para>EM associated with myeloproliferative diseases may precede them by several years.
General Prevention
Primary EM cannot be prevented. Secondary EM, if due to a known condition, can be improved and recurrences potentially prevented with adequate control of that condition.
Commonly Associated Conditions
- Myeloproliferative diseases such as polycythemia vera and essential thrombocythemia
- Connective tissue disorders such as systemic lupus erythematosus
- Insulin-dependent diabetes mellitus
- Neuropathies and spinal cord diseases
- Rheumatologic diseases such as rheumatoid arthritis
- Tobacco abuse
- Possible link with colon cancer, thyroid cancers and astrocytomas, pernicious anemia, TTP, vasculitis (5,6)
- Possible link with pregnancy
- Mercury poisoning
- Possible infectious associations include infectious mononucleosis and poxvirus.
- Calcium channel blockers (verapamil, nicardipine)
- Dopamine receptor agonists (bromocriptine, pergolide)
- Topical isopropanol
Diagnosis
History
The patient may report the following:
- A history of pain, erythema, and increased temperature of the extremities, typically the feet
- A family history of symptoms
- A history of a condition or medication associated with secondary EM
- Symptoms that are intermittent or constant (rare), often bilateral but not always symmetric, and worse at night
- Exacerbation of symptoms after exercise, alcohol consumption, exposure to higher environmental temperatures, wearing stockings or tight shoes, or the limb being in a dependent position
- Symptom relief after elevation of the affected limb, exposure to cold water, ice, or a cold floor (5)
Physical Exam
Due to the intermittent nature of symptoms, only approximately 65% of patients with EM will have abnormal findings on physical exam (5). These include redness, pain, and increased temperature of the affected regions.
Differential Diagnosis
- Fabry disease
- Peripheral neuropathy (various causes)
- Polycythemia
- Cellulitis
- Chronic venous insufficiency
- Other diseases that may present with palmar erythema include thyrotoxicosis, chronic febrile illness, leukemia, hepatic insufficiency, alcoholism, and rheumatoid arthritis (5).
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
Initial workup should be focused on excluding other causes of patient symptoms. Tissue histopathology has been shown to be nonspecific for EM and is therefore not used in diagnosis (3).
Follow-up tests & special considerations
There are no specific tests that can diagnose EM.
Diagnostic Procedures/Other
There are no specific diagnostic procedures that can diagnose EM.
Treatment
General Measures
- Avoidance of triggers: high environmental temperatures, alcohol use, heavy exercise, tight stockings and shoes
- Symptomatic relief with elevation of the affected area and application of cool compresses
- If applicable, stop any offending medications and attain better control of underlying associated or potentially causative diseases.
Medication
Treatment modalities are focused on symptom relief and there are no evidence-based guidelines for treating EM. Most recommendations found on literature review are anecdotal in nature or based on published case reports of individuals or small groups undergoing a novel treatment modality (level 3). Many patients are subjected to polypharmacy in an attempt to relieve symptoms and improve quality of life, but there is no evidence to suggest which patients will benefit from any specific treatment modality (4).
- Aspirin is the therapy of choice in patients with underlying myeloproliferative disorders. Dosing recommendations vary by publication, but some authors advocate for aspirin to be given to all EM patients unless otherwise contraindicated (5).
- Commonly prescribed medications for EM include gabapentin, SSRIs/selective-norepinephrine reuptake inhibitors (SNRIS) (sertraline, venlafaxine), benzodiazepines, NSAIDs, lidocaine patches, topical capsaicin treatments, tricyclic antidepressants, anticonvulsants, and opioids.
- Other medications reported to help select patients described in literature include misoprostol (PGE1 analog), prostacyclins, high-dose methylprednisolone with pregabalin, IV nitroprusside, and lidocaine infusions.
Issues for Referral
Erythromelalgia, once identified, can usually be managed by a primary care physician. Referral to specialists may be required in instances of refractory pain, skin damage/ulcerations from cooling therapy, or secondary infections that result from this skin damage. Patients with complications of EM or its treatment may benefit from a multidisciplinary approach to include wound specialists, vascular specialists, neurologists, pain specialists, and psychiatrists.
