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ObjectiveTo investigate the clinicopathologic features of eosinophilic granulomatosis with polyangiitis (EGPA)–associated neuropathy with a focus on the presence or absence of anti-neutrophil cytoplasmic antibodies (ANCAs).MethodsWe examined the clinical features and pathologic findings of sural nerve biopsy specimens from 82 patients with EGPA-associated neuropathy. Of these patients, 32.9% were myeloperoxidase (MPO)-ANCA positive, and 67.1% were MPO-ANCA negative. PR3-ANCA was negative in all of 78 examined patients.ResultsUpper limb symptoms were more frequently reported as initial neuropathic manifestations in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (44.4% vs 14.6%, p < 0.01). The serum levels of C-reactive protein were significantly higher in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (p < 0.05). Sural nerve biopsy specimens showed findings suggestive of vasculitis (i.e., destruction of vascular structures) in epineurial vessels; these results were seen more frequently in the MPO-ANCA–positive group than in the MPO-ANCA–negative group (p < 0.0001). Conversely, the numbers of eosinophils in the lumen of the epineurial vessels (p < 0.01) and epineurial vessels occluded by intraluminal eosinophils (p < 0.05) were higher in the MPO-ANCA–negative group than in the MPO-ANCA–positive group. Furthermore, the incidence of eosinophil infiltration in the endoneurium was higher in the MPO-ANCA–negative group than in the MPO-ANCA–positive group (p < 0.01).ConclusionsThis study suggests that the pathogenesis of EGPA comprises at least 2 distinct mechanisms: ANCA-associated vasculitis resulting in ischemic effects and inflammation, which is prominent in MPO-ANCA–positive patients, and eosinophil-associated vascular occlusion leading to ischemia and eosinophil-associated tissue damage, which is conspicuous in MPO-ANCA–negative patients.

Temperature scanning Fourier transform infrared, TS-FTIR, spectroscopy of various amorphous sugar matrixes was conducted to investigate the relationship between the glass transition temperature, T(g), of an amorphous sugar matrix and the nature of the hydrogen bonds in the matrix. An amorphous sugar matrix was prepared by air-drying an aqueous solution of sugar, and the degree of formation of hydrogen bonds in the matrix was evaluated at different temperatures using the peak positions of the IR band corresponding to the O-H stretching vibration at around 3400 cm(-1). The T(g) value increased with increasing peak position of the O-H stretching vibration at T(g) and were correlated reasonably well with the magnitude of the peak shift by the temperature increase (from 25 degrees C) to the T(g) value. This demonstrates that the amorphous sugar matrix, in which the segments are fixed by fewer hydrogen bonds, has a higher thermal resistance. The glycosidic linkage largely contributes to the restriction of the segments, pyranose ring, rather than a hydrogen bond. As the degree of polymerization of pyranose rings increases, the degree of hydrogen bond formation needed to hold the matrix in a fixed position decreases. However, the magnitude of the restriction of pyranose rings by a glycosidic linkage changes depending on the type: the restrictions imposed by alpha-1,1 and -1,6 glycosidic linkages are the tightest and most flexible of all of the types of glycosidic linkages, respectively.

Folate-deficiency neuropathy was characterized by a slowly progressive and sensory-dominant pattern, which was different from thiamine-deficiency neuropathy (i.e., beriberi neuropathy). This study demonstrates the importance of folate deficiency in the differential diagnosis of neuropathy, particularly in countries where folic acid fortification has not yet been practiced.

The newly recognized entity IgG4related disease (IgG4-RD) is characterized by an elevated IgG4 serum concentration and tissue infiltration by IgG4-positive plasma cells. We describe, for the first time, the clinical features and nerve biopsy findings of a patient with IgG4-RD who presented with neuropathy in the extremities.Observations: A 55-year-old man had histopathologically defined IgG4-RD that manifested as sensorymotor neuropathy. The neuropathic features were multiple mononeuropathies with electrophysiological findings suggestive of axonal neuropathy. Marked thickening with abundant collagen fibers and infiltration of IgG4-positive plasma cells were observed in the epineurium of the biopsied sural nerve. A moderate degree of myelinated fiber loss without evidence of segmental demyelination was present, whereas necrotizing vasculitis was not found. Oral prednisolone therapy ameliorated the neuropathic symptoms.Conclusions and Relevance: This case of IgG4-RD presented as sensory-motor neuropathy with pain and sclerosis of the skin in the extremities. The differential diagnosis of neuropathy should include IgG4-RD.