By Norman Latov, MD, PhD
Professor of Neurology and Neuroscience, Department of Neurology and the Brain and Mind Research Institute, Weill Cornell Medical College
Dr. Latov reports he is a consultant to Grifols and Baxter Pharmaceugicals; receives grant/research support from Grifols; owns stock in Therapath LLC; and participates in clinical trials for CSL Behring.
Synopsis: Nerve biopsy is a safe and highly sensitive definitive diagnostic test for systemic vasculitis, even without symptoms of peripheral neuropathy, when electrodiagnostic tests indicate an axonal neuropathy.
Source: Kurt S, et al. Asymptomatic vasculitic neuropathy. Muscle Nerve 2015;52:34-38.
Kurt and colleagues describe the clinical and electrodiagnostic features, as well as neuropathological findings, in 21 patients with asymptomatic vasculitic neuropathy. These constitute 7.8% of 270 cases of biopsy-proven vasculitic neuropathy seen in their institution over a 42-year period. The presence of vasculitis was suspected by the referring physicians based on the systemic symptoms and laboratory abnormalities, and although the patients did not have symptoms or findings on the neurological examinations that were indicative of neuropathy, screening electrodiagnostic tests showed involvement of the peripheral nerves, with features of axonal neuropathy. Subsequent nerve biopsy revealed the presence of vasculitic neuropathy in all 21 patients.
The authors report that peripheral nerve involvement is common, but can be subclinical in patients with vasculitis; electrodiagnostic studies can detect the presence of neuropathy in otherwise asymptomatic patients. The diagnosis of vasculitis can be definitively made on nerve and muscle biopsy.
The typical presentation of vasculitic neuropathy is an axonal sensorimotor neuropathy, in a multifocal distribution, with multiple organ involvement, and is associated with collagen vascular disease, hepatitis C infection, or elevated inflammatory serological markers such as erythrocyte sedimentation rate, anti-neutrophil cytoplasmic antibodies, eosinophilia, or cryoglobulinemia. However, patients with vasculitic neuropathy can also present with a distal symmetric polyneuropathy, without systemic involvement, and with normal serological studies. Other investigators have also reported vasculitic neuropathy presenting as sensory ataxic neuropathy,1 demyelinating polyneuropathy,2 or small fiber neuropathy with normal electrodiagnostic studies.3
Nerve and muscle biopsy is usually considered in the evaluation of neuropathy if the neuropathy is progressive, and no cause can be identified by other tests.4 Aside from vasculitis, nerve biopsy may reveal the presence of other potentially treatable conditions such as sarcoid, amyloidosis, or sensory chronic inflammatory demyelinating polyneuropathy, that would have otherwise been missed.5,6,7,8 Although it is an invasive procedure, nerve biopsy is relatively safe, with few adverse effects if performed by an experienced physician, as reflected in the authors’ experience. In some cases, the vasculitis can be diagnosed by skin biopsy, obviating the need for the more invasive procedure.9
There is debate regarding whether patients with progressive neuropathies of otherwise unknown etiology warrant a trial of therapy with corticosteroids prior to biopsy, or if the biopsy is unrevealing. Given that vasculitis is a multifocal inflammatory disease, the pathology can be missed in a blind biopsy specimen, especially if a sufficiently long segment of nerve is not available or an insufficient number of sections are examined. However, treatment with corticosteroids can mask the pathological changes, so that a later biopsy may be uninformative if more aggressive treatment is being considered. It is hoped that advances in peripheral nerve imaging will make it possible to identify inflammatory lesions, to help distinguish between inflammatory and non-inflammatory neuropathies, and help decide on the site of biopsy.
- Harada K, et al. Sensory ataxic dominant neuropathy associated with polyarteritis nodosa. Intern Med 2000;39:847-851.
- Mohamed A, et al. Conduction block in vasculitic neuropathy. Muscle Nerve 1998;21:1084-1088.
- Zafrir B, et al. Small fiber neuropathy due to isolated vasculitis of the peripheral nervous system. Isr Med Assoc J 2004;6:183-184.
- Vrancken AF, et al. Progressive idiopathic axonal neuropathy — a comparative clinical and histopathological study with vasculitic neuropathy. J Neurol 2004;251:269-278.
- Chin RL, et al. Sensory CIDP presenting as cryptogenic sensory polyneuropathy. J Peripher Nerv Syst 2004;9:132-137.
- Singhal NS, et al. Sarcoid polyneuropathy masquerading as chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 2015; doi:10.1002/mus.24652.
- Vital A, et al. Sarcoid neuropathy: Clinico-pathological study of 4 new cases and review of the literature. Clin Neuropathol 2008;27:96-105.
- Vital A, Vital C. Clinical neuropathology practice guide 3-2014: Combined nerve and muscle biopsy in the diagnostic workup of neuropathy — the Bordeaux experience. Clin Neuropathol 2014;33:172-178.
- Yamanaka Y, et al. Leucocytoclastic vasculitic neuropathy diagnosed by biopsy of normal appearing skin. J Neurol Neurosurg Psychiatry 2006;77:706-707.