Surgery/Other Procedures
In individual case reports, surgical sympathectomy (5), epidural injections, sympathetic blockade, and dorsal column stimulation have helped relieve patient symptoms in severe cases of EM.
Complementary & Alternative Therapies
A multidisciplinary approach to the management of chronic pain associated with severe EM should be taken to improve patient quality of life. Biofeedback, support groups, massage therapy, and mental health counseling have all been used to supplement pharmaceutical treatments.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Complete blood counts should be routinely performed to monitor for myeloproliferative disease, although there is no agreed on interval for this testing.
- Patients should be monitored for adverse reactions to their pain management regimens; this includes cooling injuries and medication dependence or abuse.
- As with all disabling illnesses, patients should be regularly screened for symptoms of depression due to the painful symptoms and frustrating trial-and-error nature of treating EM.
Patient Education
- Patients should be educated on prevention and conservative management of symptoms, the psychological toll of this disease, and the dangers of polypharmacy. They should be educated on occurrence of cold-induced injuries due to pain-alleviation measures and possibility of developing a myeloproliferative disease.
- http://www.livingwitherythromelalgia.org is an online support group for patients.
- http://www.erythromelalgia.org is a nonprofit organization that educates and supports those with erythromelalgia.
Prognosis
Morbidity and mortality are higher in patients with EM than in the general population in the United States (4). There are no clear statistics to explain this trend.
Based on information gathered at Mayo Clinic published by David et al., equal numbers of patients' EM symptoms became worse, stayed the same, or improved. In those with symptom improvement, 10% of patients' symptoms completely resolved over an average of 8.7 years.
Complications
- It is common that patients with EM require multiple office visits and medication trials for control of their symptoms, possibly leading to polypharmacy.
- There are reports of patients having cold-induced injuries secondary to pain-alleviation measures, including ischemic ulcers, infection, and possibly gangrene.
- Patients often develop psychological issues due to the debilitating symptoms of severe EM.
References
1.Davis MD, O'Fallon WM, Rogers RS III, et al. Natural history of erythromelalgia: presentation and outcome in 168 patients. Arch Dermatol. 2000;136(3):330-336.
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2.Friberg D, Chen T, Tarr G, et al. Erythromelalgia? A clinical study of people who experience red, hot, painful feet in the community. Int J Vasc Med. 2013;2013:864961.
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3.Kalgaard OM, Clausen OP, Mellbye OJ, et al. Nonspecific capillary proliferation and vasculopathy indicate skin hypoxia in erythromelalgia. Arch Dermatol. 2011;147(3):309-314.
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4.Durosaro O, Davis MD, Hooten WM, et al. Intervention for erythromelalgia, a chronic pain syndrome: comprehensive pain rehabilitation. Arch Dermatol. 2008;144(12):1578-1583.
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5.Ghosh SK, Bandyopadhyay D, Ghoshal L. Painful red hands and feet. Cleve Clin J Med. 2012;79(5):356-358.
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6.Kakizaki A, Fujimura T, Kambayashi Y, et al. Successful treatment of adult-onset erythromelalgia with steroid pulse and pregabalin. Case Rep Dermatol. 2012;4(3):242-246.
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Codes
ICD09
ICD10
SNOMED
- 37151006 Erythromelalgia (disorder)
- 403390002 Primary erythromelalgia (disorder)
- 403391003 Secondary erythromelalgia (disorder)
Clinical Pearls
- Erythromelalgia should be considered on the differential diagnosis for patients that report painful, hot, and red feet or hands.
- Erythromelalgia has a strong association with myeloproliferative diseases.
- Patients should be educated on symptom prevention and often require several modalities for pain control.
- Erythromelalgia can be debilitating and frustrating for patients; a multidisciplinary approach to treatment, including counseling and potentially social work, should be used.