Resolution of Primary Erythromelalgia Following Ibuprofen; Fire Power
Resolution of Primary Erythromelalgia Following Ibuprofen
By Jolie Krooks, BS, Chad Rudnick, MD, and Angela Weatherall, MD
Erythromelalgia presents with recurrent and symmetric burning pain, heat, and erythema of the extremities. The feet (88 percent), hands (26 percent), and legs (14 percent) are most frequently implicated; other sites include the ears, neck, and face.1 Attacks are typically intermittent (97 percent) and may last from minutes to days.1 Symptoms are pathognomonically exacerbated by heat (51 percent) and exercise (29 percent) and alleviated by cold water and/or ice (67 percent).1
Primary erythromelalgia (PEM) may be sporadic or familial and is diagnosed after eliminating causes of secondary erythromelalgia (SEM). Though patients with inherited PEM are typically young children, erythromelalgia remains more common in adults (average age 56 to 65 years).1,2 In a study of 168 patients, only three patients (two percent) were younger than 12.1
Supportive therapy includes rest, elevation, removing shoes and/or gloves, and cooling.3 While SEM is typically treated by addressing the underlying cause, there is no first-line treatment for PEM. In a review of 168 patients, Davis, et al. noted the utilization of 84 different medications.1
Herein we report a case of PEM in a six-year-old girl in remission following ibuprofen use and review the diagnosis, pathogenesis, treatment, and prognosis of pediatric PEM reported in the literature.
A six-year-old girl with a past medical history significant for asthma, eczema, and allergic rhinitis presented with erythema, burning pain, and warmth of the bilateral ulnar palms, occurring intermittently for months at the same location with no known inciting factor (Figure 1). Symptoms were exacerbated by warm water and weather and alleviated with cold compresses and ice. The patient also licked her hands several times daily to alleviate symptoms. The patient’s mother denied hyperhidrosis, joint pain, or fever in the child.
The patient’s history was significant for a several-year history of occasional eczema flare-ups on the flexural surfaces and, most commonly, the hands managed with Cetaphil body wash and a combination of Trixera wash, triamcinolone cream 0.1%, and cetirizine or hydroxyzine for flare-ups. In addition, nine months prior to her current presentation, the patient presented with large bullae and several smaller bullae on her palms. There was no pain, burning, warmth or pruritus at that time. The patient was diagnosed with dyshidrotic eczema and was treated with clobetasol ointment 0.05% and mupirocin ointment, and the bullae resolved within a week.
Current physical exam was significant for xerotic, erythematous, palms that were warm to the touch. There were no bullae present. During the office visit, the patient wanted to hold an ice pack or popsicle. She also complained of hand discomfort upon palpation. Her motor and sensation of her distal upper extremities were intact. Vital signs were normal and the remainder of her physical exam was unremarkable.
Diagnosis of PEM was made for her current presentation based on the patient’s history and physical exam findings and after an extensive work-up that eliminated secondary causes (Table 1). In addition, her previous treatment for dyshidrotic eczema including the topical steroid and mupriocin did not improve her symptoms, further supporting PEM. On laboratory testing, eosinophils and lymphocyte percentage were slightly elevated (EO# [0.52, normal 0.00-0.39], LY% [46, normal 25-45]), likely due to a recent asthma exacerbation and URI. Genetic testing for mutations in the sodium channel Na(v)1.7 was not performed. Family history was significant for asthma and childhood eczema, but not for erythromelalgia.
Fans, wet dressings, ice, and elevation of the affected extremities to alleviate pain and avoidance of hot environments to minimize attack frequency were advised. Recently, she had a febrile URI and mild asthma exacerbation for which ibuprofen was used infrequently for two weeks. During these two weeks, the patient’s burning and pain resolved. It is possible that oral ibuprofen reduced her hand discomfort. The patient has not complained of significant hand pain on four-month follow-up.
