HistoryThis section has been translated automatically.
Graves 1834; Mitchell 1872; Gerhardt 1892
DefinitionThis section has been translated automatically.
Rare neuro-vascular skin disease and functional circulatory disorder characterized by burning, painful sensations in the acral area of the hands and feet (rare). Characteristic, paroxysmal, painful, seizure-like hyperemia of the acres after exposure to heat.
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ClassificationThis section has been translated automatically.
Three forms of erythromelalgia are described:
- Primary autosomal dominant inherited erythromelalgia (erythrothermalgia) provoked by heat and muscle work (OMIM:133020).
- Secondary erythromelalgia
- Secondary erythromelalgia in various haematological diseases
- Secondary erythromelalgia in inflammatory or degenerative vascular diseases (e.g., arterial occlusive disease, thrombophlebitis)
Occurrence/EpidemiologyThis section has been translated automatically.
In Scandinavia, its incidence is estimated at 0.3-0.4/100,000 population.
EtiopathogenesisThis section has been translated automatically.
Primary erythromelalgia (erythrothermalgia) has been shown to be caused by an autosomal dominantly inherited mutation in the sodium channel-encoding SCN9A gene (Sodium-channel, voltage-gated, type 9, alpha subunit) which is located on chromosome 2q24.3 (OMIM:133020).(Klein-Weigel PF et al. 2018). This gene defect leads to defective function of the voltage-gated sodium channel.
Evidence of"small-fiber" neuropathy with pathologic sudomotor axon reflex was found in a large proportion of patients. Some (about 25%) have impaired adrenergic function, others (also about 25%) have abnormal cardiovagal function.
In secondary variants, mostly idiopathic genesis, especially in polycythemia, leukemias (chronic myeloid leukemia), diabetes mellitus, hypercholesterolemia, gout, rheumatoid arthritis, lupus erythematosus, mixed connective tissue disease, Sjögren's syndrome, AIDS, viral infections, syphilis, endangiitis obliterans, chronic perniosis, neurological diseases such as multiple sclerosis or neuropathies.
In thrombocythemias, the disturbances of cutaneous microcirculation could be explained by formation of thrombi.
Associations with the application of drugs, e.g. nifedipine, bromocriptine, norephedrine and nicardipine have been described casuistically.
Furthermore, in very rare cases, associations with carcinomas of the lung and gastrointestinal system have been described.
In China, in an endemic form of erythromelalgia, an associated virus, erythromelalgia-associated poxvirus (ERPV) has been isolated.
Associations with COVID-19 infections or COVID vaccinations are noteworthy (Gambichler T et al. 2022).
ManifestationThis section has been translated automatically.
Equal for women and men; no gender preference. Age of manifestation: 5-6th decade; less frequently in children around 10 years of age (familial form of erythromelagia).
LocalizationThis section has been translated automatically.
Leg feet (90%), hands (20-25%), nose (very rare).
Clinical featuresThis section has been translated automatically.
Intermittent (in larger series, syncopal erythromelalgia occurs in 95% of patients. In 3-5% it is permanent), painful, hyperemic, reddened and swollen skin with increased sensitivity to heat. Often burning pain. During syncope, skin temperature rises 7-8°C, blood flow is increased 10-fold. The seizures can be provoked by raising the temperature of the extremity to an individual "critical thermal point" which is between 32°C and 37°C, and by physical overload. Duration of seizures: minutes to hours. A large proportion of patients present with localized or generalized anhidrosis.
- Seizure-like, uniform redness and swelling of the affected extremities.
- Lesional hyperthermia
- Burning pain of the extremities
- Pain aggravated by heat
- Pain is immediately relieved by cooling (Note: many patients try to relieve the pain by continuous blow-drying or by ice-water baths; this is successful as long as the cooling effect lasts. Prompt recurrence after rewarming).
LaboratoryThis section has been translated automatically.
Differential diagnosisThis section has been translated automatically.
TherapyThis section has been translated automatically.
Internal therapyThis section has been translated automatically.
- Clomipramine (Anafranil) 100-200 mg/day can be tried.
- Alternatively, long-term therapy with small doses (100 mg/day) of acetylsalicylic acid or with indomethacin. In case of high platelet numbers or platelet dysfunction high doses of ASS.
- Alternative: experiment with high doses of magnesium (e.g. Magnesium Verla) p.o.
