Treatment of familial erythermalgia with the association of lidocaine and mexiletine

ArticleinAnnales de Dermatologie et de Vénéréologie 130(4):429-33 · May 2003with15 Reads
Source: PubMed
Erythermalgia is a rare acrosyndrome characterized by reddening of the skin, local increase heat and pain. The disease is frequently resistant to treatment. Recently, Kuhnert et al. presented very favorable results using a combination of lidocaine and mexiletine. We used this treatment in 4 patients suffering from familial erythermalgia. In a family exhibiting severe familial erythermalgia involving 5 members over 3 generations, we treated 4 patients aged 41, 39, 19 and 15 years. In these patients, the erythermalgia known since early childhood, progressed in the form of multiple flares (6 to 7/day) during the day and at night, lasting several hours and often accompanied by headaches. The impact of the disease on their quality of life was major. Only cold-water baths provided temporary relief, obliging them to live with their "feet in cold water". After they had been informed of the modalities of treatment and in the absence of any contraindication, notably cardiologic, 200 mg (100 mg in the youngest patient) of lidocaine were infused in 4 hours in a single intravenous injection on the first day. Mixelitine was introduced on the second day at the dose of 600 mg in 3 oral intakes (200 mg in the youngest patient). The painful paroxistic symptomatology rapidly improved and the flares had disappeared on the 3dr day, thus permitting the progressive reduction in analgesics and major improvement in quality of life. This beneficial effect persisted with oral mexiletine alone, 2 years after the infusion of lidocaine in the first patient treated (and one year after in the other patients). Primary familial erythermalgia is highly resistant to treatment. The combined action of lidocain and mexiletine, usually well tolerated (class IB antiarrythmic), blocks the sodium channels. The mechanism of action of their analgesic effect is peripheral or central or even mixed. This benefit warrants confirmation in other forms of erythermalgia.
    • "Two reports describe the partial relief of pain in the patients with IEM using lidocaine and mexiletine [12, 13]. The other study conducted by Legroux-Crespel et al. describes the relief of pain in the patients with IEM with oral administration of mexiletine [14, 15]. It has been shown that it comes to the resistance to the anesthetic infusions after a while in some patients, as well as the resistance to the anesthetic creams (mexiletine, fentanyl, and lidocaine) [11]. "
    [Show abstract] [Hide abstract] ABSTRACT: Voltage-gated sodium channels (NaV) play a crucial role in development and propagation of action potentials in neurons and muscle cells. Nav1.7 channels take a special place in modern science since it is believed that they contribute to nerve hyperexcitability. Mutations of the gene SCN9A, which codes the α subunit of Nav1.7 channels, are associated with pain perception disorders (primary erythermalgia, congenital analgesia and paroxysmal pain disorder). It is considered that the SCN9A gene mutations may cause variations in sensitivity to pain, from complete insensitivity to extreme sensitivity. Further research of the SCN9A gene polymorphism influence on pain sensitivity is essential for the understanding of the patophysiology of pain and the development of the appropriate targeted pain treatment.
