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Pain 2019 Jan 31. Epub 2019 Jan 31.

Institute of Physiology, Uniklinik RWTH Aachen, 52074 Aachen, Germany.

The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (Nav) 1.7. Still, recent studies targeting Nav1. Read More

Cureus 2018 Oct 27;10(10):e3506. Epub 2018 Oct 27.

Dermatology, East Tennessee State University Quillen College of Medicine, Johnson City, USA.

Erythromelalgia is a neurovascular disorder which causes pain, swelling, erythema, and warmth of the distal extremities. Primary disease is due to a genetic mutation in the gene, but secondary erythromelalgia can be the consequence of a variety of underlying etiologies, including drug and toxin exposures. The disease is rare, occurring in only 1. Read More

Clin Exp Dermatol 2019 Jan 4. Epub 2019 Jan 4.

Department of Dermatology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK.

Erythromelalgia is a condition characterized by episodic pain, erythema and temperature of the extremities, which is relieved by cooling and aggravated by warming. It is useful to review this topic in light of recent discoveries of the genetic mutations that now define primary erythromelalgia, as opposed to secondary erythromelalgia, which is often associated with underlying medical disorders. Read More

Pain Med 2019 Jan 3. Epub 2019 Jan 3.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Internist (Berl) 2019 Jan;60(1):90-97

Institut für Humangenetik, Uniklinik RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Deutschland.

Background: The causes for neuropathic pain are manifold and remain unexplained in the majority of cases. In recent years a growing number of pain syndromes have been attributed to mutations in genes encoding voltage-gated sodium channels. Hence, this group of rare diseases should be considered in the differential diagnostics of neuropathic pain. Read More

J Neurol Neurosurg Psychiatry 2019 Mar 15;90(3):342-352. Epub 2018 Dec 15.

Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, The Netherlands

Background: Neuropathic pain is common in peripheral neuropathy. Recent genetic studies have linked pathogenic voltage-gated sodium channel (VGSC) variants to human pain disorders. Our aims are to determine the frequency of , and variants in patients with pure small fibre neuropathy (SFN), analyse their clinical features and provide a rationale for genetic screening. Read More

J Neurosci 2019 Jan 20;39(3):382-392. Epub 2018 Nov 20.

Department of Neurology, Yale University, New Haven, Connecticut 06510,

Pain is a complex process that involves both detection in the peripheral nervous system and perception in the CNS. Individual-to-individual differences in pain are well documented, but not well understood. Here we capitalized on inherited erythromelalgia (IEM), a well characterized human genetic model of chronic pain, and studied a unique family containing related IEM subjects with the same disease-causing Na1. Read More

Handb Clin Neurol 2018 ;157:777-787

Department of Neurology, Mayo Clinic, Rochester, MN, United States. Electronic address:

Peripheral neuropathy affecting autonomic and small sensory fibers can cause abnormalities of both autonomic and behavioral thermoregulation. Quantitative autonomic and sensory neurophysiologic tests and quantification of the linear density of intraepidermal nerve fibers potentially can stratify those at risk of impaired thermoregulation during cold and heat challenges. New data relating to thermoregulatory sweating impairment in neuropathy are presented in this chapter. Read More

J Pediatr 2019 Mar 9;206:217-224.e9. Epub 2018 Nov 9.

Clinical Neurosciences (Pediatric Pain Research Group), UCL GOS Institute of Child Health, London, UK; Department of Pediatric Anesthesia and Pain Medicine, Great Ormond Street Hospital NHS Foundation Trust, London, UK. Electronic address:

Objectives: To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Na1.7 voltage-gated sodium channel, we conducted a systematic review of pediatric presentations of erythromelalgia related to SCN9A mutations, and compared pediatric clinical presentations of symptomatic erythromelalgia, with or without SCN9A mutations.

Study Design: PubMed, Embase, and PsycINFO Databases were searched for reports of inherited erythromelalgia in childhood. Read More

J Neurosci 2018 Nov 9;38(47):10180-10201. Epub 2018 Oct 9.