Diagnosis of erythromelalgia is clinical, as there is no confirmatory diagnostic test. Histologic findings are nonspecific.4 Our patient met the diagnostic criteria for PEM: episodic bilateral burning pain, warmth, and erythema of the upper or lower extremities, exacerbation by pressure, heat, and/or exercise, alleviation by elevation and/or cold, and refractoriness to treatment.5 Due to PEM’s intermittent nature, patients may not present with findings on physical exam (33 percent); in these cases, diagnosis depends on history.1 When present, physical findings include: erythema (49 percent); acrocyanosis (10 percent); ulceration (six percent); or a reticular vascular pattern (five percent).1
Underlying causes of SEM must be eliminated (Table 2). Patients diagnosed with PEM should still be monitored by CBC to assess for myeloproliferative disorder, which, when present, follows erythromelalgia onset by a median 2.5 years.6
Differential diagnoses include: Raynaud’s syndrome; complex regional pain syndrome; systemic lupus erythematosus; scleroderma; juvenile rheumatoid arthritis; dermatomyositis; hypothyroidism; Fabry disease; angiodyskinesia; cellulitis; and erysipelas.
Most patients experience decreased quality of life. Extreme discomfort often results in decreased physical activity (66 percent) and in patients taking drastic measures to alleviate discomfort, such as walking barefoot and elevating and soaking the extremities (some more than 20 hours daily). Truancy (34 percent) and other behavioral problems (28 percent) are common. On an average nine-year follow-up of 15 pediatric patients, five had stable disease (33 percent), four had improvement (27 percent), two had resolution (13 percent), one had worsening disease (seven percent), and three had died (20 percent). Mortality may result from suicide, sepsis from prolonged soaking, and treatment-related bone-marrow failure.61 Cutaneous complications include: skin maceration due to ice and/or cold water (22 percent); infection (16 percent); ulceration (13 percent); and gangrene (one percent).1
The incidence of erythromelalgia is between 0.36 to 1.3/100,00062 and more commonly affects females (3:1).1,2 PEM comprises 66 percent of cases.27
Familial PEM is inherited as an autosomal dominant63-65 mutation in SCN9A, a gene on chromosome 2q66 that encodes the alpha-subunit of Na(v)1.7 voltage-gated sodium channels.67 Mutations in Na(v)1.7, expressed by neurons involved in nociception and sympathetic outflow, render the former hyperexcitable and the latter hypoexcitable,68 thus contributing to increased cutaneous blood flow resulting in pain, warmth, and erythema.69 Alternatively, abnormal cutaneous blood flow in patients with wild-type Na(v)1.7 may be explained by the shunting hypothesis, which proposes that in erythromelalgia, cutaneous flow is not evenly distributed. Specifically, it is reduced secondary to bypassed capillaries in some areas and increased in others secondary to hypoxia-induced vasodilation.70 Pathogenesis has been attributed to endothelial dysfunction and consequent reduction in endothelial-derived nitric oxide, resulting in hypertension and vasoconstriction-induced hypoxia followed by reactive hyperemia.71 Kalgaard, et al. proposed that erythromelalgia be considered a common vascular response provoked by diverse factors, i.e. infectious, traumatic, immunologic, carcinogenic, etc.27 The multitude of factors contributing to disease pathogenesis explains the lack of universal success of a single treatment.
Inflammation is also central to disease pathogenesis.72 In addition to the inflammatory infiltrate observed histologically,4 the presenting features of erythromelalgia, especially heat, pain, and erythema, are among the cardinal signs of inflammation. Erythromelalgia has not been reported to present with vesicles unless as sequelae to excessive cold therapy and/or infection.73,74,75 Accordingly, the bullae observed in our patient were likely due to her recurring dyshidrotic eczema, also an inflammatory disease, but without erythema.76,77 The patient’s chronic inflammatory state due to her recurring asthma, eczema, and allergic rhinitis might have predisposed her to developing erythromelalgia.
