Erythromelalgia is a rare skin disorder characterized by severe burning pain, warmth, and erythema that is aggravated by heat and exercise. It is considered to be a neurovascular disorder associated with a small nerve fiber neuropathy and altered voltage-gated sodium channels. In recent years, neuromodulating agents, such as gabapentin and pregabalin, as well as topical lidocaine, were found to be useful therapies. However, there are cases of erythomelalgia that remain resistant to these conventional therapies and cause extreme suffering. Sandroni and Davis report using a novel treatment featuring combination gel of 1% amitryptiline hydrochloride and 0.5% ketamine hydrochloride in lecithin pluronic organogel applied 4 to 5 times a day in 5 patients with intractable erythromelalgia. In 4 of these patients, a significant response was noted, with the improvement rate ranging from 50% to 95%.