Departments of Neuroscience,

Strong human genetic evidence points to an essential contribution of the voltage-gated sodium channel Nav1.7 to pain sensation: loss of Nav1.7 function leads to congenital insensitivity to pain, whereas gain-of-function mutations in the gene that encodes Nav1. Read More

A A Pract 2018 Oct 3. Epub 2018 Oct 3.

From the Department of Anesthesia and Pain Medicine, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.

A 79-year-old woman with primary erythromelalgia underwent a left reverse total shoulder arthroplasty with a left interscalene nerve block, a superficial cervical plexus block, and a general endotracheal anesthetic, with no residual neurological deficits. Herein, we discuss the classification and pathophysiology of erythromelalgia along with the anesthetic considerations of peripheral nerve blockade in patients with primary erythromelalgia. Read More

Cell Rep 2018 Sep;24(12):3133-3145

Xenon Pharmaceuticals, Burnaby, BC V5G 4W8, Canada. Electronic address:

Selective block of Na1.7 promises to produce non-narcotic analgesic activity without motor or cognitive impairment. Several Na1. Read More

J Pain Res 2018 30;11:1689-1698. Epub 2018 Aug 30.

Seattle Children's Research Institute, Seattle, WA, USA,

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. Read More

Pak J Med Sci 2018 Jul-Aug;34(4):1024-1026

Dr. Asif Jan Muhammad, MBBS, MCPS, MRCP (UK). Medicine Department, Patel Hospital, ST-18, Block-4, Gulshan-e-Iqbal, Karachi, Pakistan.

Essential thrombocytosis (ET) has rarely been reported with autoimmune rheumatic disorders. We report a case of young female, diagnosed case of Rheumatoid arthritis (RA), who had been overlooked for her raised platelet counts. Later her symptoms of impending digital gangrene led to an active search for her thrombocytosis. Read More

J Vasc Surg 2018 12 17;68(6):1897-1905. Epub 2018 Aug 17.

Department of Interventional Radiology and Vascular Surgery, Peking University Third Hospital, Beijing, China.

Objective: 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. Read More

Hell J Nucl Med 2018 May-Aug;21(2):151-152. Epub 2018 Jul 12.

Dept. of Radiology, Algemeen Ziekenhuis Sint-Jan Brugge-Oostende, Ruddershove 10, B-8000 Brugge, Belgium.

The use of hyaluronic acid nanoshells has been proposed to encapsulate prodrugs and exploit the mechanisms of interactions between living cells, like endocytes or cancer cells and hyaluronic acid, which is a natural component of the extracellular matrix. In this review we describe the potential and the limits of this promising research trend and discuss the theoretical advantages of such an engineering approach. Is it a possible scalability to increase the efficacy and biodegradability of molecules like contrast media and radiotracers especially for neuroradiology and nuclear medicine studies. Read More

Eur J Pain 2018 11 11;22(10):1767-1773. Epub 2018 Jul 11.

Pain Center, TU Dresden, Germany.

Mutations in the sodium-channel Na 1.7, encoded by the gene SCN9A, are known to cause pain disorders. In particular, gain-of-function missense mutations in Na 1. Read More

Scand J Pain 2014 Oct 1;5(4):215-216. Epub 2014 Oct 1.

University of Oslo and Oslo University Hospital, Departments of Anaesthesiology and of Pain Management and Research, Nydalen PB 4950, 0424 Oslo, Norway.

Scand J Pain 2014 Oct 1;5(4):217-225. Epub 2014 Oct 1.

Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital-Rikshospitalet, Oslo, Norway.

Background and aim "Gain-of-function" mutations in voltage-gated sodium channel NaV1.7 have been linked to erythromelalgia (EM), characterized by painful hot and red hands and feet. We investigated the proportion of patients with EM that carry a mutation in NaV1. Read More

Am J Clin Hypn 2018 Jul;61(1):34-44

a University of South Florida , Tampa , FL, USA.

