Mayo Clinic in Florida

Anhidrosis: An underappreciated factor in dermatologic diseases.

Dissipation of body heat, essential to human life, is largely achieved through sweating. If sweating does not occur normally-as in patients with hypohidrosis (reduced sweating) or anhidrosis (lack of sweating)-the ability to dissipate heat via evaporative mechanisms is overwhelmed. Body temperature may rise, leading to heat-related illness, including heat intolerance, hyperthermia, heat exhaustion, heat stroke, and even death. In patients seen by a dermatologist, anhidrosis may underly and contribute to their symptoms and signs but may be difficult to detect given a limited availability of tools to measure anhidrosis. An association between anhidrosis and skin symptoms including flushing syndromes (eg, facial flushing and erythromelalgia) and widespread skin symptoms (eg, itching, burning, numbness, or tingling, and paresthesias) has recently been described. This review explores the existing dermatologic literature on anhidrosis including clues to the pathophysiology of these disorders, its relationship to skin diseases and symptoms, the tests currently available, and approaches to management. Recognition of an underlying anhidrosis by dermatologists may be important for providing optimal management for patients with heat-related symptoms.

Pediatric erythromelalgia from multidisciplinary perspectives: a scoping review.

Erythromelalgia is a rare, chronic pain disorder characterized by the triad of intense burning sensation, warmth, and redness, primarily involving the hands and feet, and usually alleviated by cold and worsened by heat. The objective of this scoping review was to: 1) map the existing literature on erythromelalgia in youth, 2) identify knowledge gaps, and 3) inform directions for future research in pediatric erythromelalgia. One hundred and sixty-seven studies reporting 411 cases of childhood-onset erythromelalgia were identified. Variability was found in reporting of clinical symptoms, the clinical presentations and diagnostic criteria used for classification of erythromelagia, the clinical assessments and investigations performed, and the types of interventions and management plans utilised. While factors to aid early recognition and optimize management have been identified, there are also significant gaps for future research to address. Ongoing efforts to develop a multicenter registry of pediatric erythromelalgia cases, with standardized data collection and reporting, will be beneficial to establish consensus recommendations for the diagnosis and management of pediatric erythromelalgia. IMPACT: This scoping review maps the existing literature on pediatric erythromelalgia. Variability was found in reporting of clinical symptoms, the clinical presentations and diagnostic criteria used for classification of erythromelagia, the clinical assessments and investigations performed, and the types of interventions and management plans utilised. The development of an international registry would immensely benefit multidisciplinary experts involved in the care of pediatric erythromelalgia and those with lived experience.

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.

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.

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: Identification of a corticosteroid-responsive subset.

Corticosteroids (CS) may benefit certain patients with erythromelalgia. Our objective was to determine clinical predictors of corticosteroid-responsive erythromelalgia. Patients with erythromelalgia who received CS were identified and stratified into corticosteroid nonresponders (NRs), partial corticosteroid responders (PSRs), complete corticosteroid responders (CSRs), and steroid responders (SRs = PSRs + CSRs). In the study variable analysis, P < .05 was considered statistically significant. The median (interquartile range) age of the 31-patient cohort was 47 years (26-57 years), and 22 (71%) were female. Fourteen (45%) were NRs, 17 (55%) SRs, 8 (26%) PSRs, and 9 (29%) CSRs. A subacute temporal profile to disease zenith (<21 days) was described in 15 (48%) patients, of whom 13 (87%) were SRs (P = .003; odds ratio [OR] = 0.069 [95% confidence interval {CI}, 0.011-0.431]). Six (67%) CSRs reported a disease precipitant (eg, surgery, trauma, or infection; P = .007; OR = 12.667 [95% CI, 2-80.142]). SR patients received CS sooner than NR at 3 (3-12) versus 24 (17-45) months (P = .003). A high-dose CS trial (≥200 mg prednisone cumulatively) was administered to 17 (55%) patients, of whom 13 (76%) were SRs (P = .012; OR = 8.125 [95% CI, 1.612-40.752]). This was a retrospective case series. An infectious, traumatic, or surgical precipitant and subacute presentation may portend CR erythromelalgia. A transient "golden window" where CS intervention is useful may exist before irreversible nociceptive remodeling and central sensitization occurs.

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.