Erythromelalgia. Part II: Differential diagnoses and management.

The management of erythromelalgia is challenging and requires multidisciplinary effort. Patient education is crucial as unsafe self-administered cooling techniques can lead to significant morbidity, including acral necrosis, infection, and amputation. The goal of management is pain control, reduction of flare frequency, and prevention of complications. This text is focused on the management of erythromelalgia and several other incompletely understood and under-recognized neurovascular disorders such as red scrotum syndrome, red ear syndrome, facial flushing, and complex regional pain syndrome.

Cyclosporine-induced erythromelalgia.

Erythromelalgia is a rare syndrome characterised by recurrent erythema, heat and burning pain in the extremities. There are two types: primary (genetic) and secondary (toxic, drug-related or associated with other diseases). We report a 42-year-old woman who developed erythromelalgia after taking cyclosporine for myasthenia gravis. Although exact mechanism for this rare adverse effect is unclear, it is reversible, and so clinicians should be aware of the association . Additional use of corticosteroids could aggravate cyclosporine's toxic effects.

Erythromelalgia in a patient with feet erythema and cyanosis.

Erythromelalgia is a rare disease characterised by a triad of a clinical syndrome of redness, warmth and painful extremities. We present the case of a male adolescent with no prior medical history who presents to our family medicine clinic with a 3-month history of bilateral feet erythema followed by episodes of cyanosis in bilateral toes. Given his history, the findings on clinical examination, and the lack of any pathology on the diagnostic testing, the patient is diagnosed with erythromelalgia. He is then counselled on both pharmacological and non-pharmacological treatments for his condition and is discharged on non-pharmacological treatment options such as leg elevation, cooling with a fan and limiting exposure to heat. The patient is also advised to perform an annual complete blood count given the association of erythromelalgia with myeloproliferative disorders.

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.

[Functional vascular acrosyndromes]. / Funktionelle akrale Durchblutungsstörungen.

Vascular acrosyndromes are characterized by sparse, uniform clinical manifestations and a variety of possible pathomechanisms. The present article focuses on the functional entities. Raynaud phenomenon is based on cold- or stress-induced vasospasms of acral arteries. It is defined by the color changes of the skin, in the typical case white-blue-red (tricolore). The long fingers are most commonly affected. The etiology is unknown, and the pathophysiology is poorly understood. A distinction is made between primary and a secondary Raynaud phenomenon. The most important underlying diseases include collagenosis, primarily systemic sclerosis, and malignancies; furthermore, medications and drugs may promote vasospasm. Treatment is aimed at preventing or breaking the vasospasm, but has been only partially effective in doing so. Acrocyanosis is a vasospastic dystonic acral disorder that results in permanent reddish-livid discoloration, especially of the hands and feet. Secondary forms occur in collagenosis, malignancies, and myelodysplastic syndromes. The etiology and pathophysiology are virtually unknown. Targeted pharmacological intervention is not possible. Unlike all other vascular acrosyndromes, erythromelalgia is characterized by hyperemia. The primary form is a genetic sodium channelopathy, while secondary forms include malignancies, connective tissue diseases, and myelodysplastic syndromes. The symptoms are often distressing and disabling. Therapy requires a multimodal approach that includes both nonpharmacological and pharmacological strategies. Close interdisciplinary collaboration is essential for the management of this disease.

Intravenous Ketamine Infusion as an Adjunctive Pain Treatment for Erythromelalgia: A Pediatric Case Report.

Erythromelalgia is a rare neurovascular pain condition characterized by erythematous, warm, and painful extremities. Symptoms are exacerbated by heat and relieved by cooling. Treatment is challenging and focuses on symptom control with various medications and therapies targeted toward eliminating destructive cooling behaviors. This pediatric case was notable because the patient's pain dramatically improved after a short-term, low-dose ketamine infusion, allowing her to finally wean off detrimental cooling practices of her extremities. Intravenous ketamine has rarely been described as an adjunctive analgesic strategy for erythromelalgia.

A reappraisal of the presence of small or large fiber neuropathy in patients with erythromelalgia.

OBJECTIVE: To assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). METHODS: Thirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve conduction studies (NCS) for large nerve fibers and specific tests for small nerve fibers: electrochemical skin conductance, cold and warm detection thresholds, and laser evoked potentials. Finally, the evaluation of vascular changes was based on the presence of clinical feature of microvascular disorders and the measurement of the Toe Pressure Index (TPI). RESULTS: While 28 patients (85%) had vascular alteration on TPI or clinical features, 23 patients (70%) had small-fiber neuropathy on neurophysiological tests, and only 10 patients (30%) had large fiber neuropathy on NCS. Regarding clinical scores, there was no difference between groups (presence or absence of large- or small-fiber neuropathy or microvascular disorder) except for a higher UENS score in patients with large fiber neuropathy. CONCLUSION: Peripheral neuropathy, mostly involving small nerve fibers, is almost as common as microvascular changes in EM, but remains inconstant and not related to a specific neuropathic pattern or higher clinical severity. SIGNIFICANCE: The association of neuropathic and vascular factors is not systematic in EM, this syndrome being characterized by different pathophysiological mechanisms leading to a common clinical phenotype.

