What is erythromelalgia

Erythromelalgia is a rare neurovascular (nerves and blood vessels) condition characterized by episodes of burning pain, redness, and swelling in various parts of the body, particularly the hands and feet and sometimes ears and face ¹. The etymology of erythromelalgia name comes from the Greek: erythros “red”, melos “limb” and algos “pain”. During the crisis the skin becomes erythematous and warm, referred by the patient as a burning pain ². Erythromelalgia may occur spontaneously (primary erythromelalgia) or secondary to neurological diseases, autoimmune diseases, or myeloproliferative disorders (secondary erythromelalgia) ³. Episodes may be triggered by increased body temperature, alcohol, and eating spicy foods. About 15% of erythromelalgia cases are caused by mutations in the SCN9A gene and are inherited in an autosomal dominant manner ⁴. Other erythromelalgia cases may be caused by unidentified genes or by non-genetic factors.

The prevalence of either primary or secondary erythromelalgia is not well known, since population studies make no difference between them. A Norwegian report states a yearly incidence of 2/100,000, where primary erythromelalgia accounts for two thirds of cases. In Sweden, the incidence was 0.36/100,000, while in the USA it was 1.3/100,000, with no difference between primary or secondary erythromelalgia ⁵.

Regarding sex, a 2-3:1 female/male ratio was observed. Davis et al. ⁶ found 72.6% of females vs. 27.4% males in a Mayo Clinic sample of 169 patients, while Parker et al. ⁷ found 41 females in a sample of 46 patients. No reasons were given to explain sex difference ⁸.

Symptoms of erythromelalgia can begin at any age. Some people may have had it from early childhood, while some are only affected as adults. Primary erythromelalgia may develop at any age. Secondary erythromelalgia occurs most often in those over 40 years of age. The mean age of onset, regardless of the clinical form, is about 50 to 60 years of age ⁹. An epidemic presentation due to high weather temperature has been reported ¹⁰.

Various studies have suggested that the combined prevalence of primary and secondary erythromelalgia is between 0.36 to 2 per 100,000 patients. Primary erythromelalgia affects males less commonly than females (ratio 1:2.5) while the opposite is true for secondary erythromelalgia (ratio 3:2). Erythromelalgia affects a range of people of diverse backgrounds, e.g., Chinese, American, European. Primary erythromelalgia with positive family history is known as Weir-Mitchell disease.

The signs and symptoms of erythromelalgia typically begin in childhood, although mildly affected individuals may have their first pain episode later in life. As individuals with erythromelalgia get older and the disease progresses, the hands and feet may be constantly red, and the affected areas can extend from the hands to the arms, shoulders, and face, and from the feet to the entire legs.

Erythromelalgia is often considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain ¹¹.

Treatment depends on the underlying cause and may include topical and/or oral medications. In some cases, the condition goes away without treatment ⁴. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly.

Managing erythromelalgia takes patience and perseverance. Only a few people are lucky enough to stumble upon their optimal treatment on the first try. Through trial and error, you and your doctor will eventually figure out what works best for you. Although there is currently no cure for erythromelalgia, it is possible to find ways to manage and improve your symptoms. Advances in research related to erythromelalgia and its treatment happen every year.

Figure 1. Erythromelalgia feet

Footnote: Lower limbs of a patient with erythromelalgia. (A) During a painful episode, the feet are erythematous, hot, and swollen. Ice packs are being used to relieve the pain. (B) Between episodes, the limbs have a reticular cutaneous pattern. (C) The same patient has excoriated and broken skin resulting from scratching and repetitive submersion in cool water.

[Source ¹² ]

Figure 2. Erythromelalgia hands (erythema and edema on both hands, more pronounced on the right)

[Source ¹³ ]

Figure 3. Erythromelalgia face

Footnote: A 58-year-old housewife had suffered intermittent hot flushing and burning pain over her face and all four limbs. (A) Pretreatment. The patient suffered severe painful erythema of her face. (B) After treatment with the first subcutaneous injection of onabotulinumtoxin A. Facial flushing improved dramatically.

[Source ¹⁴ ]

What is the difference between primary and secondary erythromelalgia?

