Introduction: SCN9A erythromelalgia (EM) is a disease subtype resulting in disproportionate pain response due to a gain-of-function mutation in the SCN9A gene NaV1.7 - a neuronal sodium channel expressed in nociceptors. The opening of these sodium channels evokes pain sensation; the SCN9A mutation causes channels to open more easily and remain open, leading to pain crises that are challenging to manage with conventional medications. Evidence-based treatments are sparse and there is no predictable approach to pain management in patients with EM. Topical and systemic sodium-channel blocking agents, such as lidocaine, have been used successfully in EM pain crises.
Description: A 15-year-old male with SCN9A-EM presented classically with erythema, warmth, swelling, and intense, bilateral burning pain of the lower extremities. He was admitted to the PICU in a pain crisis for initiation of lidocaine and ketamine infusions in combination with oral mexiletine. Following two weeks of treatment, he developed altered mental status, hypertonicity, hypotension and bradycardia progressing to uncompensated cardiogenic shock requiring multiple code doses of epinephrine and eventual intubation. Intravenous lipid emulsion was administered for presumed lidocaine toxicity, though there was no evidence of toxidrome (QRS widening, seizure, ventricular dysrhythmia) and serum lidocaine concentration was within therapeutic range. He subsequently developed progressive, severe, dysautonomia with significant blood pressure lability, requiring alternating vasopressors and systemic vasodilators. Lidocaine infusion was replaced with an alternate sodium-channel blocker, ranolazine, with similar analgesic effect.
Discussion: Pain crises attributed to SCN9A-EM typically follow a predictable pattern, though analgesic regimens are highly variable and patient specific. Concomitant dysautonomia is atypical of this subtype and has not been previously reported. Lidocaine infusions demonstrate effective analgesia; however, the significant overlap of toxicity and dysautonomia symptoms can potentially delay workup and definitive diagnosis. Alternative sodium-channel blockers less prone to toxicity, such as ranolazine, may be a better first-line treatment for EM patients with increased susceptibility to develop severe dysautonomia.
