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Peripheral Neuropathy in Small Vessel Systemic Vasculitides
Abstract & Commentary
By Michael Rubin, MD, FRCP(C), Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin is on the speaker's bureau for Athena Diagnostics, and does research for Pfizer and Merck.
Synopsis: Axonal neuropathy is common in patients with biopsy-proven small vessel systemic vasculitis (SVSV), and responds to immunosuppressive therapy.
Source: Cattaneo L, Chierici E, Pavone L, et al. Peripheral neuropathy in Wegener's granulomatosis, Churg-Strauss syndrome and microscopic polyangiitis. J Neurol Neurosurg Psychiatry 2007;78:1119-1123.
Small vessel systemic vasculitis (svsv), characterized by serologic positivity of antineutrophil cytoplasmic antibodies (ANCA) and inflammatory involvement of venules, capillaries, and arterioles, includes Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MP). Any organ system, including the peripheral nervous system (PNS), may be affected. Among the 64 consecutive patients with SVSVs included in this study, periodic neurologic and electrodiagnostic studies were performed to determine differences of PNS involvement with these conditions. Inclusion into this cohort study was based on a definitive diagnosis of vasculitis and clinical and serologic parameters, using American College of Rheumatology criteria for WG and CSS, and Chapel Hill Consensus Conference criteria for MP. Exclusionary criteria comprised other causes for neuropathy, including diabetes mellitus, alcoholism, paraproteinemia, HIV or Lyme disease, hypothyroidism, vitamin deficiency, heavy metal intoxication, cancer, celiac disease, or family history of neuropathy. Periodic follow-up for up to 88 months (mean 37 months) encompassed a neurological examination, electrodiagnostic studies of 3 motor and 4 sensory nerves with needle electromyographic study of distal leg muscles, functional disability score, and Birmingham Vasculitis Activity Score type 1 (BVAS). Statistical analysis was performed using univariate factorial ANOVA and Bonferroni corrected t tests, with statistical significance placed at 0.05
In the 64-patient cohort, 26 were diagnosed with WG, 26 with CSS, and 12 with MP. Neuropathy was seen in 27 patients, more frequently in men (p<0.01) only in the CSS group; was always axonal; and occurred early, within 2 months of systemic disease onset, in 16. Mononeuropathy or mononeuropathy multiplex was present in 16 patients, 4 presented with cranial neuropathy, and distal symmetric polyneuropathy occurred in 11. WG and MP comprised 6 each, and CSS 15. No correlation was seen between disease subset, form of neuropathy, age of onset, or antineutrophil cytoplasmic antibodies (ANCA) positivity or pattern. WG patients tended to develop neuropathy later in the course of their disease compared to CSS and MP; they also were older than non-neuropathy WG patients at the time of disease onset and diagnosis. Steroids and cyclophosphamide resulted in clinical and electrophysiologic improvement, improved functional disability score, and decreased BVAS. Only 1 WG patient experienced a relapse 4 years later.
Leukocytoclastic vasculitis, the histopathologic hallmark of SVSV, is characterized by angiocentric segmental inflammation, endothelial cell swelling, postcapillary venular wall fibrinoid necrosis, and a predominantly neutrophilic cellular infiltrate around and within dermal blood vessel walls showing fragmentation of nuclei (karyorrhexis or leukocytoclasia).1 Most forms of SVSV are idiopathic (45-54%), but bacterial and hepatitis B antigens may be present within small vessel walls, and infections (10-36%), including hepatitis B (5%), influenza vaccination, and medications (10-45%), particularly beta-lactam antibiotics and diuretics but also aspirin, interferons, and sulfonamides, may be causative. Immunoglobulin deposits within the vessel walls are scarce, engendering the designation of these disorders as pauci-immune small-vessel vasculitides. ANCA are closely associated, useful for diagnosis, and at least in some patients, correlate with disease severity and may be helpful in predicting relapse. Proper treatment can induce remission of active disease and prevent irreversible end-organ damage.
1. Iglesias-Gamarra A, Restrepo JF, Matteson EL. Curr Rheumatol Rep 2007;9:304-311.