Publications

To elucidate the features of plexin D1-immunoglobulin (Ig)G-associated neuropathic pain and its relationship to atopic myelitis (AM) in a nationwide Japanese survey. A preliminary survey questionnaire was sent to 1574 selected departments (neurology and pediatrics/pediatric neurology) to explore the...

The article presents a clinical case of secondary erythromelalgia in a comorbid patient with antiphospholipid syndrome, accompanied by burning pain, hyperemia and swelling of the lower extremities. A comprehensive examination involving a neurologist, dermatologist, and rheumatologist was conducted t...

Recent genomic research has identified variants in the SCN9A gene as a key factor in inherited erythromelalgia (IEM) pathogenesis. In this review, data are collected and analyzed to identify SCN9A sequence variants associated with IEM, demographic patterns, and treatment responses among patients. We...

Spontaneous activity of peripheral sensory nerve fibers is one of the main drivers of neuropathic pain. It can be assessed in microneurography recordings of patients' C fibers and in patch-clamp recordings of dissociated dorsal root ganglia from humans and rodents. In microneurography of human C fib...

Erythromelalgia is a rare disorder characterized by severe burning extremity pain, erythema, and increased skin temperature. Symptoms are aggravated by warming and alleviated by cooling. It is known to be associated with multiple underlying conditions, as well as reactions in response to medications...

Primary erythromelalgia (PEM) is a rare neuropathic pain disorder characterized by debilitating burning pain of the extremities relieved by cold exposure. We report a pediatric patient who developed severe, full-thickness lower extremity ulcerations infected with Alternaria alternata and complicated...

Voltage-gated sodium channel Nav1.8 plays a crucial role in regulating excitability of small dorsal root ganglion (DRG) neurons and is an emerging target for pain therapeutics. Using dynamic clamp, we systematically manipulated Nav1.8 conductance to assess its impact on action potential (AP) electro...

Polycythaemia vera (PV) is a chronic myeloproliferative disorder. PV should be suspected with hemoglobin >10.2/9.9 mmol/L (m/f) and/or PV-related features (aquagenic pruritus, erythromelalgia, atypical thrombosis, splenomegaly, thrombocytosis or leukocytosis). This case report highlights the connect...

Erythromelalgia is a rare neurovascular syndrome characterized by intense, episodic burning pain that primarily affects the feet and hands and, occasionally, the face. Symptoms are often triggered by heat and exercise, with relief typically achieved through cooling methods. However, improper use of...

Erythromelalgia is a rare, chronic pain disorder characterized by the triad of intense burning sensation, warmth, and redness, primarily involving the hands and feet, and usually alleviated by cold and worsened by heat. The objective of this scoping review was to: 1) map the existing literature on e...

Inherited erythromelalgia, small fibre neuropathy and paroxysmal extreme pain disorder are caused by gain-of-function mutations in the voltage-gated sodium channel Nav1.7. It remains unknown how different mutations in the same channel enhancing electrogenesis in sensory neurons results in such disti...

This report describes the case of a 62-year-old woman with type 2 diabetes and painful diabetic peripheral neuropathy, who, despite standard treatment, experienced persistent symptoms. Further investigation revealed erythromelalgia secondary to polycythemia vera, confirmed by bone marrow biopsy and...

: Erythromelalgia is a rare condition characterized by burning pain, redness, and warmth primarily in the extremities, usually worsened by heat and alleviated by cold. The objective of this study was to identify the top 10 priorities in pediatric erythromelalgia from multiple perspectives, including...

Red ear syndrome (RES) is a rare, poorly understood disorder characterized by episodic ear erythema and pain. Its pathophysiology remains unclear, with proposed associations to migraine, erythromelalgia, and rosacea. Existing treatments are often ineffective, emphasizing the need for novel approache...

: Erythromelalgia (EM) is an uncommon condition marked by recurring redness, intense burning sensations, and elevated limb warmth. This syndrome can be significantly debilitating, and finding effective treatment options often proves to be quite difficult. The symptoms can severely impact the quality...

In this study, we applied an induced pluripotent stem cell (iPSC)-based model of inherited erythromelalgia (IEM) to screen a library of 281 small molecules, aiming to identify candidate pain-modulating compounds. Human iPSC-derived sensory neuron-like cells, which exhibit action potentials in respon...

Pediatric neuropathic pain can be difficult to treat, may require a multimodal approach, and is often guided by adult literature given the paucity of pediatric studies. A healthy adolescent male presented with acute onset of severe bilateral lower extremity neuropathic pain diagnosed as erythromelal...

Erythromelalgia, a rare cutaneous pain syndrome, is characterized by acral burning pain and flushing, often alleviated by cold and rest. Primary erythromelalgia is caused by gain-of-function mutations of genes encoding for sodium channels, resulting in hyperexcitability of pain signaling neurons. Au...

Gain-of-function variants in the voltage-gated sodium channel Nav1.7, encoded by the SCN9A gene, have previously been identified in patients with erythromelalgia, a clinical diagnosis defined by intermittent attacks of painful, hot, swollen, and red skin, predominantly involving the hands and feet....

Polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, affects approximately 65 000 people in the US, with an annual incidence of 0.5 to 4.0 cases per 100 000 persons. Erythrocytosis (hemoglobin >16.5 mg/dL in men or...

Erythromelalgia is a condition characterized by intense burning pain, redness, and heat in the extremities that has garnered increasing attention in recent years. This literature review provides a comprehensive historical perspective and current update on primary erythromelalgia or PEM, categorizing...

Discovery efforts leading to the identification of cyclopentane carboxylic acid 31, a potent inhibitor of Na1.7 that showed high selectivity over Na1.5 and exhibited robust analgesic effects in an inherited erythromelalgia (IEM) transgenic mouse assay, are described herein. Key design elements that...

Thrombocytosis, defined as platelet counts >450 × 10⁹/L, is frequent in the pediatric population and usually secondary to inflammatory conditions or iron deficiency. Essential thrombocythemia (ET), a Philadelphia chromosome-negative myeloproliferative neoplasm, is exceptionally rare in childhood. Pe...

β-mannosidosis is an ultra-rare lysosomal storage disorder caused by a deficiency of β-mannosidase, which catalyzes the last step of glycoprotein degradation. Owing to the limited number of reported cases, information on the natural history of the disease and brain imaging is scarce. We report 6 new...

Sanwu Huangqin Decoction (SHD), a classic prescription for nourishing yin and clearing heat, is commonly used to treat febrile diseases, erythromelalgia, autoimmune liver diseases, and skin diseases. However, research on the quality standard of SHD is still in its infancy and has focused mainly on s...

Gain-of-function mutations in , which encodes the Nav1.7 voltage-gated sodium channel, are known to cause primary erythromelalgia (PEM). This condition is characterized by recurrent episodes of erythema, burning pain, and warmth in the extremities. These genetic insights have spurred the development...

Erythromelalgia is a rare condition characterized by severe paroxysmal pain in the extremities and erythema that leads to significant morbidity and incapacity. We report on the case of a female with a history of erythromelalgia, presenting with worsening bilateral leg pain and purple discoloration o...

Gain-of-function mutations which enhance activation of Na1.7, a widely expressed sodium channel in nociceptors, cause human pain disorders including inherited erythromelalgia (IEM). IEM is characterized by attacks of burning pain in distal extremities triggered by warmth, with cooling of affected li...

A 49-year-old woman presented with a 16-year history of burning pain, warmth, redness, and edema in both toes, feet, legs and calves. Despite extensive medical testing, including genetic analysis, no specific cause was identified. Initial treatments failed to improve symptoms, leading to impaired qu...

Erythromelalgia is a rare condition with no published estimates of prevalence from a diverse, nationwide cohort of American patients. We performed a cross-sectional analysis of the All of Us database to estimate the prevalence of erythromelalgia overall and by age groups. Of 410,361 participants, 47...

Polycythemia vera (PV) is a primary acquired marrow condition that causes erythrocytosis. It may present with erythromelalgia, pruritus, splenomegaly, and thrombotic events. Secondary causes of polycythemia should be ruled out before labeling a patient as having PV. Serum erythropoietin (EPO) level...

To expand understanding of the pathogenesis, presentations, and treatment of initially idiopathic small fiber polyneuropathy (SFN). We longitudinally readministered validated metrics to track disease course and treatment responses in a previously healthy woman with acute, postinfectious, skin biopsy...