    Full-text · Article · Feb 2015
    • "In comparison, gain-of-function mutations in the related SCN9A gene, which encodes NaV1.7, can result in primary erythromelalgia (PEM), either a familial or a sporadic chronic neuropathic pain syndrome (Dib-Hajj et al., 2005). Several publications have reported an analgesic effect of mexiletine in patients suffering from this monogenic pain disorder (Kuhnert et al., 1999; Legroux-Crespel et al., 2003; Dib-Hajj et al., 2005; Nathan et al., 2005; Choi et al., 2009). The apparent absence of pro-arrhythmic and other major adverse effects at analgesic doses of mexiletine points to a mode of action that preferentially affects pathological channels. "
    [Show abstract] [Hide abstract] ABSTRACT: Background and purpose: The non-selective sodium channel inhibitor mexiletine has been found to be effective in several animal models of chronic pain and has become popular in the clinical setting as an orally available alternative to lidocaine. It remains unclear why patients with monogenic pain disorders secondary to gain-of-function SCN9a mutations benefit from a low systemic concentration of mexiletine, which does not usually induce adverse neurological side effects. The aim of this study was, therefore, to investigate the biophysical effects of mexiletine on the L858F primary erythromelalgia NaV 1.7 mutation in vitro. Experimental approach: Human wild-type and L858F-mutated NaV 1.7 channels were expressed in HEK293A cells. Whole-cell currents were recorded by voltage-clamp techniques to characterize the effect of mexiletine on channel gating properties. Key results: While the concentration-dependent tonic block of peak currents by mexiletine was similar in wild-type and L858F channels, phasic block was more pronounced in cells transfected with the L858F mutation. Moreover, mexiletine substantially shifted the pathologically-hyperpolarized voltage-dependence of steady-state activation in L858F-mutated channels towards wild-type values and the voltage-dependence of steady-state fast inactivation was shifted to more hyperpolarized potentials, leading to an overall reduction in window currents. Conclusion and implications: Mexiletine has a normalizing effect on the pathological gating properties of the L858F gain-of-function mutation in NaV 1.7, which, in part, might explain the beneficial effects of systemic treatment with mexiletine in patients with gain-of-function sodium channel disorders.
    Full-text · Article · May 2014
    • "Patients should also be counseled about the use of safe cooling options such as fans and air conditioning rather than cold water itself , as ice or immersing an extremity into an icy water bath can lead to skin necrosis and ulceration [5,8]. Treatment with medications such as propranolol, gabapentin , tricyclic antidepressants, sodium nitroprusside, calcium channel blockers and intravenous lidocaine and oral mexiletine had some symptomatic benefits in a few cases and mainly in adults not in children262728293031. Medications that affect voltage-gated sodium channels show promise, although prostacyclin may provide some benefit and some patients achieved relief with gabapentin or high-dose magnesium323334. Some rare patients with EM may respond well to treatment with carbamazepine especially those with the Na v 1.7channel mutations [35]. "
    [Show abstract] [Hide abstract] ABSTRACT: Erythromelalgia is a rare clinical syndrome characterized by episodic erythema, warmth and intense burning pain, which commonly involves the extremities. For those affected, this disorder may lead to significant long-term morbidity. Unfortunately, to date, no definitive therapy is available. This case report describes an Egyptian child with primary erythromelalgia that manifested at an early age and showed partial response to therapy with cetirizine hydrochloride. This anecdotal case report may have a diagnostic value for clinicians who have not seen this disorder. A 34-month-old previously healthy right-handed Hamitic boy without any significant past medical history presented at the age of 2 years with episodic bilateral pain in his feet. His mother reported associated warmth and erythema localized to his feet that never extended beyond his ankle joints. This pain is triggered by exertion and/or warm temperature exposure and is relieved by cooling measures. The diagnosis of erythromelalgia was made based on the patient's medical history and a thorough physical examination during the episodes. No evidence of local or systemic infection was present. Other causes for the symptoms were excluded by a negative extensive diagnostic work-up. Our patient did not respond to ibuprofen (15mg/kg/dose) three times a day but partial improvement with the oral non-sedating antihistaminic cetirizine hydrochloride (2.5mg/kg/once daily) was observed. When the child stopped cetirizine hydrochloride for 1 month as a test, the symptoms became aggravated and were relieved when cetirizine therapy was restarted. Cetirizine hydrochloride had not previously been reported to have this effect in children with erythromelalgia. Erythromelalgia is a clinical syndrome of which the etiology, diagnosis and management are controversial. We describe a case of a 34-month-old Egyptian child with primary erythromelalgia that manifested at an early age. We believe that this is the first Egyptian case report of this kind in the literature. Partial response of this patient to cetirizine hydrochloride may grant us a new clue to understanding this mysterious condition.
    Full-text · Article · Feb 2014
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