Mayo Clinic in Arizona

Patient-Oriented Priorities for Pediatric Erythromelalgia: A Priority-Setting Process.

: Erythromelalgia is a rare condition characterized by burning pain, redness, and warmth primarily in the extremities, usually worsened by heat and alleviated by cold. The objective of this study was to identify the top 10 priorities in pediatric erythromelalgia from multiple perspectives, including clinicians, people with lived experience of childhood-onset erythromelalgia, and their family members. : A modified James Lind Alliance Priority-Setting Process was conducted. The top priorities were identified through four phases: (1) an international online survey to gather priorities, (2) data processing, (3) an interim prioritization online survey, and (4) a virtual workshop to set the final priorities. : In phase 1, 185 potential priorities were submitted by 74 respondents (53% patients, 24% family members, and 23% clinicians) that were developed into 68 unique research questions (phase 2). In phase 3, of the 68 questions, 50 were rated for importance by 58 participants (38% patients, 36% family members, and 26% clinicians), reducing the list to 25 questions. In phase 4, the top 10 was reached through consensus by 12 participants (33% patients, 25% family members, and 42% clinicians) across Canada, South Africa, the United States of America, and the United Kingdom. : The final priorities focused on the treatment of erythromelalgia, understanding underlying mechanisms, the association of erythromelalgia with various body systems, and generating awareness. This list is the first international patient-centered research agenda for childhood-onset erythromelalgia and a call to action from key partners to improve future research and care.

Vascular Disease Patient Information Page: Erythromelalgia.

Procedural interventions for erythromelalgia: A narrative review.

Erythromelalgia is a rare disorder characterized by episodic burning pain with redness and warmth of the extremities. Topical and systemic medications are the mainstay of management. We reviewed the published evidence for using procedural interventions to manage erythromelalgia, including their proposed mechanism of action and possible adverse effects, and included information in this review on epidural infusion, sympathetic ganglion block, sympathectomy, pulsed radiofrequency, spinal cord stimulation, dorsal root ganglion stimulation, brain stimulation, transcranial magnetic stimulation, and botulinum toxin injections. Both successful and unsuccessful outcomes have been reported. Although these procedural interventions extend the therapeutic options for erythromelalgia, the evidence for their use is limited. Case reports and small case series comprise most of the evidence. Based on our review, a multidisciplinary approach to management may be needed for patients with erythromelalgia.

Essential thrombocytosis: diagnosis, differential diagnosis, complications and treatment considerations of relevance for a cardiologist.

Essential thrombocytosis (ET) is a rare haematological malignancy, with an incidence rate of 1.5-2.5/100,000 per year. For many patients with ET the first manifestation of their underlying disease is a thrombotic or haemorrhagic complication. A recent retrospective study revealed an incidence rate of at least 2.1% in people under 40 years presenting with an acute coronary syndrome, although the diagnosis was initially missed in all cases. Thus, cardiologists face a much higher than average incidence rate of ET in their daily practice, but seem insufficiently aware of the disease. The current review summarises symptoms, (differential) diagnosis, complications and treatment considerations of ET of relevance for a cardiologist. Typical symptoms, besides thrombosis and haemorrhage, include erythromelalgia and aquagenic pruritus, while platelets > 450 × 10/l are a diagnostic for ET once other myeloproliferative neoplasms, secondary and spurious thrombocytosis have been excluded. With regard to treatment, timing of revascularisation depends on the presence of ischaemia and concurrent platelet counts. In the presence of ischaemia, revascularisation should not be delayed and adequate platelet counts can be achieved by platelet apheresis. In the absence of ischaemia, revascularisation can be delayed until adequate platelet counts have been achieved by cytoreductive therapies. Cardiologists should be aware of/screen for possible ET.

Erythromelalgia: A Review of Medical Management Options and Our Approach to Management.

Erythromelalgia (EM) is a rare disorder characterized by episodic, burning pain associated with erythema and warmth of the extremities. The feet and hands are most commonly affected. The pain can be so severe that patients may engage in behaviors, sometimes extreme, to cool the affected areas and change their lifestyle to avoid precipitating factors, such as exercise and increased ambient heat. A literature search was performed with PubMed and MEDLINE with the search term erythromelalgia. Inclusion criteria were studies on EM published after 1985 until January 1, 2022, in the English language and studies that provided information on medical treatment of EM. Studies were excluded if they were duplicates or did not include treatment data. No guidelines exist for the treatment of this complex disorder. Lifestyle modifications and pharmacologic treatments (topical and systemic) are discussed in this article, which provides a comprehensive review of published medical management options for erythromelalgia and a proposed approach to management.