In a retrospective analysis of 32 pediatric patients (mean age 14, range five to 18), Cook-Norris, et al. reported on the efficacy of various therapies with different mechanisms of action (Table 3). Topical lidocaine as the most commonly prescribed treatment.61 Other treatments in pediatric patients reported in the literature include combination of IV lidocaine and oral mexiletine,78 oral mexiletine alone,79 sodium nitroprusside,59,80 recombinant growth hormone,81 regional anesthesia blockade,82 thalamic stimulation,83 gabapentin,84,85 cetirizine,86 and steroids.87
Genetic testing for specific mutations in Na(v)1.7 is helpful in guiding treatment. Specifically, patients’ response to treatment with the sodium channel blockers lidocaine, mexiletine, and carbamazepine is limited in patients with wild-type Na(v)1.7 and treatment response varies depending on the specific mutation.73,88,89
Other treatments that target abnormal cutaneous blood flow and/or inflammation are helpful in treatment refractory patients and/or those with wild-type Na(v)1.7. Effective treatments regulating blood flow include: sodium nitroprusside;80 iloprost;90 misoprostol;91 and NSAIDs.61,92 Effective medications targeting inflammation include: prostaglandins;90,91 NSAIDs;61,92 and steroids.93
We report on a rare case of PEM in a six-year-old girl with a past medical history significant for asthma, eczema, and allergic rhinitis. Currently, our patient is not complaining of significant hand pain, which may be due to ibuprofen use for an URI. Accordingly, ibuprofen may be particularly helpful in treating erythromelalgia patients with a history of other inflammatory conditions, such as our patient, and this case adds to the case reports that have demonstrated the success of NSAIDs in treating pediatric erythromelalgia.
The authors have not received funding and do not have any conflicts of interest to disclose.
Jolie Krooks, BS is a medical student at Florida Atlantic University’s Charles E. Schmidt College of Medicine in Boca Raton, FL.
Chad Rudnick, MD is a pediatrician at Boca VIPediatrics in Boca Raton, FL.
Angela Weatherall, MD is a dermatologist at ClearlyDerm in Boca Raton, FL.
1. Davis MD, O’Fallon WM, Rogers RS, Rooke TW. Natural history of erythromelalgia: presentation and outcome in 168 patients. Arch Dermatol. 2000;136(3):330-336.
2. Friberg D, Chen T, Tarr G, van Rij A. Erythromelalgia? A clinical study of people who experience red, hot, painful feet in the community. Int J Vasc Med. 2013;2013:864961.
3. Nurowska-Wrzosek B, Tołodziecka L, Gaciong Z. Erythromelalgia: two case reports and literature review. Pol Arch Med Wewn. 2007;117(7):322-326.
4. Davis MD, Weenig RH, Genebriera J, Wendelschafer-Crabb G, Kennedy WR, Sandroni P. Histopathologic findings in primary erythromelalgia are nonspecific: special studies show a decrease in small nerve fiber density. J Am Acad Dermatol. 2006;55(3):519-522.
5. Drenth JP, Michiels JJ. Erythromelalgia and erythermalgia: diagnostic differentiation. Int J Dermatol. 1994;33(6):393-397.
6. Kurzrock R, Cohen PR. Erythromelalgia and myeloproliferative disorders. Arch Intern Med. 1989;149(1):105-109.
7. Nanayakkara PW, van der Veldt AA, Simsek S, Smulders YM, Rauwerda JA. Verapamil-induced erythermalgia. Neth J Med. 2007;65(9):349-351.
8. Drenth JP, Michiels JJ, Van Joost T, Vuzevski VD. Verapamil-induced secondary erythermalgia. Br J Dermatol. 1992;127(3):292-294.
9. Levesque H, Moore N, Wolfe LM, Courtois H. Erythromelalgia induced by nicardipine (inverse Raynaud’s phenomenon?). BMJ. 1989;298(6682):1252-1253.
10. Sunahara JF, Gora-Harper ML, Nash KS. Possible erythromelalgia-like syndrome associated with nifedipine in a patient with Raynaud’s phenomenon. Ann Pharmacother. 1996;30(5):484-486.
11. Thami GP, Bhalla M. Erythromelalgia induced by possible calcium channel blockade by ciclosporin. BMJ. 2003;326(7395):910.
12. Dupont E, Illum F, Olivarius BeF. Bromocriptine and erythromelalgia-like eruptions. Neurology. 1983;33(5):670.
13. Eisler T, Hall RP, Kalavar KA, Calne DB. Erythromelalgia-like eruption in parkinsonian patients treated with bromocriptine. Neurology. 1981;31(10):1368-1370.
