RESUMEN
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 characteristic of the condition, dermatologists can play an important role in early recognition and limitation of morbidity. The first article in this 2-part continuing medical education series reviews the epidemiology, pathogenesis, clinical manifestations, evaluation, and complications.
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Eritromelalgia , Humanos , Eritromelalgia/diagnóstico , Eritromelalgia/epidemiología , Eritromelalgia/etiología , Dolor/diagnóstico , Dolor/etiología , Eritema , Piel/patologíaRESUMEN
BACKGROUND: 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. OBJECTIVE: The objective of this study was to characterize dermatologic manifestations in patients with SFN. METHODS: Large retrospective series of biopsy-proven SFN cases seen at the Massachusetts General Hospital and Brigham and Women's Hospital (January 2000 to December 2019). RESULTS: The majority of the 301 participants included presented with at least one cutaneous manifestation [292/301 (97%)]. Pain was most common with 254/301 (84.4%) perceiving this as occurring in the skin. It was frequently described as 'burning' [95/254 (37.4%)] and affected distal [174/254 (68.5%)] slightly more than proximal [111/254 (43.7%)] limbs. Numbness [182/301 (60.5%)], edema [61/301 (20.3%)] and skin colour changes [53/301 (17.6%)], which include redness [23/53 (43%)], also had predominant distal distribution. Characteristic loss of distal hair occurred among 17/29 (59%) those reporting hair loss. Other findings with classic limb involvement, Raynaud's phenomenon [33/301 (11%)] and erythromelalgia [26/301 (8.6%)] were seen. Itch [45/301 (15%)], mostly localized [22/45 (49%)] and localized eczematous dermatitis were also found. CONCLUSION: SFN has a wide range of clinical features in which the skin is affected, with characteristic findings affecting the extremities.
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Eritromelalgia , Polineuropatías , Biopsia , Eritromelalgia/diagnóstico , Eritromelalgia/epidemiología , Eritromelalgia/etiología , Femenino , Humanos , Polineuropatías/diagnóstico , Polineuropatías/epidemiología , Estudios Retrospectivos , PielRESUMEN
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 before the onset of the symptoms. The symptoms were attributed to Paralepistopsis acromelalga. In conclusion, asking about the dietary history is considered essential when diagnosing the cause of erythromelalgia, which has multiple causative diseases, including food poisoning due to P. acromelalga.
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Eritromelalgia , Enfermedades Transmitidas por los Alimentos , Intoxicación por Setas , Anciano de 80 o más Años , Brotes de Enfermedades , Eritromelalgia/diagnóstico , Eritromelalgia/epidemiología , Eritromelalgia/etiología , Femenino , Enfermedades Transmitidas por los Alimentos/diagnóstico , Enfermedades Transmitidas por los Alimentos/epidemiología , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Intoxicación por Setas/complicaciones , Intoxicación por Setas/diagnóstico , Intoxicación por Setas/epidemiologíaRESUMEN
Resumen La eritromelalgia es una enfermedad rara, crónica, poco conocida, de difícil diagnóstico y tratamiento. Caracterizada por enrojecimiento, calor, dolor intenso y ardor en la parte distal de las extremidades. Afecta fundamentalmente manos, pies, nariz y orejas. El rubor, el dolor y el calor de las extremidades aumentan al exponerse a altas temperaturas, así como después de realizar ejercicio. Los síntomas suelen aliviarse mediante la inmersión de la extremidad afectada en agua fría. Se presenta un caso de una mujer de 33 años de edad, blanca, con afectación predominantemente en las manos. A través del interrogatorio minucioso y la realización de los exámenes complementarios realizados se concluyó que la variante etiológica que presentó la paciente era una eritromelalgia primaria o idiopática. Se impuso tratamiento con aspirina y nifedipino. La evolución clínica de la paciente fue favorable (AU).
