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If an underlying condition is found, treatment will first be directed towards treating this underlying condition. Strict regulation of blood glucose is important for patients with diabetes mellitus. In case of vitamin B6 intoxication, stopping the use of vitamin B suppletion is advised.

The natural course of small fibre neuropathy is not entirely known. In an older study about 50 percent of patients had stable complaints, whereas the complaints increased in about 30 percent and decreased in a minority of patients. Further studies will be needed to elucidate the natural course of the disease, and to explain differences in disease course between patients.