14. Monk BE, Parkes JD, Du Vivier A. Erythromelalgia following pergolide administration. Br J Dermatol. 1984;111(1):97-99.
15. Cimolai N, Cimolai T. Erythromelalgia accompanying rosuvastatin-associated myopathy. J Dermatol Case Rep. 2009;3(1):1-3.
16. Wagner DR, Spengel F, Middeke M. Erythromelalgia unmasked during norephedrine therapy: a case report. Angiology. 1993;44(3):244-247.
17. Yosipovitch G, Rechavia E, Feinmesser M, David M. Adverse cutaneous reactions to ticlopidine in patients with coronary stents. J Am Acad Dermatol. 1999;41(3 Pt 1):473-476.
18. Sertraline/fluoxetine: First report of erythromelalgia: 2 case reports. In. Vol 956: React. Wkly.; 2003:14.
19. Rey J, Cretel E, Jean R, Pastor MJ, Durand JM. Serotonin reuptake inhibitors, Raynaud’s phenomenon and erythromelalgia. Rheumatology (Oxford). 2003;42(4):601-602.
20. Alarcon-Segovia D, Diaz-Jouanen E. Case report: erythermalgia in systemic lupus erythematosus. Am J Med Sci. 1973;266(2):149-151.
21. Kraus A. Erythromelalgia in a patient with systemic lupus erythematosus treated with clonazepam. J Rheumatol. 1990;17(1):120.
22. Michiels JJ. Erythermalgia in SLE. J Rheumatol. 1991;18(3):481-482.
23. Mehle AL, Nedorost S, Camisa C. Erythromelalgia. Int J Dermatol. 1990;29(8):567-570.
24. Yosipovitch G, Krause I, Blickstein D. Erythromelalgia in a patient with thrombotic thrombocytopenic purpura. J Am Acad Dermatol. 1992;26(5 Pt 2):825-827.
25. Rey J, Crétel E, Jean R, Durand JM. Erythromelalgia in a patient with idiopathic thrombocytopenic purpura. Br J Dermatol. 2003;148(1):177.
26. Drenth JP, Michiels JJ, Van Joost T, Vuzevski VD. Erythermalgia secondary to vasculitis. Am J Med. 1993;94(5):549-550.
27. Kalgaard OM, Seem E, Kvernebo K. Erythromelalgia: a clinical study of 87 cases. J Intern Med. 1997;242(3):191-197.
28. Adamec I, Lakoš Jukić I, Habek M. Erythromelalgia as a manifestation of autonomic nervous system involvement in multiple sclerosis. Mult Scler Relat Disord. 2016;8:1-3.
29. Rauck RL, Naveira F, Speight KL, Smith BP. Refractory idiopathic erythromelalgia. Anesth Analg. 1996;82(5):1097-1101.
30. Cendrowski W. Secondary erythromelalgia in multiple sclerosis. Wiad Lek. 1988;41(21):1477-1479.
31. Saviuc P, Dematteis M, Mezin P, Danel V, Mallaret M. Toxicity of the Clitocybe amoenolens mushroom in the rat. Vet Hum Toxicol. 2003;45(4):180-182.
32. Martin JC, Lacombe D, Lefebvre D, Bonafé JL, Taïeb A, Maleville J. Erythromelalgia: a familial case. Discussion on the role of mercury. Ann Dermatol Venereol. 1994;121(4):309-314.
33. Chang XZ, Lu HM, Zhang YH, Qin J. Hypertension and erythromelalgia as prominent manifestations of mercury intoxication. Beijing Da Xue Xue Bao. 2007;39(4):377-380.
34. Beals TC, Swallow NC, Jensen A. Erythromelalgia: a novel postoperative complication. Foot Ankle Int. 2010;31(3):264-266.