Primary erythromelalgia develops on its own without any associated underlying conditions. This form may occur randomly for unknown reasons (sometimes termed ‘idiopathic erythromelalgia’), or it may be familial. Late-onset erythromelalgia is primary in about 60% of cases.

Secondary erythromelalgia develops secondarily to various underlying conditions. These may include neurologic disorders such as multiple sclerosis and peripheral neuropathy; autoimmune disorders such as lupus; and most commonly, bone marrow disorders characterized by abnormally increased production of certain blood cells (myeloproliferative disorders). Erythromelalgia occurs before symptoms of myeloproliferative disorders in 85% of cases. There has also been evidence suggesting that erythromelalgia may occur as a side effect of certain drugs (for example, bromocriptine, nifedipine, and nicardipine).

How do doctors test for erythromelalgia? I have flare ups on my hands, feet, and face.

There is no specific diagnostic test for most cases of erythromelalgia, so making a diagnosis usually relies on symptoms, a clinical exam, and the medical history.

Testing that may be done to support a suspected diagnosis or rule out other medical disorders includes:

• a complete blood count (CBC) with differential to search for evidence of a myeloproliferative disorder
• imaging studies such as X-ray of the hands and feet, which typically show no specific findings
• thermography, which may reveal elevated skin temperatures in affected areas (but this is not necessary for the diagnosis)
• biopsy which may reveal characteristic findings in people with primary erythromelalgia

SCN9A-related inherited erythromelalgia can be confirmed with genetic testing of the SCN9A gene.

The first step to diagnosing erythromelalgia is seeing your primary care doctor, who can test for some of the common causes of erythromelalgia or its symptoms, and refer you to a specialist to confirm a suspected diagnosis. There is not a specific type of doctor that always diagnoses and treats erythromelalgia. A variety of specialists (alone or in combination) may be involved in the diagnosis and treatment. These may include dermatologists, neurologists, vascular specialists, hematologists, rheumatologists, or other types of physicians. The type of specialist that is appropriate after diagnosis may depend on the underlying cause when secondary erythromelalgia is present.

The Erythromelalgia Association (TEA) has a Patient Guide (https://erythromelalgia.org/wp-content/uploads/2017/09/TEA-PatientGuideBook-1.pdf) which includes helpful information about diagnosing erythromelalgia. This guide can be used as an educational and awareness tool for patients, family and friends, and health care providers. The Erythromelalgia Association also have a Doctor Directory (https://erythromelalgia.org/resources/physician-directory/) with contact information for doctors and researchers who have been suggested by the Erythromelalgia Association members over time.

Why are my feet/hands sometimes burning hot and other times painfully cold?

It’s possible that you may also have Raynaud’s phenomenon, a condition that sometimes coexists with erythromelalgia. With this disease, fingers or toes turn white or blue in response to cold temperatures or emotional stress. Some people describe Raynaud’s as the “opposite” of erythromelalgia. If you are having these symptoms, talk to your doctor about possible treatment options.

Can certain foods cause flare-ups of erythromelalgia?

Yes, certain foods can trigger a flare-up in some people with erythromelalgia. Alcohol as well as spicy foods, such as chili peppers and garlic, have been known trigger a flare-up of this condition. Keeping a food diary may help identify which foods can cause the symptoms of erythromelalgia. You may want to contact the Erythromelalgia Association (https://erythromelalgia.org) for more information on foods that have been reported to cause flare-ups.

Do symptoms of primary erythromelalgia worsen overtime?

It is difficult to predict how a person’s primary erythromelalgia will affect them over time. The cause of primary erythromelalgia is not well understood. Much of the literature regarding the long term outlook for people with idiopathic primary erythromelalgia is compiled from individual case reports. Erythromelalgia is usually a chronic or persistent condition, however there have been cases that have fully resolved with time. Many people with primary erythromelalgia have stable symptoms, however cases of progressive disease (symptoms worsening overtime) have also been described. Pain is a characteristic/classic feature of primary erythromelalgia. Unfortunately we were not able to find information specific to painless cases of this disorder, and outcomes of these individuals.

Erythromelalgia triggers

Symptoms are usually triggered by an increase in body temperature.