Dorsal Root Ganglion Stimulation for Erythromelalgia Related Foot Pain: A Case Report and Review of the Literature.

Erythromelalgia is a rare neurovascular disorder characterized by erythema, warmth, and episodic burning pain, often felt in the face, hands, and feet. Symptoms are typically worse with heat, exercise, stress, and during the overnight hours. Management often requires a multidisciplinary approach, including pain trigger avoidance, cool water baths, and topical and oral neuropathic medications. The use of spinal cord stimulation has been described in multiple case reports with success reported out to 24 months. To our knowledge, the use of dorsal root ganglion (DRG) stimulation for erythromelalgia-related pain has not been described. Herein, we present a case of erythromelalgia-related pain at the bilateral plantar surfaces of the feet, which was treated successfully with bilateral sacral S1 nerve root DRG stimulation.

Erythromelalgia: improvement in pain with transcranial magnetic stimulation.

Facial erythromelalgia?

Thermoregulation in neuropathies.

Peripheral neuropathy affecting autonomic and small sensory fibers can cause abnormalities of both autonomic and behavioral thermoregulation. Quantitative autonomic and sensory neurophysiologic tests and quantification of the linear density of intraepidermal nerve fibers potentially can stratify those at risk of impaired thermoregulation during cold and heat challenges. New data relating to thermoregulatory sweating impairment in neuropathy are presented in this chapter. Of 516 neuropathy patients analyzed, 345 were found to have thermoregulatory sweat test (TST) abnormalities with a mean percentage of anterior body surface anhidrosis (TST%) of 12% and a significant reduction in total body sweat rate, although the rate of core temperature rise with heating (slope) was not significantly different from that of patients with a normal TST. However a subset of abnormal TST patients having 25% or greater TST% showed a significantly more rapid rise in core temperature (lower slope) than age- and sex-matched neuropathy patients with a normal TST. Etiologies of neuropathy in this more severe group included diabetes, erythromelalgia, immune-mediated autonomic neuropathy, primary systemic amyloidosis, and neuropathy associated with postganglionic-autonomic degenerative disorders.

Erythromelalgia in patients with essential thrombocythemia and polycythemia vera.

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.

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.

Spinal Cord Stimulation for Treatment of Neuropathic Pain Associated With Erythromelalgia.

Erythromelalgia is a rare disorder associated with neuropathic pain that commonly affects the lower extremities. This pain is often refractory to multimodal treatment. Both pharmacologic management and interventional anesthetic blocks have been used with varying and often limited success. To date, little experience has been gained with the use of spinal cord stimulation in treating pain associated with erythromelalgia. We present a case of successful treatment of pain secondary to erythromelalgia with a spinal cord stimulator in an 80-year-old woman. This patient had severe pain and debility secondary to erythromelalgia, having undergone trials of multiple medical therapies before presenting to our clinic. Dual-lead percutaneous spinal cord stimulation was successfully implanted without complication, leading to excellent pain control, now 18 months postimplant. Spinal cord stimulation may be a promising treatment of neuropathic pain associated with erythromelalgia.

Topical amitriptyline combined with ketamine for the treatment of erythromelalgia: a retrospective study of 36 patients at Mayo Clinic.

Erythromelalgia is an uncommon neurovascular disorder characterized by redness, increased skin temperature, and pain that usually occurs in the extremities. Treatment remains challenging because of its varying response to medical therapy. The objective of this study was to assess the response of erythromelalgia to compounded topical amitriptyline-ketamine. We retrospectively evaluated 36 patients with erythromelalgia who were treated with compounded topical amitriptyline-ketamine from January 1, 2004, through January 31, 2011. Thirty-two patients (89%) were female. Mean (standard deviation) age was 44.7 (15.8) years (range, 5-74 years). Patients applied the medication 1 to 6 times per day (median, 5 times). One patient (3%) had complete relief from symptoms, 14 (39%) had substantial relief, 12 (33%) had some relief, 7 (19%) had no relief, and 2 (6%) had local worsening of symptoms. No patients had systemic adverse effects. A majority of patients with erythromelalgia (75%) reported improvement in pain with topical application of a compounded amitriptyline-ketamine formulation. The medication was well tolerated.

Infrequent SCN9A mutations in congenital insensitivity to pain and erythromelalgia.