Although warmth is a key sign of inflammatory skin lesions, an objective assessment and follow-up of the temperature changes are rarely done in dermatology. The recent availability of accurate, sensitive and cost-effective thermography devices has made the implementation of thermography in clinical...

Erythromelalgia is a rare neurovascular condition characterized by episodic burning pain, erythema, and increased temperature of the extremities. This condition, particularly challenging in pediatric patients due to its rarity and the complexities of pain management, often results in significant dis...

While voltage-gated sodium channels Nav1.7 and Nav1.8 both contribute to electrogenesis in dorsal root ganglion (DRG) neurons, details of their interactions have remained unexplored. Here, we studied the functional contribution of Nav1.8 in DRG neurons using a dynamic clamp to express Nav1.7L848H, a...

Raynaud's syndrome is a common finding in many autoimmune conditions. Accurately diagnosing Raynaud's, and differentiating it from mimicking conditions, is imperative in rheumatologic diseases. Raynaud's syndrome and Raynaud's mimickers, especially painful Raynaud's mimickers, can prove a diagnostic...

Erythromelalgia is a rare pain disorder that is underrecognized and difficult-to-treat. It is characterized by episodes of extremity erythema and pain that can be disabling; it may be genetic, related to an underlying systemic disease, or idiopathic. Considering the prominent cutaneous features char...

The management of erythromelalgia is challenging and requires multidisciplinary effort. Patient education is crucial as unsafe self-administered cooling techniques can lead to significant morbidity, including acral necrosis, infection, and amputation. The goal of management is pain control, reductio...

Red Ear Syndrome is a burning sensation and erythema of the ear, associated with a various number of disorders including migraine, trigeminal neuralgia, autoimmune disorders etc. Theories for RES pathophysiology have developed from current understandings of comorbid conditions. Characterizing the un...

Erythromelalgia is a rare disease characterized by a triad of recurrent burning pain, redness with pain, and hot flashes in the legs during attacks. We report the case of a 40-year-old woman who suffered from refractory erythromelalgia for 15 years and was successfully managed with Kampo medicine an...

The present study reports a case of osimertinib-induced erythromelalgia in a patient with metastatic lung adenocarcinoma. Osimertinib is an antineoplastic drug that irreversibly inhibits the epidermal growth factor receptor (EGFR) pathway by binding to the intracellular receptor tyrosine kinase site...

Erythromelalgia (EM), is a familial pain syndrome characterized by episodic 'burning' pain, warmth, and erythema. EM is caused by monoallelic variants in SCN9A, which encodes the voltage-gated sodium channel (NaV) NaV1.7. Over 25 different SCN9A mutations attributed to EM have been described to date...

Erythromelalgia is a rare syndrome with a generally unknown etiology. Whether primary or secondary, this condition is characterized by paroxysmal episodes of erythema, pain, and heat in the extremities. We report two cases of erythromelalgia occurring after the initiation of treatment with inflixima...

Essential thrombocythemia (ET) is a rare chronic myeloproliferative hematologic disorder, leading to an elevated platelet count. Two-thirds of patients are asymptomatic during their lifetime, while others may experience symptoms like redness, congestion, and erythromelalgia after long symptom-free i...

Leprosy, or Hansen's disease, is an ancient infectious disease characterized by varied clinical presentations influenced by the host's immune response. This study aimed to explore the atypical manifestations of Hansen's disease in a cohort of 15 biopsy-confirmed patients admitted to the Department o...

Hemorrhagic events are a rare but potentially fatal complication in patients with polycythemia vera (PV). We analyzed the characteristics of hemorrhagic events in 267 patients with PV. A median follow-up of 4.8 years revealed that 23 (8.6%) hemorrhagic events occurred. Significantly more hemorrhagic...

Erythromelalgia is a rare disorder characterized by episodic burning pain with redness and warmth of the extremities. Topical and systemic medications are the mainstay of management. We reviewed the published evidence for using procedural interventions to manage erythromelalgia, including their prop...

Botulinum neurotoxin type A BoNT/A is used off-label as a third line therapy for neuropathic pain. However, the mechanism of action remains unclear. In recent years, the role of voltage-gated sodium channels (Nav) in neuropathic pain became evident and it was suggested that block of sodium channels...

Erythromelalgia is a rare, highly debilitating disorder characterised by severe episodes of discomfort, erythema, and desquamation of the extremities. Its causes include genetic factors, medications, and several underlying medical conditions. This paper describes a novel cause of erythromelalgia thr...

Erythromelalgia, which has primary and secondary presentations, causes heat, pain, and redness in the skin. The condition seems to have an autonomic basis, with vasomotor dysfunction causing dilatation of some blood vessels and constriction of others. No consistently effective treatments have been r...

Essential thrombocytosis (ET) is a hematopoietic stem cell disorder in which the overproduction of platelets without a definable cause occurs. Its incidence is 1-2 per 100,000 population with female preponderance. These myeloproliferative disorders are associated with many dermatological manifestati...

Because one toxic component of Paralepistopsis acromelalga, clitidine, is not commercially available as a reagent and because standards are difficult to obtain, a quantitative NMR method that requires no standard was investigated for this study. To compare the quantitative values obtained using the...

There has been significant progress in our understanding of the molecular basis by which nociceptors transduce and transmit noxious (tissue damaging) stimuli. This is dependent on ion channels, many of which are selectively expressed in nociceptors. Mutations in such proteins have recently been link...

Cervical sympathetic or stellate ganglion blocks (SGBs) have been commonly used in the treatment of painful conditions like complex regional pain syndrome (CRPS). However, there is literature to suggest its utility in managing non-painful conditions as well. The focus of this literature review is to...

Single nucleotide polymorphisms are the most common form of DNA alterations at the level of a single nucleotide in the genomic sequence. Genome-wide association studies (GWAS) were carried to identify potential risk genes or genomic regions by screening for SNPs associated with disease. Recent studi...

Voltage-gated sodium channels (Nav) are key players in excitable tissues with the capability to generate and propagate action potentials. Mutations in the genes encoding Navs can lead to severe inherited diseases, and some of these so-called channelopathies show temperature-sensitive phenotypes, for...

Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with persistent pain. Chemogenetics has shown promise as a means to suppress such excitability, yet chemogenetic approaches suitable for human applications are needed. PSAM-GlyR is a modular system b...

Essential thrombocytosis (ET) is a rare haematological malignancy, with an incidence rate of 1.5-2.5/100,000 per year. For many patients with ET the first manifestation of their underlying disease is a thrombotic or haemorrhagic complication. A recent retrospective study revealed an incidence rate o...

Gain-of-function mutations in Scn9a, which encodes the peripheral sensory neuron-enriched voltage-gated sodium channel Na1.7, cause paroxysmal extreme pain disorder (PEPD), inherited erythromelalgia (IEM), and small fiber neuropathy (SFN). Conversely, loss-of-function mutations in the gene are linke...

Erythromelalgia is a descriptive term for severe burning pain and erythema in the distal extremities relieved by cold and exacerbated by heat. Pediatric case series to date are relatively small. We extracted and analyzed medical record data for 42 pediatric patients to describe clinical characterist...

Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative neoplasm that results in increased myeloproliferation. It is a debilitating disease characterized by the overproduction of red blood cells, but it also can result in increased white blood cells and platelets. Patients experie...

Primary erythromelalgia (EM) is a rare clinical syndrome characterized by recurrent erythema, burning pain and warmth of the extremities. The symptoms greatly compromise the patients' quality of life leading to severe disability. SCN9A mutations can be the cause of the disease. Dermatologists are of...

Primary erythromelalgia (PEM) is a rare condition characterized by severe burning pain, erythema, and increased temperature in the extremeties. Mutations in the Nav1.7 sodium channel encoded by the SCN9A are responsible for PEM. The pathophysiology of PEM is unclear, but the involvement of neurogeni...

Erythromelalgia is a rare disease characterised by a triad of a clinical syndrome of redness, warmth and painful extremities. We present the case of a male adolescent with no prior medical history who presents to our family medicine clinic with a 3-month history of bilateral feet erythema followed b...

Effective treatment of pain remains an unmet healthcare need that requires new and effective therapeutic approaches. NaV1.7 has been genetically and functionally validated as a mediator of pain. Preclinical studies of NaV1.7-selective blockers have shown limited success and translation to clinical s...

Erythromelalgia (EM) is a rare disorder characterized by episodic, burning pain associated with erythema and warmth of the extremities. The feet and hands are most commonly affected. The pain can be so severe that patients may engage in behaviors, sometimes extreme, to cool the affected areas and ch...

