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Sample records for erythromelalgia

  1. Genetics Home Reference: erythromelalgia

    MedlinePlus

    ... Bennett DL, Wood JN, Kinali M. Novel mutations mapping to the fourth sodium channel domain of Nav1. ... and late-onset inherited erythromelalgia: genotype-phenotype correlation. Brain. 2009 Jul;132(Pt 7):1711-22. doi: ...

  2. Primary erythromelalgia: a review.

    PubMed

    Tang, Zhaoli; Chen, Zhao; Tang, Beisha; Jiang, Hong

    2015-01-01

    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 and no evidence showed a gender preference. Clinical onset of PE is often in the first decade of life. Burning pain is the most predominant symptom and is usually caused and precipitated by warmth and physical activities. Reported cases of PE contain both inherited and sporadic forms. Genetic etiology of PE is mutations on SCN9A, the encoding gene of a voltage-gated sodium channel subtype Nav1.7. Diagnosis of PE is made upon clinical manifestations and screening for mutations on SCN9A. Exclusion of several other treatable diseases/secondary erythromelalgia is also necessary because of the lack of biomarkers specifically for PE. Differential diagnoses can include Fabry disease, cellulites, Raynaud phenomenon, vasculitis and so on. Diagnostic methods often involve complete blood count, imaging studies and thermograph. Treatment for PE is unsatisfactory and highly individualized. Frequently used pain relieving drugs involve sodium channel blockers such as lidocaine, carbamazepine and mexiletine. Novel drugs such as PF-05089771 and TV-45070 could be promising in ameliorating pain symptoms due to their Nav1.7 selectivity. Patients' symptoms often worsen over time and many patients develop ulcerations and gangrenes caused by excessive exposure to low temperature in order to relieve pain. This review mainly focuses on PE and the causative gene SCN9A--its mutations and their effects on Nav1.7 channels' electrophysiological properties. We propose a genotype-channelopathy-phenotype correlation network underlying PE etiology which could provide guidance for future therapeutics. PMID:26419464

  3. Primary erythromelalgia: a review.

    PubMed

    Tang, Zhaoli; Chen, Zhao; Tang, Beisha; Jiang, Hong

    2015-01-01

    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 and no evidence showed a gender preference. Clinical onset of PE is often in the first decade of life. Burning pain is the most predominant symptom and is usually caused and precipitated by warmth and physical activities. Reported cases of PE contain both inherited and sporadic forms. Genetic etiology of PE is mutations on SCN9A, the encoding gene of a voltage-gated sodium channel subtype Nav1.7. Diagnosis of PE is made upon clinical manifestations and screening for mutations on SCN9A. Exclusion of several other treatable diseases/secondary erythromelalgia is also necessary because of the lack of biomarkers specifically for PE. Differential diagnoses can include Fabry disease, cellulites, Raynaud phenomenon, vasculitis and so on. Diagnostic methods often involve complete blood count, imaging studies and thermograph. Treatment for PE is unsatisfactory and highly individualized. Frequently used pain relieving drugs involve sodium channel blockers such as lidocaine, carbamazepine and mexiletine. Novel drugs such as PF-05089771 and TV-45070 could be promising in ameliorating pain symptoms due to their Nav1.7 selectivity. Patients' symptoms often worsen over time and many patients develop ulcerations and gangrenes caused by excessive exposure to low temperature in order to relieve pain. This review mainly focuses on PE and the causative gene SCN9A--its mutations and their effects on Nav1.7 channels' electrophysiological properties. We propose a genotype-channelopathy-phenotype correlation network underlying PE etiology which could provide guidance for future therapeutics.

  4. Erythromelalgia with subsequent digital necrosis, glomerulonephritis, and antiphospholipid antibodies.

    PubMed

    Paira, Sergio; Cassano, Gustavo; Korol, Virginia; Ortiz, Alberto; Roverano, Susana

    2005-08-01

    Erythromelalgia is a condition of extremities characterized by redness, increased temperature, and burning pain. We describe the first reported case of erythromelalgia in a young woman with digital necrosis and mesangial nephritis associated with antiphospholipid antibodies. The symptoms and necrosis completely resolved with treatment with corticosteroids. We discuss the differential diagnosis of this entity and highlight the importance of a follow up of these patients, because erythromelalgia may precede a myeloproliferative disorder or systemic lupus erythematosus by months or years.

  5. The Complexity of Pain Management in Patients with Erythromelalgia.

    PubMed

    Patel, Neha; Chen, Emily; Cucchiaro, Giovanni

    2015-11-01

    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 blistering and multiple episodes of superinfection. After a successful trial of spinal cord stimulation, she had a permanent implantation procedure. The spinal cord stimulator relieved her pain and improved function but not the sensation of burning pain. However, this pain resolved after she started daily mexiletine. This case demonstrates that erythromelalgia sometimes can be managed successfully with a combination of pharmacologic and interventional procedures. PMID:26528699

  6. [A case of primary erythromelalgia (erythermalgia) treated with neural blockade].

    PubMed

    Takeda, S; Tomaru, T; Higuchi, M

    1989-03-01

    A case of primary erythromelalgia which was treated successfully with lumbar sympathetic block and total spinal block (TSB) is reported. The patient was a 21-year-old woman with 18-year history of pain, burning, swelling, redness and warm sensation in both feet and lower part of the legs that caused the patient to soak her feet and legs frequently in ice cold water in order to obtain pain relief. The patient had been treated with a variety of medications including aspirin, indomethacin, methysergide maleate, and carbamazepine with no relief. Recently, the excessive exposure to cold water had caused extensive immersion foot (trench foot) with secondary infection (fusarium infection). Treatment with bilateral lumbar sympathetic block had markedly improved the symptom. Furthermore, treatment with TSB against causalgic state was performed 8 times for 4 months. During this period, the patient experienced the symptom which was much milder than those before treatment with TSB. Lumbar sympathetic block and TSB are useful methods for treatment of primary erythromelalgia.

