Sjögren Syndrome and Neuropathy
Abstract & Commentary
Source: Gorson KC, Ropper AH. Positive salivary gland biopsy, Sjögren syndrome, and neuropathy: Clinical implications. Muscle Nerve. 2003;28:553-560.
What characteristics of a neuropathy make Sjögren syndrome the likely diagnosis? Sjögren syndrome may be defined as a tetrad of dry mouth, dry eyes, positive serology (antinuclear antibody [ANA], rheumatoid factor [RF], or anti-SSA/SSB), and positive minor salivary gland biopsy. Peripheral neuropathy is commonly associated. Between 1995 and 2001, 54 consecutive neuropathy patients were seen for diagnostic evaluation that included lip biopsy. Criteria for lip biopsy comprised 1) idiopathic polyneuropathy; 2) sicca symptoms in a patient with idiopathic polyneuropathy or a second possible cause for neuropathy (lupus, monoclonal gammopathy of undetermined significance, mixed connective tissue disorder, ethanol abuse, hyperlipidemia, celiac disease); or 3) positive Sjögren serology (ANA > 1:160, RF >1:160, or positive anti-SSA/SSB antibodies). Exclusionary criteria included a previous diagnosis of Sjögren syndrome, lymphoma, AIDS, or sarcoidosis. All patients underwent electrodiagnostic studies. Biopsy interpretation was performed by a pathologist, blinded to the clinical information. Positive diagnosis required at least 2 foci of inflammatory cells defined as a cellular infiltrate of 50 or more lymphocytes. Non-neuropathy patients (n = 38) with sicca symptoms or salivary gland tumor or swelling who underwent lip biopsy served as controls. Statistical analysis was provided by Fisher’s exact test, the Kruskal-Wallis analysis of variance, or the Wilcoxon matched sign rank test, with a P value of < 0.05 considered significant.
Twenty patients (37%) were biopsy positive for Sjögren syndrome and had a shorter duration of symptoms (mean, 27 months vs 44 months), with more frequently expressed systemic complaints (rash, joint pain, Raynaud’s syndrome) than biopsy-negative patients. No significant difference was seen with respect to the frequency of sicca symptoms, neuropathy severity or distribution, or motor or sensory scores using the MRC and modified Neurological Impairment Scales. Neuropathy in biopsy-positive patients was most often a painful distal predominantly small-fiber sensory axonal neuropathy (n = 7), but painless sensory or sensorimotor polyneuropathy (n = 6), mononeuritis multiplex or painless sensory ataxic neuropathy (n = 3, each), and combined painful neuropathy with sensory ataxia (n = 1) were also seen. Anti-SSA/SSB positivity, ANA > 1;160, or any serological abnormality of ANA, RF, or SSA/SSB were more common in the biopsy-positive group, but elevated ESR or cerebrospinal fluid protein were not. Only 5 biopsy-positive patients had all components of the diagnostic tetrad. Four of 38 controls (11%) were biopsy positive but significantly less so (P < .007) than neuropathy patients. Lip biopsy should be considered in idiopathic polyneuropathy even in the absence of sicca symptomatology, and positive biopsy would suggest a diagnosis of neuropathy secondary to Sjögren syndrome.
Genetics, hormones, environmental factors, and infectious agents are believed to play a role in the pathogenesis of Sjögren syndrome.1 Human leukocyte antigens (HLA) confer a specific genetic susceptibility in certain populations and appear to affect autoantibody formation as well. Interleukin-10 promoter polymorphisms remain controversial regarding a role in Sjögren etiopathogenesis. Male fetal cells and DNA have been detected in almost 50% of salivary gland biopsies in one Sjögren study, supporting a role for microchimerism in generating autoimmunity. Strong female gender bias in Sjögren syndrome underscores the importance of sex hormones in immunoregulation, but their precise role remains unclear. Viruses, including Epstein-Barr, hepatitis C, HTLV, and other retroviruses, may trigger Sjögren syndrome, but this raises an interesting conundrum as diagnostic criteria for the syndrome specifically exclude sicca symptoms associated with distinct viral infection such as AIDS. Understanding the cause of this condition awaits further investigation. — Michael Rubin, Associate Professor of Clinical Neurology and Neuroscience, New York Presbyterian Hospital- Cornell Campus; Assistant Editor, Neurology Alert.
1. Hansen A, et al. Curr Opin Rheumatol. 2003;15: 563-570.
What characteristics of a neuropathy make Sjögren syndrome the likely diagnosis?
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