteriole vasculitis and microvasculitis. Brain. 2025;148(3):1031-1042.

Vasculitic neuropathy occurs when inflammation causes blood vessel wall damage and peripheral nerve ischemia. This condition can cause significant morbidity as the result of pain and weakness. Early diagnosis is essential for positive outcomes. The clinical presentation and associated features may vary by the vessel size involved. Vasculitic neuropathy can be associated with primary or secondary systemic vasculitis but also can be isolated to peripheral nerves.

This retrospective review was performed to compare data for nerve large-arteriole vasculitis and nerve microvasculitis in nerve biopsy-confirmed cases seen at the Mayo Clinic between Jan. 1, 2001, and Dec. 31, 2020. Cases were selected from neuropathological reports. Inclusion criteria included only nerve biopsies interpreted as either diagnostic or highly suggestive of nerve large-arteriole vasculitis or nerve microvasculitis. Cases with only perivascular inflammatory collections but without vessel wall destruction or with vessel wall damage without associated inflammation were excluded to improve specificity.

The sural nerve was the most commonly biopsied (80%), followed by the superficial peroneal nerve (13%). After dividing the patients into two groups based on pathological findings, clinical data including demographics, clinical presentation, associated conditions, systemic involvement, laboratory findings, electrodiagnostic studies, and clinical course were collected. Patients with insufficient clinical information were excluded.

The study identified 278 cases: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Clinical manifestations evaluated included tempo of presentation (acute, subacute, chronic), age at symptom onset, time to diagnosis, time to plateau, neuropathic pattern (multiple mononeuropathies, distal asymmetric polyneuropathy, radiculoplexus neuropathy, distal symmetric polyneuropathy, sensory polyneuropathy, and polyradiculoneuropathy), involved nerve segments (proximal upper, distal upper, proximal lower, distal lower), autonomic involvement, constitutional symptoms, and associated organ involvement, among others.

Non-systemic vasculitis was defined as vasculitic neuropathy with no or mild systemic clinical symptoms or serologic abnormalities. Systemic vasculitis had systemic clinical symptoms or serologic abnormalities and could involve multiple organs and systems or be limited to one organ.

Systemic autoimmune diseases were more commonly found associated with nerve large-arteriole vasculitis (70.4% vs. 22.9%). Nerve large-arteriole vasculitis was especially associated with rheumatoid arthritis, polyarteritis nodosa, eosinophilic granulomatosis with polyangitis, and microscopic polyangitis. Diabetes was more commonly associated with nerve microvasculitis. The vasculitis in Sjӧgren’s syndrome occurred in both vasculitis types without a statistically significant difference.

The mean age of symptom onset was similar in both groups and was late-50s to 60 years. No significant sex differences were found between the two pathological groups. The tempo of presentation was statistically different between the two groups. Nerve large-arteriole vasculitis presented with a more acute onset of less than one month (50.4% vs. 26.8%) than nerve microvasculitis. Nerve microvasculitis also has a longer time to diagnosis (10.5 vs. 4.3 months) and a longer time to plateau.

Analysis of the neuropathic pattern of presentation showed that the classically described pattern of multiple mononeuropathies was not frequently seen in either pathological group (18.4% of nerve large-arteriole vasculitis and 13.7% of nerve microvasculitis). Distal asymmetric polyneuropathy was the most common presentation of nerve large-arteriole vasculitis (48.0%). In contrast, nerve microvasculitis presented most commonly as radiculoplexus neuropathy (32.0%).

Sensorimotor symptoms and pain were seen in the majority of both pathological groups. Pain was seen in 87.2% of nerve large-arteriole vasculitis and in 85.6% of nerve microvasculitis. Autonomic symptoms were more common in nerve microvasculitis patients (24.2% vs. 7.2%).

One highly significant difference between nerve large-arteriole vasculitis and nerve microvasculitis is that there is more evidence of systemic vasculitis in nerve large-arteriole vasculitis. Primary systemic vasculitis was found in 46.4% of nerve large-arteriole vasculitis and secondary systemic vasculitis was found in 30.4% of nerve large-arteriole vasculitis. In contrast, 70.6% of nerve microvasculitis cases had non-systemic involvement. The clinical pattern of radiculoplexus neuropathy was associated with nerve microvasculitis.

Systemic symptoms and laboratory abnormalities both were associated with nerve large-arteriole vasculitis, including higher non-nerve organ involvement, constitutional symptoms, and elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antineutrophil cytoplasmic antibodies (ANCA), and antinuclear antibodies (ANA).

Commentary

The aim of this study was to determine if there were differences in clinical features, neuropathic patterns, associated autoimmune diseases, lab abnormalities, and systemic involvement between nerve large-arteriole vasculitis and nerve microvasculitis. Nerve large-arteriole vasculitis and nerve microvasculitis were found to have overlapping but distinct clinical features.

Nerve large-arteriole vasculitis more commonly presents with acute onset, distal asymmetric polyneuropathy associated with other autoimmune diseases, and systemic involvement. Nerve microvasculitis usually presents as a subacute or chronic non-systemic vasculitis with more autonomic involvement and more often as a radiculoplexus neuropathy or polyradiculopathy.

Jennifer Langsdorf, MD, is Assistant Professor of Neurology, Peripheral Neuropathy Center, Weill Cornell Medical College.