Paroxysmal Extreme Pain Disorder

Paroxysmal Extreme Pain Disorder

Paroxysmal extreme pain disorder is an uncommon cause of severe, episodic, burning rectal, perineal, ocular, and mandibular pain. Also known as familial rectal pain syndrome, paroxysmal extreme pain disorder is caused by autosomal dominant abnormalities in the voltage-gated sodium channel Na V 1.7 that are induced by mutations of the gene SCN9A.

These mutations cause impairment of the ability of these specific sodium channels to inactivate, causing prolonged action potentials resulting in increased pain sensation and sympathetic nervous system activity.

Paroxysmal extreme pain disorder manifests itself clinically in infancy, with paroxysms of severe pain triggered by defecation, teething, eating, micturition, wiping of the perineum, and other painful stimuli such as injections. In older patients, attacks can be triggered by swallowing medications, sexual intercourse, and trauma.

Painful attacks can be triggered in some patients suffering from paroxysmal extreme pain disorder simply by the thought of a physical trigger.

Fear of triggers may condition some patients to avoid painful triggers at all costs, leading to physical consequences such as constipation. Attacks last between seconds to a few hours. Between attacks, the patient is pain free.

Associated symptoms include tonic, nonepileptic seizures, apnea, tachycardia, asystole, and harlequin skin changes and cutaneous flushing of skin in the painful areas.

What are the Symptoms of Paroxysmal Extreme Pain Disorder?

Paroxysmal extreme pain disorder is characterized by attacks of severe, episodic, burning pain of the rectum, eyes, and mandible. Tachycardia may be noted during attacks and patients may appear anxious, screaming or crying out in pain. Some patients may experience tonic nonepileptic seizures lasting for seconds to minutes.

These tonic episodes are often associated with apnea and, rarely, asystole. These tonic episodes tend to ameliorate in adulthood.

Sympathetically mediated skin abnormalities including flushing, sharply demarcated erythema, and harlequin skin changes are common. Excessive salivation and pupillary abnormalities are frequently observed with mandibular pain.

How is Paroxysmal Extreme Pain Disorder diagnosed?

With the exception of special genetic testing of the SCN9A gene, testing in patients with paroxysmal extreme pain disorder is usually normal.

Specifically, magnetic resonance imaging, computed tomography, ultrasound imaging, electromyography, and laboratory testing are nondiagnostic. During attacks, electrocardiogram may reveal sinus tachycardia. Electroencephalogram is normal between attacks.

Differential Diagnosis

Paroxysmal extreme pain disorder is very rare and is often initially misdiagnosed as colic in infants. The tonic episodes and associated apnea and asystole can lead to many diagnostic misadventures, with epilepsy often diagnosed.

Given the rarity of the disease and lack of readily available specific testing, it must be considered a diagnosis of exclusion and other causes of severe paroxysmal rectal pain including proctalgia fugax must be considered.


Unfortunately, at the present time there is no specific treatment for paroxysmal extreme pain disorder. Carbamazepine is reported to be effective in reducing the severity and frequency of painful attacks.

Given the chronicity of this condition, opioid analgesics and other controlled substances should be avoided. Behavioral interventions such as guided imagery and relaxation techniques may be beneficial in selected patients.

Complications and Pitfalls

The major problem in the care of patients thought to have paroxysmal extreme pain disorder is the failure to identify potentially serious pathology of the anus or rectum secondary to primary tumor or invasion of these structures by pelvic tumor.

Although uncommon, occult rectal infection remains a possibility, especially in an immunocompromised patient with cancer.

Early detection of infection is crucial to avoid potentially life-threatening sequelae.

Clinical Pearls

Heritable diseases affecting ion changes are responsible for a clinically diverse number of diseases in humans that have in common paroxysmal dysfunction of excitable tissues. Paroxysmal extreme pain disorder is one such disease.

The paroxysms of pain associated with paroxysmal extreme pain disorder are extremely severe, with women suffering from this disease who have given birth noting that their episodic attacks are far worse than the pain they experienced during childbirth.

The potential for life-threatening apnea and systole should not be underestimated and consideration should be given to training caregivers in advanced life support techniques.


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