Edit concept Create issue ticket

Erythromelalgia

Erythermalgia

Erythromelalgia is a rare neurovascular peripheral pain disorder in which blood vessels on the extremities are blocked to become hyperemic and inflamed.


Presentation

The most prominent presenting symptom in this disorder is the recurrent episodes of erythema and painful burning sensation mainly affecting the upper or lower limbs. The pain is normally burning type with tenderness and shooting or a radiating pattern. The pain usually affects lower extremities and the symptoms can also affect the ears and face. In the lower limbs, soles and toes of feet are commonly affected, very rarely involving the knees. In the upper extremities, both hands and fingers are affected. Mostly both upper as well as lower extremities are affected bilaterally.

The characteristic symptom of erythromelalgia is warm, red, tender and painful hands and legs, aggravated by warmth or hanging the limb downwards which is classically ameliorated by cool application and elevation. Burning pain in paroxysms is a cardinal sign of this disorder.
Sometimes the episodes last for an hour or two, while other times there is persistent pain. Flare ups are also a common occurrence wherein the attack starts with itching followed by burning and pain sensation. Theses flare ups can last for a few minutes to a whole day.
During an episode of erythromelalgia the extremity appears warm, tender, swollen and looks mottled. The pain can be so excruciating that it can disrupt normal functioning of the patient.
Common triggers of episodes of pain are alcohol, tea, caffeine, pressure and warmth. Symptoms of Raynaud's phenomenon are known to occur in between attacks of erythromelalgia. This is purely coincidental and there seems to be no correlation between the two. The burning pain is so intense that patients avoid usage of socks as it generates more heat, triggering an attack, and prefer to stay in cooler places.

Hyperosmia
  • Olfaction testing using the Sniffin'T test did not demonstrate hyperosmia. One subject had evidence of orthostatic hypotension.[ncbi.nlm.nih.gov]
Burning Feet
  • Diagnosing Burning Feet Most people who have burning feet have a likely cause (such as diabetes ) that can be identified. For these people, the diagnosis of burning feet due to neuropathy is straightforward, and additional testing is not needed.[webmd.com]
  • I have burning feet with intense pain. I try to walk and it is so bad can't do it. My feet will swell and turn bright red.[ourhealth.com]
  • Erythromelalgia and Burning Feet Syndrome Erythromelalgia is believed to give rise to a condition called “Burning Feet Syndrome”, that is common among individuals over 50 years of age.[hxbenefit.com]
  • Erythromelalgie / Erythromelalgia / burning feet 20 Tips for Chronic Inflammation Symptoms & Their Natural Remedy I'll set you on fire with one touch. ETS (Combine fire, glow and crack effect in Adobe Photoshop to create a realistic burning image.[pinterest.de]
Heat Intolerance
  • intolerance, and relief with cooling Course: The prognosis and course vary widely.[drpribut.com]
  • The same might be true for arachnoiditis patients and could thus account for heat intolerance.[theaword.org]
  • “Hallmarks” or characteristics of erythromelalgia include triggering or worsening of symptoms with exposure to heat (heat intolerance) or exercise and relief with cooling.[rarediseases.org]
Limb Pain
  • Severe bilateral distal limb pain and vasodilation persisted despite the use of many antihyperalgesics. Pathological examination of cutaneous nerve endings revealed severe small-fiber predominant axonopathy.[ncbi.nlm.nih.gov]
  • "Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy". Neurology . 67 (9): 1563–7. doi : 10.1212/01.wnl.0000231514.33603.1e . PMID 16988069 . a b Sheets PL, Jackson JO, Waxman SG, Dib-Hajj SD, Cummins TR (2007).[en.wikipedia.org]
  • Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy. Neurology. 2006; 67 :1563–7. [ PubMed : 16988069 ] Choi JS, Zhang L, Dib-Hajj SD, Han C, Tyrrell L, Lin Z, Wang X, Yang Y, Waxman SG.[ncbi.nlm.nih.gov]
  • Choi JS, Dib-Hajj SD, Waxman SG (2006) Inherited erythermalgia: Limb pain from an S4 charge-neutral Na channelopathy. Neurology 67: 1563–1567. View Article Google Scholar 29.[journals.plos.org]
Edema of the Hand
  • […] of the hands and feet) Neuropathies Painful neuropathies associated with diabetes mellitus, alcoholism, HIV infection, idiopathic small fiber neuropathy, and Lyme disease may cause burning pain similar to erythromelalgia but are much less likely to be[ncbi.nlm.nih.gov]
Dependent Rubor
  • Leo Buerger, MD, was the first to describe dependent rubor associated with marked atherosclerosis.[ncbi.nlm.nih.gov]
Dependent Rubor
  • Leo Buerger, MD, was the first to describe dependent rubor associated with marked atherosclerosis.[ncbi.nlm.nih.gov]
Orthostatic Hypotension