Mutations in SCN9A have been reported in (1) congenital insensitivity to pain (CIP); (2) primary erythromelalgia; (3) paroxysmal extreme pain disorder; (4) febrile seizures and recently (5) small fibre sensory neuropathy. We sought to investigate for SCN9A mutations in a clinically well-characterised cohort of patients with CIP and erythromelalgia. We sequenced all exons of SCN9A in 19 clinically well-studied cases including 6 CIP and 13 erythromelalgia (9 with family history, 10 with small-fibre neuropathy). The identified variants were assessed in dbSNP135, 1K genome, NHLBI-Exome Sequencing Project (5400-exomes) databases, and 768 normal chromosomes. In erythromelalgia case 7, we identified a novel Q10>K mutation. In CIP case 6, we identified a novel, de novo splicing mutation (IVS8-2A>G); this splicing mutation compounded with a nonsense mutation (R523>X) and abolished SCN9A mRNA expression almost completely compared with his unaffected father. In CIP case 5, we found a variant (P610>T) previously considered causal for erythromelalgia, supporting recently raised doubt on its causal nature. We also found a splicing junction variant (IVS24-7delGTTT) in all 19 patients, this splicing variant was previously considered casual for CIP, but IVS24-7delGTTT was in fact the major allele in Caucasian populations. Two novel SCN9A mutations were identified, but frequently polymorphism variants are found which may provide susceptibility factors in pain modulation. CIP and erythromelalgia are defined as genetically heterogeneous, and some SCN9A variants previously considered causal may only be modifying factors.

Results of computer-assisted sensory evaluation in 41 patients with erythromelalgia.

Erythromelalgia is a rare disorder characterized by the clinical syndrome of burning pain, warmth and redness of the limbs. Neurological abnormalities (both large- and small-fibre neuropathy) are common. There have been few published reports on the sensory status of patients with erythromelalgia. To investigate the results of quantitative sensation testing in erythromelalgia using computer-assisted sensory evaluation, including vibratory detection threshold, cool detection threshold and heat-pain threshold (HPT). Patients who underwent dermatological or neurological evaluation of suspected erythromelalgia at our institution and received a final diagnosis of erythromelalgia were identified from a master diagnosis index covering the period January 1994 to June 2008. A retrospective chart review was performed. Main outcome measures were sensory abnormalities (e.g. pain, burning sensation, tingling) in response to heat, cooling and vibration during computer-assisted sensory testing. In total, 41 patients with erythromelalgia were enrolled in the study and underwent computer-assisted sensory evaluation. Of these, 34 patients (82.9%) had abnormal results. The commonest abnormality was isolated HPT: 11 patients (26.8%) had heat hypoalgesia and 18 (43.9%) had heat hyperalgesia, whereas only 2 (4.9%) of the healthy control patients had hyperalgesia on testing. Multiple sensory modalities were found to be abnormal in patients with erythromelalgia, with the commonest clinical abnormality being isolated heat-pain abnormality. These findings lend support to the notion that neuropathy underlies the clinical diagnosis of erythromelalgia. Future studies will explore the nature of the relationship between these sensory abnormalities and the clinical features of erythromelalgia.

Severe case and literature review of primary erythromelalgia: novel SCN9A gene mutation.

Erythromelalgia is a rare clinical syndrome characterized by intermittent heat, redness, swelling and pain more commonly affecting the lower extremities. Symptoms are mostly aggravated by warmth and are eased by a cold temperature. In some cases, symptoms can be very severe and disabling. Erythromelalgia can be classified as either familial or sporadic, with the familial form inherited in an autosomal dominant manner. Recently, there has been a lot of progress in studying Na(v)1.7 sodium channels (expressed mostly in the sympathetic and nociceptive small-diameter sensory neurons of the dorsal root ganglion) and different mutations affecting the encoding SCN9A gene that leads to channelopathies responsible for some disorders, including primary erythromelalgia. We present a severe case of progressive primary erythromelalgia caused by a new de novo heterozygous missense mutation (c.2623C>G) of the SCN9A gene which substitutes glutamine 875 by glutamic acid (p.Q875E). To our knowledge, this mutation has not been previously reported in the literature. We also provided a short literature review about erythromelalgia and Na(v) sodium channelopathies.

Incidence of erythromelalgia: a population-based study in Olmsted County, Minnesota.

To estimate the population-based incidence of erythromelalgia. Background Only one report describing the incidence of erythromelalgia has been published previously. A population-based analysis of data from the Rochester Epidemiology Project. Tertiary care medical centre in Olmsted County, Minnesota (a rural county in the south-eastern portion of the state). Thirty-three residents of Olmsted County with a diagnosis of erythromelalgia during the study period. Age- and sex-specific incidence rates of erythromelalgia were determined. None. Population-based incidence rate. The overall age- and sex-adjusted incidence rate (95% confidence interval, 95% CI) was 1.3 (0.8-1.7) per 100,000 people per year. The incidence of primary and secondary erythromelalgia was 1.1 (0.7-1.5) and 0.2 (0.02-0.4) per 100,000 people per year, respectively. The age-adjusted incidence rates (95% CI) were 2.0 (1.2-2.7) per 100,000 women and 0.6 (0.1-1.1) per 100,000 men. The study was limited by the small sample size and potential variability in recognition of erythromelalgia. The population-based incidence of erythromelalgia has increased with each decade in Olmsted County over the past three decades; overall incidence was 1.3 per 100,000 people per year, approximately 5 times higher than previously reported.

