Erythromelalgia is a rare condition characterized by burning pain, erythema, swelling, and increased temperature usually in the extremities. We present an unusual presentation of erythromelalgia of the ears in a patient who has been refractory to multiple therapies and in whom relief of symptoms was achieved with the use of mexiletine. A review of clinical presentation, pathophysiology, and therapeutic options are presented.
Erythromelalgia (EM) is a rare disabling disorder of unclear etiology characterized by recurrent burning pain, erythema, and increased temperature of the affected area, typically feet and/or hands, but there are also reports of EM of the ears .
The associated pain is aggravated by warm environments and dependent position and is relieved by cold and frequent immersion into ice-cold water. This is a constant feature and is considered pathognomonic .
More common in men, EM may occur alone or be secondary to a myeloproliferative disorder, autoimmune disease, and associated with mercury poisoning, vasculitis, peripheral neuropathy, diabetes, hypertension, and drugs. Primary EM is an autosomal dominant neuropathic disorder involving a mutation in a voltage-gated sodium channel subunit Na v 1.7 that is expressed in nociceptive and sympathetic neurons . EM is refractory to treatment. As an example in a review of data for 168 patients with EM at the Mayo clinic, patients had used 84 different types of medications .
In 2004, we presented a case report of refractory EM of the ears in this journal . Since then, the patient has tried multiple therapeutic options without response. Mexiletine was given, resulting in significant improvement of symptoms. We summarize our experience with this patient.
A 58-year-old Hispanic man, with no significant comorbidities and an 8-year history of progressive burning pain and redness of the ears, has been seen in our service since 2003. He was diagnosed with primary EM.
Initially, the symptoms were sporadic, several episodes monthly, related to warm temperatures and physical activity, and had gradually worsened to the point of being constant and disturbing his sleep. He reported 9/10 pain and daily flares with pain, swelling, and redness. The use of cold water spray and avoidance of warm environments ameliorated his symptoms. On examination, both ears were involved, compromising the entire helix and antihelix, and he had pink to red, tender, and swollen plaques; no other areas were involved .
A biopsy of involved skin showed superficial and deep perivascular inflammation with prominent endothelial cells consistent with EM. Fungus and mycobacterium cultures were negative. An extensive laboratory analysis that included autoimmune workup came up negative or within normal limits except for serum qualitative cryoglobulin that was positive. Therefore, a workup to rule out viral hepatitis, multiple myeloma, Waldenstrom’s macroglobulinemia, lymphoproliferative disorders, rheumatoid arthritis, and systemic lupus erythematosus was performed with negative results.
He has received multiple medications resulting in various responses ranging from transient and mild improvement to no response at all. Table 1 summarizes the medication that he used.
|Antihistamines: diphenhydramine, fexofenadine, loratadine|
|Vasoactive drugs: calcium channel blockers (nifedipine, nicardipine, amlodipine), β-blockers (propranolol), nitrates (nitroglycerin ointment)|
|Nonsteroidal antiinflammatory drugs (acetylsalicylic acid, celecoxib, misoprostol)|
|Medications with effect on neurotransmitters: selective serotonin reuptake inhibitor (sertraline), Serotonin – norepinephrine reuptake inhibitors (venlafaxine), benzodiazepine (diazepam), tricyclic antidepressants (amitriptyline, doxepin), anticonvulsant (gabapentin), antipsychotics (risperidone)|
|Steroid analogs: prednisone, stanozolol, oxalondrone, ethisterone|
|Immunosuppresants: cyclosporin A, methotrexate, sirolimus|
|Antimicrobials: doxycycline, clarithromycin, minocyclin, dapsone|
|Other: magnesium sulfate, thalidomide, pentoxifylline, enoxaparine, isotretinoin, Melgatin (Berlin Homeo Products, Berlin, Germany) (herbal supplement), zonulin (novel human protein)|
|Topicals: fluocinonide, topical lidocaine, procaine + lidocaine, capsaicin, estrogen, ketamine 0.5% + amitriptyline 1% gel|
|Procedures: ganglion nerve block, acupuncture|
Mexiletine, 100 mg, 3 times a day was started on April 2009. After 3 weeks of treatment, the patient reported significant relief of symptoms. Reported side effects were mild and included headache, nausea, and heart burn.
An increase in the dose to 200 mg 3 times a day was attempted resulting in a dramatic improvement in pain and redness of his ears. However, the patient could not tolerate it because of a dose-dependent increase in the side effects.
At present, the patient is taking 100 mg of mexiletine 3 times a day with reduction in pain and disease flares.