  7. Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse.

    PubMed

    Chuquilin, Miguel; Dhand, Upinder K

    2016-02-01

    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 woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse. PMID:26804376

  8. Impaired skin vasomotor reflexes in patients with erythromelalgia.

    PubMed

    Littleford, R C; Khan, F; Belch, J J

    1999-05-01

    Erythromelalgia (EM) is a chronic disorder characterized by intermittent burning pain, warmth and erythema of the extremities. Increasing the local temperature and dependency of the affected limb(s) precipitates the symptoms, whereas direct cooling and elevation of the limb(s) can provide partial relief. Our previous findings showed that patients with EM have enhanced cutaneous vascular tone at rest and during stimulation, which may be due to an increase in sympathetic neural activity. To test this, we measured skin vasoconstrictor responses to contralateral arm cold challenge (CC) and inspiratory gasp (IG) using laser Doppler flowmetry at the toe pulp and fingertip. These areas were chosen because of their dense sympathetic innervation. An index of the vasoconstrictor response (between 0 and 1) was calculated from the change in skin perfusion from baseline following CC and IG. In control subjects, vasoconstrictor responses to CC at the toe and fingertip were both 0. 70+/-0.02 (mean+/-S.E.M.), which were significantly greater (P<0. 001) than corresponding values in patients with EM (0.37+/-0.04 and 0.45+/-0.04 respectively). Similarly, vasoconstrictor responses to IG were significantly greater (P<0.001) at the toe and fingertip in control subjects (0.70+/-0.03 and 0.70+/-0.02 respectively) compared with values in EM patients (0.27+/-0.03 and 0.45+/-0.15 respectively). These data show that, in contrast with control subjects, patients with EM have diminished sympathetic vasoconstrictor responses to both CC and IG. Denervation supersensitivity may play a part by increasing vasoconstrictor responses to circulating catecholamines, leading to a reduction in skin blood flow. Therefore an interplay between neural and vasoactive agents may be involved in the pathophysiology of EM. PMID:10209083

  9. Erythromelalgia presenting with premature exfoliation of primary teeth: a diagnostic dilemma.

    PubMed

    Prabhu, Neeta; Alexander, Sherene; Wong, Peter; Cameron, Angus

    2012-01-01

    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 isolation or in association with other myeloproliferative disorders. Unfortunately, no therapy is effective consistently in managing the symptoms, although early diagnosis can aid in psychological counseling and minimizing the frequency and severity of the attacks. The purpose of this report was to describe the case of a child presenting with premature loss of primary teeth and the difficulties in determining the final diagnosis of erythromelalgia, which responded positively to low-grade aspirin therapy.

  10. Reduced skin capillary density during attacks of erythromelalgia implies arteriovenous shunting as pathogenetic mechanism.

    PubMed

    Mørk, Cato; Kvernebo, Knut; Asker, Claes L; Salerud, E Göran

    2002-10-01

    Erythromelalgia is characterized by burning pain, erythema, and increased temperature in acral skin. The pain is aggravated by warming and relieved by cooling. Increased microvascular arteriovenous shunting in deep dermal plexa has been hypothesized as the pathogenetic mechanism of pain in affected skin, inducing hypoxia during pain attacks. The aim of this study was to quantify skin capillary density in erythromelalgic patients before and after heat provocation, as increased skin temperature should increase the need for nutritive blood supply by the capillaries. Fourteen patients and 10 healthy control subjects were studied using an enhanced technique of computer-assisted analysis of capillary bed morphology and temperature measurements before and after central body heating. The increase in acral skin temperature was significantly higher (p < 0.05) in the eight patients where symptoms were induced after heat provocation, compared to asymptomatic patients and healthy control subjects. The number of visible capillaries in a field of view (1.7 mm2) decreased significantly (p = 0.01) in erythromelalgia patients from 105 (62-137) (median with total range) to 89 (49-118) after warming in areas with numerous arteriovenous anastomoses (nail bed region). In symptomatic patients an even more significant reduction was observed (p = 0.01). The capillary size was also significantly reduced (p < 0.05) from 41.0 (31.5-50.5) (arbitrary units) to 37.3 (33.0-46.0) in symptomatic patients. The change in capillary density in the nail bed area was significantly larger in erythromelalgia patients -17 (-49 to 39) compared to controls 0 (-47 to 13) (p < 0.05), and in symptomatic patients -19 (-49 to -12) compared to asymptomatic patients -8 (-48 to 39) (p < 0.05) and controls (p < 0.01). The reduced skin capillary density after heating is compatible with increased microvascular arteriovenous shunting of blood and a corresponding relative deficit in nutritive perfusion (steal phenomenon

  11. SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing.

    PubMed

    Kist, Andreas M; Sagafos, Dagrun; Rush, Anthony M; Neacsu, Cristian; Eberhardt, Esther; Schmidt, Roland; Lunden, Lars Kristian; Ørstavik, Kristin; Kaluza, Luisa; Meents, Jannis; Zhang, Zhiping; Carr, Thomas Hedley; Salter, Hugh; Malinowsky, David; Wollberg, Patrik; Krupp, Johannes; Kleggetveit, Inge Petter; Schmelz, Martin; Jørum, Ellen; Lampert, Angelika; Namer, Barbara

    2016-01-01

    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 chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient's peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations. To evaluate the impact of the p.M650K mutation on neuronal firing and channel gating, we performed current and voltage-clamp recordings on transfected sensory neurons (DRGs) and neuroblastoma cells. The p.M650K mutation shifted steady-state fast inactivation of Nav1.8 to more hyperpolarized potentials and did not significantly alter any other tested gating behaviors. The AP half-width was significantly broader and the stimulated action potential firing rate was reduced for M650K transfected DRGs compared to WT. We discuss the potential link between enhanced steady state fast inactivation, broader action potential width and the potential physiological consequences.

