Zhang L

Chemical lumbar sympathectomy in the treatment of recalcitrant erythromelalgia.

Erythromelalgia is highly disabling and treatment is often very challenging. There have been solitary case reports that it might benefit from sympathectomy. This study sought to evaluate the short-term and long-term efficacy of chemical lumbar sympathectomy (CLS) for treatment of recalcitrant erythromelalgia and try to identify a CLS-responsive subset. Patients with recalcitrant erythromelalgia were recruited from a tertiary hospital over a 10-year period. L3 to L4 CLS was performed using 5% phenol. The pain intensity score (visual analog scale [VAS] 0-10) was assessed before CLS and at 1 day, 1 week, 3 months, 6 months, 1 year, and 2 years after CLS. A VAS decrease of 90%-100% is defined as complete response, 60%-89% as major partial response. Relapse was defined by a return of a VAS score of 5 or higher. SCN9A gene mutations were screened. Thirteen patients were enrolled, with a median age of 15 years. The mean follow-up was 6.2 ± 3.8 years. SCN9A gene mutation was identified in five patients having family histories. The VAS was 8.2 ± 2.0 at baseline; it decreased to 4.9 ± 2.7 at 1 day and 1.9 ± 3.0 at 1 week after CLS. Nine patients (69.2%) achieved complete response at 1 week after CLS, including three patients with SCN9A gene mutation. Among the three complete response patients having the gene mutation, two reverted to major partial response and one relapsed at 2 years after CLS. Among the six complete response patients without mutation, five maintained complete response and one relapsed. Among the four patients who did not achieve complete response, one patient died at 3.5 months and one patient had an amputation performed at 4 months after CLS. CLS provides a valid option for the treatment of recalcitrant erythromelalgia. It takes about 1 week to achieve full efficacy. Relapse may occur, especially in patients with an SCN9A gene mutation.

Long-term remission of primary erythermalgia with R1150W polymorphism in SCN9A after chemical lumbar sympathectomy.

Primary erythermalgia (PEM) is recalcitrant and long-term remission is difficult to achieve. Favorable results of treatment using carbamazepine or mexiletine have been identified in some PEM patients with SCN9A gene mutations. However, no therapeutic studies regarding patients without pathogenic SCN9A gene mutation have been reported. Here we present a PEM case with R1150W polymorphism in SCN9A and a five-year remission was achieved by chemical lumbar sympathectomy (CLS). A 15-year-old girl with severe PEM attacks in both feet and lower legs was treated with CLS and followed up for five years. The encoding exons and their flanking sequences in the SCN9A gene were amplified and sequenced. A 50% immediate pain reduction was achieved after CLS. Burning pain, erythema and swelling in the lower legs disappeared in four days, and all ulceration healed in a month. The patient resumed normal exercise five months after CLS. There were no relapses in the following five years. R1150W polymorphism in SCN9A was detected in the patient and her healthy father. Long-term remission was achieved after CLS in this PEM case with R1150W polymorphism in SCN9A. The effectiveness of CLS and phenotype/genotype of PEM should be further studied in larger samples.

Mexiletine-responsive erythromelalgia due to a new Na(v)1.7 mutation showing use-dependent current fall-off.

Inherited erythromelalgia (IEM), characterized by episodic burning pain and erythema of the extremities, is produced by gain-of-function mutations in sodium channel Na(v)1.7, which is preferentially expressed in nociceptive and sympathetic neurons. Most patients do not respond to pharmacotherapy, although occasional reports document patients as showing partial relief with lidocaine or mexiletine. A 7-year-old girl, with a two-year history of symmetric burning pain and erythema in her hands and feet, was diagnosed with erythromelalgia. Treatment with mexiletine reduced the number and severity of pain episodes. We report here a new IEM Na(v)1.7 mutation in this patient, and its response to mexiletine. SCN9A exons from the proband were amplified and sequenced. We identified a single nucleotide substitution (T2616G) in exon 15, not present in 200 ethnically-matched control alleles, which substitutes valine 872 by glycine (V872G) within DII/S5. Whole-cell patch-clamp analysis of wild-type and mutant Na(v)1.7 channels in mammalian cells show that V872G shifts activation by -10 mV, slows deactivation, and generates larger ramp currents. We observed a stronger use-dependent fall-off in current following exposure to mexiletine for V872G compared to wild-type channels. These observations suggest that some patients with IEM may show a favorable response to mexiletine due to a use-dependent effect on mutant Na(v)1.7 channels. Continued relief from pain, even after mexiletine was discontinued in this patient, might suggest that early treatment may slow the progression of the disease.

Mutation hotspots of SCN9A in primary erythermalgia.