Workup

A thorough history and investigation for underlying disease should be done. Erythromelalgia maybe indicate signs of polycythemia or thrombocytopenia. Relief with aspirin guides the physician in diagnosis [7].
Due to periodic episodes of pain, clinical examination may be difficult unless a patient is able to provide a correct and accurate picture of pain and symptoms. Between attacks, physical examination is normal. However, if any doubt exists, application of heat or warmth on the affected extremities can trigger an attack to confirm diagnosis. During an episode of pain [8], the affected extremity on palpation is warm, tender, appears red and mottled. Very rarely the disorder progresses to necrosis or ischemic ulceration. This occurs with secondary infection. Palpating for splenomegaly and lymphadenopathy should be done during physical examination for suspected cases of erythromelalgia.

Laboratory investigations include a complete blood count along with differential count to detect any underlying myeloproliferative disorder. Keep a tab on platelet counts as well as hematocrit levels. Other laboratory tests are nonspecific. Thermography [9] is done to detect temperature rises of affected extremity, but this not a diagnostic test. Histologically, a decreased capillary density and capillary perfusion is observed. Other than a proper clinical history there is no definite diagnostic test for erythromelalgia. Investigations should be done to detect any underlying myeloproliferative diseases or blood dyscrasias. Often it might take even months for doctors to come to a diagnosis.

Immunoglobulin A Decreased
  • Treatment with intravenous immunoglobulin significantly decreased the frequency and severity of her symptoms.[ncbi.nlm.nih.gov]
Lymphocytic Infiltrate
  • Histology commonly shows capillary proliferation, swelling of endothelial cells, perivascular edema, and chronic inflammation with sparse lymphocytic infiltrate.[ncbi.nlm.nih.gov]
  • Among the 17 secondary EM cases, sparse perivascular lymphocyte infiltrations were observed in the biopsy specimens from 2 patients with chronic myelogenous leukemia and 1 patient with diabetes mellitus.[ncbi.nlm.nih.gov]

Treatment

Therapy for both primary and secondary erythromelalgia includes medications, general conservative measures and surgical options. In secondary erythromelalgia, it is vital to treat the underlying  cause of the disorder. Symptomatic treatment is followed for primary cases of erythromelalgia.
Drug therapy includes a number of oral medications such as aspirin which relieves symptoms of erythromelalgia with underlying myeloproliferative diseases. Antidepressants and anticonvulsants are also given. Sometimes an individual's response to drugs is variable and may show a better reaction with a combination of medications. Intravenous medications of prostaglandin and nitroprusside are also given [10].
General measures include cooling and elevation of affected limb. Constant cooling is not advisable as it will only provide temporary relief. Other complicated problems can arise due to constant cooling for differences in temperature which will result in frequent flare ups. This can further lead to skin maceration, ulceration, gangrene and amputation. Avoidance of hot surroundings to prevent any attack is essential. Vigorous exercise can also trigger an episode of intense pain and are not recommended. No special dietary considerations are advised for this disorder.
The scope of surgical options in the treatment of erythromelalgia is very limited and does not play a significant role. Sympathectomy has been done wherein the sympathetic nerve fibers have been cut to help in cutting off the pain sensation.

Prognosis

There is no single drug therapy for this disorder and patients show a variety of responses to drugs. Remission of erythromelalgia is quite frequent and common. People who respond well to aspirin show less morbidity and remission. Early onset cases of erythromelalgia are more stubborn to treat and show variable response to drugs. Complications are less frequent and occur more in individuals with a platelet disorder. Ulceration, necrosis and gangrene are common complications which can occur on the affected extremities. Repeated ulceration or necrosis can lead to infection which may require amputation. Otherwise, most cases can be controlled with drugs without disturbing an individual's daily activities.