- Experimental: Prostaglandin-E1 (Alprostadil), e.g. Caverject i.v., followed by nitroprusside sodium (e.g. Nipruss).
Operative therapieThis section has been translated automatically.
In severe therapy-resistant cases a temporary borderline blockade with local anesthesia is recommended. If the treatment is successful and the autonomic dysregulation is permanently broken through, permanent sympathetic lysis (borderline blockade with alcohol) should then be discussed.
Progression/forecastThis section has been translated automatically.
Often chronic course. Individually very variable (remissions, progression, stable disease possible). Children have a more favorable prognosis according to individual case reports.
Note(s)This section has been translated automatically.
- Diagnosis based on the clinic.
- Typically, patients cool their extremities in cold water during a seizure. This results in sudden freedom from symptoms. Recurrence of symptoms when the body warms up. Exclusion of other functional or organic circulatory disorders.
- Possibly capillary microscopy. Search for causes of secondary erythromyalgia.
LiteratureThis section has been translated automatically.
- Birk J et al (2015) Ice water and ventilators: complicating course of erythromelalgia. JDDG 13 (Suppl 1): 67
- da Costa AF et al (2014) Therapeutic success with local botulinum toxin in erythromelalgia. Pain Physician 17:E658-660
- Davis M et al (2006) Thermoregulatory sweat testing in patients with erythromelalgia. Arch Dermatol 142: 1583-1588
- Duchatelet S et al (2013) A new TRPV3 missense mutation in a patient with Olmsted syndrome and erythromelalgia. JAMA Dermatol 150:303-306
- Gambichler T et al (2022) Cutaneous findings following COVID-19 vaccination: review of world literature and own experience. J Eur Acad Dermatol Venereol 36:172-180.
- Gerhardt CA (1892) On erythromelalgia. Berl Klin Wochenschr 29: 1125-1126.
- Graves RJ (1834) Clinical Lectures on the Practice of Medicine. Fannin, Dublin, Ireland
- Han JH et al (2012) Paraneoplastic erythromelalgia associated with breast carcinoma. Int J Dermatol 51:878-880.
- Harrison J et al (2003) The use of regional anaesthetic blockade in a child with recurrent erythromelalgia. Arch Dis Child 88: 65-66
- Klein-Weigel PF et al (2018) Erythromelalgia. Vasa 47:91-97.
- Michiels JJ et al (2015) Aspirin-responsive, migraine-like transient cerebral and ocular ischemic attacks and erythromelalgia in JAK2-positive essential thrombocythemia and polycythemia vera. Acta Haematol 133:56-63
- Mitchell SW (1872) Clinical Lecture On Certain Painful Affections of the Feet. Philadelphia Medical Times 3: 81-82, 113-115.
- Mitchell SW (1878) On a rare vaso-motor neurosis of extremities and on the maladies with which it may be confounded. Am J Med Sci 76: 17-36
- Mørk C et al (1999) Erythromelalgia as a paraneoplastic syndrome in a patient with abdominal cancer. Acta Derm Venereol 79:394.
- Stadler T et al. (2015) Erythromelalgia mutation Q875E Stabilizes the Activated State of Sodium Channel Nav1.7. J Biol Chem PubMed PMID: 25575597.
- Thami GP et al (2003) Erythromelalgia induced by possible calcium channel blockade by ciclosporin. BMJ 326: 910
- Wollina U (2015) Burning feet in polycythemia vera - peripheral sensorimotor axonal neuropathy with erythromelalgia. Int J Gen Med 8:69-71
- Zambrano N et al (2012) Metanephric adenoma of the kidney associated with polycythemia and erythromelalgia: report of one case. Rev MedChil 140:629-632.
Incoming links (19)Acroerythrosis indolens bechterew; Acroerythrosis paraesthetica; Acromelalgia; Burning feet syndrome; Calcium antagonists, side effects; Dermatitis-arthritis syndromes; Erythema; Erythermalmalgia; Erythralgia; Erythrocyanosis crurum puellarum; ... Show all
Outgoing links (18)Anhidrosis (overview); Bupivacaine; Burning feet syndrome; Diabetes mellitus skin changes; Gout; Hypercholesterolemia familial autosomal dominant; Leukemia cutis; Lupus erythematosus (overview); Mixed connective tissue disease; Nifedipine; ... Show all
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