This can happen:

• after exercising
• when wearing warm socks, gloves or tight shoes
• after entering a warm room
• when feeling stressed
• when drinking alcohol or eating spicy food
• when you’re dehydrated

Exercise

Exercise increases blood flow and body warmth. Because this is likely to trigger a flare of erythromelalgia symptoms, it may be challenging for many individuals with erythromelalgia to stay active. For some, erythromelalgia flares and swelling in the feet may make walking or running difficult. Instead, swimming can be a good option, because it is not weight-bearing and the cool water temperature may minimize flaring. Gentler exercises such as some types of yoga and Pilates also keep your body temperature lower and may allow your feet to remain elevated. For outdoor activities, take advantage of cooler temperatures in the early morning or evening. No matter what type of exercise works best for you, keeping your indoor environment cool and breaking up your exercise routine into shorter sections can make any program more manageable. Despite the temporary discomfort, there is no evidence that exercise will worsen your condition. To the contrary, doctors believe that adhering to an exercise program—even a moderate one—improves your overall health and can help manage stress and pain levels.

Foods

Some people find that certain foods will provoke or worsen an erythromelalgia flare. Spicy foods and alcohol are common triggers. If you think that your erythromelalgia symptoms are affected by the foods you eat, you can experiment by removing one type of food at a time and keeping a diary to track any potential link between foods and flaring. If food triggered flares require you to make any major changes to your diet, it is important to discuss these changes with your doctor to ensure that you are still getting proper nutrition.

Bathing

Most people with erythromelalgia have had to make adjustments to their bathing routine, such as lowering the water temperature, bathing less frequently, showering instead of bathing in a tub, changing the time of day they bathe (many people with erythromelalgia experience worse flares in the evening), or keeping a door or window open to cool the bathroom. When even lukewarm water is enough to provoke a flare, other options include running cool water into a bathtub to stand in while showering or sitting on a shower stool in order to keep your feet out of the warm water.

Sleep

Erythromelalgia flares are frequently worse at night, as sleep itself can be a trigger for some people. In preparation for sleep, the brain signals the body to cool down by directing blood flow away from the core, causing the extremities to become warmer ¹⁵. Erythromelalgia sufferers may be unable to tolerate bed sheets on the affected area and may find some relief by using a fan or portable air conditioning unit. People with erythromelalgia may also take their erythromelalgia medications or sleep aids at bedtime.

Does avoiding triggers improve the long term outlook of people with primary erythromelalgia?

Avoiding triggers is key to the management of current symptoms, but little is known regarding how this affects the long-term course of an individual’s condition.

Erythromelalgia causes

In most cases of erythromelalgia, the cause is unknown. However, it’s sometimes due to another underlying medical condition or a faulty gene inherited from a parent.

Primary erythromelalgia includes both inherited erythromelalgia, which is hereditary and caused by mutations of the SCN9A gene, which encodes for the Nav1.7 type sodium channel receptor ⁴ and idiopathic erythromelalgia, which has no identifiable cause. Idiopathic erythromelalgia is the most common form ¹.

Mutations in SCN9A gene are responsible for familial (inherited) erythromelalgia and sporadic forms of the condition. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell’s ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.

Painful conditions of genetic origin include erythromelalgia, paroxysmal extreme pain disorder, small fiber neuropathy and disautonomy, all related to SCN9A ¹⁶.

The SCN9A gene mutations that cause primary erythromelalgia result in NaV1.7 sodium channels that open more easily than usual and stays open longer than normal, increasing the flow of sodium ions into nociceptors (these detect nerve-related pain) and normally amplifies the nociceptive pain signals. This increase in sodium ions enhances transmission of pain signals, leading to the dilation of the small blood vessels that become congested with blood and symptoms of erythromelalgia. It is unknown why the pain episodes associated with erythromelalgia mainly occur in the hands and feet.

An estimated 15 percent of cases of erythromelalgia are caused by mutations in the SCN9A gene. Other cases are thought to have a nongenetic cause or may be caused by mutations in one or more as-yet unidentified genes. In some individuals, symptoms are precipitated by puberty, suggesting a hormonal influence.

The primary erythromelalgia could be classified according the age of onset as “early” if it appears in the first two decades of life or “late” ¹³. The age of onset of the symptoms has been correlated with sodium (Na+) channel voltage activation produced by pathogenic SCN9A variants. The late onset of symptoms could be associated with mutations producing less Na+ channel activation and lower neuron excitability ¹⁷.