Erythromelalgia (EM) is a rare disease, which is still poorly characterized. In the present paper, we compared the hand perfusion of one female EM patient, under challenges, with a healthy control group. Using a laser Doppler flowmeter (LDF) with an integrated thermal probe, measurements were taken...

Voltage-gated sodium channels in peripheral nerves conduct nociceptive signals from nerve endings to the spinal cord. Mutations in voltage-gated sodium channel NaV1.7 are responsible for a number of severe inherited pain syndromes, including inherited erythromelalgia (IEM). Here, we describe the neg...

We show here that hyperpolarization-activated current (I ) unexpectedly acts to inhibit the activity of dorsal root ganglion (DRG) neurons expressing WT Nav1.7, the largest inward current and primary driver of DRG neuronal firing, and hyperexcitable DRG neurons expressing a gain-of-function Nav1.7 m...

Voltage-gated sodium channel Nav1.7, encoded by the SCN9A gene, has been linked to diverse painful peripheral neuropathies, represented by the inherited erythromelalgia (EM) and paroxysmal extreme pain disorder (PEPD). The aim of this study was to determine the genetic etiology of patients experienc...

Erythromelalgia is a rare syndrome characterised by recurrent erythema, heat and burning pain in the extremities. There are two types: primary (genetic) and secondary (toxic, drug-related or associated with other diseases). We report a 42-year-old woman who developed erythromelalgia after taking cyc...

In this Part 2 of a 2-part continuing medical education series, we review the epidemiology of peripheral vascular disease, its association with cutaneous symptoms, and the diagnosis and evaluation of cutaneous features of vascular disorders. As peripheral vascular disease becomes more prevalent glob...

Gain-of-function mutations in voltage-gated sodium channel Na1.7 cause severe inherited pain syndromes, including inherited erythromelalgia (IEM). The structural basis of these disease mutations, however, remains elusive. Here, we focused on three mutations that all substitute threonine residues in...

An 18-year-old female with a history of atopic march, hyperhidrosis, and eosinophilic esophagitis was diagnosed with erythromelalgia and gastrointestinal dysautonomia secondary to presumed autoimmune small fiber neuropathy. The patient experienced significant clinical improvements after the initiati...

Mexiletine, a class IB antiarrhythmic, is a structural analog of lidocaine. Our knowledge of mexiletine overdose is based on lidocaine overdose reports. Only a few cases of mexiletine overdose have been reported, including fatal overdoses. Mexiletine toxicity primarily affects the central nervous, c...

In children, erythromelalgia is a rare chronic pain syndrome characterized by erythema, severe burning pain, and itching of affected feet. Unfortunately, there is no definitive therapy available currently. Here, we report a case of primary erythromelalgia and the treatment response in a 10-year-old...

The applicability of a method for simultaneous analysis of Acromelic acids A, B, and Clitidine, which are venomous constituents of Paralepistopsis acromelalga, was assessed for three simulations: tempura, chikuzenni, and soy sauce soup. All components were detectable for all cooking methods. No inte...

Erythromelalgia is a rare disease, involving pain, edema, redness, and hyperthermia in the limbs. It is extremely refractory to drugs, has no defined treatment, and causes psychological comorbidities in the patient. We describe a case of erythromelalgia involving a 17-year-old boy who had been suffe...

The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical pre...

The genital skin may be affected by a variety of dermatoses, be it inflammatory, infectious, malignant, idiopathic, or others. The red scrotum syndrome is characterized by persistent erythema of the scrotum associated with a burning sensation, hyperalgesia, and itching. Its cause is unknown, but pro...

Erythromelalgia (EM) is a rare disease characterized by recurrent episodes of erythema, pain, and burning dysesthesia, most often involving the extremities. A rare, atypical presentation involves the face. There are no current guidelines, with overall lack of consensus for the treatment of EM, and t...

Voltage-gated sodium channels are essential for the generation and conduction of electrical impulses in excitable cells. Sodium channel Na 1.7, encoded by the SCN9A-gene, has been of special interest in the last decades because missense gain-of-function mutations have been linked to a spectrum of ne...

Paroxysmal vascular acrosyndromes are related to a peripheral vasomotor disorder and presented as paroxysmal color changes of the fingers. They include primary Raynaud's phenomenon (RP), which is the most common, secondary RP and erythermalgia. They are to be distinguished from non-paroxysmal acrosy...

Erythromelalgia is a rare neurovascular disease that causes episodes of pain, redness, and warmth in the extremities, and can be debilitating. Currently, there is no universally effective treatment for erythromelalgia. As the precise etiology of erythromelalgia remains obscure, presently available t...

Premature loss of primary teeth can occur as a consequence of dental trauma, neonatal tooth extraction, early childhood caries, or periodontal problems, or it can be a manifestation of systemic disease. This review aims to present systemic disorders that can lead to premature loss of deciduous teeth...

Erythromelalgia is a disabling syndrome of paroxysmal vasodilation affecting the feet, hands and face characterised by patient's cooling behaviour to achieve symptom relief. It can be primary or secondary and although a rare disorder it has been described in children and adolescents. We describe the...

Vascular acrosyndromes are characterized by sparse, uniform clinical manifestations and a variety of possible pathomechanisms. The present article focuses on the functional entities. Raynaud phenomenon is based on cold- or stress-induced vasospasms of acral arteries. It is defined by the color chang...

Erythromelalgia is a rare clinical syndrome involving erythema, warmth, and burning pain in one or more of the extremities. Primary erythromelalgia is idiopathic and can begin during childhood or adulthood. In the pediatric population, auricular erythromelalgia is rare, and its etiology is not well...

Cellulitis is among the more common conditions diagnosed and treated within pediatric emergency departments. However, unusual distribution, recurrence, and/or poor response to antibiotics may point towards another pathologic process. This case presentation illustrates a teenager with recurrent episo...

Primary erythromelalgia is a rare autosomal-dominant condition due to pathogenic variant in the SCN9A gene, characterized by childhood onset of excruciating pain, redness, and warmth of acral sites. Patients often resort to ice water baths and other cooling measures to manage the discomfort. Hypothe...

Because typical and atypical features of small fibre polyneuropathy (SFN) in the skin have not been fully elucidated, the diagnosis is often made by the exclusion of alternative conditions rather than by its identification as a primary syndrome. The objective of this study was to characterize dermat...

Cutaneous reactions after COVID-19 vaccination have been commonly reported; however, histopathologic features and clinical correlations have not been well characterized. We evaluated for a history of skin biopsy all reports of reactions associated with COVID-19 vaccination identified in an internati...

A 37-year-old man with severe obstructive sleep apnea presented to the emergency department with burning pain, redness and swelling in his hands and feet, worsening for several weeks. Pertinent laboratory studies revealed polycythemia. Erythromelalgia is a clinical diagnosis characterized by painful...

There is growing evidence that not only the novel coronavirus disease (COVID-19) but also the COVID-19 vaccines can cause a variety of skin reactions. In this review article, we provide a brief overview on cutaneous findings that have been observed since the emerging mass COVID-19 vaccination campai...

We report the first case, to our knowledge, of a patient who developed erythromelalgia after receiving oestrogen-progestin replacement therapy (Femoston). The patient had complete remission after taking glycyrrhizin and pregabalin for 3 months. This case expands the spectrum of erythromelalgia and p...

In this case report, we describe the difficulty in finding a suitable treatment for a nine-year-old girl with erythromelalgia. Initially, she could only find pain relief through immersion of her hands and feet in buckets of cool water. Her pain did not respond to outpatient treatments, and she was u...

Red Ear Syndrome is an uncommon disorder that can affect all age groups. It is frequently referred to Dermatology as it can present similarly to erythromelalgia. Although the exact pathophysiology is unknown, a common hypothesis suggests a shared pathophysiological background with migraine due to th...

Erythromelalgia is a rare neurovascular pain condition characterized by erythematous, warm, and painful extremities. Symptoms are exacerbated by heat and relieved by cooling. Treatment is challenging and focuses on symptom control with various medications and therapies targeted toward eliminating de...

Erythromelalgia is an infrequent syndrome with a profound impact on quality of life. Its management is usually challenging and multiple treatments have been reported with variable response rates. To the best of our knowledge, we present the first case of erythromelalgia successfully treated with top...

Human induced pluripotent stem cells (hiPSCs) are a promising approach to study neurological and neuropsychiatric diseases. Most methods to record the activity of these cells have major drawbacks as they are invasive or they do not allow single cell resolution. Genetically encoded voltage indicators...