Mindfulness-based cognitive hypnotherapy integrates mindfulness, cognitive-behavioral therapy, and hypnotherapy to improve physical, emotional, mental, and/or spiritual aspects of skin disorders. Meditation, including mindfulness meditation, and hypnosis both utilize trance phenomena to help produce focalization and specific improvements in skin disorders through psycho-neuro-endocrine-immunologic mechanisms. Hypnosis, cognitive hypnotherapy, focused meditation, and mindfulness meditation are discussed with respect to improving various skin disorders including acne, acne excoriée, alopecia areata, atopic dermatitis, congenital ichthyosiform erythroderma, dyshidrotic dermatitis, erythema nodosum, erythromelalgia, furuncles, glossodynia, herpes simplex, hyperhidrosis, ichthyosis vulgaris, lichen planus, neurodermatitis, nummular dermatitis, postherpetic neuralgia, prurigo nodularis, pruritus, psoriasis, rosacea, trichotillomania, urticaria, verruca vulgaris, and vitiligo. Read More

J Am Acad Dermatol 2018 05;78(5):e129

Dermatology Department, Tulane University, New Orleans, Louisiana.

J Am Acad Dermatol 2018 05;78(5):e127

Department of Dermatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

An Bras Dermatol 2018 Jan-Feb;93(1):86-94

Private practice - Rosario, Argentina.

The low prevalence of erythromelalgia, classified as an orphan disease, poses diagnostic and therapeutic difficulties. The aim of this review is to be an update of the specialized bibliography. Erythromelalgia is an infrequent episodic acrosyndrome affecting mainly both lower limbs symmetrically with the classic triad of erythema, warmth and burning pain. Read More

Br J Dermatol 2018 Sep 5;179(3):783-784. Epub 2018 Jul 5.

University Paris Descartes, Paris, France.

Yale J Biol Med 2018 03 28;91(1):63-66. Epub 2018 Mar 28.

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT.

Prog Cardiovasc Dis 2018 Mar - Apr;60(6):567-579. Epub 2018 Mar 10.

Division of Cardiovascular Medicine, Ohio State University Wexner Medical Center, Columbus, OH. Electronic address:

In the contemporary era of medical diagnosis via sophisticated radiographic imaging and/or comprehensive serological testing, a focused physical examination remains paramount in recognizing the cutaneous manifestations of chronic vascular disease. Recognition of the unique cutaneous signs of lymphatic and venous hypertension assists in the diagnosis as well as the staging and classification of both lymphedema and chronic venous insufficiency. Awareness of explicit dermatologic vasomotor manifestations aids not only in the identification of acrocyanosis, Raynaud phenomenon, pernio, and erythromelalgia but also mitigates confusion related to their clinical overlap. Read More

Int J Dermatol 2019 Jan 10;58(1):101-102. Epub 2018 Mar 10.

Mayo Clinic School of Medicine, Rochester, MN, USA.

Rev Bras Anestesiol 2018 Sep - Oct;68(5):531-534. Epub 2018 Feb 3.

Universidade Federal de São Paulo (UNIFESP), Disciplina de Anestesiologia, Dor e Medicina Intensiva, São Paulo, SP, Brasil. Electronic address:

Erythromelalgia is a neuropathic pain syndrome due to an autosomal dominant gene, characterized by erythema, increased skin temperature and burning pain in hands and feet, whose treatment is often unsatisfactory. In this paper, we report a case of a 9 years old female patient whose first episode of burning pain, erythema and edema of the hands, without triggering factors, had instant relief after immersion in cold water. She presented with systemic arterial hypertension and had seizures. Read More

Handb Exp Pharmacol 2018 ;246:355-369

Institute of Physiology, Uniklinik RWTH Aachen University, Aachen, Germany.

Chronic pain patients are often left with insufficient treatment as the pathophysiology especially of neuropathic pain remains enigmatic. Recently, genetic variations in the genes of the voltage-gated sodium channels (Navs) were linked to inherited neuropathic pain syndromes, opening a research pathway to foster our understanding of the pathophysiology of neuropathic pain. More than 10 years ago, the rare, inherited pain syndrome erythromelalgia was linked to mutations in the subtype Nav1. Read More

Vasa 2018 Feb 4;47(2):91-97. Epub 2018 Jan 4.

