A case of primary erythermalgia with encephalopathy

Abstract

Sirs, Primary erythermalgia is an autosomal dominant disorder characterized by burning pain in the limbs [10]. Encephalopathic symptoms associated with primary erythermalgia have previously been reported but are not well understood [9]. A 19-year-old woman has been followed for primary erythermalgia from childhood. Her sister had a similar phenotype and died as a result of uncontrolled sepsis. Her father was also affected, but less severely. A mutation in SCN9A has been reported in this family [3] (family 4, exon 5, c.647T [ C, p.F216S). Her symptoms, which have become more intense over time, could not be relieved by sympathectomy, lidocaine injection, or morphine, but they improved moderately when treated with oral mexiletine combined with ice applied to her legs. At the end of 2007, the mexiletine was replaced by a low dose of clonazepam and paracetamol because of continuing discomfort. Two months later, she became drowsy and mentally confused, presenting with auditory and visual hallucinations, deep psychomotor slowdown, and cerebellar ataxia without focal deficit or pyramidal syndrome. Hypothermia (31 C), hypoglycemia (3.65 mmol l), and hypercalcemia (2.66 mmol l) were observed. Despite our advice, she continued to use ice to reduce the pain. A cerebrospinal fluid analysis and the cerebral magnetic resonance imaging (MRI) examination did not reveal any abnormalities. However, the electroencephalography (EEG) showed aspecific encephalopathic features. Following admission to hospital, the patient was treated with a combination of risperidone, clonazepam, oral steroid, and mexiletine, which improved the erythermalgia, encephalopathic symptoms, and laboratory anomalies. The hypothermia disappeared. The combined drug treatment was stopped within a few days, but mexiletine therapy was continued. A clue to the pathogenesis of primary erythermalgia was first reported by Yang et al. [11] and then confirmed by Drenth et al. [3], both of whom identified mutations in SCN9A, which encodes the Nav1.7 sodium channel. These mutations, such as p.F216S [1], cause a hyperpolarizing shift in the voltage dependence of channel activation, which allows the channel to be activated by smaller than normal depolarizations. In humans, Nav1.7 channels are selectively expressed in the peripheral nervous system within the dorsal root ganglion and sympathetic ganglion neurons [4]. The hyperexcitability produced by these SCN9A mutations appears to account, at least in part, for the pain experienced by patients [4]. However, our patient also presented symptoms of encephalopathy, hypothermia, and hypoglycemia. To date, the pathomechanism of this erythermalgiaassociated encephalopathy remains obscure. Two cases of primary erythermalgia associated with encephalopathy have been reported previously [6, 9]. One of these [9] was very similar to ours: a 15-year-old boy who developed hypothermia, somnolence, and ataxic gait. However, in this case, the brain MRI revealed increased signal intensity in the splenium of the corpus callosum, which is in contrast to our normal MRI findings, although the EEG was very J. Seneschal A. Taieb Department of Dermatology and Pediatric Dermatology, Saint Andre and Pellegrin Hospitals, Bordeaux University Hospitals, 1 Rue Jean Burguet, 33000 Bordeaux, France e-mail: julien.seneschal@free.fr