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Erythromelalgia Misdiagnosed As Cellulitis

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Erythromelalgia Misdiagnosed As Cellulitis CONTINUING MEDICAL EDUCATION Erythromelalgia Misdiagnosed as Cellulitis LT Mark Eaton, MC, USNR; LCDR Sean Murphy, MC, USNR GOAL To understand erythromelalgia OBJECTIVES Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Describe the clinical presentation of erythromelalgia in patients. 2. Explain the pathophysiology of erythromelalgia. 3. Discuss the treatment options for erythromelalgia. CME Test on page 32. This article has been peer reviewed and is accredited by the ACCME to provide continuing approved by Michael Fisher, MD, Professor of medical education for physicians. Medicine, Albert Einstein College of Medicine. Albert Einstein College of Medicine designates Review date: December 2004. this educational activity for a maximum of 1 This activity has been planned and implemented category 1 credit toward the AMA Physician’s in accordance with the Essential Areas and Policies Recognition Award. Each physician should of the Accreditation Council for Continuing Medical claim only that credit that he/she actually spent Education through the joint sponsorship of Albert in the activity. Einstein College of Medicine and Quadrant This activity has been planned and produced in HealthCom, Inc. Albert Einstein College of Medicine accordance with ACCME Essentials. Drs. Eaton and Murphy report no conflict of interest. The authors report off-label use of aspirin, gabapentin, heparin, lidocaine patches, misoprostol, serotonin reuptake inhibitors, ticlopidine, topical capsaicin, tricyclic antidepressants, and warfarin for the treatment of erythromelalgia. Dr. Fisher reports no conflict of interest. This case report examines the presentation of a Treatments target symptom alleviation, as well as patient with erythromelalgia that was misdiag- diagnosis and treatment of causative factors. nosed as cellulitis on several prior occasions. Cutis. 2005;75:37-40. The presentation of bilateral acral edema and erythema, especially in the setting of myelopro- liferative and/or connective tissue diseases, rythromelalgia is a rare syndrome that is charac- should alert the physician to the possibility of terized by intense burning pain, erythema, and alternate diagnoses, including erythromelalgia. Ewarmth of the acral sites. The feet are predomi- nantly involved with the hands being the second most common site.1 A primary form exists that usu- Accepted for publication November 18, 2004. ally presents in adolescence or youth; secondary Dr. Eaton is a Naval Flight Surgeon at Naval Air Facility, forms usually present later in life and are attributed Washington, DC. Dr. Murphy is a dermatology resident, National to various causes such as myeloproliferative diseases, Naval Medical Center, Bethesda, Maryland. Reprints: LT Mark Eaton, MC, USNR, Naval Air Facility, connective tissue disorders, diabetes mellitus, and 2 Washington, 1 San Diego Loop, Bldg 3198, Andrews Air Force medication use, among others. Diagnosis is based on Base, MD 20762-5518 (e-mail: [email protected]). the patient’s medical history and clinical findings. VOLUME 75, JANUARY 2005 37 Erythromelalgia Treatment strategies include removal of the offend- in favor of a ␤-blocker for her hypertension. The ing agents or processes, symptomatic relief with patient was advised to continue taking aspirin daily, cooling agents and/or pain medications, and medi- and the treatment team was advised to search for cations that target the pathophysiology involved, further connective tissue disease via laboratory namely microvascular injury and thrombosis.1 examination. The patient was discharged that day; at her 10-day follow-up, symptoms had totally Case Report resolved with the discontinuation of nifedipine and A 55-year-old white woman reported to the derma- the initiation of propranolol. At one month post- tology department for evaluation of onychomyco- discharge, the patient’s symptoms remained absent. sis. She was an inpatient at a tertiary hospital who was receiving intravenous antibiotics for a diagno- Comment sis of chronic recurrent cellulitis; it was thought Erythromelalgia is a striking pain syndrome that that her chronic onychomycosis was the portal of occurs almost twice as often in women as in men.1 entry for these recurrent infections. The symptoms Primary disease with early onset is especially rare, of this episode began 2 days prior, when she noted with less than 30 cases reported in the literature. bilateral swelling of the feet and lower legs and Secondary disease, especially that related to myelo- burning accompanied throughout the day by proliferative disorders, is less rare, with an esti- increased redness and pain, similar to her 7 previ- mated incidence of 2.5 to 3.3 