Thermoregulatory sweat testing in patients with erythromelalgia.

To examine the results of thermoregulatory sweat testing in patients with erythromelalgia and to compare them with the results of other neurophysiologic tests of small-fiber nerve function. Retrospective study. Tertiary referral center. Thirty-two consecutive patients with erythromelalgia who had thermoregulatory sweat testing in addition to vascular and nerve testing. The following information was abstracted for each patient: demographics, clinical presentation, and results of thermoregulatory sweat testing, vascular (noninvasive) testing, and nerve testing (electromyography and autonomic reflex screen, including quantitative sudomotor axon reflex test). Results of thermoregulatory sweat testing to evaluate small-fiber neuropathy, compared with other tools used to estimate small-fiber neuropathy. Thermoregulatory sweat testing results were abnormal in 28 (88%) of 32 patients, and quantitative sudomotor axon reflex test results were abnormal in 22 patients (69%). Abnormalities noted on thermoregulatory sweat testing varied from local hypohidrosis or anhidrosis to global anhidrosis. Global or almost-global anhidrosis was present in 8 patients (25%); in 19 patients (59%) the anhidrosis was distal, and 1 other patient (3%) had a less specific pattern of anhidrosis (multifocal or regional). The area of anhidrosis generally corresponded to the area that was symptomatic of the erythromelalgia. Small-fiber neuropathy is prevalent in most patients with erythromelalgia. Thermoregulatory sweat testing is a sensitive and useful marker of small-fiber neuropathy in these patients.

Erythromelalgia.

Skin blood flow in adult human thermoregulation: how it works, when it does not, and why.

The thermoregulatory control of human skin blood flow is vital to the maintenance of normal body temperatures during challenges to thermal homeostasis. Sympathetic neural control of skin blood flow includes the noradrenergic vasoconstrictor system and a sympathetic active vasodilator system, the latter of which is responsible for 80% to 90% of the substantial cutaneous vasodilation that occurs with whole body heat stress. With body heating, the magnitude of skin vasodilation is striking: skin blood flow can reach 6 to 8 L/min during hyperthermia. Cutaneous sympathetic vasoconstrictor and vasodilator systems also participate in baroreflex control of blood pressure; this is particularly important during heat stress, when such a large percentage of cardiac output is directed to the skin. Local thermal control of cutaneous blood vessels also contributes importantly--local warming of the skin can cause maximal vasodilation in healthy humans and includes roles for both local sensory nerves and nitric oxide. Local cooling of the skin can decrease skin blood flow to minimal levels. During menopause, changes in reproductive hormone levels substantially alter thermoregulatory control of skin blood flow. This altered control might contribute to the occurrence of hot flashes. In type 2 diabetes mellitus, the ability of skin blood vessels to dilate is impaired. This impaired vasodilation likely contributes to the increased risk of heat illness in this patient population during exposure to elevated ambient temperatures. Raynaud phenomenon and erythromelalgia represent cutaneous microvascular disorders whose pathophysiology appears to relate to disorders of local and/or reflex thermoregulatory control of the skin circulation.

Polycythemia vera: a comprehensive review and clinical recommendations.

More than a century has elapsed since the appearance of the modern descriptions of polycythemia vera (PV). During this time, much has been learned regarding disease pathogenesis and PV-associated molecular aberrations. New information has allowed amendments to traditional diagnostic criteria. Phlebotomy remains the cornerstone treatment of PV, whereas myelosuppressive agents may augment the benefit of using phlebotomy for thrombosis prevention in high-risk patients. Excessive aspirin use is contraindicated in PV, although the use of lower-dose aspirin has been shown to be safe and effective in alleviating microvascular symptoms including erythromelalgia and headaches. Recent studies have shown the utility of selective serotonin receptor antagonists for treating PV-associated pruritus. Nevertheless, many questions remain unanswered. What is the specific genetic mutation or altered molecular pathway that is causally related to the disease? In the absence of a specific molecular marker, how is a working diagnosis of PV made? What evidence supports current practice in the management of PV? This article summarizes both old and new information on PV; proposes a modern diagnostic algorithm to formulate a working diagnosis; and provides recommendations for patient management, relying whenever possible on an evidence-based approach.