Sections

Treatment

Approach Considerations

Evaluation and treatment can be conducted in an outpatient setting. Treatment is primarily medical and supportive. Local measures, such as cooling or elevating the extremity, may relieve symptoms. Avoid excessive warming or dependency of the extremity. The environment should be modified so that it is not too hot.

A number of topical and systemic medications have been used for treatment of erythromelalgia.^[35]Case reports describe successful use of spinal cord stimulation and ganglion stimulation and blocks.^{[36, 37, 38, 39]}

With secondary erythromelalgia, treatment of the underlying disease process may lead to improvement or resolution of the erythromelalgia.^[35]In patients with myeloproliferative disorders, chemotherapy to reduce the platelet count often alleviates symptoms, but it is not universally effective. Some patients with polycythemia vera have responded to phlebotomy. A hematologist may be consulted if an associated myeloproliferative disorder is present.

Surgery probably has no role in the management of erythromelalgia except to treat the rare complication of gangrene. Surgical sympathectomy has been attempted, with variable results.

No specific dietary restrictions are necessary. Vigorous exercise may induce an acute episode and should therefore be avoided.

Pharmacologic Therapy

For primary erythromelalgia, the best therapy is unknown. A wide range of agents has been studied, including the following^[34]:

Vascular agents - Aspirin, prostaglandins
Sodium channel blockers - Lidocaine, mexiletine, carbamazepine, oxcarbazepine
Calcium channel blockers - Amlodipine, nifedipine, diltiazem, high-dose oral magnesium ^[40]
Antidepressants - Tricyclic antidepressants, serotonin reuptake inhibitors
Anticonvulsants - Gabapentin, pregabalin
Antihistamines
Immunosuppressants

Case reports of treatment with propranolol, epinephrine, biofeedback, sodium nitroprusside, gabapentin, and typhoid vaccine appear in the literature, as well as case series with intravenous bupivacaine, and lidocaine plus mexiletine.^[41]

Medications that affect voltage-gated sodium channels (eg, lidocaine and its oral form, mexiletine) show promise. In hereditary erythromelalgia, however, sensitivity to lidocaine may be determined by the patient's specific SCN9A genotype.^{[42, 43, 44, 34]}

Prostacyclin may provide some benefit.^[45] In a pilot study of 12 patients, iloprost (a synthetic prostacyclin analogue) improved symptoms.^[45] A double-blind, crossover, placebo-compared study of the prostaglandin E1 analog misoprostol in 21 patients with erythromelalgia found that it reduces symptoms and microvascular arteriovenous shunting.^[46]

Topical therapy has been studied, including transdermal lidocaine.^[47] A study in 12 patients reported benefit with the alpha1-agonist midodrine, 0.2%, compounded in a moisturizing skin cream and applied topically three times a day during symptoms.^[48] Poterucha et al treated 36 patients with compounded topical amitriptyline-ketamine; 75% of those patients reported a reduction in pain.^[49]

A Mayo Clinic study in 31 patients found that response to treatment with corticosteroids was more likely to occur in patients who reported a precipitant for their erythromelalgia (eg, surgery, trauma, or infection) and in those who had a subacute temporal profile to disease zenith (< 21 days). In addition, patients who responded to steroids started treatment sooner—at 3 (3-12) versus 24 (17-45) months (P = 0.003).^[50]

In cases that are associated with other disorders, treating the original disease might improve symptoms. One case report described a patient with seronegative polyarthritis who developed erythromelalgia and was successfully treated with intravenous immunoglobulins.^[51]

For erythromelalgia related to thrombocytosis, aspirin is usually the treatment of choice. Other nonsteroidal anti-inflammatory drugs (NSAIDs) provide relief of short duration. Anagrelide may be an alternative. Other platelet-inhibiting agents (eg, ticlopidine and dipyridamole) have no effect.

Monitor for complications, response to treatment, and development of a myeloproliferative disorder because erythromelalgia often precedes the clinical appearance of polycythemia vera or essential thrombocythemia.

Medication

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Media Gallery

Cardinal symptoms of erythromelalgia.

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Author

Drew H Barnes, MD Fellow Physician, Hospice and Palliative Medicine, The Ohio State University Wexner Medical Center

Drew H Barnes, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Claudia M da Costa Dourado, MD Clinical Assistant Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Program Director, Hematology and Medical Oncology Fellowship Program, Attending Physician, Division of Hematology and Medical Oncology, Department of Medicine, Einstein Medical Center Philadelphia

Claudia M da Costa Dourado, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Ali T Taher, MD, PhD, FRCP Professor of Medicine, Associate Chair of Research, Department of Internal Medicine, Division of Hematology/Oncology, Director of Research, NK Basile Cancer Center, American University of Beirut Medical Center, Lebanon

Disclosure: Nothing to disclose.

Antoine N Saliba, MD Post-Doctoral Research Fellow, Division of Hematology/Oncology, Department of Internal Medicine, American University of Beirut Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

Robert J Nardino, MD Director, Internal Medicine Residency Program, Assistant Clinical Professor, Department of Internal Medicine, Hospital of Saint Raphael, Yale University School of Medicine

Robert J Nardino, MD is a member of the following medical societies: American College of Physicians, Association of Program Directors in Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Andrea LM Silber, MD Medical Oncologist, Father Michael J McGivney Center for Cancer Care, Saint Raphael Hospital

Andrea LM Silber, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Society of Preventive Oncology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Erythromelalgia Treatment & Management

Approach Considerations

Pharmacologic Therapy

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