Secondary erythromelalgia are caused by another disease. Common causes of secondary erythromelalgia include myeloproliferative disorders, peripheral neuropathy, autoimmune diseases, and nerve damage. In addition, some medications have been linked to the onset of erythromelalgia. In some cases, when the underlying cause is addressed, secondary erythromelalgia symptoms will improve or resolve completely. In myeloproliferative disorders the bone marrow produces excessive numbers of cells, e.g. polycythemia vera (increased red cells), and essential thrombocythemia (increased platelets). Erythromelalgia presents before the appearance of the myeloproliferative disorder in 85% of cases. Occasionally secondary erythromelalgia can occur in association with paraneoplastic disorders, autoimmune neuropathies and rarely diabetes, rheumatological and infectious diseases.

Other medical conditions

Erythromelalgia sometimes results from an underlying condition, such as:

• a blood disorder – such as polycythaemia
• nerve damage – for example, caused by peripheral neuropathy
• multiple sclerosis (MS)
• an autoimmune problem – such as lupus or rheumatoid arthritis, where the immune system attacks the body’s own tissues

It may also be caused by certain medications. Your doctor will be able to give you more information on this.

Comorbidities must be taken into account since they increase hospitalization, increase medication taking, and mortality rate, thus worsening the perception of quality of life of these patients. Davis et al. ¹⁸ report the following comorbidity percentages as follows: smoking (50%) hypertension (13.7%), hyperlipidemia (11.3%) and diabetes mellitus (2.4%).

The functional acrosyndrome is closely related. The presence of erythema pernio and in second place, livedo reticularis, is frequent in patients with acrocyanosis, erythromelalgia and less in cases of Raynaud`s disease. Both Raynaud and erythromelalgia are microvascular disorders with local alterations or impaired thermoregulation that could be due to interrelated underlying mechanisms. Heidrich confirmed the coexistence of erythromelalgia, acrocyanosis and Raynaud ¹⁹.

Small fiber neuropathy is considered as an early disorder in painful diabetic neuropathy that contributes to the presence of distal ulcers. Moreover, it might be an interaction between the latter neuropathy and the microcirculation in these patients. The diabetic microangiopathy and neuropathy could add up to the erythromelalgia with an overlapping of signs and symptoms generating difficulties in the diagnosis and also complicating the disorder ²⁰.

Some authors report the presence of headaches in these patients. This symptom is common in patients with polycythemia vera associated with erythromelalgia as the principal disorder. Nevertheless, no relationship between the etiopathogenesis of erythromelalgia and headache have been described up to now in the literature ²¹.

Genetic cause

In some people with primary erythromelalgia, the disease is caused by a faulty gene, mutations in SCN9A gene. Erythromelalgia can run in families when the faulty gene is passed down from a parent to their child (inherited).

The faulty gene causes changes in the way pain signals are delivered to the brain, increasing or strengthening them.

Inheritance pattern

Primary erythromelalgia occurs in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause erythromelalgia disorder ⁴. In some of these instances, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of erythromelalgia in their family.

Erythromelalgia symptoms

The three main symptoms of erythromelalgia are heat, pain and redness in the skin. The feet are most commonly affected, but the hands, arms, legs, ears and face can be too.

The pain can range from mild, with only a minor tingling feeling like pins and needles, up to a severe burning pain, which can be bad enough to make walking, standing, socializing, exercising and sleeping difficult. It can have a significant impact on work or school life.

People with erythromelalgia typically suffer episodes or “flare-ups” of pain lasting from a few minutes to days. The flare-ups usually start as an itching sensation, which worsens to pain, and tender, mottled red skin that feels warm or hot to the touch.