Primary erythromelalgia, while uncommon, may significantly decrease the quality of life of those affected. While many patients with erythromelalgia require systemic therapy, there is no standard of care for this condition. Herein, we report a 7-year-old girl who experienced resolution of erythromela...

The symptoms of a rheumatic disease may also be a sign of a proliferative process. These include conditions that present with skin and vascular changes such as systemic sclerosis and Raynaud's phenomenon with peripheral ischaemia and ulceration. Furthermore, the less common conditions - erythromelal...

Primary erythrocytic (PEM) is a rare autosomal dominant single gene disease. Most of the changes of gene loci can be found by whole exon gene sequencing, and the clinical symptoms and patient survival can be improved by specific site-to-site drug treatment. The other manifestations of this patient p...

An isolation method for Acromelic acids A, B and Clitidine, which are venomous constituents of Paralepistopsis acromelalga was developed. Highly purified products were obtained from the mushroom extract using silica gel, ODS, ion-exchange column chromatography and preparative TLC. Using those result...

Erythermalgia, a rare painful disorder, is characterized by recurrent pain attacking, warmth, and erythema that mainly involves the distal extremities. Red ear syndrome shares similar clinical features of erythermalgia afflicting the external ear with unilateral/bilateral distribution. The treatment...

A married couple of a 62-year-old woman and a 64-year-old man as well as their neighbor, an 84-year-old woman, visited the hospital complaining of a burning sensation on their hands and feet that had presented on the same day. They had consumed mushrooms that had been picked on a mountain five days...

Erythromelalgia (EM) is a rare autosomal dominant neuropathy characterized by the combination of severe burning pain and erythematous warm extremities. Chronic pain control is most often unsuccessful and a completely effective therapy is yet to be identified. Recent studies have reported significant...

Vixotrigine is a voltage and use dependent sodium channel blocker currently under development for treatment of various neuropathic pain indications. The objective of this work was to develop a population pharmacokinetic model and assess effects of various covariates on pharmacokinetic parameters of...

Erythromelalgia (EM) is a rare autosomal dominant neuropathy characterized by the combination of severe burning pain and erythematous warm extremities. Chronic pain control is most often unsuccessful and a completely effective therapy is yet to be identified. Recent studies have reported significant...

Acral vascular syndrome clinically presents as digital ischemia with Raynaud's phenomenon and erythromelalgia but can be rarely seen in the malignant condition. Patients may present pain, permanent digital blanching or cyanosis, and desquamation or ulceration of the fingers. Acral vascular syndrome...

Secondary polycythemia (SP) occurs as a result of increase erythropoietin levels most commonly as a result of tissue hypoxia. Symptoms such as erythromelalgia, pruritis, and bleeding, which are frequently seen in polycythemia vera (PV), do not commonly occur in SP. Phlebotomy is considered one of th...

Cold hypersensitivity in the hands and feet is a common clinical symptom in Asian women. Currently, treatment of cold hypersensitivity in the hands and feet is still limited to traditional Chinese medicine, mainly herbal medicine. However, many patients with cold hypersensitivity in the hands and fe...

Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. A provider-facing registry-based study collected cases of cutaneous manifestations afte...

Erythromelalgia is a rare neurovascular disorder characterized by erythema, warmth, and episodic burning pain, often felt in the face, hands, and feet. Symptoms are typically worse with heat, exercise, stress, and during the overnight hours. Management often requires a multidisciplinary approach, in...

A 4-year-old boy with atypical, complete DiGeorge and CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities and ear abnormalities) syndromes presented with frequent episodes of a painful, markedly erythematous eruption associated with swelling. Evaluation reveal...

We describe a case of a woman with uncomplicated Type 2 diabetes mellitus, presenting with severe burning pains and intense redness of the legs, for which only cooling could provide relief. Although the description was classic of erythromelalgia, the lack of familiarity of the disorder caused consid...

The sensation of pain is common to both animals and human beings. Its threshold, intensity, tolerability, and characteristics are variable and depend on ethnicity, gender, stress exposure, co-existing mental disorders, such as depression or anxiety, social and economical background, as well as on ge...

Mutations in the voltage-gated sodium channel Nav1.7 are linked to human pain. The Nav1.7/N1245S variant was described before in several patients suffering from primary erythromelalgia and/or olfactory hypersensitivity. We have identified this variant in a pain patient and a patient suffering from s...

Erythromelalgia is a rare hereditary channelopathy affecting the Nav1.7 sodium channel. Patients afflicted with this condition suffer from pain in their hands and feet, with vasomotor changes including flushing and redness to the distal upper and lower extremities. Current treatment modalities for t...

Erythromelalgia (EM) is a rare disorder, of which the pathophysiology is poorly understood. Though primary EM is thought to be an autosomal-dominant inherited disorder or of idiopathic origin, secondary EM is associated, most often, with myeloproliferative diseases. Pain management is the primary th...

To assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). Thirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve condu...

There is a pressing need for understanding of factors that confer resilience to pain. Gain-of-function mutations in sodium channel Nav1.7 produce hyperexcitability of dorsal root ganglion neurons underlying inherited erythromelalgia, a human genetic model of neuropathic pain. While most individuals...

Mutations in voltage-gated sodium channels (Navs) can cause alterations in pain sensation, such as chronic pain diseases like inherited erythromelalgia. The mutation causing inherited erythromelalgia, Nav1.7 p.I848T, is known to induce a hyperpolarized shift in the voltage dependence of activation i...

The small-fiber polyneuropathies (SFN) are a class of diseases in which the small thin myelinated (Aδ) and/or unmyelinated (C) fibers within peripheral nerves malfunction and can degenerate. SFN usually begins in the farthest, most-vulnerable axons, so distal neuropathic pain and symptoms from micro...

A 19-year-old-woman experienced severe burning pain in the lower extremities with erythema and swelling. She was diagnosed with primary erythromelalgia (PE). The pain was unresponsive to medications but relieved by immersing her feet in cold water. We performed a multilevel lumbar sympathetic gangli...

The voltage-gated sodium channel Na 1.7 is essential for adequate perception of painful stimuli. Mutations in the encoding gene, SCN9A, cause various pain syndromes in humans. The hNa 1.7/A1632E channel mutant causes symptoms of erythromelalgia and paroxysmal extreme pain disorder (PEPD), and its ma...

In children, erythromelalgia is a rare but difficult to manage condition that results in bilateral episodic pain and redness in distal extremities. It is heat intolerant and relieved by cooling. Management of erythromelalgia is difficult and requires a complex multidisciplinary approach. We present...

Several pharmacological treatments are recommended for Raynaud's phenomenon (RP) secondary to systemic sclerosis, but they only have modest efficacy. A way to efficiently identify new drugs is drug repurposing, which can be based on signature matching. The signature could be derived from chemical st...

Erythema ab igne is a thermal-associated skin condition that can occur secondary to persistent direct or indirect contact with heat. Historically, erythema ab igne has been linked to fireplace and stove exposures; more recently, it has been associated with heaters, hot water bottles, and laptops. A...

Small-fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology. The data of four children/adolescents presenting with erythromelalgia and neuropathic pain from 2014 to 2019 were collected retrospectively...

The aim of the studywas to determine the risk of thrombosis among patients with Essential thrombocythemia based on the modern criteria of diagnosis and to reveal the treatment accordingmethods of research in Georgia. We analyzed clinical manifestations of 25 cases of Essential thrombocythemia diagno...

Olmsted syndrome is a genodermatosis characterized by painful and mutilating palmoplantar keratoderma (PPK) that progresses from infancy onward and lacks an effective treatment. It is most often caused by mutations in the transient receptor potential vanilloid 3 (TRPV3) gene. In animal models and ke...

Contactin-associated protein 2-like (caspr2) antibodies have been discovered recently. Since then a multitude of patients with caspr2 antibodies presenting with different neurological symptoms have been reported. Here, we describe three patients with caspr2 antibodies with different types of pain/no...

Myeloproliferative neoplasms are a heterogeneous group of disorders resulting from the abnormal proliferation of one or more terminal myeloid cells-established complications include thrombosis and haemorrhagic events; however, there is limited evidence to suggest an association with arterial hyperte...

A 61-year-old woman with a history of primary aldosteronism caused by unilateral hyperplasia of the adrenal gland presented with a 2-week history of redness and severe pain in the right thumb and thenar regions. She had initially visited a dermatologist and was diagnosed with cellulitis and treated...