ASBTRACT Erythromelalgia is a rare, chronic, little known disease, of difficult diagnosis and treatment. It is characterized by redness, heat, and intense pain and burning in the distal part of the extremities. It mainly affects hands, feet, nose and ears. The flushing, pain and warmth of the extremities increase when exposed to high temperatures as well as after exercise. The symptoms are usually relieved by immersing the affected limb in cold water. The authors present the case of a white, 33-years-old woman, with predominantly involved hand. Through a detailed interview and complementary tests they concluded that the etiological variant presented by the patient was a primary or idiopathic erythromelalgia. Treatment with aspirin and nifedipine was prescribed; the clinical progress of the patient was successful (AU).
Asunto(s)
Humanos , Femenino , Signos y Síntomas , Eritromelalgia/epidemiología , Diagnóstico Clínico , Evolución Clínica , Eritromelalgia/diagnóstico , Eritromelalgia/tratamiento farmacológicoRESUMEN
Erythromelalgia is a rare syndrome characterized by the intermittent or, less commonly, by the permanent occurrence of extremely painful hyperperfused skin areas mainly located in the distal extremities. Primary erythromelalgia is nowadays considered to be a genetically determined neuropathic disorder affecting SCN9A, SCN10A, and SCN11A coding for NaV1.7, NaV1.8, and NaV1.9 neuronal sodium channels. Secondary forms might be associated with myeloproliferative disorders, connective tissue disease, cancer, infections, and poisoning. Between the pain episodes, the affected skin areas are usually asymptomatic, but there are patients with typical features of acrocyanosis and/or Raynaud's phenomenon preceding or occurring in between the episodes of erythromelalgia. Diagnosis is made by ascertaining the typical clinical features. Thereafter, the differentiation between primary and secondary forms should be made. Genetic testing is recommended, especially in premature cases and in cases of family clustering in specialized genetic institutions after genetic counselling. Multimodal therapeutic intervention aims toward attenuation of pain and improvement of the patient's quality of life. For this purpose, a wide variety of nonpharmacological approaches and pharmacological substances for topical and systemic use have been proposed, which are usually applied individually in a step-by-step approach. Prognosis mainly depends on the underlying condition and the ability of the patients and their relatives to cope with the disease.
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Eritromelalgia , Eritromelalgia/diagnóstico , Eritromelalgia/epidemiología , Eritromelalgia/genética , Eritromelalgia/terapia , Predisposición Genética a la Enfermedad , Humanos , Técnicas de Diagnóstico Molecular , Dimensión del Dolor , Fenotipo , Valor Predictivo de las Pruebas , Factores de Riesgo , Resultado del TratamientoRESUMEN
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 sodium channel subtype Nav1.7. Secondary erythromelalgia is associated with myeloproliferative disorders, drugs (bromocriptine, calcium channel blockers), or clinical conditions such as rheumatic diseases or viral infection. Primary familial erythromelalgia include genetics and sporadic forms associated with small fibers neuropathy. Aspirin is a useful treatment of erythromelagia associated with myeloproliferative disorders. Treatment of primary erythromelalgia is difficult, individualized, with sodium channel blockers such as lidocaine, carbamazepine and mexiletine.
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Eritromelalgia/diagnóstico , Eritromelalgia/terapia , Bloqueadores de los Canales de Calcio/uso terapéutico , Técnicas y Procedimientos Diagnósticos , Eritromelalgia/clasificación , Eritromelalgia/epidemiología , Humanos , Bloqueadores de los Canales de Sodio/uso terapéuticoRESUMEN
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.
