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Paroxysmal extreme pain disorder
A rare, genetic, neurological disorder characterized by severe episodic perirectal pain accompanied by skin flushing that is typically precipitated by defecation. Ocular and submaxillary pain, associated with triggers including cold or other irritants, may become more prominent with age.
ORPHA:46348Classification level: Disorder
This disorder is rare but about a dozen families have been described.
This condition presents at childbirth or in the first year of life with episodes of severe rectal and peri-rectal pain following bowel movements. This is often accompanied by reflex anoxic seizures (RAS). Finally, there can be a color change down one half of the body; either horizontally from the waist down or involving one half of the body as in the harlequin phenomenon. Adults experience similar attacks although they are rare. Triggers include defecation, tactile stimulation in the peri-rectal area, unexpected falls, sexual activity and vivid dreams. Older children and adult patients are affected by painful eye and jaw crises. Other symptoms that may accompany the pain include tonic nonepileptic seizures, tachycardia and bradycardia, bronchospasm, lacrimation, hypersalivation, and rhinorrhea. Patients may have any or all of these in different episodes. The pain is typically felt in the deep tissues and can start with an itch-like sensation, which becomes burning and escalates to sharp, lancinating or a stabbing sensation. Pain appears suddenly and can last from seconds to several minutes.
This disorder is caused by mutations in the sodium channel gene SCN9A (2q24.3). The mutations confer a gain-of-function by impairing fast-activation of sodium channel NaV1.7, which is preferentially expressed in dorsal root ganglion and sympathetic ganglion neurons.
Diagnosis is based on a careful history, a normal examination and normal electroencephalography (EEG), electrocardiogram (ECG) and nerve conduction studies. Screening for SCN9A mutations can provide confirmatory information.
Differential diagnoses include primary erythermalgia and hyperekplexia.
Paroxysmal extreme pain disorder follows an autosomal dominant pattern of inheritance.
Management and treatment
In children it is important to manage the inevitable constipation that ensues from stool withholding secondary to fear of defecation. The frequency of painful episodes may be reduced by medications used in the management of chronic neuropathic pain disorders, namely anticonvulsants. Carbamazepine, an activity-dependent sodium channel blocker, is the most effective of these treatments.
With maturation, rectal pain may be accompanied by or replaced by periocular or perimandibular pain.