Etiology

Erythromelalgia can be classified into primary erythromelalgia or secondary erythromelalgia depending on the underlying cause [2]. Primary erythromelalgia usually occurs due to an unknown cause i.e. idiopathic. These cases usually happen spontaneously at any age with no underlying trigger. But some genetic mutations can be accounted for the causation of primary erythromelalgia, like those in a gene called Na (v) 1.7 which basically encodes for sodium ion channel within cells.
Secondary erythromelalgia occurs due to some underlying pathology or some medical conditions. Most common causes of secondary erythromelalgia are myeloproliferative disorders wherein the bone marrow produces excessive cells such as in polycythemia vera or thrombocytopenia. In almost 80% of cases, erythromelalgia occurs prior to onset of myeloproliferative disorders.
Other causes of secondary erythromelalgia include neurological diseases such as multiple sclerosis and peripheral neuropathy and autoimmune diseases such as lupus. Early onset [3] erythromelalgia usually occurs before the age of 25, while the mean age for late onset of erythromelalgia is 61 years. Both these types are primary in etiology with an inherited link.

Epidemiology

Most patients of primary erythromelalgia are usually women. Early onset primary erythromelalgia is slightly rarer as compared to cases with underlying myeloproliferative diseases. Recent studies show that erythromelalgia is becoming more common with every decade. Many cases may go unnoticed due to lack of knowledge of this rare disease. Early onset cases usually have a median age of ten years of onset while adult onset erythromelalgia cases start by the fifth or sixth decade. Pediatric cases have a variable progress and onset and are mostly accompanied by a considerable degree of morbidity and can be even fatal in some occasion. Incidence of erythromelalgia is more prominent in females with the early onset cases having a male to female ratio of 1:2.5, while secondary erythromelalgia has a male to female ratio of 3:2 with most of the cases due to myeloproliferative diseases. In U.S., the incidence of erythromelalgia cases is about 1.3 per 10000 people every year with women being about 2 per 10000 people and men being only about 0.6 per 10000 [4]. The mean age of detection and diagnosis is around 61 years of age.

Sex distribution
Age distribution

Pathophysiology

The basic pathological findings in erythromelalgia are mainly microvascular shuntings. Erythromelalgia is considered more a complex disease than a defined condition by itself. This hypothesis suggests microvascular arteriovenous shunting [5] along with spontaneously occurring tissue hypoxia and hyperemia. Therefore, inflammation happens due to some infection, trauma or tumor. This AV shunting can be induced because of a variety of conditions. The postulated hypothesis suggests that the hypoxia results due to irregularities in blood flow in the skin along with reduced nutritional perfusion and increased thermoregulatory perfusion. In addition to this, there is some neurogenic pathway also responsible for hyperactivity and hypersensitivity of C-fibers and postganglionic dysfunction of sympathetic nervous system. Thus, this seems to be the postulated pathway in pathway in primary erythromelalgia.

Secondary erythromelalgia is associated with some underlying disorder, usually thrombocytopenia. Biopsy samples of skin have showed arteriolar fibrosis and occlusion with thrombi of platelets. Decreased platelet survival along with excessive aggregability of platelets has been noted too. In cases with no underlying thrombocytopenia, the pathology is less clearly understood. In inherited cases of erythromelalgia, certain genetic mutations of sodium ion channels that are expressed in peripheral nerves have been seen. These mutations cause dorsal root ganglion neuron excitability along with a delayed onset of clinical symptoms. Molecular biology may have the answers for understanding this disorder [6].

Prevention

Since there is no known cause for this disorder, there are no definite preventive measures. Certain general measures of prevention to avoid pain attacks include:

  • Avoiding very hot surroundings
  • Avoid wearing socks or gloves in summer
  • Do not indulge in very vigorous activity
  • Refrain from intake of alcohol, caffeine and other stimulants

Intake of food rich in Vitamin B such as whole grains, brown rice, peanuts and dairy products can improve immunity and help in ameliorating pain symptoms. These methods might be enough to bring cases of primary erythromelalgia in control.

