Sir, there is a wealth of evidence suggesting increased incidence of genuine resistance to the effects of local anaesthesia in patients with Ehers-Danlos Syndrome (EDS) and other syndromes on the Joint Hypermobility Syndrome (JHS) spectrum, yet there is little guidance on how these patients should be managed.1,2

As many as 88% of EDS patients report anaesthetic resistance as being either complete, partial or rapidly waning in effect. This is reported across all available anaesthetics, with articaine 4% offering only marginal benefit.3

Anecdotal evidence indicates those with anaesthetic resistance often avoid elective procedures, culminating in increased morbidity, increased incidence of extractions and repeated need for sedation or GA to undergo required treatment.4There are inevitably detrimental implications to such experiences: dental neglect, dental anxiety/phobia and lowered self-esteem. A more pleasurable patient experience for this cohort of patients must become a priority and there may finally be a glimmer of hope in doing so.

A recent small scale familial study found those with a well-defined history of anaesthetic resistance and JHS to have mutation of the SCN5A gene, responsible for variant voltage-gated sodium channel 1.5 (Nav1.5) in peripheral nerves. This mutation was not present in those family members without JHS and no history of anaesthetic resistance.5

Given that local anaesthetics' mechanism of action depends on reversibly binding to Nav channels, it seems logical to argue that mutant variants would not be adequately bound by local anaesthetics and thus explain the lack of inactivation and ultimately lack of anaesthesia.6Further study into variant Nav channels, their mutant genes and novel agents aimed at specific receptor binding is an area requiring further exploration in collaboration with geneticists. The lack of present research into the underlying mechanisms means we are no closer to doing what we are passionate about as clinicians: to offer pain free, effective treatment to this exceptional cohort of patients.