Erythromelalgia: Vasculopathy, Neuropathy, or Both?

Davis, Mark D.P.; Sandroni, Paola; Rooke, Thom W.; Low, Phillip A.

doi:10.1001/archderm.139.10.1337

Cited by 107 publications

(30 citation statements)

References 25 publications

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“…(Scale bars, 50 m.) ability (increased threshold and attenuated repetitive firing) within sympathetic ganglion neurons. The latter observation provides a molecular basis for the sympathetic dysfunction that has been reported (26,27) in erythermalgia. Moreover, this observation suggests the more general hypothesis that other ion channel mutations may have differing physiological effects in different cell types in which the channel is normally expressed.…”

Section: Discussionmentioning

confidence: 73%

A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons

Rush

Dib‐Hajj

Liu

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

352

315

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Disease-producing mutations of ion channels are usually characterized as producing hyperexcitability or hypoexcitability. We show here that a single mutation can produce hyperexcitability in one neuronal cell type and hypoexcitability in another neuronal cell type. We studied the functional effects of a mutation of sodium channel Nav1.7 associated with a neuropathic pain syndrome, erythermalgia, within sensory and sympathetic ganglion neurons, two cell types where Nav1.7 is normally expressed. Although this mutation depolarizes resting membrane potential in both types of neurons, it renders sensory neurons hyperexcitable and sympathetic neurons hypoexcitable. The selective presence, in sensory but not sympathetic neurons, of the Nav1.8 channel, which remains available for activation at depolarized membrane potentials, is a major determinant of these opposing effects. These results provide a molecular basis for the sympathetic dysfunction that has been observed in erythermalgia. Moreover, these findings show that a single ion channel mutation can produce opposing phenotypes (hyperexcitability or hypoexcitability) in the different cell types in which the channel is expressed.inherited erythermalgia ͉ neuropathic pain ͉ primary erythromelalgia ͉ sodium channelopathy M utations in voltage-gated sodium channels have been associated with a number of neurological disorders including inherited epilepsy, muscle disorders, and primary erythermalgia, an autosomal dominant neuropathy characterized by pain of the extremities in response to mild warmth. Recent studies have demonstrated mutations in primary erythermalgia in Na v 1.7 (1), a sodium channel that is preferentially expressed within primary sensory [such as nociceptive dorsal root ganglion (DRG)] and sympathetic ganglion [e.g., superior cervical ganglion (SCG)] neurons (2-6). The Na v 1.7 mutations characterized to date produce changes in channel physiology that include hyperpolarizing shifts in activation, depolarizing shifts in steadystate inactivation, slowing of deactivation, and an increase in the ''ramp'' current evoked by slow, small depolarizations, all augmenting the response of Na v 1.7 channels to small stimuli (3, 6, 7). One of these mutations, F1449V, has been assessed at the level of cell function within DRG neurons, where it produces hyperexcitability (3). However, the effects on cell function of Na v 1.7 mutations have not been assessed in sympathetic ganglion neurons, where Na v 1.7 is also present.Because different ensembles of channels are present within DRG and SCG neurons, we hypothesized that the same sodium channel mutation might have different effects on excitability in these two neuronal types. Here we test this hypothesis for one of the first Na v 1.7 erythermalgia mutations to be characterized, L858H (2, 7). We show that although the L858H mutation produces a depolarizing shift in resting membrane potential (RMP) in both cell types, it renders DRG neurons hyperexcitable and SCG neurons hypoexcitable. We demonstrate that the opposing functi...

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Section: Discussionmentioning

confidence: 73%

A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons

Rush

Dib‐Hajj

Liu

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

352

315

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“…Investigations such as thermoregulatory sweat testing and quantitative sudomotor axon reflex test supported the diagnosis of small fiber neuropathy in patients with EM 22–24. Other studies suggest vascular causes, with pain from chronic perfusion deficit and tissue ischemia 25,26…”

Section: Introductionmentioning

confidence: 95%

Current pain management strategies for patients with erythromelalgia: a critical review

Tham¹,

Giles²

2018

JPR

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Erythromelalgia (EM) is a rare disorder characterized by erythematous, warm, painful extremities, which is often precipitated by cold conditions. The pathophysiology of EM is incompletely understood. Recent investigations have identified sodium channelopathy as a genetic cause for this pain condition, classified as primary inherited EM. Other subtypes are idiopathic EM and secondary EM. The management of pain in EM is challenging as no single therapy has been found to be effective. There is varying response to pharmacotherapy and significant variability within this clinical population, resulting in a stepwise trial and error approach. Consequently, EM is often associated with poorer health-related quality of life with higher morbidity. There is currently no consensus or guidelines on management of pain in EM. This is a review of the literature on management of pain using pharmacologic, procedural intervention and nonpharmacologic treatment in children and adults with EM.

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“…[4] A small fiber neuropathy leading to disturbance of neural control of vascular muscle tone and increased episodic blood flow to the affected area has been demonstrated in most patients and erythromelalgia is considered to be a prototype of painful neuropathies. [5] In leprosy a damage to vascular innervation due to sympathetic nerve damage causes loss of vascular tone and stasis of capillary blood. [1] Endarteritis leading to ischemia of nerves may be responsible for the sensory, motor, and autonomic disturbances.…”

Section: Discussionmentioning

confidence: 99%

Hansen′s disease associated with erythromelalgia mimicking Lupus erythematosus

Damodar

Prabhu

Balakrishnan

et al. 2014

Indian Dermatol Online J

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Hansen's disease, though considered to be at the verge of elimination in many countries including India, still continues to surprise patients and dermatologists alike. This is mainly due to its varying and unconventional presentations which may lead to initial misdiagnosis and prolongation of treatment. Here we describe an unusual case presenting with erythematous photosensitive facial lesions associated with erythromelalgia of the finger tips, provisionally diagnosed as SLE. A subsequent histopathology examination proved it to be Hansens’ disease Borderline Tuberculoid variety. Hansen's disease can be termed as the modern great imitator, displacing the traditional great imitator, syphilis.

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Erythromelalgia: Vasculopathy, Neuropathy, or Both?

Abstract: To assess the frequency and type of vascular changes and neurologic abnormalities in patients with erythromelalgia.Design: Prospective study of patients with no spontaneous symptoms at the time of their visit and with provoked symptoms.

Cited by 107 publications

References 25 publications

A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons

A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons

Current pain management strategies for patients with erythromelalgia: a critical review

Hansen′s disease associated with erythromelalgia mimicking Lupus erythematosus

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