  12. SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing

    PubMed Central

    Neacsu, Cristian; Eberhardt, Esther; Schmidt, Roland; Lunden, Lars Kristian; Ørstavik, Kristin; Kaluza, Luisa; Meents, Jannis; Zhang, Zhiping; Carr, Thomas Hedley; Salter, Hugh; Malinowsky, David; Wollberg, Patrik; Krupp, Johannes; Kleggetveit, Inge Petter; Schmelz, Martin; Jørum, Ellen; Namer, Barbara

    2016-01-01

    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 chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient’s peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations. To evaluate the impact of the p.M650K mutation on neuronal firing and channel gating, we performed current and voltage-clamp recordings on transfected sensory neurons (DRGs) and neuroblastoma cells. The p.M650K mutation shifted steady-state fast inactivation of Nav1.8 to more hyperpolarized potentials and did not significantly alter any other tested gating behaviors. The AP half-width was significantly broader and the stimulated action potential firing rate was reduced for M650K transfected DRGs compared to WT. We discuss the potential link between enhanced steady state fast inactivation, broader action potential width and the potential physiological consequences. PMID:27598514

  13. SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing.

    PubMed

    Kist, Andreas M; Sagafos, Dagrun; Rush, Anthony M; Neacsu, Cristian; Eberhardt, Esther; Schmidt, Roland; Lunden, Lars Kristian; Ørstavik, Kristin; Kaluza, Luisa; Meents, Jannis; Zhang, Zhiping; Carr, Thomas Hedley; Salter, Hugh; Malinowsky, David; Wollberg, Patrik; Krupp, Johannes; Kleggetveit, Inge Petter; Schmelz, Martin; Jørum, Ellen; Lampert, Angelika; Namer, Barbara

    2016-01-01

    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 chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient's peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations. To evaluate the impact of the p.M650K mutation on neuronal firing and channel gating, we performed current and voltage-clamp recordings on transfected sensory neurons (DRGs) and neuroblastoma cells. The p.M650K mutation shifted steady-state fast inactivation of Nav1.8 to more hyperpolarized potentials and did not significantly alter any other tested gating behaviors. The AP half-width was significantly broader and the stimulated action potential firing rate was reduced for M650K transfected DRGs compared to WT. We discuss the potential link between enhanced steady state fast inactivation, broader action potential width and the potential physiological consequences. PMID:27598514

  14. Successful treatment of adult-onset erythromelalgia with steroid pulse and pregabalin.

    PubMed

    Kakizaki, Aya; Fujimura, Taku; Kambayashi, Yumi; Watabe, Akiko; Aiba, Setsuya

    2012-09-01

    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 1,000 mg/day dramatically improved her pain as evaluated by the visual analog scale. Although the patient's pain gradually developed again, it could be controlled with pregabalin. Our present case might suggest a possible, optimal therapy for adult-onset EM. PMID:23275767

  15. Successful Treatment of Adult-Onset Erythromelalgia with Steroid Pulse and Pregabalin

    PubMed Central

    Kakizaki, Aya; Fujimura, Taku; Kambayashi, Yumi; Watabe, Akiko; Aiba, Setsuya

    2012-01-01

    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 1,000 mg/day dramatically improved her pain as evaluated by the visual analog scale. Although the patient's pain gradually developed again, it could be controlled with pregabalin. Our present case might suggest a possible, optimal therapy for adult-onset EM. PMID:23275767

  16. Inherited erythromelalgia due to mutations in SCN9A: natural history, clinical phenotype and somatosensory profile.

    PubMed

    McDonnell, Aoibhinn; Schulman, Betsy; Ali, Zahid; Dib-Hajj, Sulayman D; Brock, Fiona; Cobain, Sonia; Mainka, Tina; Vollert, Jan; Tarabar, Sanela; Waxman, Stephen G

    2016-04-01

    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 consisted of reports of genetic and/or clinical characterization of individual patients. This paper describes the pattern of pain, natural history, somatosensory profile, psychosocial status and olfactory testing of 13 subjects with primary inherited erythromelalgia with mutations of SCN9A, the gene encoding Na(v)1.7. Subjects were clinically profiled using questionnaires, quantitative sensory testing and olfaction testing during the in-clinic phase of the study. In addition, a detailed pain phenotype for each subject was obtained over a 3-month period at home using diaries, enabling subjects to self-report pain attacks, potential triggers, duration and severity of pain. All subjects reported pain and heat in the extremities (usually feet and/or hands), with pain attacks triggered by heat or exercise and relieved mainly by non-pharmacological manoeuvres such as cooling. A large proportion of pain attacks (355/1099; 32%) did not involve a specific trigger. There was considerable variability in the number, duration and severity of pain attacks between subjects, even those carrying the same mutation within a family, and within individuals over the 12-13 week observation period. Most subjects (11/13) had pain between attacks. For these subjects, mean pain severity between pain attacks was usually lower than that during an attack. Olfaction testing using the Sniffin'T test did not demonstrate hyperosmia. One subject had evidence of orthostatic hypotension. Overall, there was a statistically significant correlation between total Hospital Anxiety and Depression Scale scores (P= 0.005) and pain between attacks and for Hospital Anxiety and Depression Scale Depression scores and pain

