Diagnosis Sjögren disease–associated neuropathy or ganglionopathy should be suspected in an older woman with sensory neuropathy or neuronopathy, particularly if sicca symptoms are present. There may be telangiectasias over the bridge of the nose, on the lips, and fingers. The evaluation is aided by the Schirmer and Rose Bengal tests, which usually demonstrate a reduction of tearing. Even without this confirmatory test, we have found it advisable to perform a biopsy of the lip (at the epithelial–mucosal juncture) to detect inflammatory changes in the small salivary glands. This is a minor office procedure in most instances. The diagnosis of Sjögren syndrome from the biopsy requires at least 2 collections of 50 or more lymphocytes in a 4-mm2 specimen. Some patients have serologic abnormalities such as antinuclear antibodies (anti-Ro, also termed SS-A, and anti-La, or SS-B) or monoclonal immunoglobulins, particularly of the IgM subclass. The frequency of specific Sjögren-specific antibodies varies between series; they may be useful as screening tests, but the lip biopsy appears to be more sensitive. In our series of 20 cases with minor salivary gland biopsies that demonstrated inflammatory changes diagnostic of the syndrome, only 6 had serologic evidence of the disease and 2 had positive serologic tests but a negative biopsy (Gorson and Ropper, 2003). The sedimentation rate in our patients was often slightly elevated; however, only 5 of our 20 had a value greater than 40 mm/min and many have had normal or only slightly elevated C-reactive protein levels. The main differential diagnostic entity, if the neuropathy appears subacutely, is a paraneoplastic sensory ganglionitis.
Mellgren and also Leger and their colleagues have stressed that a proportion of unexplained polyneuropathies in middle and late life are putatively caused by Sjögren syndrome. The latter authors found typical Sjögren abnormalities in the lip biopsies of 7 of 32 patients with chronic axonal polyneuropathy that could not otherwise be classified. Several other studies have corroborated this finding of inflammatory disruption of the minor salivary glands in obscure neuropathies, particularly in older women and in some men. The diagnosis in our clinics has not been nearly as frequent in this group. Nonetheless, a search for Sjögren disease may be revealing in otherwise obscure sensory neuropathies.
Nerve biopsies have variably revealed necrotizing vasculitis, inflammatory cell infiltrates, and focal nerve fiber destruction. Usually, the CSF protein is normal and there is no cellular reaction. The few times a dorsal root ganglion has been examined in autopsy material; there were infiltrates of mononuclear cells and lymphocytes and destruction of nerve cells.
Treatment Corticosteroids in doses of approximately 60 mg daily of prednisone, cyclophosphamide (100 mg per day), and rituximab (1,000 mg per day, 2 weeks apart) have been used when the neuropathy is severe and are indicated when there is vasculitis involving renal and pulmonary structures. We have initially administered prednisone 60 mg daily, sometimes in tandem with intermittent plasma exchange, but with little evidence of response, before adding a second immunosuppressive agent.
The review of the neurologic manifestations of Sjögren syndrome by Lafitte and by Berkowitz and colleagues are recommended.