Other symptoms may include:

• swelling of the affected body part
• sweating in the affected area more or less than you usually would
• purple discoloration when there is no flare-up

Primary and secondary erythromelalgia are characterized by episodes of erythema (marked redness), warmth and burning sensation of the limbs. The erythema could be mild to moderate with clear or ill-defined limits. During the episode, the warmth sensation is perceived by the patient and confirmed by the clinician. Pain is described by the patient as a burning sensation or as an electric shock or a throb. Some patients refer allodynia and/or hyperalgesia while others complain from itch. Edema and numbness in the limbs are observed in a low frequency. Parker et al. ⁷ described the more frequent symptoms as follows: burning (96%), warmth (93%), pain (87%), redness (83%), inflammation (65%) and numbness (54%). The compromise could be bilateral and symmetric, but it could also be unilateral. The extension is variable from the terminal phalanx of the toes to the whole limb. The skin frequently presents distal anhidrosis or hypohidrosis ¹⁸.

All the circulatory regions of the extremities could be affected, either single or multiple. In a great deal of reports, more than 80% of the lower limbs are affected, in contrast with 25% of upper limbs. They were also described in the face, ears and tongue. The episodes are intermittent or rarely continuous, lasting 2-3 hours. In the interval between episodes, the limb could be normal or cyanotic, with cold skin and numbness. Sometimes livedo reticularis could be present ¹⁸.

Lower extremities such as the soles of feet and toes are most commonly involved. Rarely does the pain extend up to include the knees. Upper extremity involvement includes the fingers and hands. Often both feet and hands are involved and both sides of the body (bilateral) are affected. It may affect one side of the body (unilateral), particularly in secondary cases. Less frequently, symptoms may also appear in the face, ears and other parts of the body.

The classic description of erythromelalgia is red, painful, warm hands or feet, brought on by warming or hanging the limb downward, and relieved with cooling and elevation.

• Some patients notice a continual burning, while others are troubled by intermittent flare-ups.
• Flare-ups may last minutes to days and typically occur late in the day and continue through the night.
• Usually attacks begin with an itching sensation, progressing to a more severe pain with a burning sensation.
• During an attack the affected extremity becomes warm, tender, swollen, and appears dusky red and sometimes mottled.
• Pain may be so intense that the patient cannot walk.
• Cooling (with fan or immersion in cold water) and elevating the extremity can relieve symptoms.

Symptoms often become so bad that normal functioning and quality of life are greatly affected. Patients avoid warm weather and may even relocate to cooler climates. Many cannot wear socks or closed shoes even in winter. Some patients become virtually housebound by continuous flare-ups and pain.

Erythromelalgia prevention

The prevention is based on a strict control of triggering events, i.e. heat exposure or pressure, standing position for a long time, physical activity, emotions, and/or stress, alcohol ingestion, spicy food, vasodilator drugs, night time, exposure to chronic vibration or even light skin contact in severe cases ⁶.

Symptoms could be improved with cold water or ice contact and raising the limb, nevertheless there is no improvement with analgesics ¹⁸.

Erythromelalgia complications

Erythromelalgia complications are related to the impairment of the barrier function, ischemia and neuropathy. The most frequent is secondary infection followed by fissures, blisters, painful ulcers, cyanosis, gangrene or necrosis. Occasionally, wounds can become secondarily infected, which, if severe enough, may lead to amputation.

Many patients know that burning pain is relieved with cold water or ice, an electric fan or staying in places with low temperature. Some of these methods lead to skin maceration followed by epidermis slough thus increasing the damage to the skin barrier. Cold could trigger long lasting vasoconstriction provoking ischemia and tissue necrosis, what could be interpreted by patients as aggravation of the disorder. Cutaneous dystrophies could increase pain and at the same time slow skin repair, deteriorating their quality of life and leading to social isolation, and in case of hypothermia adding a life-threatening risk. The patient must be advised to discontinue these practices. Some patients could develop skin automutilation behavior; although its mechanism is unknown, the poor quality of life could be related to this condition ¹⁸.

Erythromelalgia prognosis

Davis et al. ¹⁸ reported that after an eight-year follow up, 31% of patients exhibit deterioration, 25% had no change, 30% improved and 10% had a complete remission. Spontaneous remissions have also been known to occur ³. There is a tendency for chronicity, with sleep and appetite disturbances, as well as anxiety and depression. The patients use open shoes and sleep with uncovered feet even in cold weather. They cannot walk long distances or be in a standing position for long time, nor practice any sport or dance. Due to these symptoms, both children and adults loose days of study, sport or work with resentment of their ludic and social activity. Due to their condition, they are prone to accidents at work and at home. If the episodes continue for a prolonged time, bed rest is recommended, otherwise a wheel chair must be considered. The affected quality of life could become a disability. Morbidity and mortality rates are higher in these patients in comparison with individuals matched by sex and age in the general population ²².

