INTRODUCTION
Erythromelalgia is an uncommon neurovascular disorder characterized by redness, increased skin temperature, and pain that usually occurs in the extremities. It is a heterogeneous disorder, with wide variation in severity and age and time course of onset.1 In addition, it has been reported to occur in areas other than the extremities, including the ears, nose, face, and neck.2 Patients with erythromelalgia have higher morbidity and mortality rates than age-matched controls, and they also have increased risk of myeloproliferative disorders.1
Treatment of erythromelalgia remains challenging because of its varying response to medical therapy, which can result in a trial-and-error approach. Treatments that reportedly have been used for erythromelalgia include aspirin, nonsteroidal anti-inflammatory drugs, opioids, β-blockers, antihistamines, vasodilators, anticonvulsants, antidepressants, clonidine, corticosteroids (oral and topical), lidocaine (topical), mexiletine, and misoprostol, among others. However, according to a retrospective study of 168 erythromelalgia patients by Davis et al,1 few of these treatments are consistently effective.
Recent advances have been made in the understanding of the biochemical basis of erythromelalgia. Mutations in the sodium-channel gene SCN9A cause membrane hyperexcitability in sensory neurons, and these mutations have been associated with familial erythromelalgia.3 Thus, the development of new treatments for erythromelalgia has incorporated study of compounds that block sodium channels,4 including mexiletine (a class 1b antiarrhythmic medication) and topical lidocaine.5,6
In 2006, Sandroni and Davis7 reported successfully treating 4 of 5 patients with erythromelalgia at Mayo Clinic by using topical amitriptyline-ketamine. When applied topically, amitriptyline acts primarily as a sodium channel blocker to dull neuropathic pain. In addition, ketamine has been hypothesized to act through a number of pathways, including binding of receptors for N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate, and kainate. These medications may act synergistically to limit transmission of painful stimuli. In addition, the same biochemical effects may prevent vasodilation, thereby reducing the characteristic redness and warmth of the disorder.
In this study, we retrospectively evaluated the outcome of patients with erythromelalgia who received treatment with topical amitriptyline-ketamine at Mayo Clinic (Rochester, MN) since 2004.