  17. Primary erythromelalgia in a child responding to intravenous lidocaine and oral mexiletine treatment.

    PubMed

    Nathan, Aruna; Rose, John B; Guite, Jessica W; Hehir, David; Milovcich, Karen

    2005-04-01

    Erythromelalgia is a rare, chronic, debilitating condition characterized by redness, warmth, and severe burning pain of the distal extremities. The feet are more commonly affected than the hands. Pain is precipitated by increases in temperature and by exercise. Patients often obtain relief by immersing the affected extremity in cold water. The pain is often refractory to treatment. For many patients, multiple pain medications have been useless in achieving complete relief of pain symptoms. Previous reports of erythromelalgia among adolescents indicated prolonged relief of pain with sodium nitroprusside infusions, epidural infusions of local anesthetics, or gabapentin treatment. We present a case of an 11-year-old, white, male child with primary erythromelalgia, whose initial symptoms started in his preschool years and whose childhood was marked by escalating episodes of pain with warmth and redness of his feet, precipitated especially by increases in temperature and by activity. All conventional pain management techniques had failed to relieve our patient of his symptoms, and he obtained some relief only by soaking his affected extremities in ice water. He had experienced minimal benefit from seeing a pain psychologist, who helped him develop techniques to cope with the pain. At the time of presentation, the patient's episodes of pain had increased to 15 to 20 per day, and there was evidence of chronic immersion injury to the skin of his feet. Before his most recent hospitalization, the pain had spread to involve his hands as well. The patient was overwhelmed with anxiety and could not participate in school or social activities at the time of admission. During his current hospitalization, he did show some therapeutic response to sodium nitroprusside infusion, which unfortunately had to be discontinued because of side effects and because his family desired to leave the ICU environment, which was stressful to the patient. He also had some response to lumbar epidural

  18. Erythromelalgia in the pediatric patient: role of computed-tomography-guided lumbar sympathetic blockade

    PubMed Central

    Kundu, Anjana; Rafiq, Mahmood; Warren, Patrick S; Tobias, Joseph D

    2016-01-01

    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 population. We report a series of three cases of primary EM in pediatric patients involving the lower extremities, refractory to medical treatment that responded favorably to computed-tomography-guided lumbar sympathetic blockade. There was a significant improvement in pain scores, quality of life, and overall function as well as decreased analgesic requirements. Lumbar sympathetic blockade should be considered as a therapeutic modality in pediatric and adolescent patients with EM who are refractory to other treatments. PMID:27799815

  19. Primary erythromelalgia with leukonychia combined with ulcerations and infection by Monilia guilliermondii.

    PubMed

    Yuan, Zhengyong; He, Changxiao

    2011-03-01

    An 8-year-old girl presented with recurrent redness, warming, and pain of the lower extremities for more than 4 years, with exacerbation and accompanying swelling for the past 1 year and ulcers for 1 month. The episodes were triggered by exertion and heat. Her family history revealed that her mother had experienced similar symptoms. Physical examination showed proximal white nails and the distal border in normal color. There was some ulceration in the dorsum of the feet with thick, yellowish secretions, covered by some crusted lesions. Laboratory culture result showed that there were many Monilia guilliermondii in the ulcer specimen. Finally, she was diagnosed with juvenile onset of primary erythromelalgia and was given symptomatic treatment for neuropathic pain and pedal ulcers.

  20. Early detection of an epidemic erythromelalgia outbreak using Baidu search data.

    PubMed

    Gu, Yuzhou; Chen, Fengling; Liu, Tao; Lv, Xiaojuan; Shao, Zhaoming; Lin, Hualiang; Liang, Chaobin; Zeng, Weilin; Xiao, Jianpeng; Zhang, Yonghui; Huang, Cunrui; Rutherford, Shannon; Ma, Wenjun

    2015-07-28

    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 Baidu search data for the same period. After keyword selection, filtering and composition, the most correlated lag of the EM Search Index was used for comparison and linear regression model development. This study also explored the spatial distribution of epidemic EM in China during this period based on EM Search Index. The EM Search Index at lag 2 was most significantly associated with daily case counts in Foshan (ρ = 0.863, P < 0.001). It captured an upward trend in the outbreak about one week ahead of official report and the linear regression analysis indicated that every 1.071 increase in the EM Search Index reflected a rise of 1 EM cases 2 days earlier. The spatial analysis found that the number of EM Search Indexes increased in the middle of Guangdong Province and South China during the outbreak period. The EM Search Index may be a good early indicator of an epidemic EM outbreak.

  1. Early detection of an epidemic erythromelalgia outbreak using Baidu search data.

    PubMed

    Gu, Yuzhou; Chen, Fengling; Liu, Tao; Lv, Xiaojuan; Shao, Zhaoming; Lin, Hualiang; Liang, Chaobin; Zeng, Weilin; Xiao, Jianpeng; Zhang, Yonghui; Huang, Cunrui; Rutherford, Shannon; Ma, Wenjun

    2015-01-01

    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 Baidu search data for the same period. After keyword selection, filtering and composition, the most correlated lag of the EM Search Index was used for comparison and linear regression model development. This study also explored the spatial distribution of epidemic EM in China during this period based on EM Search Index. The EM Search Index at lag 2 was most significantly associated with daily case counts in Foshan (ρ = 0.863, P < 0.001). It captured an upward trend in the outbreak about one week ahead of official report and the linear regression analysis indicated that every 1.071 increase in the EM Search Index reflected a rise of 1 EM cases 2 days earlier. The spatial analysis found that the number of EM Search Indexes increased in the middle of Guangdong Province and South China during the outbreak period. The EM Search Index may be a good early indicator of an epidemic EM outbreak. PMID:26218589

  2. A large temperature fluctuation may trigger an epidemic erythromelalgia outbreak in China

    NASA Astrophysics Data System (ADS)

    Liu, Tao; Zhang, Yonghui; Lin, Hualiang; Lv, Xiaojuan; Xiao, Jianpeng; Zeng, Weilin; Gu, Yuzhou; Rutherford, Shannon; Tong, Shilu; Ma, Wenjun

    2015-03-01

    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. We searched all peer-reviewed literature on primary epidemic EM outbreaks in China. A two-stage model was used to characterize the relationship between temperature fluctuation and epidemic EM outbreaks. We observed that epidemic EM outbreaks were reported from 13 provinces during 1960-2014 and they mainly occurred between February and March in southern China. The majority of EM cases were middle school students, with a higher incidence rate in female and resident students. The major clinical characteristics of EM cases included burning, sharp, tingling and/or stinging pain in toes, soles and/or dorsum of feet, fever, erythema and swelling. A large ``V''-shaped fluctuation of daily average temperature (TM) observed during the epidemic EM outbreaks was significantly associated with the number of daily EM cases (β = 1.22, 95%CI: 0.66 ~ 1.79), which indicated that this ``V''-shaped fluctuation of TM probably triggered the epidemic EM outbreaks.