Red Ear Syndrome (RES) is a condition often considered to be a localized form of erythromelalgia. It can be related to structural cervical defects or idiopathic. RES is generally very difficult to treat. A 57-year-old male presented to the dermatology clinic complaining of a 4-month history of inter...

There is a huge need for pharmaceutical agents for the treatment of chronic Neuropathic Pain (NP), a complex condition where patients can suffer from either hyperalgesia or allodynia originating from central or peripheral nerve injuries. To date, the therapeutic guidelines include the use of tricycl...

Red ear syndrome has been reported in the literature to have similarities to erythromelalgia with auricular involvement; however, the distinction between the two is controversial. Red ear syndrome has previously been classified as idiopathic (primary) or secondary, with headaches being the most comm...

Erythromelalgia (EM) is a rare disorder of small nerve fibres that leads to painful flushing and burning paresthesisas of the distal extremities and is typically associated with heat or physical activity; relief is found using cooling measures. Its effects are often debilitating in the general popul...

Erythromelalgia is a rare disease that is associated with hemato-oncological diseases or after taking certain drugs and toxins, but it can also occur as an independent clinical picture, for example, due to mutations in the sodium channel Na1.7. Clinically, there is a characteristic triad of attack-l...

Clinical recognition of vascular acrosyndromes is often challenging. The term Raynaud's phenomenon (RP) is commonly overused to describe any form of cold-related disorder. This study aims to formally evaluate peripheral vascular symptoms affecting the population, aged ≤ 40 years, and identify any co...

We identified a homozygous missense mutation in the gene encoding NAD synthesizing enzyme NMNAT2 in two siblings with childhood onset polyneuropathy with erythromelalgia. No additional homozygotes for this rare allele, which leads to amino acid substitution T94M, were present among the unaffected re...

A 68-year-old female with a history of sporadic type and presumably secondary erythromelalgia with chronic intractable pain presented for foot surgery. The procedure was performed with combined general anesthesia and regional anesthesia consisting of the placement of a popliteal pain catheter for po...

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 clini...

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...

Red scrotum syndrome (RSS) (also known as male genital dysesthesia) is a rarely recognized entity characterized by scrotal erythema accompanied by a burning sensation, pain, hyperesthesia/dysesthesia, increased temperature and pruritus. Although its physiopathology is unknown, it has increasingly be...

The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (NaV) 1.7. Still, recent studies targeting NaV1.7 in clinical trials have provided conflicting results. Here, we differentiated induced pluripotent stem cells from IEM patients wi...

Acute pain is adaptive, but chronic pain is a global challenge. Many chronic pain syndromes are peripheral in origin and reflect hyperactivity of peripheral pain-signaling neurons. Current treatments are ineffective or only partially effective and in some cases can be addictive, underscoring the nee...

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 op...

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 mod...

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 different...

Inherited erythromelalgia (IEM), caused by mutations in Na1.7 channel is characterized by episodic neuropathic pain triggered especially by warm temperature. However, the mechanism underlying the temperature-dependent episodic attacks of IEM remains elusive. We investigated the electrophysiological...

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 pa...

Erythromelalgia is a rare and very difficult to treat pain syndrome that usually presents as severe bilateral burning pain in the extremities. Here we present a case of a 34-year-old female with erythromelalgia who we treated successfully with a lumbar epidural infusion of ropivacaine and fentanyl....

Erythermalgia is a rare cutaneous disease characterized by episodic attacks of burning pain, erythema, and increased temperature. It primarily involves the extremities, with possible extensions to the ears, face, neck, and scrotum; in rare instances, it may afflict the ears, face, or the scrotum alo...

Selective block of Na1.7 promises to produce non-narcotic analgesic activity without motor or cognitive impairment. Several Na1.7-selective blockers have been reported, but efficacy in animal pain models required high multiples of the IC for channel block. Here, we report a target engagement assay u...

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 exp...

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 Nav1.7 cause painful neuropathies, such as i...

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 1.7 have been shown to be causal in primary erythromelalgia. We present a patient with erythromelalgia, pain attacks and hyperosmia with a mu...

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 an...

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...

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 app...

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 disord...

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, thermoa...

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 erythr...

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 su...

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 tho...

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 conditio...

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...

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 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 wit...

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 lymphat...

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...

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 path...

Inherited erythromelalgia (IEM) is a chronic pain disorder caused by gain-of-function mutations of peripheral sodium channel Nav1.7, in which warmth triggers severe pain. Little is known about the brain representation of pain in IEM. Here we study two subjects with the IEM Nav1.7-S241T mutation usin...

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). Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful...

Erythromelalgia (EM) is a rare neurovascular disorder characterized by intermittent severe burning pain, erythema, and warmth in the extremities on heat stimuli. To investigate the underlying pathophysiology, peripheral axonal excitability studies were performed and changes with heating and therapy...

Fabry disease is an X-linked genetic disorder caused by the mutations of α-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary er...

Corticosteroids (CS) may benefit certain patients with erythromelalgia. Our objective was to determine clinical predictors of corticosteroid-responsive erythromelalgia. Patients with erythromelalgia who received CS were identified and stratified into corticosteroid nonresponders (NRs), partial corti...

Erythromelalgia is a rare intermittent vascular acrosyndrome characterized by the combination of recurrent burning pain, warmth and redness of the extremities. It is considered in its primary form as an autosomal dominant neuropathy related to mutations of SCN9A, the encoding gene of a voltage-gated...

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. Na1.7 is preferentially expressed within peripheral sensory and sympathetic neurons. Here, we describe a...

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...

Erythromelalgia is often refractory and resistant to many forms of treatment. Numerous therapeutic options have been tried, but effective treatment remains elusive. The sympathetic nervous system has been involved in various painful conditions of neuropathic, vascular, and visceral origin. Sympathet...

Gain-of-function mutations in SCN9A gene that encodes the voltage-gated sodium channel NaV1.7 have been associated with a wide spectrum of painful syndromes in humans including inherited erythromelalgia, paroxysmal extreme pain disorder and small fibre neuropathy. These mutations change the biophysi...

Leo Buerger, MD, was the first to describe dependent rubor associated with marked atherosclerosis. Historically, dependent rubor has been described as erythromelalgia (or erythromelia), and terms such as chronic rubor, reactionary rubor, induced rubor, and hyperemic response have also been used to d...

Erythromelalgia is a clinical diagnosis based on intermittent warmth, erythema, and pain in the distal extremities. One problem facing physicians is how to objectively test for this disease. Given that other painful conditions of the distal extremities (ie, neuropathy related to human immunodeficien...

Voltage-gated sodium channels (Navs) are crucial for the generation and propagation of action potentials in all excitable cells, and therefore for the function of sensory neurons as well. Preclinical research over the past 20 years identified three Nav-isoforms in sensory neurons, namely Nav1.7, Nav...

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 i...

The Na1.7 sodium channel is preferentially expressed within dorsal root ganglion (DRG) and sympathetic ganglion neurons. Gain-of-function mutations that cause the painful disorder inherited erythromelalgia (IEM) shift channel activation in a hyperpolarizing direction. When expressed within DRG neuro...

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 encodi...

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 Nav1.7 have been shown to be able to render Nav1.7-exp...

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 pai...

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, c...

To review our clinical experience of this rare condition and describe the clinical features and response to therapy in a cohort of patients with erythromelalgia (EM), a rare condition, characterised by paroxysmal hyperthermia of the extremities with erythema, pain and intense burning. A review was m...

The Nav1.7 channel critically contributes to the excitability of sensory neurons, and gain-of-function mutations of this channel have been shown to cause inherited erythromelalgia (IEM) with neuropathic pain. In this study, we report a case of a severe phenotype of IEM caused by p.V1316A mutation in...

Many skin and skin-related diseases affect the sexes unequally, with attendant implications for public health and resource allocation. To evaluate better the incidence of skin and skin-related diseases affecting males vs. females, we reviewed published population-based epidemiology studies of skin d...

Polycythaemia vera (PV), a condition characterized by blood hyperviscosity due to the expansion of the erythrocyte mass is the most common entity among all Philadelphia chromosome-negative myeloproliferative neoplasms. Arterial and venous thrombotic events are leading determinants of morbidity and m...

The sodium channel Nav 1.9 is expressed in peripheral nociceptors and has recently been linked to human pain conditions, but the exact role of Nav 1.9 for human nociceptor excitability is still unclear. C-nociceptors from two patients with late onset of erythromelalgia-like pain, signs of small fibe...

