Evidence of abnormal epidermal nerve fiber density in fibromyalgia: clinical and immunologic implications.

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 immune-mediated process; and that measurement of ENFD may be a useful clinical tool in FM.

Atypical presentation of Behçet's disease with central nervous system involvement successfully treated with infliximab.

Central nervous system involvement is a rare and serious complication of Behçet's disease (BD). Herein, we describe a patient with an atypical central lesion, who experienced progressive hypesthesia of the right arm and sensory loss of the trigeminal nerve together with intense headache. A repeated biopsy was necessary to conclusively establish the diagnosis of BD. Therapy with infusions of infliximab led to a remarkable full remission. TNFα-blocking therapy was successfully replaced by azathioprine. The present well-illustrated case demonstrates the difficulty of establishing the diagnosis of BD with central nervous system involvement, the dramatic benefit of short given TNF-α-blocking agent, and the long-term remission with azathioprin.

Lateralization of T-lymphocyte responses in patients with stroke. Effect of sympathetic dysfunction?

BACKGROUND AND PURPOSE: A number of clinical observations indicate that stroke affects the course of immune-mediated diseases by lateralization of the disease manifestations, such as arthritis. The purpose of this study was to assess the impact of early stroke on lateralization of immune responsiveness. METHODS: The delayed-type hypersensitivity (DTH) reaction to purified protein derivative was used as an in vivo measure of antigen-specific T-lymphocyte reactivity. Assessment of axon reflex vasodilation was simultaneously used to test for cutaneous sympathetic activity. RESULTS: There were no significant differences with regard to lateralization of DTH reactivity when all stroke patients were tested. However, patients with minor stroke displayed a significant (P < .001) decrease of DTH reaction on the paretic side compared with the contralateral side. In contrast, patients with major stroke showed a significant increase (P = .022) of DTH reaction on the paretic side. Patients with left hemiparesis had a significantly greater (P = .045) DTH response on the affected side than patients with a right hemiparesis. In addition, only the patients with motor deficit but not with sensory deficit or aphasia displayed side differences in DTH responses. When electrically evoked axon reflexes were studied in relation to DTH reactions, a significant correlation (r = .64; P < .001) was found between side asymmetries of DTH responses and side asymmetries of axon reflexes in an innervated skin area. No similar relation was present in skin areas where cutaneous sympathetic activity had been blocked by regional anesthesia. CONCLUSIONS: Early stroke lateralizes T-cell-mediated cutaneous inflammation. This effect depends on (1) the localization of the brain lesion, (2) the clinical course of the disease, and (3) the presence of motor deficit and may be mediated by (4) alteration of the cutaneous sympathetic nerve traffic.

Sensory neuropathy associated with monoclonal immunoglobulin M to GD1b ganglioside.

A 67-year-old woman with a sensory polyneuropathy was shown to have a serum monoclonal immunoglobulin M lambda antibody with a titer of 1:10,000 toward GD1b ganglioside. The immunoglobulin M also reacted with some other gangliosides containing disialosyl groups such as GD2, GD3, and GQ1b, but it did not react with GM1, LM1, or GD1a. The principal reactive ganglioside in human cauda equina was GD1b.

Peripheral neuropathy and benign IgG paraproteinaemia.

Three patients with peripheral neuropathy and an associated benign IgG paraproteinaemia are described. No direct immunological evidence for an aetiological role of the paraprotein was found, and the implications of this are discussed.