Erythromelalgia diagnosis

There are controversies regarding the accepted diagnostic criteria since not all cases are included ¹³. While pending new diagnostic criteria, experts recommend that accurate and detailed questioning be performed. The physical examination of the skin, can present acrocyanosis, telangiectasias, vascular dilations and red nails.

• A list of doctors who have been recommended by members of the Erythromelalgia Association for treating erythromelalgia can be found here (https://erythromelalgia.org/resources/faqs/).

Keys for medical history questioning:

• Month and year of onset attacks
• Family history
• Frequency of occurrence
• Relation with triggers: cold, warmth. emotions, physical activity, humidity
• Duration and characteristics of the episodes
• Approximate triggering temperature
• Symptoms and signs diminish with cold or warmth?
• Color change of limbs depending on their position
• Current medication indicated by a professional or not
• Unhealthy habits: smoking, alcohol, social drugs
• Work and sport activity

Primary erythromelalgia is a clinical diagnosis based on the presence of the triad of recurrent redness, burning pain and warmth of extremities.

Family history of erythromelalgia can support a familial primary erythromelalgia versus sporadic cases. There are no specific guidelines for SCN9A genetic testing, but these can be considered in young patients in whom there is a positive family history and when secondary causes have been excluded. Genetic testing may have impact on family planning given 50% probability of heritability of the condition by offspring.

Investigation for underlying causes is essential to exclude secondary erythromelalgia. Erythromelalgia may be an early sign of polycythaemia (raised red cells) or thrombocythaemia (raised platelets), where symptoms may precede diagnosis of the myeloproliferative disorder by 2.5 years. These diseases are detected by full blood count. Further tests may be necessary.

Diagnosis is based fairly much on the clinical picture, hence is often difficult because of the intermittent nature of the disease. Provided the patient gives a good description of their symptoms, a tentative diagnosis may be made. If in doubt, a trial of immersing an affected area in hot water for 10–30 minutes may sometimes provoke an attack and support the diagnosis.

Erythromelalgia treatment

No single therapy works well for every person with erythromelalgia (erythromelalgia). Often it is necessary to try different treatments or combinations of treatments until the best therapy is found. In some cases erythromelalgia may go away on its own. If erythromelalgia is being caused by another medical disorder (secondary erythromelalgia), treating the underlying disorder may improve or completely resolve erythromelalgia symptoms. The treatment of symptoms of both primary and secondary erythromelalgia is through general non-medical measures, drug therapy and surgical intervention.

Treatment options for erythromelalgia include creams applied to the skin (topical creams), medications, certain supplements, and mind-body therapies (such as cognitive behavioral therapy or CBT). If all other treatment options have failed, epidural anesthesia, nerve blocks, or surgery may be considered depending on the severity of the pain.

Most cases of primary erythromelalgia are refractory to pharmacotherapy and response to pain therapeutics is variable. Most of these therapies have only been validated in case reports or smaller studies.

Elevation and cooling the skin

• Cooling or elevating the extremity may relieve symptoms. The skin can be cooled using a fan, cool water, a cool surface or cool gel packs.
• However, avoid using ice or anything that’s too cold, and don’t soak hands or feet for a long time in cold water. This can lead to hypothermia or skin damage.
• Care is needed around cold water immersions, although it will provide temporary relief, it can cause many other serious problems. Frequent immersion into cold water can create a vicious cycle, as the changes in temperature may cause reactive flaring when the affected area warms up again. This can also lead to maceration of the skin, non-healing ulcers, infection, gangrene and amputation.

Medications for the skin

• Some medications that are applied directly to the skin (topical medication) have been found to help relieve the symptoms of erythromelalgia. These may be in the form of creams, gels, sprays or patches. You may be prescribed a capsaicin cream or patch to make the heat receptors in your skin less sensitive. Topical capsaicin cream has been reported with varying results.
• Lidocaine (a local anaesthetic) may also be prescribed in the form of a cream, gel or spray. Your doctor will be able to give you more information about these medications and if they’re right for you. You can also speak to your pharmacist about lidocaine creams.