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Salud Global/estadística & datos numéricos , Factores Sexuales , Enfermedades de la Piel/epidemiología , Eritromelalgia/complicaciones , Eritromelalgia/epidemiología , Femenino , Herpes Genital/complicaciones , Herpes Genital/epidemiología , Herpes Zóster/complicaciones , Herpes Zóster/epidemiología , Humanos , Incidencia , Masculino , Minnesota/epidemiología , Síndrome Postrombótico/complicaciones , Síndrome Postrombótico/epidemiología , Enfermedades de la Piel/etiologíaRESUMEN
Etiological and clinical heterogeneity of small fiber neuropathy (SFN) precludes a unifying approach and necessitates reliance on recognizable clinical syndromes. Symptoms of SFN arise from dysfunction in nociception, temperature, and autonomic modalities. This review focuses on SFN involving nociception and temperature, examining epidemiology, etiology, clinical presentation, diagnosis, pathophysiology, and management. Prevalence of SFN is 52.95 per 100,000 population, and diabetes and idiopathic are the most common etiologies. Dysesthesia, allodynia, pain, burning, and coldness sensations frequently present in a length-dependent pattern. Additional autonomic features in gastrointestinal, urinary, or cardiovascular systems are frequent but poorly objectified. SFN is diagnosed by intraepidermal nerve fiber density and quantitative sensory and autonomic tests in combination with normal nerve conduction. Pathophysiological understanding centers on sodium channel dysfunction, and genetic forms are beginning to be understood. Treatment is directed at the underlying etiology supported by symptomatic treatment using antidepressants and anticonvulsants. Little is known about long-term outcomes, and systematic cohort studies are needed.
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Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Neuropatías Diabéticas/fisiopatología , Eritromelalgia/fisiopatología , Hiperalgesia/fisiopatología , Parestesia/fisiopatología , Anticonvulsivantes/uso terapéutico , Antidepresivos/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/etiología , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/terapia , Manejo de la Enfermedad , Eritromelalgia/complicaciones , Eritromelalgia/epidemiología , Eritromelalgia/terapia , Humanos , Hiperalgesia/etiología , Conducción Nerviosa , Nocicepción/fisiología , Parestesia/etiología , Canales de Sodio , TemperaturaRESUMEN
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.
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Minería de Datos/métodos , Brotes de Enfermedades , Epidemias , Eritromelalgia/epidemiología , Vigilancia de la Población/métodos , Pueblo Asiatico , China/epidemiología , Diagnóstico Precoz , Eritromelalgia/diagnóstico , Eritromelalgia/etnología , Geografía , Humanos , Modelos Lineales , Reproducibilidad de los ResultadosRESUMEN
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 (ß = 1.22, 95%CI: 0.66 ~ 1.79), which indicated that this "V"-shaped fluctuation of TM probably triggered the epidemic EM outbreaks.
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Brotes de Enfermedades , Eritromelalgia/epidemiología , Eritromelalgia/etiología , Temperatura , China/epidemiología , Eritromelalgia/diagnóstico , Femenino , Geografía Médica , Humanos , Masculino , Vigilancia de la PoblaciónRESUMEN
OBJECTIVE: To assess the prevalence of restless leg syndrome (RLS) in patients with ankylosing spondylitis (AS) and to investigate factors potentially associated with RLS. METHODS: One hundred and thirty patients diagnosed with AS according to modified New York criteria and 91 age- and sex-matched healthy control subjects were included in this study. The diagnosis of RLS was made according to the criteria of the International RLS Study Group. The factors associated with RLS were evaluated. Electrophysiological procedures were performed in a group of patients with RLS. RESULTS: RLS was significantly more common in patients with AS (30.8%) than in healthy controls (13.2%). When AS patients with RLS were compared with AS patients without RLS, it was seen that peripheral arthritis, uveitis, anemia, smoking and polyneuropathy were significantly higher in the former group. CONCLUSION: RLS is common in patients with AS and iron deficiency, smoking and small fiber neuropathy seem to be possible causes.
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Síndrome de las Piernas Inquietas/epidemiología , Espondilitis Anquilosante/epidemiología , Adulto , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/epidemiología , Estudios de Casos y Controles , Eritromelalgia/diagnóstico , Eritromelalgia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Síndrome de las Piernas Inquietas/diagnóstico , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Espondilitis Anquilosante/diagnóstico , Turquía/epidemiologíaRESUMEN
BACKGROUND: Small-fiber neuropathies (SFN) are diseases of small nerve fibers that are characterized by autonomic and sensory symptoms. OBJECTIVE: We sought to evaluate sensory symptoms, especially pruritus, in patients with SFN. METHODS: A questionnaire was given to patients with SFN. RESULTS: In all, 41 patients responded to the questionnaire (71.9% response rate). The most frequent sensory symptoms were burning (77.5%), pain (72.5%), heat sensations (70.2%), and numbness (67.5%). Pruritus was present in 68.3% of patients. It appeared most often in the evening, and was localized to the limbs in a distal-to-proximal gradient, although the back was the most frequent location (64%). Exacerbating factors were fatigue, xerosis, sweating, hot temperature, and stress. Cold water was an alleviating factor. LIMITATIONS: Recall bias associated with filling out the questionnaire, relatively small sample size, and the uncontrolled, retrospective nature of the study were limitations. CONCLUSION: Pruritus occurs frequently in patients with SFN and could be recognized as a possible presenting symptom, especially if there are other sensory or autonomic symptoms.