35. Garrett SJ, Robinson JK. Erythromelalgia and pregnancy. Arch Dermatol. 1990;126(2):157-158.
36. Michiels JJ, Abels J, Steketee J, van Vliet HH, Vuzevski VD. Erythromelalgia caused by platelet-mediated arteriolar inflammation and thrombosis in thrombocythemia. Ann Intern Med. 1985;102(4):466-471.
37. Michiels J, Berneman Z, Schroyens W, van Urk H. Aspirin-responsive painful red, blue, black toe, or finger syndrome in polycythemia vera associated with thrombocythemia. Annals of Hematology. 2003;82:153-159.
38. van Genderen PJ, Michiels JJ. Erythromelalgia: a pathognomonic microvascular thrombotic complication in essential thrombocythemia and polycythemia vera. Semin Thromb Hemost. 1997;23(4):357-363.
39. McCarthy L, Eichelberger L, Skipworth E, Danielson C. Erythromelalgia due to essential thrombocythemia. Transfusion. 2002;42(10):1245.
40. Bernardini K, Lanthaler AJ, Buratti T, Mitterer M. Monolateral renal infarction and erythromelalgia in a case of chronic myelogenous leukemia. Am J Hematol. 2006;81(3):224-225.
41. Han JH, Lee JB, Kim SJ, Lee SC, Won YH, Yun SJ. Paraneoplastic erythromelalgia associated with breast carcinoma. Int J Dermatol. 2012;51(7):878-880.
42. Mørk C, Kalgaard OM, Kvernebo K. Erythromelalgia as a paraneoplastic syndrome in a patient with abdominal cancer. Acta Derm Venereol. 1999;79(5):394.
43. Michiels JJ, Hagemeyer A, Prins ME. Thrombocythaemic erythromelalgia in chronic myeloproliferative and myelodysplastic disorders. Neth J Med. 1989;35(1-2):4-10.
44. Lantrade P, Didier A, Ille H, et al. Malignant thymoma and paroxystal peripheral disease, a case report. Ann Med Interne (Paris). 1980;131(4):228-230.
45. Levine AM, Gustafson PR. Erythromelalgia: case report and literature review. Arch Phys Med Rehabil. 1987;68(2):119-121.
46. Confino I, Passwell JH, Padeh S. Erythromelalgia following influenza vaccine in a child. Clin Exp Rheumatol. 1997;15(1):111-113.
47. Influenza virus vaccine: Erythromelalgia in a child: case report. Reactions Weekly. 1997;649:9.
48. Rabaud C, Barbaud A, Trechot P. First case of erythermalgia related to hepatitis B vaccination. J Rheumatol. 1999;26(1):233-234.
49. Clayton C, Faden H. Erythromelalgia in a twenty-year-old with infectious mononucleosis. Pediatr Infect Dis J. 1993;12(1):101-102.
50. Mørk C, Kalgaard OM, Myrvang B, Kvernebo K. Erythromelalgia in a patient with AIDS. J Eur Acad Dermatol Venereol. 2000;14(6):498-500.
51. Damodar SS, Smitha P, Nirmal B, Sudhir NU, Ballambat PS. Hansen’s disease associated with erythromelalgia mimicking Lupus erythematosus. Indian Dermatol Online J. 2014;5(1):59-62.
52. Zheng ZM, Zhang JH, Hu JM, Liu SF, Zhu WP. Pox viruses isolated from epidemic erythromelalgia in China. Lancet. 1988;331(8580):296.
53. Herskovitz S, Loh F, Berger AR, Kucherov M. Erythromelalgia: association with hereditary sensory neuropathy and response to amitriptyline. Neurology. 1993;43(3 Pt 1):621-622.
54. Vendrell J, Nubiola A, Goday A, et al. Erythromelalgia associated with acute diabetic neuropathy: an unusual condition. Diabetes Res. 1988;7(3):149-151.
55. Wollina U. Burning feet in polycythemia vera - peripheral sensorimotor axonal neuropathy with erythromelalgia. Int J Gen Med. 2015;8:69-71.
56. Mellion ML, Silbermann E, Gilchrist JM, Machan JT, Leggio L, de la Monte S. Small-fiber degeneration in alcohol-related peripheral neuropathy. Alcohol Clin Exp Res. 2014;38(7):1965-1972.