  3. Primary erythromelalgia in a 12-year-old boy: positive response to sodium channel blockers despite negative SCN9A mutations.

    PubMed

    Jakob, A; Creutzfeldt, R; Staszewski, O; Winterpacht, A; Berner, R; Hufnagel, M

    2012-09-01

    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 guidance. We report on a 12-year-old boy and his first occurrence of primary erythromelalgia. Genetic findings for mutations in the SCN9A gene, which encodes for the α-subunit of sodium channel NaV1.7, were negative. Although initial treatment with sodium nitroprusside was ineffective, subsequent medication with lidocaine and mexiletine, in combination with gabapentin, was successful. Despite negative findings for mutations in the sodium channels, the use of sodium channel blockers should be considered in these patients. PMID:22170168

  4. Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia.

    PubMed

    Cao, Lishuang; McDonnell, Aoibhinn; Nitzsche, Anja; Alexandrou, Aristos; Saintot, Pierre-Philippe; Loucif, Alexandre J C; Brown, Adam R; Young, Gareth; Mis, Malgorzata; Randall, Andrew; Waxman, Stephen G; Stanley, Philip; Kirby, Simon; Tarabar, Sanela; Gutteridge, Alex; Butt, Richard; McKernan, Ruth M; Whiting, Paul; Ali, Zahid; Bilsland, James; Stevens, Edward B

    2016-04-20

    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 channel leads to aberrant sensory neuronal activity and extreme pain, particularly in response to heat. Five patients with IEM were treated with a new potent and selective compound that blocked the Nav1.7 sodium channel resulting in a decrease in heat-induced pain in most of the patients. We derived induced pluripotent stem cell (iPSC) lines from four of five subjects and produced sensory neurons that emulated the clinical phenotype of hyperexcitability and aberrant responses to heat stimuli. When we compared the severity of the clinical phenotype with the hyperexcitability of the iPSC-derived sensory neurons, we saw a trend toward a correlation for individual mutations. The in vitro IEM phenotype was sensitive to Nav1.7 blockers, including the clinical test agent. Given the importance of peripherally expressed sodium channels in many pain conditions, our approach may have broader utility for a wide range of pain and sensory conditions.

  5. A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers.

    PubMed

    Wu, Min-Tzu; Huang, Po-Yuan; Yen, Chen-Tung; Chen, Chih-Cheng; Lee, Ming-Jen

    2013-01-01

    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 responsible for PE. Three missense mutations of SCN9A gene have recently been identified in Taiwanese patients including a familial (I136V) and two sporadic mutations (I848T, V1316A). V1316A is a novel mutation and has not been characterized yet. Topologically, I136V is located in DI/S1 segment and both I848T and V1316A are located in S4-S5 linker region of DII and DIII domains, respectively. To characterize the elelctrophysiological manifestations, the channel conductance with whole-cell patch clamp was recorded on the over-expressed Chinese hamster overy cells. As compared with wild type, the mutant channels showed a significant hyperpolarizing shift in voltage dependent activation and a depolarizing shift in steady-state fast inactivation. The recovery time from channel inactivation is faster in the mutant than in the wild type channels. Since warmth can trigger and exacerbate symptoms, we then examine the influence of tempearture on the sodium channel conduction. At 35°C, I136V and V1316A mutant channels exhibit a further hyperpolarizing shift at activation as compared with wild type channel, even though wild type channel also produced a significant hyperpolarizing shift compared to that of 25°C. High temperature caused a significant depolarizing shift in steady-state fast inactivation in all three mutant channels. These findings may confer to the hyperexcitability of sensory neurons, especially at high temperature. In order to identifying an effective treatment, we tested the IC₅₀ values of selective sodium channel blockers, lidocaine and mexiletine. The IC₅₀ for mexiletine is lower for I848T mutant channel as compared to that of the wild type and other two

  6. The Biophysical Basis Underlying Gating Changes in the p.V1316A Mutant Nav1.7 Channel and the Molecular Pathogenesis of Inherited Erythromelalgia

    PubMed Central

    Huang, Chiung-Wei; Huang, Po-Yuan; Lee, Ming-Jen; Kuo, Chung-Chin

    2016-01-01

    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 the Nav1.7 channel. Mechanistically, we first demonstrate that the Navβ4 peptide acts as a gating modifier rather than an open channel blocker competing with the inactivating peptide to give rise to resurgent currents in the Nav1.7 channel. Moreover, there are two distinct open and two corresponding fast inactivated states in the genesis of resurgent Na+ currents. One is responsible for the resurgent route and practically existent only in the presence of Navβ4 peptide, whereas the other is responsible for the “silent” route of recovery from inactivation. In this regard, the p.V1316A mutation makes hyperpolarization shift in the activation curve, and depolarization shift in the inactivation curve, vividly uncoupling inactivation from activation. In terms of molecular gating operation, the most important changes caused by the p.V1316A mutation are both acceleration of the transition from the inactivated states to the activated states and deceleration of the reverse transition, resulting in much larger sustained as well as resurgent Na+ currents. In summary, the genesis of the resurgent currents in the Nav1.7 channel is ascribable to the transient existence of a distinct and novel open state promoted by the Navβ4 peptide. In addition, S4–5 linker in domain III where V1316 is located seems to play a critical role in activation–inactivation coupling, chiefly via direct modulation of the transitional kinetics between the open and the inactivated states. The sustained and resurgent Na+ currents may therefore be correlatively enhanced by specific mutations involving this linker and relevant regions, and thus marked hyperexcitability in corresponding neural tissues as

  7. Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7.