Small fiber neuropathy (SFN) is a debilitating condition that often leads to pain and autonomic dysfunction. In the last few decades, SFN has been gaining more attention, particularly in adults. However, literature about SFN in children remains limited. The present article reports the cases of 2 ado...

Mutations in the voltage-gated sodium channel Nav1.7 are linked to inherited pain syndromes such as erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). PEPD mutations impair Nav1.7 fast inactivation and increase persistent currents. PEPD mutations also increase resurgent currents, whi...

Erythromelalgia (EM) is a debilitating neurovascular disease that is refractory to numerous treatment modalities. The present study reported the case of a 72-year-old woman diagnosed with EM secondary to polycythemia vera (PV), who was effectively treated with the use of patient-controlled epidural...

The Red Ear syndrome (RES) is an intriguing syndrome originally described for the first time nearly 20 years ago. RES is characterized by unilateral/bilateral episodes of pain and burning sensation of the ear, associated with ipsilateral erythema. RES episodes are indeed isolated in some patients, b...

There is a need for more effective pharmacotherapy for chronic pain, including pain in inherited erythromelalgia (IEM) in which gain-of-function mutations of sodium channel NaV1.7 make dorsal root ganglion (DRG) neurons hyperexcitable. To determine whether pain in IEM can be attenuated via pharmacot...

Voltage-gated sodium channel Nav1.7 is a central player in human pain. Mutations in Nav1.7 produce several pain syndromes, including inherited erythromelalgia (IEM), a disorder in which gain-of-function mutations render dorsal root ganglia (DRG) neurons hyperexcitable. Although patients with IEM suf...

Erythromelalgia is a rare condition characterized by burning pain, erythema and increased temperature of the hands or the feet. Its etiology is not completely understood but it is believed that the underlying cause is a peripheral vascular dysfunction that leads to simultaneous tissue hypoxia and hy...

Fabry disease is a rare X-linked metabolic disorder characterized by a deficiency in the enzyme alpha-galactosidase A. Both males and females can be affected. The main presenting symptom is pain in the extremities, whereas at a more advanced stage, the manifestations include hypertrophic cardiomyopa...

Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old...

We present a 49-year-old man with type I erythromelalgia, demonstrating a newly reported histological feature of striking perivascular mucin. There is a single previously reported case in the literature describing these histological features. This patient had a comorbid history of primary myelofibro...

The evaluation and management of childhood pain syndromes of neuromuscular origin have distinct challenges, as the patterns of disease presentation and the ability of a child to describe symptoms may differ from that of an adult. Advances in scientific and clinical knowledge are leading to significa...

Paralepistopsis acromelalga, formerly known as Clitocybe acromelalga, is a rare poisonous mushroom. The mycotoxins in this mushroom cause symptoms resembling those of erythromelalgia; however, its pathogenesis remains unclear. In this report, a patient who received nicotinic acid treatment for P. ac...

In common with other chronic pain conditions, there is an unmet clinical need in the treatment of inherited erythromelalgia (IEM). TheSCN9Agene encoding the sodium channel Nav1.7 expressed in the peripheral nervous system plays a critical role in IEM. A gain-of-function mutation in this sodium chann...

Inherited erythromelalgia, the first human pain syndrome linked to voltage-gated sodium channels, is widely regarded as a genetic model of human pain. Because inherited erythromelalgia was linked to gain-of-function changes of sodium channel Na(v)1.7 only a decade ago, the literature has mainly cons...

Thoracic sympathetic ablation was introduced over a century ago. While some of the early indications have become obsolete, new ones have emerged. Sympathetic ablation is being still performed for some odd indications thus prompting the present study, which reviews the evidence base for current pract...

Erythromelalgia (EM) is an uncommon condition characterized by erythema, increased skin temperature, and burning pain, most frequently occurring in the lower extremities. The pain is generally very severe and treatment can be extremely challenging, especially in the pediatric and adolescent populati...

Gain-of-function mutations in the tetrodotoxin (TTX) sensitive voltage-gated sodium channel (Nav) Nav1.7 have been identified as a key mechanism underlying chronic pain in inherited erythromelalgia. Mutations in TTX resistant channels, such as Nav1.8 or Nav1.9, were recently connected with inherited...

Erythromelalgia is a rare disorder associated with neuropathic pain that commonly affects the lower extremities. This pain is often refractory to multimodal treatment. Both pharmacologic management and interventional anesthetic blocks have been used with varying and often limited success. To date, l...

Primary erythromelalgia (PE ORPHA90026) is a rare autosomal dominant neuropathy characterized by the combination of recurrent burning pain, warmth and redness of the extremities. The incidence rate of PE ranges from 0.36 to 1.1 per 100,000 persons. Gender ratio differs according to different studies...

Seven patients diagnosed with erythromelalgia (EM) were investigated by microneurography to record from unmyelinated nerve fibers in the peroneal nerve. Two patients had characterized variants of sodium channel Nav1.7 (I848T, I228M), whereas no mutations of coding regions of Navs were found in 5 pat...

The SCN9A gene codes for the sodium voltage-gated channel NaV 1.7. Gain of function mutations cause pain disorders such as primary erythromelalgia, paroxysmal extreme pain disorder, and small fiber neuropathy. Loss of function mutations lead to congenital insensitivity to pain. We report the case of...

Postural tachycardia syndrome (POTS) is a syndrome of excessive tachycardia with orthostatic challenge, and relief of such symptoms with recumbence. There are several proposed subtypes of the syndrome, each with unique pathophysiology. Numerous symptoms such as excessive tachycardia, lightheadedness...

A 15-year-old girl diagnosed with erythromelalgia was admitted to the hospital with severe pain in her feet associated with burning, pruritus, erythema, and swelling. She had not responded to conventional management and received some relief only from cold bath immersions, which resulted in chronic b...

The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is exemplified by the heterogeneity of clinical phenotypes associated with its mutation. Gain-of-function mutations are typically pain-causing and have been associated with inherited erythromelalgia (IEM) and paroxysmal ex...

The skin is a morphologically complex organ that serves multiple complementary functions, including an important role in thermoregulation, which is mediated by a rich vasculature that is innervated by sympathetic and sensory endings. Two autosomal dominant disorders characterized by episodes of seve...

Raynaud’s phenomenon (RP) is characterised by paroxysmal reversible episodes of vasospasm, usually involving peripheral small vessels of the fingers or toes and resulting in a triple-colour change starting with pallor and followed by cyanosis and erythema. Attacks are typically triggered by cold or...

Although erythromelalgia (EM) has been documented in the literature for almost 150 years, it is still poorly understood. To overcome this limitation, we examined the spatial distribution of epidemic EM, and explored the association between temperature fluctuation and epidemic EM outbreaks in China....

The human voltage-gated sodium channel Nav1.7 plays a crucial role in transmission of noxious stimuli. The inherited pain disorder erythromelalgia (IEM) has been linked to Nav1.7 gain-of-function mutations. Here we show that the IEM-associated Q875E mutation located on the pore module of Nav1.7 prod...

Microneurography is a unique neurophysiological technique allowing direct recording of unmyelinated postganglionic sympathetic or afferent nociceptive fibers by tungsten needles inserted into a peripheral nerve fascicle. In recent years, microneurography has been used to ascertain autonomic impairme...

Dozens of epidemic erythromelalgia (EM) outbreaks have been reported in China since the mid-twentieth century, and the most recent happened in Foshan City, Guangdong Province early 2014. This study compared the daily case counts of this recent epidemic EM outbreak from February 11 to March 3 with Ba...

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increase in blood platelets and dominated by a predisposition to vascular events. Cutaneous manifestations can complicate its course. itching has been the most common symptom reported; however, the percentage has ran...

Erythromelalgia is a rare clinical syndrome characterized by erythema, increased temperature, and severe burning pain that can be aggravated by warmth or relieved by cold. Erythromelalgia occurs either as a primary, idiopathic form, or secondary to a number of diseases and conditions. Although fairl...

Essential thrombocythemia (ET) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by sustained thrombocytosis and megakaryocytic hyperplasia. It is an uncommon hematological malignancy which primarily affects elderly individuals. The rational of this study was to determi...

Erythromelalgia (EM) is a rare disabling clinical syndrome more commonly known to affect the lower extremities. There is no single effective treatment for this disease that often requires a multidisciplinary approach. Herein, we report the case of a 31-year-old woman affected by primary erythromelal...

