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Erythromelalgia (primary)
Affected individuals experience recurrent episodes of severe pain, particularly in response to heat or exercise. This condition can significantly impact daily life and is often associated with genetic changes in the *SCN9A* gene.
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Overview
Erythromelalgia is a rare disorder primarily affecting the extremities, such as the hands and feet. It is characterised by episodes of burning pain, increased skin temperature, and redness. These symptoms are often triggered by warmth, pressure, or physical activity and can vary in intensity and duration [PMID:33678553]. The term 'erythromelalgia' derives from Greek words meaning 'red limb pain'.
Primary erythromelalgia refers to cases where an underlying cause, such as another medical condition or medication, cannot be identified. Genetic factors are often implicated in primary forms of the condition. While symptoms typically begin in childhood or adolescence, onset can occur at any age [PMID:19762645].
Symptoms & clinical features
The main symptoms of erythromelalgia include intense burning pain, redness, and warmth, most commonly affecting the feet, but sometimes also the hands or less often other body parts. The affected skin may appear swollen or discoloured, ranging from dusky red to purplish [PMID:33678553].
Episodes of erythromelalgia are often triggered by factors that increase skin temperature or blood flow, such as warm environments, exercise, wearing socks, or even hanging the affected limb down. Cooling the affected area may provide temporary relief, but prolonged cooling strategies must be used with caution as some individuals can develop complications like skin damage. While symptoms can be constant for some, others experience intermittent flares that can last from minutes to hours or even days.
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Affected organs
Erythromelalgia primarily affects the skin and peripheral nervous system. The main signs and symptoms are observed in the extremities, especially the hands and feet. The condition is thought to involve the small nerves in the skin that control blood vessel constriction and dilation, as well as those that transmit pain and temperature sensations. There are typically no signs of inflammation or damage to joints or larger organs.
Risks & severity
The severity of primary erythromelalgia can vary significantly between individuals, even within the same family. Symptoms can range from mild discomfort that is manageable with lifestyle adjustments to severe, debilitating pain that significantly impacts quality of life, sleep, and ability to perform daily activities. Some individuals may experience constant pain, while others have infrequent episodes.
Primary erythromelalgia is considered a chronic condition, meaning it is long-lasting. The age of onset also varies, with some experiencing symptoms from infancy and others developing them later in life [PMID:19762645]. There are no specific lifetime risk figures for associated complications beyond the pain itself, but persistent severe pain can lead to psychological distress and reduced mobility.
Genetic causes
Primary erythromelalgia is often caused by pathogenic variants in the *SCN9A* gene. This gene provides instructions for making a protein that forms part of a sodium channel called NaV1.7. These sodium channels are crucial for the proper functioning of nerve cells, especially in transmitting pain signals.
*SCN9A* is primarily expressed in sensory neurons, which detect sensations like pain, temperature, and touch. Pathogenic variants in *SCN9A* associated with erythromelalgia typically lead to a 'gain-of-function' effect, meaning the sodium channels become overly active [PMID:19762645]. This increased activity makes nerve cells more excitable, leading to the exaggerated pain response, warmth, and redness characteristic of the condition.
- SCN9A sodium voltage-gated channel alpha subunit 9The SCN9A gene provides instructions for a key component of the NaV1.7 sodium channel, vital for transmitting electrical signals in nerve cells, particularly those involved in pain sensation.
Inheritance pattern
Primary erythromelalgia caused by *SCN9A* variants is inherited in an autosomal dominant pattern. This means that only one copy of the altered gene is needed to cause the condition. If an individual has a pathogenic *SCN9A* variant, there is a 50% chance in each pregnancy that their child will also inherit the variant and be at risk of developing erythromelalgia.
Autosomal dominant inheritance means the condition affects males and females equally. while someone may inherit the genetic variant, the severity and age of onset of symptoms can vary. Sometimes, a person can develop erythromelalgia because of a new (de novo) genetic variant, meaning it was not inherited from either parent.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosing primary erythromelalgia typically involves a clinical assessment based on the characteristic symptoms of burning pain, redness, and warmth triggered by heat, and relieved by cooling. While there are no specific diagnostic tests to confirm erythromelalgia through a blood test or imaging in all cases, genetic testing can confirm a diagnosis of primary erythromelalgia when a pathogenic variant is identified in genes like *SCN9A*.
Referral to a clinical geneticist or neurologist is often recommended when primary erythromelalgia is suspected, especially in cases with an early onset or a family history of the condition. Genetic testing for primary erythromelalgia is available within the NHS Genomic Medicine Service (GMS) under relevant R-codes for neuropathic pain conditions. A clinical geneticist or other specialist can arrange this testing and offer genetic counselling to explain the results and their implications for the individual and their family.
Management & lifestyle
Current management strategies for erythromelalgia aim to reduce symptoms and improve quality of life, as there is currently no cure. Avoiding triggers such as heat, strenuous exercise, and prolonged standing often helps manage symptoms. Cooling measures, such as air conditioning or immersing feet in cool water, can provide temporary relief, but caution is advised to prevent skin damage or complications.
Various medications may be considered to help manage the pain, including certain pain medications or drugs that affect nerve excitability. The specific treatment approach will be tailored to the individual's symptoms and discussed with a specialist, typically a neurologist or pain specialist. Regular consultations with healthcare providers are important to monitor the condition and adjust management strategies as needed.
UK care pathway
In the UK, individuals suspected of having primary erythromelalgia can access care through the NHS. Initial assessment usually occurs with a GP, who may then refer to specialist services such as neurology or pain management clinics. If a genetic cause is suspected, referral to a clinical genetics service is appropriate. Here, genetic testing facilitated by the NHS Genomic Medicine Service may be offered, often under an R-code referring to specific rare neurological conditions, to identify a causative genetic variant. Genetic counsellors are available to provide support and information throughout this process, discussing inheritance patterns and implications for family members.
Frequently asked questions
What triggers erythromelalgia flares?
Flares are often triggered by warmth or heat, physical activity, prolonged standing, or anything that increases blood flow to the affected area. Cooling the affected limbs usually provides temporary relief.
Is erythromelalgia a painful condition?
Yes, erythromelalgia is characterised by intense burning pain. The severity of this pain can vary between individuals and can significantly impact daily life.
Can I pass erythromelalgia to my children?
If your primary erythromelalgia is due to an autosomal dominant genetic variant, there is a 50% chance for each child to inherit the variant. A genetic counsellor can provide detailed information specific to your family's situation.
What should I do during an erythromelalgia flare?
During a flare, try to cool the affected area gently, for example, by exposing it to cool air or elevating the limb. Avoid extreme cold or prolonged immersion in water, as this could cause skin damage or rebound symptoms. Consult your healthcare provider for personalised advice on managing flares.
Is there a cure for primary erythromelalgia?
Currently, there is no cure for primary erythromelalgia. Treatment focuses on managing symptoms and avoiding triggers, which can significantly improve quality of life. Research is ongoing into new therapies.
References
- Drenth JP, van Genderen PJ, Michiels JJ. Thrombocythemic erythromelalgia, primary erythermalgia, and secondary erythermalgia: three distinct clinicopathologic entities. Angiology. 1994. PMID: 8203771