2 Poliklinik, Funktionsbereich und Hiller Forschungszentrum für Rheumatologie, Medizinische Fakultät, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.

Erythromelalgia is a rare syndrome characterized by the intermittent or, less commonly, by the permanent occurrence of extremely painful hyperperfused skin areas mainly located in the distal extremities. Primary erythromelalgia is nowadays considered to be a genetically determined neuropathic disorder affecting SCN9A, SCN10A, and SCN11A coding for NaV1.7, NaV1. Read More

J Clin Oncol 2018 Jan 5;36(3):220-224. Epub 2017 Dec 5.

Neil P. Shah, University of California, San Francisco, San Francisco, CA.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. Read More

Headache 2018 02 28;58(2):306-308. Epub 2017 Nov 28.

Department of Clinical Neurological Sciences, London Health Sciences Centre (LHSC), University of Western Ontario, London, Ontario, Canada.

Mol Pain 2017 Jan-Dec;13:1744806917745179. Epub 2017 Nov 22.

1 Lilly Research Centre, 1539 Eli Lilly and Company , Windlesham, UK.

Background The Na1.7 subtype of voltage-gated sodium channels is specifically expressed in sensory and sympathetic ganglia neurons where it plays an important role in the generation and transmission of information related to pain sensation. Human loss or gain-of-function mutations in the gene encoding Na1. Read More

Int J Dermatol 2018 Jan 20;57(1):83-85. Epub 2017 Nov 20.

Department of Clinical-Surgical, Diagnostic and Pediatric Science, Institute of Dermatology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.

Workplace Health Saf 2018 Apr 9;66(4):169-172. Epub 2017 Nov 9.

1 California State University, Monterey Bay.

A 36-year-old woman sustained a Grade 2 ankle sprain at work. Two days after the injury, the ankle and foot became red and she complained of "intense burning pain." First diagnosed with complex reflex sympathetic dystrophy, the employee was prescribed medications that provided some pain relief; a subsequent temporary nerve block provided additional relief. Read More

Pediatr Rev 2017 Nov;38(11):511-519

Division of Pediatric Rheumatology, Department of Pediatrics, University of Michigan, Ann Arbor, MI.

Curr Mol Med 2017 ;17(6):450-457

Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Background: Primary erythromelalgia (PE) is a dominant inherited disorder characterized by recurrent pain, redness, and warmth of the extremities that is caused by gain-of-function mutations in Nav1.7 encoding gene SCN9A. Most of the PE-causing mutations of Nav1. Read More

Clin Exp Dermatol 2018 Jan 4;43(1):100-102. Epub 2017 Oct 4.

Department of Dermatology, Ninewells Hospital, Dundee, UK.

Mol Med Rep 2017 Nov 5;16(5):6780-6786. Epub 2017 Sep 5.

Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000‑354 Coimbra, Portugal.

Oral leukoplakia and erythroleukoplakia are common oral potentially malignant disorders diagnosed in the oral cavity. The specific outcome of these lesions remains to be elucidated, as their malignant transformation rate exhibits great variation. The ability to predict which of those potentially malignant lesions are likely to progress to cancer would be vital to guide their future clinical management. Read More

Case Rep Med 2017 16;2017:6969285. Epub 2017 Jul 16.

University of Texas Health Sciences Campus in San Antonio (UTHSCSA), San Antonio, TX, USA.

Spinal cord stimulators have commonly been used to treat multiple pain conditions. This case report represents a unique case of using multiple spinal cord stimulators for widespread small fiber neuropathy pain. This case report concerns patient JJ who first presented with generalized neuropathic pain. Read More

BMJ Case Rep 2017 Jul 26;2017. Epub 2017 Jul 26.

Center for Neuroscience and Regeneration Research, Yale University School of Medicine, Veteran Affairs Medical Center, West Haven, Connecticut, USA.