Vascular acrosyndromes are associated with vasomotor disorders. They may be paroxysmal, like Raynaud's phenomenon, whitening of the fingers on exposure to cold, or erythromelalgia, a painful form of erythema induced by exposure to heat. Others are permanent or semi-permanent, such as acrocyanosis, c...

Erythermalgia is a very rare acrosyndrome mainly characterized by lower limbs pain. It is either primitive or secondary. Concomittence of erythermalgia and diabetes is a coincidence and since the latter induces neuropathic and vascular lesions, erythermalgia is then considered as a consequence. We r...

The Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conse...

Voltage-gated sodium channels (Nav) are widely expressed as macro-molecular complexes in both excitable and non-excitable tissues. In excitable tissues, the upstroke of the action potential is the result of the passage of a large and rapid influx of sodium ions through these channels. NaV dysfunctio...

Polycythemia vera is a rare myeloproliferative disease. Cutaneous symptoms are uncommon. We report about a 72-year-old female patient with JAK2(V617F) -positive polycythemia who developed peripheral sensorimotor axonal neuropathy and erythromelalgia. Possible causes and treatment are discussed.

Migraine-like cerebral transient ischemic attacks (MIAs) and ocular ischemic manifestations were the main presenting features in 10 JAK2(V617F)-positive patients studied, with essential thrombocythemia (ET) in 6 and polycythemia vera (PV) in 4. Symptoms varied and included cerebral ischemic attacks,...

Mushrooms are a recognized component of the human diet, with versatile medicinal properties. Some mushrooms are popular worldwide for their nutritional and therapeutic properties. However, some species are dangerous because they cause toxicity. There are many reports explaining the medicinal and/or...

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 NaV1.7 or in other pain-related genes and...

Essential thrombocythemia is a rare type of myeloproliferative disorder. Cerebral, myocardial, and peripheral thrombosis are all frequent complications of the disease. A 71-year-old man presented with severe coronary artery disease, associated with cerebral vascular ischemic changes and erythromelal...

This open-label, prospective, observational study aimed to evaluate treatment response, efficacy therapy and safety to IFN α-2b for the essential thrombocythemia (ET) and polycythemia vera (PV) with JAK2V617F positive mutation. A total of 123 ET patients received IFNα-2b therapy with JAK2V617F posit...

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 gai...

Raynaud's phenomenon (RP) is characterized by repeated vasospastic attacks of the distal extremities induced by cold, humidity, vibrations or emotional stress. It typically presents a triphasic colour change from white (palor; vasoconstriction) to blue (cyanosis) and red (reactive hyperaemia). The s...

Erythermalgia is a rare cutaneous disorder characterized by attacking of erythema, pain and increased temperature, which primarily involves the extremities and may infrequently extend to the neck, face, ears and even the scrotum. We reported an 18-year-old woman who presented with 3 years history of...

Erythermalgia is a peripheral vascular disease triggered by exposure to heat. The primary infantile form is rare. No cases have been described in infants. We report a case in a 6-month-old child revealed by crying bouts associated with erythema of the lower limbs. A 6-month-old child was brought in...

Olmsted syndrome (OS) is a rare keratinizing disorder characterized by excessive epidermal thickening of the palms and soles, with clinical and genetic heterogeneity. Approximately 50 cases have been reported, with the molecular basis described in only 9. Recently, TRPV3 (transient receptor potentia...

Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδ and C) fibers. Voltage-gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where NaV 1.7, NaV 1.8, a...

The discovery of genetic variants that substantially alter an individual's perception of pain has led to a step-change in our understanding of molecular events underlying the detection and transmission of noxious stimuli by the peripheral nervous system. For example, the voltage-gated sodium ion cha...

Erythromelalgia is a rare clinical syndrome characterized by episodic attacks of burning pain, erythema, and increased temperature, primarily affecting the extremities, and in rare instances, involving the ear, face, neck, and the scrotum. The dermatoscopic features of erythromelalgia in a case with...

Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited "paroxysmal extreme pain disorder" (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes...

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 treatm...

Erythromelalgia due to heterozygous gain-of-function SCN9A mutations usually presents as a pure sensory-autonomic disorder characterized by recurrent episodes of burning pain and redness of the extremities. We describe a patient with an unusual phenotypic presentation of gross motor delay, childhood...

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 ca...

Erythromelalgia is a rare condition characterized by constant or paroxysmal burning pain, erythema, and the elevation of skin temperature in the extremities. Recently, the impairment of C-fiber function due to autoimmune system involvement is considered as the primary cause of erythromelalgia. Howev...

Small fibre neuropathy (SFN) is characterised by structural injury selectively affecting small diameter sensory and/or autonomic axons. The clinical presentation is dominated by pain. SFN complicates a number of common diseases such as diabetes mellitus and is likely to be increasingly encountered....

The link between sodium channel Nav1.7 and pain has been strengthened by identification of gain-of-function mutations in patients with inherited erythromelalgia (IEM), a genetic model of neuropathic pain in humans. A firm mechanistic link to nociceptor dysfunction has been precluded because assessme...

The skin may exhibit the first clinical evidence of a systemic disease and may provide the first clues to a diagnosis in malignancies. Erythroderma is defined as generalized redness and scaling and it is a clinical manifestation of a variety of underlying diseases including, rarely, solid tumors. Br...

Cutaneous pain sensations are mediated largely by C-nociceptors consisting of both mechano-sensitive (CM) and mechano-insensitive (CMi) fibres that can be distinguished from one another according to their characteristic axonal properties. In healthy skin and relative to CMi fibres, CM fibres show a...

Erythromelalgia is a rare disorder that simulates a small fiber neuropathy and patients often have painful erythematous extremities during episodes. It is of two types: A primary or inherited form that is sometimes associated with a Na channel mutation or a secondary disorder associated with an unde...

Mutations in voltage-gated sodium channels, especially Nav1.7, can cause the genetic pain syndromes inherited erythromelalgia, small fiber neuropathy, paroxysmal extreme pain disorder, and chronic insensitivity to pain. Functional analysis of these mutations offers the possibility of understanding t...

Small-fibre neuropathies (SFNs) can be defined as diseases of small nerve fibres. Because their symptoms are mainly located in the skin in the initial stages, dermatologists may frequently be confronted with these diseases. Moreover, skin biopsies and the subsequent measurement of intraepidermal ner...

Sodium channel NaV1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic ganglion neurons. Gain-of-function NaV1.7 mutations/variants have been identified in the painful disorders inherited erythromelalgia and small-fiber neuropathy (SFN). DRG neurons transfected with these ch...

This presentation is a clinical narrative and long term follow up (6-16 years) of 21 prospectively studied patients with essential thrombocythaemia (ET) in Kuwait. The median age (55.9 years) is younger than reported by others. Two patients were below the age of 40 years with one of them presenting...

Chronic pain is usually underestimated in children, due to lack of knowledge and its specific signs. In addition to suffering, chronic pain causes a physical, psychological, emotional, social, and financial burden for the child and his family. Practitioners may find themselves in a situation of fail...

We conducted a literature review of patients' conditions described under persistent genital arousal disorder and restless genital syndrome, vulvodynia and male genital skin pain of unknown aetiology (penoscrotodynia). Our aim is to improve the understanding of the condition, unify nomenclature and p...

In-frame deletion mutation (Del-L955) in NaV1.7 sodium channel from a kindred with erythromelalgia hyperpolarizes activation. Del-L955 twists the S6 helix, displacing the Phe960 activation gate. Replacement of Phe960 at the correct helical position depolarizes activation. Radial tuning of the activa...

Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory...

Erythromelalgia is an uncommon neurovascular disorder characterized by redness, increased skin temperature, and pain that usually occurs in the extremities. Treatment remains challenging because of its varying response to medical therapy. The objective of this study was to assess the response of ery...

Gain-of-function missense mutations of SCN9A gene, which encodes voltage-gated sodium channel Nav1.7, alter channel's biophysical properties causing painful disorders which are refractory to pharmacotherapy in the vast majority of patients. Here we report a novel SCN9A mutation (ca.T3947C) in exon 2...

Erythromelalgia is a rare disorder characterized by reddening, severe burning pain, and swelling of the extremities. Food poisoning by Clitocybe acromelalga, a poisonous mushroom, is known to induce erythromelalgia; however, its treatment protocol remains unclear. We describe here three cases of ery...