    PubMed

    Namer, Barbara; Ørstavik, Kristin; Schmidt, Roland; Kleggetveit, Inge-Petter; Weidner, Christian; Mørk, Cato; Kvernebo, Mari Skylstad; Kvernebo, Knut; Salter, Hugh; Carr, Thomas Hedley; Segerdahl, Märta; Quiding, Hans; Waxman, Stephen George; Handwerker, Hermann Otto; Torebjörk, Hans Erik; Jørum, Ellen; Schmelz, Martin

    2015-09-01

    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 patients with EM. Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the patients with EM showed spontaneous activity. In the patient with mutation I848T, all nociceptors, but not sympathetic efferents, displayed enhanced early subnormal conduction in the velocity recovery cycles and the expected late subnormality was reversed to supranormal conduction. The larger hyperpolarizing shift of activation might explain the difference to the I228M mutation. Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the patient carrying the I848T mutation, confirming in human subjects that the presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant channels. The characteristic pattern of changes in conduction velocity observed in the patient with the I848T gain-of function mutation in Nav1.7 could be explained by axonal depolarization and concomitant inactivation of Nav1.7. If this were true, activity-dependent hyperpolarization would reverse inactivation of Nav1.7 and account for the supranormal CV. This mechanism might explain normal pain thresholds under resting conditions. PMID:25993546

  8. Specific changes in conduction velocity recovery cycles of single nociceptors in a patient with erythromelalgia with the I848T gain-of-function mutation of Nav1.7.

    PubMed

    Namer, Barbara; Ørstavik, Kristin; Schmidt, Roland; Kleggetveit, Inge-Petter; Weidner, Christian; Mørk, Cato; Kvernebo, Mari Skylstad; Kvernebo, Knut; Salter, Hugh; Carr, Thomas Hedley; Segerdahl, Märta; Quiding, Hans; Waxman, Stephen George; Handwerker, Hermann Otto; Torebjörk, Hans Erik; Jørum, Ellen; Schmelz, Martin

    2015-09-01

    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 patients with EM. Irrespective of Nav1.7 mutations, more than 50% of the silent nociceptors in the patients with EM showed spontaneous activity. In the patient with mutation I848T, all nociceptors, but not sympathetic efferents, displayed enhanced early subnormal conduction in the velocity recovery cycles and the expected late subnormality was reversed to supranormal conduction. The larger hyperpolarizing shift of activation might explain the difference to the I228M mutation. Sympathetic fibers that lack Nav1.8 did not show supranormal conduction in the patient carrying the I848T mutation, confirming in human subjects that the presence of Nav1.8 crucially modulates conduction in cells expressing EM mutant channels. The characteristic pattern of changes in conduction velocity observed in the patient with the I848T gain-of function mutation in Nav1.7 could be explained by axonal depolarization and concomitant inactivation of Nav1.7. If this were true, activity-dependent hyperpolarization would reverse inactivation of Nav1.7 and account for the supranormal CV. This mechanism might explain normal pain thresholds under resting conditions.

  9. William Harvey and his gout.

    PubMed

    Hart, F D

    1984-04-01

    In William Harvey's day almost any or every arthropathy was termed gout. This is evident in the case histories of some of his patients and in his own case, where his own cold water therapy would suggest the correct diagnosis was not gout but erythromelalgia (Weir Mitchell's disease).

  10. [The acrodynic form of the Riley-Day syndrome].

    PubMed

    Tridon, P; Vidailhet, C; Schweitzer, F

    1989-01-01

    The authors report the case of a 10-year-old girl who died after suffering from severe erythromelalgia combined with digestive and general disorders associated with multiple vegetative disturbances (high blood pressure, hypothermia, colic and urinary disorders, raised catecholamine levels) for 2 years. Although the appearance of the tongue was normal and in spite of the absence of genetic criteria the diagnosis of Riley-Day dysautonomia was made and its association with neural crest disorders was indicated.

  11. Extreme Thrombocytosis and Cardiovascular Surgery

    PubMed Central

    Natelson, Ethan A.

    2012-01-01

    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 occlusive arterial disease. We present the differential diagnosis of conditions that may lead to extreme thrombocytosis, 3 cases (each of which illustrates a different potential complication), and a review of the pertinent medical literature. Correcting excessive thrombocytosis is typically not difficult, whether electively or acutely, and effective therapy usually controls thrombosis and excessive hemorrhage postprocedurally. PMID:23304015

  12. Painful Na-channelopathies: an expanding universe.

    PubMed

    Waxman, Stephen G

    2013-07-01

    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-associated insensitivity to pain but also common painful neuropathies. We have learned that mutations of NaV1.8, as well as mutations of NaV1.7, can cause painful Na-channelopathies. Moreover, recent studies combining atomic level structural models and pharmacogenomics suggest that the goal of genomically guided pain therapy may not be unrealistic.

  13. Off-pump myocardial revascularization in a high-risk patient with essential thrombocythemia.

    PubMed

    Darwazah, Ahmad K; Madi, Hamad; Zagha, Rami; Hawash, Yahia

    2014-10-01

    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 erythromelalgia. His platelet count was 1,486 ×10(3)/μL. The patient underwent successful myocardial revascularization by means of an off-pump technique after his platelet count had been reduced by hydroxycarbamide administration. We conclude that the use of off-pump cardiopulmonary bypass in high-risk patients with essential thrombocythemia is safe. Reducing platelet count via the administration of hydroxycarbamide and the careful balancing of antiplatelets and anticoagulants is crucial in determining the outcome of surgery. PMID:25425991

  14. Toxicological Profiles of Poisonous, Edible, and Medicinal Mushrooms

    PubMed Central

    Jo, Woo-Sik; Hossain, Md. Akil

    2014-01-01

    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 toxic effects of these fungal species. Cases of serious human poisoning generally caused by the improper identification of toxic mushroom species are reported every year. Different substances responsible for the fatal signs and symptoms of mushroom toxicity have been identified from various poisonous mushrooms. Toxicity studies of mushroom species have demonstrated that mushroom poisoning can cause adverse effects such as liver failure, bradycardia, chest pain, seizures, gastroenteritis, intestinal fibrosis, renal failure, erythromelalgia, and rhabdomyolysis. Correct categorization and better understanding are essential for the safe and healthy consumption of mushrooms as functional foods as well as for their medicinal use. PMID:25346597

  15. [Paraneoplastic rheumatic syndromes].

