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Paroxysmal extreme pain disorder
PEPD primarily affects the skin, eyes, and lower rectum, leading to severe, burning pain attacks. These episodes often begin in infancy and can be triggered by temperature changes, stress, or eating. It is a lifelong condition, but management strategies can help reduce symptoms.
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Overview
Paroxysmal Extreme Pain Disorder (PEPD) is a very rare inherited condition that causes recurrent episodes of severe pain. The term "paroxysmal" refers to the sudden onset and resolution of these pain attacks. Individuals with PEPD experience intense, burning pain, most commonly affecting the skin of the face, eyes, and lower part of the body, including the rectum [PMID:16053916].
These painful episodes typically begin shortly after birth or during early infancy. Triggers for these attacks can be diverse, including changes in temperature, emotional stress, physical activity, or consuming certain foods. The severity and frequency of pain episodes can vary significantly among affected individuals, even within the same family.
Symptoms & clinical features
The main symptom of PEPD is recurrent episodes of severe, burning pain. These attacks most frequently involve the skin, especially around the eyes, jaw, and lower body. The pain can be debilitating and often described as a searing or burning sensation. During these episodes, affected skin areas may become red or flushed.
In addition to the skin, pain can also affect the eyes, leading to redness and tearing. Another common symptom is pain in the lower rectum, which can be accompanied by involuntary clenching of the muscles in that area [PMID:24177265]. Some individuals may also experience changes in heart rate or blood pressure during pain attacks. The intensity and duration of these episodes are variable, sometimes lasting from minutes to hours.
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Affected organs
PEPD primarily affects the nervous system, leading to pain signals being misinterpreted or overactive. The most noticeable impact is on sensory nerve endings in the skin, eyes, and mucous membranes of the rectum. While the pain is perceived in these areas, the underlying issue is related to how nerves transmit pain signals.
There are generally no structural abnormalities or damage to these organs themselves. The eyes may become red and watery during an attack, and the skin may flush, but these are temporary effects of the pain rather than intrinsic organ damage. The heart and blood vessels can also be indirectly affected, as some individuals experience fluctuations in heart rate and blood pressure during severe pain episodes.
Risks & severity
PEPD is a lifelong condition, and the severity of pain episodes can vary greatly. Some individuals may experience frequent, intense attacks that significantly impact their daily lives, while others might have less frequent or milder episodes. The condition typically presents in infancy, often within the first few months of life.
While PEPD is not considered life-threatening, the chronic and often unpredictable nature of the pain can lead to significant distress and reduced quality of life. There are no known specific lifetime risks beyond the pain episodes themselves, although managing chronic pain can sometimes have wider health implications. The condition's rarity means exact prevalence figures are not well established, but it is considered extremely rare worldwide.
Genetic causes
Paroxysmal Extreme Pain Disorder is caused by pathogenic variants in the SCN9A gene. This gene provides instructions for making one part of a sodium channel called NaV1.7. Sodium channels are tiny pores in the cell membranes of nerve cells that regulate the flow of sodium ions into and out of the cell.
The NaV1.7 channel is predominantly found in sensory neurons, particularly those involved in transmitting pain signals (nociceptors), and in olfactory (smell) sensory neurons. Pathogenic variants in SCN9A in PEPD typically lead to a gain-of-function, meaning the NaV1.7 channel becomes overly active or stays open for too long [PMID:16053916]. This increased activity makes nerve cells more excitable, leading to the misfiring of pain signals and the characteristic severe pain episodes.
- 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
PEPD is inherited in an autosomal dominant (AD) pattern. This means that only one copy of the altered SCN9A gene in each cell is sufficient to cause the condition. A person with PEPD has a 50% chance of passing the altered gene, and therefore the condition, to each of their children.
In some cases, the genetic change can occur spontaneously (a 'de novo' variant) in an individual, meaning they are the first in their family to have the condition. For families where PEPD has been diagnosed, genetic counselling can provide detailed information about inheritance patterns and potential implications for family planning.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
The diagnosis of PEPD is primarily based on clinical symptoms and is confirmed through genetic testing. If a doctor suspects PEPD based on the characteristic pain episodes and age of onset, they may refer the individual for genetic testing. This typically involves a blood test to analyse the SCN9A gene.
Genetic testing can identify pathogenic variants in SCN9A, confirming the diagnosis. In the UK, genetic testing for rare neurological conditions, including PEPD, is usually accessed through the NHS Genomic Medicine Service (GMS). Referral to a clinical genetics service is often the route for initiating such testing, with relevant NHS R-codes like R426 (inherited neuropathies) or R251 (early onset pain syndromes) potentially applying.
Management & lifestyle
Management for PEPD focuses on reducing the frequency and severity of pain episodes and improving quality of life, as there is no specific cure. Treatment often involves medications that help stabilise nerve cell activity, such as anti-epileptic drugs like carbamazepine or mexiletine, which can sometimes reduce pain [PMID:24177265].
Identifying and avoiding individual triggers is also an important part of managing the condition. This might include strategies to minimise exposure to extreme temperatures or stress. A multidisciplinary approach, involving pain specialists, neurologists, and genetic counsellors, can help develop a comprehensive management plan. The aim is to tailor interventions to the individual's specific symptoms and needs.
UK care pathway
In the UK, individuals suspected of having PEPD would typically be referred to a clinical genetics service or a specialist paediatric neurology team within the NHS. Genetic testing is available through the NHS Genomic Medicine Service (GMS) for conditions like PEPD, under relevant test directories and R-codes. A genetic counsellor can provide support and information regarding the genetic aspects of the condition, including inheritance risks and family planning. This pathway ensures access to specialist diagnostic services and ongoing clinical care coordination within the NHS.
Frequently asked questions
When do symptoms of PEPD usually start?
Symptoms of Paroxysmal Extreme Pain Disorder typically begin in early infancy, often within the first few months of life. The first painful episodes are usually noticed during this period.
What triggers PEPD pain attacks?
Pain attacks in PEPD can be triggered by various factors, including changes in temperature, emotional stress, physical activity, or consuming certain foods. Identifying and avoiding personal triggers can be a key part of managing the condition.
Is Paroxysmal Extreme Pain Disorder inherited?
Yes, PEPD is inherited in an autosomal dominant manner. This means that if one parent has the condition, there is a 50% chance that each child will inherit the altered gene and develop PEPD. Sometimes, the genetic change can occur spontaneously.
What kind of doctors treat PEPD?
Individuals with PEPD are typically cared for by a team of specialists, which may include neurologists, pain management specialists, and clinical geneticists. Genetic counsellors also play an important role in providing information and support to affected families.
Can PEPD be cured?
Currently, there is no cure for Paroxysmal Extreme Pain Disorder. However, various treatments and management strategies are available to help reduce the frequency and severity of pain episodes, aiming to improve the individual's quality of life.