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Eritromelalgia/epidemiología , Prurito/epidemiología , Actividades Cotidianas/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Causalidad , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prurito/prevención & control , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
Small fiber neuropathy represents a significant component of diabetic sensorimotor polyneuropathy (DSPN) which has to date been ignored in most recommendations for the diagnosis of DSPN. Small fibers predominate in the peripheral nerve, serve crucial and highly clinically relevant functions such as pain, and regulate microvascular blood flow, mediating the mechanisms underlying foot ulceration. An increasing number of diagnostic tests have been developed to quantify small fiber damage. Because small fiber damage precedes large fiber damage, diagnostic tests for DSPN show good sensitivity but moderate specificity, because the gold standard which is used to define DSPN is large fiber-weighted. Hence new diagnostic algorithms for DSPN should acknowledge this emerging data and incorporate small fiber evaluation as a key measure in the diagnosis of DSPN, especially early neuropathy.
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Diabetes Mellitus/diagnóstico , Neuropatías Diabéticas/diagnóstico , Eritromelalgia/diagnóstico , Fibras Nerviosas/patología , Animales , Diabetes Mellitus/epidemiología , Neuropatías Diabéticas/epidemiología , Diagnóstico Diferencial , Eritromelalgia/epidemiología , Humanos , Piel/inervaciónAsunto(s)
Eritromelalgia/diagnóstico , Eritromelalgia/epidemiología , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To characterize the burden of idiopathic painful peripheral neuropathy with small fiber involvement (idiopathic SFN) by pain severity in the US. METHODS: One hundred previously diagnosed idiopathic SFN subjects were enrolled during routine office visits. Subjects completed a one-time questionnaire, and investigators reported clinical characteristics and healthcare resource use, based on 6 month retrospective chart review. Annualized direct and indirect costs were estimated. Results were stratified across pain severity groups. RESULTS: Mean age was 63.5 years; 53.0% were female; 76.0% had moderate or severe pain. Most common comorbidities were sleep disturbance/insomnia (37.0%), anxiety (34.0%), and depressive symptoms (33.0%). Overall mean health status (0.59; -0.11-1.00 scale), physical and mental health (31.7 and 45.6, respectively, 0-100 scale), sleep index (45.1; 0-100 scale), and pain interference with function (5.0; 0-10 scale) differed by pain severity, with worse outcomes among those with greater pain (all p < 0.002). 84.0% were prescribed ≥1 SFN medication. 16.0% were employed; mean overall work impairment was 36.9%. Annualized average adjusted direct and indirect costs per subject ($8055 and $13,733, respectively) differed by pain severity. CONCLUSIONS: Idiopathic SFN subjects with pain experience moderate or severe pain, which negatively impacts health status, function, and productivity, and leads to substantial direct and indirect costs.