Medications taken by mouth

A number of different medications taken by mouth (orally) may help to relieve the symptoms of erythromelalgia.

You may need to try several different medications, under the supervision of your doctor, before you find the one or the combination that works best for you.

Your treatment options will also depend on the type of erythromelalgia you have. Many treatments require referral to a specialist centre so benefits and potential side effects can be closely monitored.

The types of medication your doctor may prescribe include:

• Aspirin – relieves symptoms of erythromelalgia related to thrombocytosis (NOT for children)
• Dietary supplements – such as magnesium, which can help open up your blood vessels
• Sodium channel blockers – mexiletine has been shown to improve pain, especially in patients with V872G mutation
• Calcium antagonists – nifedipine, diltiazem
• Prostaglandins – misoprostol
• Medications used for neuropathic pain:
  • Serotonin re-uptake inhibitors – venlafaxine, sertraline, fluoxetine, paroxetine
  • Tricyclic antidepressants – amitriptyline or nortriptyline, imipramine, duloxetine, venlafaxine
  • Anticonvulsants – gabapentin, carbamazepine
• Prescription-only painkillers

In most patients with primary erythromelalgia, their symptoms remain refractory to sodium channel blockers and other treatment, and symptoms tend to progress over time. Quality of life can be greatly affected due pain and disability due to pain, secondary tissue damage (ulcers, necrosis, gangrene) or self-harming behaviours can be an issue.

Medications given via a drip

In some cases, when oral medication has not managed to control the symptoms, medicine may be given directly into the bloodstream via a drip (intravenous infusion). Intravenous infusions of nitroprusside, lignocaine (lidocaine) and prostaglandin. Lidocaine, a local anaesthetic that can help nerve-related pain, can be given this way. But how long it works for varies between people.

Your doctor will explain this procedure to you and how you should prepare for it.

Novel Nav1.7 agents

• Several drugs are undergoing clinical trials in primary erythromelalgia. Examples include Nav1.7 channel modulators (PF-05089771) and NAV1.7 channel blockers (TV-45070).

Surgical intervention

• Surgical sympathectomy (a procedure in which the sympathetic nerve fibres are selectively cut)
  • Thoracic sympathectomy for hands
  • Lumbar sympathectomy for feet

Patients respond quite variably and no single therapy has proved consistently effective.

Erythromelalgia diet

Some people find that certain foods will provoke or worsen an erythromelalgia flare. Spicy foods and alcohol are common triggers. If you think that your erythromelalgia symptoms are affected by the foods you eat, you can experiment by removing one type of food at a time and keeping a diary to track any potential link between foods and flaring. If food triggered flares require you to make any major changes to your diet, it is important to discuss these changes with your doctor to ensure that you are still getting proper nutrition.

Mental-health support

Depression and anxiety often arise in people with chronic conditions, especially ones that cause pain and discomfort. A mental-health professional may be able to help you deal with the psychological challenges of erythromelalgia, including coping with day-to-day pain, adjusting to changes in your life, managing relationships with loved ones, making medical decisions, and even grieving the losses that you may have experienced due to erythromelalgia. Therapists —including psychologists, licensed clinical social workers, and other licensed therapists—who specialize in chronic pain and illness may be best suited to handle your specific needs, but any therapist with whom you feel comfortable can provide invaluable support.

If you are housebound or on a fixed income and have difficulty getting to see a therapist regularly, an increasing number of therapists provide services online, through video conferencing. Also, reading books on pain and stress management may be useful.

Cognitive Behavioral Therapy (CBT)

The Royal College of Psychiatrists defines cognitive behavioral therapy as a way of talking about:

• How you think about yourself, the world and other people
• How what you do affects your thoughts and feelings.

They say that CBT can help you to change how you think (the cognitive part) and what you do (the behavioral part). These changes can help you to feel better. Unlike some of the other talking treatments, it focuses on the “here and now” difficulties. Instead of focusing on the causes of your distress or symptoms in the past, it looks for ways to improve your state of mind now.