Erythromelalgia clinically presents with episodic burning, erythema, and warmth of acral sites. It can be divided into primary and secondary associated with myeloproliferative and autoimmune conditions. Histology commonly shows capillary proliferation, swelling of endothelial cells, perivascular ede...

We identified and clinically investigated two patients with primary erythromelalgia mutations (PEM), which are the first reported to map to the fourth domain of Nav1.7 (DIV). The identified mutations (A1746G and W1538R) were cloned and transfected to cell cultures followed by electrophysiological an...

Erythromelalgia is a rare neurovascular pain syndrome characterized by a triad of redness, increased temperature, and burning pain primarily in the extremities. Erythromelalgia can present as a primary or secondary form, and secondary erythromelalgia associated with a myeloproliferative disease such...

The universe of painful Na-channelopathies--human disorders caused by mutations in voltage-gated sodium channels--has recently expanded in three dimensions. We now know that mutations of sodium channels cause not only rare genetic 'model disorders' such as inherited erythromelalgia and channelopathy...

Ploycythaemia vera (PV) is most common of chronic myeloproliferative disorder that involves the multipotent haemaotopoietic progenitor cells. PV has indolent course and recognised either by incidental discovery of high haemoglobin or haemtocrit. PV may present with aquagenic pruritus (AP) for years...

Erythromelalgia is a rare disorder characterized by 3 major symptoms: warmth, redness, and burning pain. It involves the feet and, to a lesser extent, the hands, head, and ears. We report the case of a 27-year-old man presenting with a 15-year history of episodes with edema, local hyperthermia, and...

Voltage-gated sodium channels are essential for electrogenesis in excitable cells. The isoform Nav1.7 is primarily expressed in nociceptors. Mutations of the SCN9A gene, which codes for the α-subunit of Nav1.7, are the cause of primary erythromelalgia and paroxysmal extreme pain disorder, two rare n...

We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records compr...

Erythromelalgia is a rare disease whose etiology is poorly understood. It is characterized by paroxysmal attacks of erythema, pain, and warmth of the extremities and can be primary or secondary. We report a case of primary familial erythromelalgia and stress the difficulties in its therapeutic manag...

Primary erythromelalgia (EM) is an autosomal dominant disorder caused by mutations of SCN9A. It is clinically characterized by reddish discoloration and episodic burning sensation of distal extremities triggered by warmth. We report a 49-year-old male with primary EM caused by SCN9A mutation (p.F216...

Mutations in SCN9A have been reported in (1) congenital insensitivity to pain (CIP); (2) primary erythromelalgia; (3) paroxysmal extreme pain disorder; (4) febrile seizures and recently (5) small fibre sensory neuropathy. We sought to investigate for SCN9A mutations in a clinically well-characterise...

We recruited a population of people who clinically suffer from the symptoms of erythromelalgia, red, hot, painful feet made worse by heat and improved by cooling, to better characterise this population and measure their quality of life (QOL). Ninety-two individuals completed the QOL surveys, and 56...

Primary erythromelalgia (PE) is an autosomal dominant neurological disorder characterized by severe burning pain and erythema in the extremities upon heat stimuli or exercise. Mutations in human SCN9A gene, encoding the α-subunit of the voltage-gated sodium channel, Na(v)1.7, were found to be respon...

We report an 11-year-old boy with localized secondary erythromelalgia on his left medial thigh. The episodes responded well to indomethacin and prednisone but recurred after the medications were stopped. The disease was stable after being treated for 5 months.

Adult-onset erythromelalgia (EM) is a rare disease characterized by episodic bouts of burning pain and erythema for which the optimal therapy is unclear. In this report, we describe a 68-year-old Japanese woman with adult-onset EM. Intravenous administration of methylprednisolone sodium succinate 1,...

Erythromelalgia is a rare disorder characterized by recurrent pain attacks, swelling and redness in the distal extremities. The primary forms of the disorder are caused by mutations in voltage-gated sodium channels. Treatment is difficult and controlled therapeutic studies offer little to no guidanc...

We have utilized a novel application of human genetics, illuminating the important role that rare genetic disorders can play in the development of novel drugs that may be of relevance for the treatment of both rare and common diseases. By studying a very rare Mendelian disorder of absent pain percep...

Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain c...

We report a 21-year-old male, presenting with erythromelalgia and polycythemia. A solid renal mass of the lower pole of the right kidney was discovered. The patient was subjected to a right open partial nephrectomy. The pathological study of the surgical specimen showed a metanephric adenoma of the...

Essential thrombocythemia (ET) is a clonal stem cell disease characterized by isolated thrombocytosis and thrombohemorrhagic complications. We describe an unusual case of ET primarily presenting with skin symptoms including erythromelalgia and livedo reticularis (racemosa-type). Persistent thrombocy...

We identified a patient with severe inherited erythromelalgia secondary to an L858F mutation in the voltage-gated sodium channel Na(v)1.7. The patient reported severe ongoing foot pain, which was exquisitely sensitive to limb cooling. We confirmed this heat hypersensitivity using quantitative sensor...

Erythromelalgia has not been well characterized in the pediatric population. We sought to review our experience of erythromelalgia in the pediatric age group. We conducted a retrospective review of patients 18 years of age and younger with a diagnosis of erythromelalgia who were examined at Mayo Cli...

Erythromelalgia is a rare disorder characterized by the clinical syndrome of burning pain, warmth and redness of the limbs. Neurological abnormalities (both large- and small-fibre neuropathy) are common. There have been few published reports on the sensory status of patients with erythromelalgia. To...

Erythromelalgia is a rare condition characterized by episodic painful erythema and warmth often affecting, but not limited to, the distal extremities. This condition is notoriously difficult to treat. We report a young female patient with seronegative polyarthritis who presented with a 6-year histor...

Erythromelalgia (EM) incidence has not been well studied and there are only two studies published on this subject as far as we know. The aims are to study the incidence of this rare condition in the south of Sweden, to report the clinical experience from a single centre including characterisation of...

Mutations in the SCN9A gene leading to deficiency of its protein product, Na(v)1.7, cause congenital indifference to pain (CIP). CIP is characterized by the absence of the ability to sense pain associated with noxious stimuli. In contrast, the opposite phenotype to CIP, inherited erythromelalgia (IE...

A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodi...

Erythromelalgia is a rare clinical syndrome characterized by intermittent heat, redness, swelling and pain more commonly affecting the lower extremities. Symptoms are mostly aggravated by warmth and are eased by a cold temperature. In some cases, symptoms can be very severe and disabling. Erythromel...

Voltage-gated sodium channels play a pivotal role in pain transmission. They are widely expressed in nociceptive neurons, and participate in the generation of action potentials. Alteration in ionic conduction of these channels causes abnormal electrical firing, thus renders neurons hyperexcitable. S...

Extreme thrombocytosis is a major risk factor for excessive bleeding and for thrombosis, either of which can complicate cardiovascular surgical and interventional procedures. Extreme thrombocytosis can also cause an unusual syndrome, erythromelalgia, that results in a type of chronic microvascular o...

Erythromelalgia is an extremely rare neurovascular disorder, characterized by symptoms of red, hot, and painful extremities. There is considerable confusion regarding the etiology and pathogenesis of this condition, and the diagnosis is essentially a clinical one. This condition may occur in isolati...

Sodium channel Na(V)1.7 is critical for human pain signalling. Gain-of-function mutations produce pain syndromes including inherited erythromelalgia, which is usually resistant to pharmacotherapy, but carbamazepine normalizes activation of Na(V)1.7-V400M mutant channels from a family with carbamazep...

Erythromelalgia is a rare disorder that typically affects the skin of the feet, hands, or both, that is characterized by red skin, warmth, and a burning quality of pain. It usually affects both sides of the body, but may manifest unilaterally. Cooling of the affected areas usually results in symptom...

Erythromelalgia is a rare disorder frequently associated with myeloproliferative disorders. We describe a case of elderly patient diagnosed with myeloproliferative disorder in remission. The patient was on aspirin for secondary prevention of stroke and was taken off aspirin and developed erythromela...

Erythromelagia is a condition characterized by attacks of burning pain and inflammation in the extremeties. An epidemic form of this syndrome occurs in secondary students in rural China and a virus referred to as erythromelalgia-associated poxvirus (ERPV) was reported to have been recovered from thr...

Paraneoplastic rheumatic syndromes are defined as those events associated with cancer that occur away from the primary tumor or its metastases and are induced by the presence of the tumor through biological products like hormones, peptides, autocrine or paracrine mediators, antibodies or cytotoxic l...