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Eritromelalgia/economía , Eritromelalgia/fisiopatología , Estado de Salud , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Costo de Enfermedad , Costos y Análisis de Costo , Estudios Transversales , Evaluación de la Discapacidad , Eficiencia , Eritromelalgia/epidemiología , Femenino , Humanos , Masculino , Salud Mental/estadística & datos numéricos , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Postural tachycardia syndrome (POTS) is a disorder of orthostatic intolerance characterized by excessive tachycardia of unknown etiology. Our objective in this study was to evaluate the correlation between C-fiber involvement as shown by skin biopsy and adrenergic cardiac metaiodobenzylguanadine (MIBG) uptake in POTS patients. METHODS: Skin biopsies of 84 patients with POTS were examined by Protein Gene Product 9.5 (PGP9.5) immunohistochemistry and were compared with MIBG myocardial scintigraphy imaging data. RESULTS: Mean intraepidermal nerve fiber (IENF) density was in the lower normal age-adjusted range, 7.2 ± 2.9/mm (normal ≥ 7/mm), and was slightly below the normal range in 45% of POTS patients. MIBG uptake was reduced in 21% of patients. Low IENF density correlated with reduced cardiac MIBG uptake (r = 0.39, P = 0.001). CONCLUSIONS: A subset of neuropathic POTS patients may harbor mild small fiber neuropathy with abnormalities of unmyelinated nerve fibers in the skin associated with reduced myocardial postganglionic sympathetic innervation.
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Eritromelalgia/diagnóstico , Eritromelalgia/patología , Corazón/inervación , Degeneración Nerviosa/diagnóstico , Degeneración Nerviosa/patología , Síndrome de Taquicardia Postural Ortostática/complicaciones , 3-Yodobencilguanidina/metabolismo , Adolescente , Adulto , Biopsia , Estudios de Cohortes , Comorbilidad , Eritromelalgia/epidemiología , Femenino , Corazón/diagnóstico por imagen , Humanos , Incidencia , Masculino , Miocardio/metabolismo , Miocardio/patología , Degeneración Nerviosa/epidemiología , Fibras Nerviosas Amielínicas/patología , Síndrome de Taquicardia Postural Ortostática/patología , Estudios Retrospectivos , Piel/inervación , Piel/patología , Tomografía Computarizada de Emisión de Fotón Único , Adulto JovenRESUMEN
INTRODUCTION: 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. METHODS: We describe a patient with an unusual phenotypic presentation of gross motor delay, childhood-onset erythromelalgia, extreme visceral pain episodes, hypesthesia, and self-mutilation. The investigation of the patient's motor delay included various biochemical analyses, a comparative genomic hybridization array (CGH), electromyogram (EMG), and muscle biopsy. Once erythromelalgia was suspected clinically, the SCN9A gene was sequenced. RESULTS: The EMG, CGH, and biochemical tests were negative. The biopsy showed an axonal neuropathy and neurogenic atrophy. Sequencing of SCN9A revealed a heterozygous missense mutation in exon 7; p.I234T. CONCLUSIONS: This is a case of global motor delay and erythromelalgia associated with SCN9A. The motor delay may be attributed to the extreme pain episodes or to a developmental perturbation of proprioceptive inputs.
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Trastornos de la Destreza Motora/genética , Mutación Missense/genética , Canal de Sodio Activado por Voltaje NAV1.7/genética , Índice de Severidad de la Enfermedad , Trastornos Somatomorfos/genética , Carbamazepina/uso terapéutico , Preescolar , Comorbilidad , Eritromelalgia/tratamiento farmacológico , Eritromelalgia/epidemiología , Eritromelalgia/genética , Femenino , Humanos , Hipoestesia/tratamiento farmacológico , Hipoestesia/epidemiología , Hipoestesia/genética , Mexiletine/uso terapéutico , Trastornos de la Destreza Motora/tratamiento farmacológico , Trastornos de la Destreza Motora/epidemiología , Trastornos Somatomorfos/tratamiento farmacológico , Trastornos Somatomorfos/epidemiología , Resultado del TratamientoRESUMEN
OBJECTIVE: Sudomotor dysfunction due to small fiber neuropathy can be observed very early in pre-diabetes. The aim of this study was to assess the predictive power of EZSCAN, a non invasive, quick and simple measurement of sudomotor function to identify glucose impairment. RESEARCH DESIGN AND METHODS: The study was performed in 76 German subjects at risk of diabetes. Glucose metabolism was assessed by using, oral glucose tolerance test (OGTT) at baseline and after 2 year follow-up. Sudomotor function was evaluated by measuring hand and foot electrochemical sweat conductances to calculate a risk score. RESULTS: At baseline, 38 patients had normal glucose tolerance (NGT), 34 had pre-diabetes (impaired fasting glucose, IFG and/or impaired glucose tolerance, IGT) and 4 had newly diagnosed type 2 diabetes. The AUC values for FPG, 2h-OGTT glucose, 1h-OGTT glucose, HbA1C and EZSCAN score to predict pre-diabetes were 0.50, 0.65, 0.64, 0.72 and 0.76, respectively. Subjects having a moderate or high EZSCAN score (>50) at baseline had a substantially increased risk for having IFG and/or IGT at follow-up visit presented by an odds ratio of 12.0 [1.4-100.5], the OR for having 1h-OGTT ≥ 8.6mmol/L at follow-up was 9.8 [1.0-92.8] and for having HbA1C ≥ 5.7% was 15.7 [1.9-131.5] compared to subjects with low EZSCAN risk. CONCLUSIONS: This preliminary study, which must be confirmed in a larger population, shows that EZSCAN risk score is associated with diabetes progression which have implications for prevention and disease management.