    PubMed

    Gracia-Ramos, Abraham Edgar; Vera-Lastra, Olga Lidia

    2012-01-01

    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 lymphocytes. Of these, hypertrophic osteoarthropathy, carcinomatous polyarthritis, dermatomyositis/polymyositis, and paraneoplastic vasculitis are the most frequently recognized. Other less known associations are based upon a smaller number of case reports, and include palmar fasciitis, panniculitis, erythema nodosum, Raynaud¥s phenomenon, erythromelalgia and Lupus-like syndrome. Usually the clinical course of rheumatic paraneoplastic syndrome and cancer parallels the resolution of the tumor usually leads to resolution of this syndrome. It is difficult make the distinction between idiopathic rheumatic syndromes from those that result from cancer. Still, there are several clinical data that can guide us to the presence of an occult malignancy, and should be identified as the detection of cancer can lead to early treatment and better prognosis.

  16. Sex differences in the incidence of skin and skin-related diseases in Olmsted County, Minnesota, United States, and a comparison with other rates published worldwide.

    PubMed

    Andersen, Louise K; Davis, Mark D P

    2016-09-01

    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 disorders performed utilizing Rochester Epidemiology Project data. Females had a higher incidence of the following diseases: connective tissue diseases (scleroderma, morphea, dermatomyositis, primary Sjögren syndrome, systemic lupus erythematosus [not in all studies]), pityriasis rosea, herpes progenitalis, condyloma acuminatum, hidradenitis suppurativa, herpes zoster (except in children), erythromelalgia, venous stasis syndrome, and venous ulcers. Males had a higher incidence of psoriasis and psoriatic arthritis, basal cell carcinoma (exception, females aged ≤40 years), squamous cell carcinoma, and lentigo maligna. Incidence rates were equal in males and females for cutaneous malignant melanoma (exception, higher in females aged 18-39 years), lower-extremity cellulitis, cutaneous nontuberculous mycobacterial infection, Behçet disease, delusional infestation, alopecia areata, and bullous pemphigoid. Many of the population-based sex-specific incidence rates of skin and skin-related diseases derived from the Rochester Epidemiology Project are strikingly different from those estimated elsewhere. In general, females are more commonly affected by skin and skin-related diseases. The reasons for this imbalance remain to be determined and are likely multifactorial. PMID:27009931

  17. Fractal Dimension Characterization of in-vivo Laser Doppler Flowmetry signals

    NASA Astrophysics Data System (ADS)

    Srinivasan, Gayathri; Sujatha, N.

    Laser Doppler Blood Flow meter uses tissue backscattered light to non-invasively assess the blood flow rate. qualitatively. As there is large spatial variability and the temporal heterogeneity in tissue microvasculature, the measured blood flow rate is expressed in relative units. A non-linear approach in order to understand the dynamics of the microcirculation led to the fractal characterization of the blood flow signals. The study presented in the paper aims to analyze the fractal behavior of Laser Doppler Flow (LDF) signals and to quantitatively estimate the fractal dimension of waveforms using Box-Counting method. The measured Fractal dimension is an estimate of temporal variability of tissue perfusion. The rate at which fractal dimension varies as a function of location between individuals, exhibits a weak correlation with time. Further studies with a larger number of subjects are necessary to test the generality of the findings and if changes in dimension are reproducible in given individuals. In conclusion, the fractal dimension determined by Box-counting method may be useful for characterizing LDF time series signals. Future experiments evaluating whether the technique can be used to quantify microvascular dysfunction, as commonly occurring in conditions such as Diabetes, Raynaud's phenomenon, Erythromelalgia and Achenbach syndrome needs to be evaluated.

  18. Sodium channel slow inactivation interferes with open channel block

    PubMed Central

    Hampl, Martin; Eberhardt, Esther; O’Reilly, Andrias O.; Lampert, Angelika

    2016-01-01

    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, which involve the voltage-dependent release of an open channel blocker. In contrast, IEM mutations, whenever tested, leave resurgent currents unchanged. Accordingly, the IEM deletion mutation L955 (ΔL955) fails to produce resurgent currents despite enhanced persistent currents, which have hitherto been considered a prerequisite for resurgent currents. Additionally, ΔL955 exhibits a prominent enhancement of slow inactivation (SI). We introduced mutations into Nav1.7 and Nav1.6 that either enhance or impair SI in order to investigate their effects on resurgent currents. Our results show that enhanced SI is accompanied by impaired resurgent currents, which suggests that SI may interfere with open-channel block. PMID:27174182