Summary

Erythromelalgia is a rare skin condition which typically affects the skin of the hands and feet and rarely the face and other parts of the body. This condition is primarily characterized by burning heat, redness and intense pain. This rare disorder is also termed as Mitchell's disease after the person, Silas Weir Mitchell, who described it. The name of this condition is derived from 3 Greek words- "erythros" meaning red, "melos" meaning limbs and "algos" meaning pain. Frequently, this condition is also known as acromelalgia, red neuralgia or erythermalgia. This condition is an uncommon peripheral vascular disease [1] which happens when the arteries in the extremities get blocked on and off which results in inflammation. The episodes of pain are triggered or aggravated by pressure, heat, exertion and stress and these attacks are periodic.
The intense burning pain can lead to impairment of functioning in daily routine. Individuals with this disorder have to adjust to avoid exacerbation of the symptoms. The cause remains unclear, but five percent of cases with erythromelalgia have an inherited tendency which demonstrates the role of genetic mutations in the etiology of this disorder. Diagnosis is mainly clinical with few tests for detection of causes. The treatment is mainly rest, elevating the affected extremity, avoiding heat or warmth, and local application of cold. Relief with cold is a characteristic sign of patients with erythromelalgia. Many medications are available which provide a certain level of relief, thus no single medication can be advised. Many over-the-counter pain relief drugs, anticonvulsants and antidepressants have been tried which help the patients to some extent. Thus, a combination of medications is given to help the patient in an effective manner. In any case, being a progressive condition, it not properly treated this chronic disorder  can hamper the quality.

Patient Information

Erythromelalgia is a rare vascular disorder associated with an increased blood flow to hands and legs resulting in severe redness, warmth and burning sensation. It happens due to some abnormality in the blood flow and nervous system. This abnormality is not clearly understood, so no exact cause for this disorder is known. This usually can also have an adult or late onset, at around 50-60 years which is a very common form. It can also have an early age onset in the pediatric group. Erythromelalgia can be of two types, primary and secondary, based on the presence of some underlying blood disorder such as increased production of blood cells like platelets. Primary form of erythromelalgia has no underlying medical cause.
The characteristic symptom of this condition is unbearable burning pain, warmth and severe redness of limbs, which is relieved only by cool application and elevation of the limb. It usually affects both upper and lower extremities. Warmth and heat aggravate and trigger the episodes of pain. This is a chronic, remitting disorder with recurrent attacks.
The treatment options are variable and every individual shows a different response. A diagnosis is made on physical examination, and certain blood tests may be done to detect the underlying blood disorder. No definite diagnostic test is available. Treatment is usually with oral medications such as aspirin, anti –inflammatory drugs, painkillers and combination of medications. Dosages are increased gradually depending on patient's response. Other general preventive measures should be followed such as avoidance of warmth, heat and vigorous exercises. This condition is treatable, but every individual shows a different response.

References

Article

  1. Drenth JP, van Genderen PJ, Michiels JJ. Thrombocythemic erythromelalgia, primary erythermalgia, and secondary erythermalgia: three distinct clinicopathologic entities. Angiology. 1994 Jun;45(6):451-3.
  2. Michiels JJ, Drenth JP, Van Genderen PJ. Classification and diagnosis of erythromelalgia and erythermalgia. Int J Dermatol. Feb 1995;34(2):97-100.
  3. Han C, Dib-Hajj SD, Lin Z, Li Y, et al. Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation. Brain. Jul 2009;132(Pt 7):1711-22.
  4. Davis MD, O'Fallon WM, Rogers RS 3rd, Rooke TW. Natural history of erythromelalgia: presentation and outcome in 168 patients. Arch Dermatol. Mar 2000;136(3):330-6.
  5. Charkoudian N. Skin blood flow in adult human thermoregulation: how it works, when it does not, and why. Mayo Clin Proc. May 2003;78(5):603-12.
  6. Waxman SG, Dib-Hajj SD. Erythromelalgia: a hereditary pain syndrome enters the molecular era. Ann Neurol. Jun 2005;57(6):785-8.
  7. Michiels JJ, Abels J, Steketee J, et al. Erythromelalgia caused by platelet-mediated arteriolar inflammation and thrombosis in thrombocythemia. Ann Intern Med. Apr 1985;102(4):466-71.
  8. Orstavik K, Weidner C, Schmidt R, et al. Pathological C-fibers in patients with a chronic painful condition. Brain. Mar 2003;126(Pt 3):567-78.
  9. Mork C, Kalgaard OM, Kvernebo K. Impaired neurogenic control of skin perfusion in erythromelalgia. J Invest Dermatol. Apr 2002;118(4):699-703.
  10. Moody S, Pacheco S, Butler IJ, Koenig MK. Secondary Erythromelalgia Successfully Treated With Intravenous Immunoglobulin. J Child Neurol. 2012 Jul;27(7):922-3.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-22 09:19