57. Kikuchi I, Inoue S, Tada S. A unique erythermalgia in a patient with von Recklinghausen neurofibromatosis. J Dermatol. 1985;12(5):436-442.
58. Markel, J. Erythromelalgia: a report of a case of its association with chronic gout with relief of symptoms for two years after intravenous administration of typhoid vaccine. In. Vol 381938:73-74.
59. Drenth JP, Michiels JJ, Ozsoylu S. Acute secondary erythermalgia and hypertension in children. Erythermalgia Multidisciplinary Study Group. Eur J Pediatr. 1995;154(11):882-885.
60. Kasapcopur O, Akkus S, Erdem A, et al. Erythromelalgia associated with hypertension and leukocytoclastic vasculitis in a child. Clin Exp Rheumatol. 1998;16(2):184-186.
61. Cook-Norris RH, Tollefson MM, Cruz-Inigo AE, Sandroni P, Davis MD, Davis DM. Pediatric erythromelalgia: a retrospective review of 32 cases evaluated at Mayo Clinic over a 37-year period. J Am Acad Dermatol. 2012;66(3):416-423.
62. Alhadad A, Wollmer P, Svensson A, Eriksson KF. Erythromelalgia: Incidence and clinical experience in a single centre in Sweden. Vasa. 2012;41(1):43-48.
63. Thompson GH, Hahn G, Rang M. Erythromelalgia. Clin Orthop Relat Res. 1979(144):249-254.
64. Cohen IJ, Samorodin CS. Familial erythromelalgia. Arch Dermatol. 1982;118(11):953-954.
65. Finley WH, Lindsey JR, Fine JD, Dixon GA, Burbank MK. Autosomal dominant erythromelalgia. Am J Med Genet. 1992;42(3):310-315.
66. Drenth JP, Finley WH, Breedveld GJ, et al. The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32. Am J Hum Genet. 2001;68(5):1277-1282.
67. Yang Y, Wang Y, Li S, et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet. 2004;41(3):171-174.
68. Rush A, Dib-Hajj S, Liu S, et al. A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. Proceedings of the National Academy of Sciences. 2006;103.
69. Davis, MD, Sandroni P, Rooke T, Low P. Erythromelalgia: vasculopathy, neuropathy, or both? A prospective study of vascular and neurophysiologic studies in erythromelalgia. Arch Dermatol. 2003;139:1337-1343.
70. Mork C, Asker CL, Salerud EG, Kvernebo K. Microvascular arteriovenous shunting is a probable pathogenetic mechanism in erythromelalgia. J Invest Dermatol. 2000;114(4):643-646.
71. Chan MK, Tucker AT, Madden S, Golding CE, Atherton DJ, Dillon MJ. Erythromelalgia: an endothelial disorder responsive to sodium nitroprusside. Arch Dis Child. 2002;87(3):229-230.
72. Nassar MA, Stirling LC, Forlani G, et al. Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci U S A. 2004;101(34):12706-12711.
73. Wu MT, Huang PY, Yen CT, Chen CC, Lee MJ. A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers. PLoS One. 2013;8(1):e55212.
74. Huang CW, Lai HJ, Huang PY, Lee MJ, Kuo CC. The Biophysical Basis Underlying Gating Changes in the p.V1316A Mutant Nav1.7 Channel and the Molecular Pathogenesis of Inherited Erythromelalgia. PLoS Biol. 2016;14(9):e1002561.
75. Jang HS, Jung D, Kim S, et al. A case of primary erythromelalgia improved by mexiletine. Br J Dermatol. 2004;151(3):708-710.
76. Fox T. Dyshidrosis: cheiro-pompholyx. Lancet. 1876;107:651.
77. Wollina U. Pompholyx or dyshidrosis. Expert Review of Dermatology. 2009;4:403-411.
78. Nathan A, Rose JB, Guite JW, Hehir D, Milovcich K. Primary erythromelalgia in a child responding to intravenous lidocaine and oral mexiletine treatment. Pediatrics. 2005;115(4):e504-507.