  19. The clinical approach to small fibre neuropathy and painful channelopathy

    PubMed Central

    Themistocleous, Andreas C; Ramirez, Juan D; Serra, Jordi; Bennett, David L H

    2014-01-01

    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 diagnosis of SFN is demanding as clinical features can be vague and nerve conduction studies normal. New diagnostic techniques, in particular measurement of intraepidermal nerve fibre density, have significantly improved the diagnostic efficiency of SFN. Management is focused on the treatment of the underlying cause and analgesia, as there is no neuroprotective therapy. A recent and significant advance is the finding that a proportion of cases labelled as idiopathic SFN are in fact associated with gain of function mutations of the voltage-gated sodium channels Nav1.7 and Nav1.8 (encoded by the genes SCN9A and SCN10A, respectively). There is a further group of heritable painful conditions in which gain of function mutations in ion channels alter excitability of sensory neurones but do not cause frank axon degeneration; these include mutations in Nav1.7 (causing erythromelalgia and paroxysmal extreme pain disorder) and TRPA1 (resulting in familial episodic pain disorder). These conditions are exceptionally rare but have provided great insight into the nociceptive system as well as yielding potential analgesic drug targets. In patients with no pre-existing risk factor, the investigation of an underlying cause of SFN should be systematic and appropriate for the patient population. In this review, we focus on how to incorporate recent developments in the diagnosis and pathophysiology of SFN into clinical practice. PMID:24778270

  20. Can robots patch-clamp as well as humans? Characterization of a novel sodium channel mutation

    PubMed Central

    Estacion, M; Choi, J S; Eastman, E M; Lin, Z; Li, Y; Tyrrell, L; Yang, Y; Dib-Hajj, S D; Waxman, S G

    2010-01-01

    Ion channel missense mutations cause disorders of excitability by changing channel biophysical properties. As an increasing number of new naturally occurring mutations have been identified, and the number of other mutations produced by molecular approaches such as in situ mutagenesis has increased, the need for functional analysis by patch-clamp has become rate limiting. Here we compare a patch-clamp robot using planar-chip technology with human patch-clamp in a functional assessment of a previously undescribed Nav1.7 sodium channel mutation, S211P, which causes erythromelalgia. This robotic patch-clamp device can increase throughput (the number of cells analysed per day) by 3- to 10-fold. Both modes of analysis show that the mutation hyperpolarizes activation voltage dependence (−8 mV by manual profiling, −11 mV by robotic profiling), alters steady-state fast inactivation so that it requires an additional Boltzmann function for a second fraction of total current (∼20% manual, ∼40% robotic), and enhances slow inactivation (hyperpolarizing shift −15 mV by human, −13 mV robotic). Manual patch-clamping demonstrated slower deactivation and enhanced (∼2-fold) ramp response for the mutant channel while robotic recording did not, possibly due to increased temperature and reduced signal-to-noise ratio on the robotic platform. If robotic profiling is used to screen ion channel mutations, we recommend that each measurement or protocol be validated by initial comparison to manual recording. With this caveat, we suggest that, if results are interpreted cautiously, robotic patch-clamp can be used with supervision and subsequent confirmation from human physiologists to facilitate the initial profiling of a variety of electrophysiological parameters of ion channel mutations. PMID:20123784

  1. Evidence of Small-Fiber Polyneuropathy in Unexplained, Juvenile-Onset, Widespread Pain Syndromes

    PubMed Central

    Klein, Max M.

    2013-01-01

    OBJECTIVE: We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. METHODS: Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. RESULTS: Age at illness onset averaged 12.3 ± 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). CONCLUSIONS: More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies. PMID:23478869

  2. Differential axonal conduction patterns of mechano-sensitive and mechano-insensitive nociceptors--a combined experimental and modelling study.

    PubMed

    Petersson, Marcus E; Obreja, Otilia; Lampert, Angelika; Carr, Richard W; Schmelz, Martin; Fransén, Erik

    2014-01-01

    -induced switch in nociceptors phenotype, in particular NaV1.7 which has already been identified clinically as a principal contributor to chronic pain states such as inherited erythromelalgia. PMID:25136824

  3. Differential Axonal Conduction Patterns of Mechano-Sensitive and Mechano-Insensitive Nociceptors – A Combined Experimental and Modelling Study

    PubMed Central

    Petersson, Marcus E.; Obreja, Otilia; Lampert, Angelika; Carr, Richard W.; Schmelz, Martin; Fransén, Erik

    2014-01-01

    -induced switch in nociceptors phenotype, in particular NaV1.7 which has already been identified clinically as a principal contributor to chronic pain states such as inherited erythromelalgia. PMID:25136824

  4. Essential thrombocythemia

    PubMed Central

    Brière, Jean B

    2007-01-01

    Essential thrombocythemia (ET) is an acquired myeloproliferative disorder (MPD) characterized by a sustained elevation of platelet number with a tendency for thrombosis and hemorrhage. The prevalence in the general population is approximately 30/100,000. The median age at diagnosis is 65 to 70 years, but the disease may occur at any age. The female to male ratio is about 2:1. The clinical picture is dominated by a predisposition to vascular occlusive events (involving the cerebrovascular, coronary and peripheral circulation) and hemorrhages. Some patients with ET are asymptomatic, others may experience vasomotor (headaches, visual disturbances, lightheadedness, atypical chest pain, distal paresthesias, erythromelalgia), thrombotic, or hemorrhagic disturbances. Arterial and venous thromboses, as well as platelet-mediated transient occlusions of the microcirculation and bleeding, represent the main risks for ET patients. Thromboses of large arteries represent a major cause of mortality associated with ET or can induce severe neurological, cardiac or peripheral artery manifestations. Acute leukemia or myelodysplasia represent only rare and frequently later-onset events. The molecular pathogenesis of ET, which leads to the overproduction of mature blood cells, is similar to that found in other clonal MPDs such as chronic myeloid leukemia, polycythemia vera and myelofibrosis with myeloid metaplasia of the spleen. Polycythemia vera, myelofibrosis with myeloid metaplasia of the spleen and ET are generally associated under the common denomination of Philadelphia (Ph)-negative MPDs. Despite the recent identification of the JAK2 V617F mutation in a subset of patients with Ph-negative MPDs, the detailed pathogenetic mechanism is still a matter of discussion. Therapeutic interventions in ET are limited to decisions concerning the introduction of anti-aggregation therapy and/or starting platelet cytoreduction. The therapeutic value of hydroxycarbamide and aspirin in high risk