Erythromelalgia of the ears: an unusual variant and response to therapy

Journal of Drugs in Dermatology, March, 2008 by David R. Berk, Arthur Z. Eisen

Introduction

Erythromelalgia is an idiopathic condition characterized by episodes of erythematous, warm, burning acral skin, which is exacerbated by heat and relieved by cold. Erythromelalgia can be primary or secondary to various conditions including myeloproliferative disorders, vasculitis, and lupus erythematosus. The pathogenesis of erythromelalgia may involve microvascular arteriovenous shunting (1) and/or a small-fiber neuropathy. (2) Activating mutations in the SCN9A gene, that encodes the neuronal voltage-gated sodium channel Nav1.7, cause hereditary erythromelalgia. (3)

Erythromelalgia usually affects the feet (90%) and/or hands (25%). (4) To our knowledge, only 2 cases of erythromelalgia involving the ears have been reported previously. (4,5) The authors present a 65-year-old woman with erythromelalgia of the ears with disabling symptoms whose diagnosis was delayed for 6 years. The patient failed to respond to numerous therapies before rapidly improving with oral amitriptyline and topical amitriptyline 1% and ketamine gel 0.5%.

[FIGURE 1 OMITTED]

Case Report

A 65-year-old Caucasian woman presented with pruritus, burning pain, and red ears of 6 years duration. The patient's symptoms were exacerbated by heat and pressure, which she relieved partially by cooling fans and ice packs, and sleeping upright with head propped. The patient had visited specialists in dermatology (4 physicians), neurology, otolaryngology, allergy, acupuncture, and chiropractic, and had unsuccessfully tried numerous topical therapies, including corticosteroids, pimecrolimus, lidocaine, doxepin, chlorpheniramine, ammonium lactate, terbinafine, and mupirocin. She had not responded to oral corticosteroids, antibiotics, antihistamines, terbinafine, and escitalopram. Her current medications included alendronate, naproxen, a multivitamin, and calcium. A physical examination revealed blanchable erythema involving both ears (Figure 1) that were very warm to touch. The laboratory analysis revealed a normal complete blood cell count, metabolic panel, and thyroid function. A shave biopsy of the left helix revealed an atrophic epidermis with mild hyperkeratosis and ectatic vascular spaces in the papillary dermis, without basement membrane thickening, erythrocyte extravasation, or vasculitis (Figure 2).

[FIGURE 2 OMITTED]

Based on the clinical findings, erythromelalgia of the ears was diagnosed. The patient showed only a moderate improvement with oral amitriptyline (25 mg) nightly for 2 weeks but then showed a greater improvement using amitriptyline 1% and ketamine 0.5% in pluronic lecithin organogel (6) 5 times daily and aspirin 325 mg daily. Symptoms were 75% improved within 3 days. The patient no longer slept upright or needed ice packs or fans. She discontinued the amitriptyline 1% and ketamine 0.5% organogel within the first 3 weeks. Nine weeks later, her symptoms were 90% improved overall. Her symptoms flared when she attempted to taper the oral amitriptyline, but remitted upon resuming the amitriptyline 1% and ketamine 0.5% organogel and oral amitriptyline 25 mg nightly. At a 6-month follow-up, the patient's symptoms were markedly improved compared to baseline. Subsequently, organogel was increased to amitriptyline 2% and ketamine 1% and applied 3 times daily, and after 1 month, the patient was asymptomatic with only a mild erythema of the ears.

Discussion

We are aware of only 2 reported cases of erythromelalgia involving the ears. (4,5) Most recently, Ramirez and Kirsner (5) reported a 53-year-old Hispanic male with a 3-year history of erythromelalgia of the ears who failed to respond to topical anesthetics and oral steroids, amitriptyline, propanolol, stanozol, nifidepine, and diazepam. Davis et al (4) described 1 patient with erythromelalgia of the ears as part of a series of 168 patients with erythromelalgia. In other studies involving a total of 158 patients, (7,8) no cases of erythromelalgia of the ears were identified.

The differential diagnosis of erythromelalgia of the ears includes relapsing polychondritis, sarcoidosis, leprosy, and red ear syndrome. Red ear syndrome is characterized by painful erythema of the ear and adjacent skin, which is often unilateral and associated with migraines, temporomandibular joint dysfunction, glossopharyngeal or trigeminal neuralgia, or cervical nerve injuries. (9)

Recently, autosomal dominant hereditary erythromelalgia has been linked to activating mutations in SCN9A, which encodes Nav1.7, a neuronal voltage-gated sodium channel expressed in nociceptive dorsal root ganglion neurons and sympathetic ganglion neurons. (3) Mutations which cause erythromelalgia tend to produce hyperexcitability of dorsal root ganglion neurons, (10) hypoexcitability of sympathetic ganglion neurons, (10) and decreased lidocaine sensitivity. (11) At the molecular levels, disease-causing mutations may activate Nav1.7 in a temperature-dependent fashion, which could explain the temperature dependence of clinical symptoms in erythromelalgia. (12) Activating mutations in Nav1.7 have also been linked to autosomal dominant paroxysmal extreme pain disorder, previously referred to as familial rectal pain, which is characterized by brief, paroxysmal mandibular, ocular, and/or rectal pain and autonomic disregulation, including flushing. (13) In contrast to activating mutations in Nav1.7, loss-of-function mutations in Nav1.7 have recently been linked to hereditary congenital indifference to pain. (14)