79. Iqbal J, Bhat MI, Charoo BA, Syed WA, Sheikh MA, Bhat IN. Experience with oral mexiletine in primary erythromelalgia in children. Ann Saudi Med. 2009;29(4):316-318.
80. Ozsoylu S, Coşkun T. Sodium nitroprusside treatment in erythromelalgia. Eur J Pediatr. 1984;141(3):185-187.
81. Cimaz R, Rusconi R, Fossali E, Careddu P. Unexpected healing of cutaneous ulcers in a short child. Lancet. 2001;358(9277):211-212.
82. Harrison CM, Goddard JM, Rittey CD. The use of regional anaesthetic blockade in a child with recurrent erythromelalgia. Arch Dis Child. 2003;88(1):65-66.
83. Delye H, Lagae L, Vermylen J, Nuttin B. Thalamic stimulation as a treatment for primary erythromelalgia: technical case report. Neurosurgery. 2005;57(4 Suppl):E404; discussion E404.
84. Faddoul D. A 10-year-old boy with severe pain in the toes. Diagnosis: erythromelalgia. Pediatr Ann. 2011;40(3):128-129.
85. McGraw T, Kosek P. Erythromelalgia pain managed with gabapentin. Anesthesiology. 1997;86(4):988-990.
86. Al-Minshawy SM, El-Mazary AA. An Egyptian child with erythromelalgia responding to a new line of treatment: a case report and review of the literature. J Med Case Rep. 2014;8:69.
87. Pfund Z, Stankovics J, Decsi T, Illes Z. Childhood steroid-responsive acute erythromelalgia with axonal neuropathy of large myelinated fibers: a dysimmune neuropathy? Neuromuscul Disord. 2009;19(1):49-52.
88. Sheets PL, Jackson JO, Waxman SG, Dib-Hajj SD, Cummins TR. A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivity. J Physiol. 2007;581(Pt 3):1019-1031.
89. Fischer T, Gilmore E, Estacion M, et al. A novel Nav1.7 mutation producing carbamazepine-responsive erythromelalgia. Ann Neurol. 2009;65:733-741.
90. Kalgaard OM, Mørk C, Kvernebo K. Prostacyclin reduces symptoms and sympathetic dysfunction in erythromelalgia in a double-blind randomized pilot study. Acta Derm Venereol. 2003;83(6):442-444.
91. Mørk C, Salerud EG, Asker CL, Kvernebo K. The prostaglandin E1 analog misoprostol reduces symptoms and microvascular arteriovenous shunting in erythromelalgia-a double-blind, crossover, placebo-compared study. J Invest Dermatol. 2004;122(3):587-593.
92. Krishnan SG, Yesudian DP, Jayaraman M, Janaki VR, Raj BJ. Erythromelalgia responding to aspirin. Indian J Dermatol Venereol Leprol. 1996;62(3):204-205.
93. Morales PS, Escobar RG, Lizama M, et al. Paediatric hypertension-associated erythromelalgia responds to corticosteroids and is not associated with SCN9A mutations. Rheumatology (Oxford). 2012;51(12):2295-2296.
Fire Power: Sometimes You Need to Let Employees Go
In the latest edition of Practice Path MD, Lisa Waite explains how and why to fire staffers who just don’t fit. Read the full story here!
“The true definition of leadership reminds us that leadership can be messy and even scary, but a leader is called to manage the workforce to success. In part, you can’t retain the one in risk of sacrificing the many. You must sacrifice the one to maintain the culture and ‘civilization.’ I once heard a conference speaker, express. ‘It must be one for all, never all for one.’ Drucker reinforces this, ‘Letting the wrong people hang around is unfair to all the right people, as they inevitably find themselves compensating for other’s ineffectiveness.’
You can’t shy away from these hard calls. One client of a national snack food organization recently remarked that “releasing” people remains his biggest leadership challenge. I noted that a benchmark of his leadership in these circumstances is not having to remove people but more importantly his willingness to do so. I suggested that his concern about what others think about his leadership effectiveness will only worsen with indecision and hesitancy. Keeping poor performers is unfair to all the great performers who pick up the slack.”