If you are not sure you want to commit to a long course of sessions with a clinical psychologist, there are various resources on the Internet which will provide an introduction to CBT or even a course of computer-aided CBT sessions:

• Developed by the Australian National University, MoodGYM (https://moodgym.com.au/) is a fun, free interactive web program that teaches the principles of CBT using flashed diagrams and online exercises. MoodGYM (https://moodgym.com.au/) demonstrates the relationship between thoughts and emotions, and works through dealing with stress and relationship break-ups, as well as teaching relaxation and meditation techniques. It consists of five modules (why you feel the way you do, changing the way you think, changing ‘warped’ thoughts, knowing what makes you upset, assertiveness and interpersonal skills training), an interactive game, anxiety and depression assessments, downloadable relaxation audio, a workbook and feedback assessment. Scientific trials have shown that using two or more modules is linked to significant reductions in depression and anxiety symptoms. These benefits last after 12 months. MoodGYM has won several IT and health awards, and has over 1,000,000 users worldwide. MoodGYM (https://moodgym.com.au/)

• Living Life to the Full (https://llttf.com/) is a free online life skills course for people feeling distressed. It aims to provide easy access to CBT skills in a way that cuts through jargon. It helps you understand why you feel as you do, and to learn new ways of improving how you feel, by making changes in your thinking, activities, sleep and relationships. The course is based on the idea of helping you to help yourself. It is supported by a series of CBT self-help workbooks that can be used between the e-learning sessions. These encourage you to put what you are learning into practice, and to stop, think and reflect on what you are learning. Living Life to the Full (https://llttf.com/)

• FearFighter (http://www.fearfighter.com/) delivers CBT over the internet, useful for those who may be concerned about the stigma associated with seeing a therapist. Taking only three months to complete, with minimal telephone support, FearFighter helps you improve even if you have virtually no computer skills. You are encouraged to use FearFighter as often as you wish but for at least once a week. It helps you identify specific problems, work on realistic treatment goals, and monitor achievement of those goals by repeated self-exposure. You get scheduled brief helpline support to a total of one hour over 10 weeks. FearFighter helps you to work out exactly what brings on your fear, so you can learn how to face it until it subsides. This is called exposure therapy. It consists of nine steps that need to be worked through one by one to obtain the greatest benefits. Like a therapist, FearFighter asks you to return every week to report on how you’ve been doing. You can ask it to print out questionnaires and graphs of your progress. It guides you through CBT as much as a therapist does.
  • Step 1: Welcome to FearFighter – Introduces the system, asks you to rate your problem on the Fear Questionnaire (FQ) and Work & Social Adjustment Scale (WSA), and asks about suicidal feelings and alcohol misuse.
  • Step 2: How to Beat Fear – Explains the principles of CBT, with case examples. You are asked to keep a daily record of your triggers.
  • Step 3: Problem Sorting – Helps you identify your triggers, shows you scenarios relevant to your problem, and helps you personalise your triggers and rate them on a 0-8 scale.
  • Step 4: How to Get a Helper – Explains the value of recruiting a CBT co-therapist and gives hints on how to find one.
  • Step 5: Setting Goals – Guides you through the process of setting good goals and tests them. You record and rate these on the system and can print personalised homework diaries.
  • Step 6: Managing anxiety – Offers a menu of coping strategies for use during CBT homework.
  • Step 7: Rehearsing Goals – Guides you on how to practise personal coping strategies during both imagined and live CBT homework.
  • Step 8: Carrying On – Reviews progress with the help of graphs, allows new goals to be devised, and offers feedback and advice.
  • Step 9: Troubleshooting – Offers a menu of tips on overcoming common sticking points in treatment.

You may have found that when you avoid things that make you panic or feel uncomfortable, the situation tends to get worse and worse. FearFighter can teach you how to face your fear until you adapt and no longer want to run away from it. It helps you learn to face the things that make you panic, such that, with time, you’ll find that, one by one, they’ll get easier.

Self-exposure therapy guided by computer is as effective as clinician-guided therapy and both are superior to relaxation to improve phobia/panic. FearFighter has been tested in four clinical trials and is as effective as the best CBT therapists.

Approved by the National Institute of Clinical Excellence (NICE), free access can only be prescribed by your doctor in England and Wales. FearFighter (http://www.fearfighter.com/).

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