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Diabetes Mellitus Tipo 2/diagnóstico , Eritromelalgia/diagnóstico , Estado Prediabético/diagnóstico , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Progresión de la Enfermedad , Conductividad Eléctrica , Eritromelalgia/epidemiología , Eritromelalgia/fisiopatología , Femenino , Alemania/epidemiología , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estado Prediabético/epidemiología , Estado Prediabético/fisiopatología , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Sudoración , Factores de TiempoRESUMEN
OBJECTIVE: To determine the minimum incidence and minimum prevalence rates of small-fiber neuropathy (SFN) in a well-defined region in the southern part of the Netherlands. METHODS: In this cross-sectional study with retrospective data collection, we used data of patients diagnosed with pure SFN at our Small Fiber Neuropathy Center between January 2006 and December 2011 to calculate minimum incidence and prevalence rates. RESULTS: A total of 88 patients were diagnosed with SFN (mean age 56.9 years, SD 11.8, range 34-81; 44.3% women, 55.7% men). The overall minimum incidence over 2010 and 2011 was 11.73 (95% confidence interval 7.12-18.22) cases/100,000 inhabitants/year. The overall minimum prevalence was 52.95 (95% confidence interval 42.47-65.23) cases/100,000. Incidence and prevalence rates were higher in men than in women, as were the rates in elderly patients compared with younger patients. CONCLUSIONS: The minimum incidence and prevalence rates of SFN are presented. We found that SFN is more frequently seen in men and more often diagnosed in elderly patients. These rates probably are an underestimation and are expected to increase in the coming years, since the awareness of SFN is increasing worldwide.
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Eritromelalgia/diagnóstico , Eritromelalgia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Prevalencia , Estudios RetrospectivosRESUMEN
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 analysis in whole-cell configuration. The investigated patients presented with PEM, while age of onset was very different (3 vs. 61 years of age). Electrophysiological characterization revealed that the early onset A1746G mutation leads to a marked hyperpolarizing shift in voltage dependence of steady-state activation, larger window currents, faster activation kinetics (time-to-peak current) and recovery from steady-state inactivation compared to wild-type Nav1.7, indicating a pronounced gain-of-function. Furthermore, we found a hyperpolarizing shift in voltage dependence of slow inactivation, which is another feature commonly found in Nav1.7 mutations associated with PEM. In silico neuron simulation revealed reduced firing thresholds and increased repetitive firing, both indicating hyperexcitability. The late-onset W1538R mutation also revealed gain-of-function properties, although to a lesser extent. Our findings demonstrate that mutations encoding for DIV of Nav1.7 can not only be linked to congenital insensitivity to pain or paroxysmal extreme pain disorder but can also be causative of PEM, if voltage dependency of channel activation is affected. This supports the view that the degree of biophysical property changes caused by a mutation may have an impact on age of clinical manifestation of PEM. In summary, these findings extent the genotype-phenotype correlation profile for SCN9A and highlight a new region of Nav1.7 that is implicated in PEM.