cases per million 1 3 ous episodes over the past 1 ⁄2 years. She stated that people per year. she experienced chills but no other constitutional The pathophysiology of erythromelalgia is not symptoms of fever or rigor. It was noted that her completely understood but seems to involve a feet and legs did feel warm. number of contributing factors. In erythromelalgia The patient’s medical history included poly- secondary to thrombocythemia, microthrombi and cythemia vera diagnosed several years prior that arteriolar fibrosis have been demonstrated, as well was treated with phlebotomy and aspirin 325 mg as intrinsic platelet defects such as an increased daily; diabetes mellitus, for which she was taking propensity to aggregate and shortened platelet sur- metformin; hypertension, for which she was treated vival.4 Primary disease, which frequently does not with nifedipine and valsartan; and recurrent cel- demonstrate such platelet findings, demonstrates lulitis, for which she had been taking prophylactic abnormal vascular dynamics resulting from arterio- clindamycin since her previous admission venous shunting and a mismatch between ther- 1.5 months prior. moregulatory and nutritive perfusion.5 Another Results of a physical examination revealed an postulation is dysfunctional sympathetic vasocon- afebrile woman with nontender distal edema of the strictor response.6 Davis et al7 have demonstrated bilateral lower extremities. Erythematous dorsal in a prospective study that most patients with feet, ankles, and distal lower extremities also were erythromelalgia, in addition to other forms of noted (Figure). No ulcerations were present, and neuropathy, also have small fiber neuropathy. no regional lymph nodes were enlarged or tender. Determining the likely pathogenesis based on the Nails were dystrophic and thickened. clinical presentation is important in developing a Laboratory test results revealed an elevated treatment strategy. white blood cell count of 15.4ϫ103/␮L, hemoglobin The clinical presentation of erythromelalgia is level of 10.6 g/dL, hematocrit level of 34.3%, and similar to that described in this case report. Burn- platelet count of 405ϫ103/␮L. ing, erythema, and warmth of acral sites are the On admission, blood cultures were drawn, and predominant features and may be present con- the patient was given vancomycin (she was allergic stantly, wax and wane, or disappear entirely to penicillin and nafcillin). During an interview the between episodes.1 These episodes can last hours, following day, it was noted that her symptoms days, months, and even seasons, and are frequently began synchronously with her use of nifedipine associated with exacerbating factors such as heat, 18 months prior. The symptoms had never fully exercise, fever, and dependent posture.2 If left resolved between the onset of the event and admis- untreated, erythromelalgia can progress towards sion to the hospital, and the symptoms were incited acrocyanosis and even peripheral gangrene.1 In the by dependence of the legs and exercise. The derma- largest study to date, Davis et al1 noted a signifi- tology consultant diagnosed erythromelalgia cant decrease in survival compared with age- and instead of cellulitis and recommended treatment gender-matched controls. This same study pointed with ice applications, cool water immersion baths, to an overrepresentation of death by suicide, and discontinuation of the calcium channel blocker myeloproliferative disease, and connective tissue 38 CUTIS® Erythromelalgia Treatment strategies are for- mulated in the context of causative factors. Diagnosis and treatment of the underlying disease process is paramount in alleviating erythromelalgia but is not always successful. In erythromelalgia secondary to thrombocythemia, especially in polycythemia vera, antiplatelet therapy is usually helpful. Aspirin is the first-line treatment of choice because its effects are longer lasting. Other non- steroidal anti-inflammatory drugs may be substituted in the event of aspirin sensitivity.1 Alterna- tive antiplatelet medications such as ticlopidine, warfarin, and heparin have not been shown to be effective.4 Removal of causative medications should be investigated and is diagnostic when successful. Implicated med- ications include nifedipine, per- golide, bromocriptine, felodipine, and nicardipine.9 Symptomatic treatment with lifestyle changes is a cornerstone of treatment and involves a reduction in exposure to exacerbating factors such as heat, exercise, fever, and depen- dent posture, as well as the appli- cation of cooling modalities, Erythematous and edematous distal extremities seen in erythromelalgia. elevation of affected areas, and rest. The addition of some medi- disease compared with the general population. The cations is often beneficial, and case reports
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