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.

Spinal Cord Stimulation in the Treatment of Pediatric Erythromelalgia.

BACKGROUND: In children, erythromelalgia is a rare but difficult to manage condition that results in bilateral episodic pain and redness in distal extremities. It is heat intolerant and relieved by cooling. Management of erythromelalgia is difficult and requires a complex multidisciplinary approach. CASE DESCRIPTION: We present a case of successful treatment of erythromelalgia with short-term spinal cord stimulation in a 12-year-old girl. The patient had severe burning pain, having undergone trials of multiple medical therapies before presenting to our department. Dual-lead spinal cord stimulator electrodes were successfully implanted without complication, leading to excellent pain control, now 8 months postimplant. CONCLUSIONS: This case spurs interest for future research in neuromodulation as part of the multimodal regimen to treat pediatric erythromelalgia.

Small-fiber neuropathy associated with autoinflammatory syndromes in children and adolescents.

INTRODUCTION: Small-fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology. METHODS: The data of four children/adolescents presenting with erythromelalgia and neuropathic pain from 2014 to 2019 were collected retrospectively from the electronic database of a pediatric medical center. RESULTS: Results of clinical and/or electrophysiological evaluation excluded large nerve fiber involvement. Skin biopsy results confirmed small-fiber neuropathy. According to genetic analysis, two patients were heterozygous and one was homozygous for mutations in the familial Mediterranean fever (MEFV) gene. Behcet disease was diagnosed in the fourth patient. Treatment with anti-interleukin-1 agents, intravenous immunoglobulin, and glucocorticoids was beneficial. DISCUSSION: The diagnosis of small-fiber neuropathy should be considered in children/adolescents presenting with erythromelalgia. A thorough investigation is required to reveal the underlying disorder. Clinicians should be alert to the peripheral neurological manifestations of autoinflammatory syndromes because effective treatments are available.

Vascular acrosyndromes in young adult population. Definition of clinical symptoms and connections to joint hypermobility.

OBJECTIVES: Clinical recognition of vascular acrosyndromes is often challenging. The term Raynaud's phenomenon (RP) is commonly overused to describe any form of cold-related disorder. This study aims to formally evaluate peripheral vascular symptoms affecting the population, aged ≤ 40 years, and identify any correlations to joint hypermobility (JH). PATIENTS AND METHODS: Fifty patients (31 males, 19 females) with vasomotor symptoms enrolled in this five-year prospective observational study. Clinical examination by a rheumatologist and a vascular surgeon was performed along with cardiology, echocardiographic and Doppler evaluation. Patients underwent blood cell count, biochemistry, thyroid and selectively immunologic testing. Twenty-four (48%) of them performed nailfold capillaroscopy. The SPSS for Windows, v.17.0, Chicago, USA, was used for the statistical analyses. RESULTS: Twenty-eight patients (56%) presented with erythromelalgia (EM), 6 (12%) with acrocyanosis (AC) and 9 (18%) as a combination of the above disorder. RP diagnosed in five (10%) while two patients (4%) presented as a mix of EM-RP. There was no correlation with abnormal laboratory tests. Increased incidence of JH was found in EM and AC patients. Among those who were tested with nailfold capillaroscopy, 75% had abnormalities ranged from mild to autoimmune-like diseases. CONCLUSIONS: Erythromelalgia is the commonest functional vasculopathy in young population followed by acrocyanosis and a combination of these conditions. Joint hypermobility is markedly increased, indicating that dysautonomy may be considered the causative factor following a trigger event. Overall, RP was observed in 14% of patients. Clinical recognition of these disorders avoids unnecessary investigation. Key Points • Vascular acrosyndromes in young adults are commonly functional disorders resembling vascular algodystrophy induced by thermic stress. • Dysautonomy of joint hypermobility is the co-factor influencing the appearance of the vascular disorders. • Raynaud's phenomenon accounts to approximately 14% of vascular acrosyndromes presented in the young adult population.

Review of primary and secondary erythromelalgia.

Erythromelalgia is a condition characterized by episodic pain, erythema and temperature of the extremities, which is relieved by cooling and aggravated by warming. It is useful to review this topic in light of recent discoveries of the genetic mutations that now define primary erythromelalgia, as opposed to secondary erythromelalgia, which is often associated with underlying medical disorders.