Inherited erythromelalgia (IEM) is a well-described pain disorder caused by mutations of sodium channel Na1.7, a peripheral channel expressed within dorsal root ganglion and the sympathetic ganglion neurons. Clinically, IEM is characterised by paroxysmal attacks of severe pain, usually in the distal extremities, triggered by warmth or exercise. Read More

Arq Neuropsiquiatr 2017 Jul;75(7):491

Universidade Federal de São Paulo, Departamento de Neurologia e Neurocirurgia, Divisão de Doenças Neuromusculares, São Paulo SP, Brasil.

Br J Pharmacol 2018 Jun 30;175(12):2261-2271. Epub 2017 Jul 30.

Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.

Background And Purpose: Pharmacotherapy for pain currently involves trial and error. A previous study on inherited erythromelalgia (a genetic model of neuropathic pain due to mutations in the sodium channel, Na 1.7) used genomics, structural modelling and biophysical and pharmacological analyses to guide pharmacotherapy and showed that carbamazepine normalizes voltage dependence of activation of the Na 1. Read More

Dermatol Online J 2017 Apr 15;23(4). Epub 2017 Apr 15.

Baylor College of Medicine, Houston, Texas.

Erythromelalgia is a rare disorder characterized by burning pain, erythema, and increased temperature typically involving the distal extremities. Although it can progress to involve the face, erythromelalgia presenting only on the face is particularly rare. This disorder is often misdiagnosed when it presents on the extremities and is even more likely to be misdiagnosed when presenting only on the face, delaying appropriate treatment and causing considerable frustration for the patient. Read More

J Pain Res 2017 27;10:973-977. Epub 2017 Apr 27.

Department of Anesthesiology, Perioperative & Pain Medicine, Stanford University, Palo Alto.

A 41-year-old woman presented with burning and erythema in her extremities triggered by warmth and activity, which was relieved by applying ice. Extensive workup was consistent with adult-onset primary erythromelalgia (EM). Several pharmacological treatments were tried including local anesthetics, capsaicin, ziconotide, and dantrolene, all providing 24-48 hours of relief followed by symptom flare. Read More

Eur J Pain 2017 09 18;21(8):1316-1325. Epub 2017 Apr 18.

Section of Clinical Neurophysiology, Department of Neurology, Oslo University Hospital - Rikshospitalet, Norway.

Objectives: Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM).

Methods: Lidocaine (0.25, 0. Read More

J Am Acad Dermatol 2017 Mar 26;76(3):506-511.e1. Epub 2016 Oct 26.

Department of Neurology, Mayo Clinic, Rochester, Minnesota; Department of Anesthesiology, Pain Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Corticosteroids (CS) may benefit certain patients with erythromelalgia.

Objectives: Our objective was to determine clinical predictors of corticosteroid-responsive erythromelalgia.

Methods: Patients with erythromelalgia who received CS were identified and stratified into corticosteroid nonresponders (NRs), partial corticosteroid responders (PSRs), complete corticosteroid responders (CSRs), and steroid responders (SRs = PSRs + CSRs). Read More

Rev Med Interne 2018 Feb 11;39(2):99-106. Epub 2017 Apr 11.

U1096, service de médecine interne, Normandie univ, UNIROUEN, 76000 Rouen, France.

Small fiber neuropathy (SFN) is still unknown. Characterised by neuropathic pain, it typically begins by burning feet, but could take many other expression. SFN affects the thinly myelinated Aδ and unmyelinated C-fibers, by an inherited or acquired mechanism, which could lead to paresthesia, thermoalgic disorder or autonomic dysfunction. Read More

J Biol Chem 2017 06 5;292(22):9262-9272. Epub 2017 Apr 5.

From the Department of Neurology,

Dominant mutations in voltage-gated sodium channel Na1.7 cause inherited erythromelalgia, a debilitating pain disorder characterized by severe burning pain and redness of the distal extremities. Na1. Read More

Pan Afr Med J 2016;25:226. Epub 2016 Dec 7.

Service d'Orthopédie, Hôpital Sahloul, Sousse, Tunisie.