Painful small-fiber neuropathy in Sjögren syndrome

Chai, Josiah; Herrmann, DN; Stanton, Michael; Barbano, Richard L.; Logigian, Eric L.

doi:10.1212/01.wnl.0000176034.38198.f9

Cited by 138 publications

(134 citation statements)

References 10 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…We did not, however, eliminate patients with FM who had symptoms of dry mouth or dry eye, as might be seen in patients with Sjögren's syndrome (25), even though this disorder has been associated with small fiber neuropathy (26), because these symptoms are rather common in FM (27). Nevertheless, none of our patients with FM had evidence of anti-Ro or anti-La antibodies, and none had historical evidence of keratoconjunctivitis sicca (25).…”

Section: Discussionmentioning

confidence: 95%

Evidence of Abnormal Epidermal Nerve Fiber Density in Fibromyalgia: Clinical and Immunologic Implications

Xavier

Winter

2014

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective. A subset of patients with fibromyalgia (FM) exhibit a large fiber demyelinating peripheral polyneuropathy akin to that seen in chronic inflammatory demyelinating polyneuropathy (CIDP). It has been suggested that this demyelinating process is likely to be immune mediated. Because it is known that similar large fiber neuropathic lesions may be associated with a cutaneous small fiber neuropathy, we sought to determine the prevalence of small fiber neuropathy, as measured by epidermal nerve fiber density (ENFD), in a series of patients with FM and clinically healthy control subjects.Methods. Forty-one consecutive patients with FM and 47 control subjects underwent a 3-mm punch skin biopsy at the proximal thigh and distal leg near the ankle, for analysis of the ENFD. Patients with FM who had clinical evidence of a disorder known to be associated with small fiber neuropathy were excluded. The patients with FM also underwent pinwheel testing and vibratory testing for hypesthesia and serologic testing for a series of cytokine, circulating immune complex, and complement measurements.Results. All patients with FM had evidence of stocking hypesthesia. The ENFD of patients with FM was lower than that of control subjects at both the calf (mean ؎ SD 5.8 ؎ 2.8 versus 7.4 ؎ 1.9; P ‫؍‬ 0.0002) and thigh (9.3 ؎ 3.2 versus 11.3 ؎ 2.0; P ‫؍‬ 0.0007). There was an inverse correlation between calf ENFD and age at the time of skin biopsy in patients with FM (r ‫؍‬ ؊0.29, P ‫؍‬ 0.03) but not in control subjects; however, analysis of covariance showed that this relationship could not be explained by aging alone. Serologic evaluation showed an inverse correlation between calf ENFD in patients with FM and the interleukin-2 receptor (IL-2R) level (r ‫؍‬ ؊0.28, P ‫؍‬ 0.04). However, an inverse correlation between thigh ENFD and serum IL-2R levels did not reach significance (P ‫؍‬ 0.08). Analysis of thigh-to-calf ENFD ratios suggested that the ENFD decline in FM is affected by both a diffuse and a length-dependent process.Conclusion. The calf and thigh ENFD in patients with FM is significantly diminished compared with that in control subjects. Advancing age alone cannot explain this finding. Calf ENFD was inversely correlated, although weakly, with serum levels of IL-2R. These findings suggest that small fiber neuropathy is likely to contribute to the pain symptoms of FM; that pain in this disorder arises, in part, from a peripheral immunemediated process; and that measurement of ENFD may be a useful clinical tool in FM.

show abstract

Section: Discussionmentioning

confidence: 95%

Evidence of Abnormal Epidermal Nerve Fiber Density in Fibromyalgia: Clinical and Immunologic Implications

Xavier

Winter

2014

Arthritis & Rheumatology

View full text Add to dashboard Cite

show abstract

“…Isolated trigeminal neuropathy was reported in 7 % of a series of 30 patients with Sjögren's syndrome-associated neuropathy [15]; many cases are seronegative survey of 120 patients with SS, 25 % had definite neuropathy, with pure small-fiber attribution most common [15]. Not all patients with SS neuropathy report dry eyes or mouth, and in a series of 20 patients, only 55 % were seropositive for SS-A/SS-B antibodies [16,17]. In seronegative patients with high clinical suspicion, biopsy of minor (lip) salivary glands and/or testing for anti-Ro52/TRIM21 antibodies should be considered [18].…”

Section: Immune-mediated Painful Sensory Ganglionitis/neuronitismentioning

confidence: 99%

“…[10] There is no consensus on how best to treat Sjögren syndrome (SS). Some patients receive no immunotherapy, and among those treated, there is no standard regime [16,17]. Common immunotherapies include hydroxychloroquine low-dose glucocorticoids (<20 mg/day), and high-dose glucocorticoids (>20 mg/day).…”

Section: Immune-mediated Painful Sensory Ganglionitis/neuronitismentioning

confidence: 99%

“…In addition to ganglionitis, Sjögren's also causes painful distal SFPN [81]. In a series of 20 pathologically confirmed SS cases, one-third had pure SFN, one-third had mixed large and small fiber involvement, and one-third were not fully characterizable [17]. My group found SS-A/SS-B antibodies in 9.2 % of the 98 tested patients with objectively verified SFPN [82].…”

Section: Small-fiber Polyneuropathymentioning

confidence: 99%

See 1 more Smart Citation

Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies

Oaklander

2016

Neurotherapeutics

View full text Add to dashboard Cite

The best-known peripheral neuropathies are those affecting the large, myelinated motor and sensory fibers. These have well-established immunological causes and therapies. Far less is known about the somatic and autonomic "small fibers"; the unmyelinated C-fibers, thinly myelinated A-deltas, and postganglionic sympathetics. The small fibers sense pain and itch, innervate internal organs and tissues, and modulate the inflammatory and immune responses. Symptoms of small-fiber neuropathy include chronic pain and itch, sensory impairment, edema, and skin color, temperature, and sweating changes. Small-fiber polyneuropathy (SFPN) also causes cardiovascular, gastrointestinal, and urological symptoms, the neurologic origin of which often remains unrecognized. Routine electrodiagnostic study does not detect SFPN, so skin biopsies immunolabeled to reveal axons are recommended for diagnostic confirmation. Preliminary evidence suggests that dysimmunity causes some cases of small-fiber neuropathy. Several autoimmune diseases, including Sjögren and celiac, are associated with painful small-fiber ganglionopathy and distal axonopathy, and some patients with "idiopathic" SFPN have evidence of organ-specific dysimmunity, including serological markers. Dysimmune SFPN first came into focus in children and teenagers as they lack other risk factors, for example diabetes or toxic exposures. In them, the rudimentary evidence suggests humoral rather than cellular mechanisms and complement consumption. Preliminary evidence supports efficacy of corticosteroids and immunoglobulins in carefully selected children and adult patients. This paper reviews the evidence of immune causality and the limited data regarding immunotherapy for small-fiberpredominant ganglionitis, regional neuropathy (complex regional pain syndrome), and distal SFPN. These demonstrate the need to develop case definitions and outcome metrics to improve diagnosis, enable prospective trials, and dissect the mechanisms of small-fiber neuropathy.

show abstract

“…Epidermal nerve fiber density, as measured by immunostained panaxonal marker protein gene product ("PGP 9.5")(see chapter by Konttinen et al), is reduced in patients with burning feet-in many cases in a non-length dependent distribution (27).…”

Section: Role Of Cell-mediated Immunitymentioning

confidence: 99%