Data da submissão: 6 de Março de 2021 CARTA AO EDITOR Data da aprovação: 17 de Março de 2021

ERYTHROMELALGIA - AN UNCOMMON CHALLENGING ENTITY

ERITROMELALGIA - UMA ENTIDADE DESAFIADORA INCOMUM

Vitorino Modesto dos Santos, Laura Campos Modesto

DOI - 10.5935/2236-5117.2021v58a44

small fiber neuropathies, neurofibromatosis, and Vitorino Modesto dos Santos – Armed Forces Hospital and Catholic University, multiple sclerosis), gout, astrocytoma, Brasília-DF, Brazil, Internal Medicine - Brasília - DF, Brasil. colon cancer, thyroid cancer, and breast cancer, Laura Campos Modesto – University Center of Brasília (Uniceub), Brasília-DF, medications (bromocriptine, nifedipine, verapamil, Brazil, Medical Course - Brasília - DF, Brasil. topical isopropanol, pergolide, and simvastatin), arterial hypertension, venous insufficiency, pregnancy, Correspondência: Vitorino Modesto dos Santos. Quadra SMPW 1-5 Quadra 14 Conjunto 2, Lote 7, Casa A, Park Way, Brasília - DF, Brasil alcohol abuse, and mercury poisoning. The common - CEP: 71741402 hypothesis for both types of EM is that symptoms occur

Internet: [email protected] by skin hypoxia due to increased arteriovenous shunting and imbalance between thermoregulatory and nutritive perfusion.1 The symptoms of EM typically appear under influence of warm or exercise and improve by cooling Conflito de interesses: não existem conflitos de interesse. the affected regions; the episodes commonly occur at night periods and the affected regions characteristically remain normal between the acute crises. Although the To the Editor classical manifestations are more often bilateral, they may appear unilaterally mainly in the secondary EM; (EM) (burning feet syndrome, while lesions uniquely affecting the face are exceeding erythermalgia, Gerhardt disease, or Mitchell disease) uncommon and more frequently course misdiagnosed.1-5 is the triad of redness, warmth, and burning pain, more often in lower extremities.1-5 Silas Weir Mitchell initially EM (or erythermalgia) can be also classified by the described the clinical features of erythromelalgia in 1878, responsiveness to the administration of aspirin in: EM and Smith and Allen proposed the term erythermalgia in of essential thrombocytosis and polycythemia vera 1938.1,2 Primary EM may be idiopathic or inherited, often (platelet mediated, and aspirin responsive); primary appearing in the first two decades of life,1-5 the incidence erythermalgia (idiopathic or inherited autosomal ranges from 0.25 to 2 per 100,000 people per year, while dominant neuropathy, and aspirin resistant); and 49.1 years is the mean age of onset in the secondary secondary erythermalgia (aspirin resistant and associated type.1 Inherited EM is an autosomal dominant neuropathy with myeloproliferative disorders, myelofibrosis, viruses, with hyperexcitability of nociceptive fibers that causes autoimmune diseases, diabetes, and adverse-effects of aching responses to usually non-painful stimuli.1 bromocriptine, nifedipine, verapamil, topic isopropanol, Primary EM may have co-morbidities (hypertension, pergolide, and simvastatin).1 atrial fibrillation, diabetes, Raynaud’s phenomenon, peripheral neuropathy, low back pain, , Manifestations of the EM secondary type are usually bullous pemphigoid, gastroesophageal reflux, chronic milder and often relieve after the treatment of the constipation, Clostridium difficile infection, joint underlying cause.1 Polyneuropathy, acrocyanosis, hypermobility syndrome, and hyperosmia.4 Secondary peripheral arterial disease, lipodermatosclerosis, EM may be associated with myeloproliferative disorders Raynaud phenomenon, cellulitis, gout, Fabry disease, (polycythemia vera, idiopathic thrombocytopenia, vasculitis, and frostbite are differential diagnoses.1 leukemia, cryoglobulinemia, pernicious anemia, and Without treatment guidelines, various pharmacological systemic mastocytosis), infections (HIV, influenza, and surgical therapies are employed: avoid potential syphilis, and poxvirus), autoimmune diseases (systemic triggers; aspirin for one month; topical drugs for two lupus erythematosus, , mixed to four weeks; and drugs as gabapentin, pregabalin, or connective tissue disease, Sjogren’s syndrome), venlafaxine for two to four months. In myeloproliferative neurologic diseases (reflex sympathetic dystrophy, disorders aspirin is the first choice and other non-

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steroidal anti-inflammatory drugs (NSAIDs) are patient’s suffering. They commented on this rare and used too.1,4 Other options include prostaglandins, debilitating disease, which is usually diagnosed by serotonin and norepinephrine reuptake inhibitors, exclusion, a condition more frequently secondary to calcium channels blockers, mexiletine, lidocaine, hematologic malignant disorders, autoimmune diseases, capsaicin, midodrine, epidural sympathetic blockage, infections, besides the adverse-effect of medicines as and peripheral nerve blocks. Multidisciplinary teams simvastatin.5 with rheumatology, vascular surgery, dermatology, infectious disease and podiatry specialists yield better Worthy of note, the incidence of EM increased in outcomes.4 Olmsted County, Minnesota in the period from 1978 to 2008 up to 1.3 per 100,000 people per year (near Modesto dos Santos et al., reported a young man 5 times greater than 0.25 to 0.33 found in Norway in presenting for the third time the asymmetrical triad of 1998) with female preponderance and median age EM affecting the hands, and the right elbow and foot.2 He of diagnosis of 61 years.3,4 The small epidemiological denied use of alcohol and tobacco, or drug abuse; and studies performed in USA, Sweden and Norway might there was no similar case in his family. The manifestations had not estimate the real prevalence of EM, in addition typically worsened by sun exposure, and alleviated with to the possibility of missed diagnosis or non-reported local cooling.2 The rest of physical examination, and cases.4 A major concern is about management of EV, and laboratory routine determinations were unremarkable. no established classification criteria for diagnosis due to He did not utilize aspirin, although antihistamines, the lack of consensus in regard to clinical presentation NSAIDs, and corticosteroids did not result in significant and associated comorbid conditions.4 improvement. The characteristics of the present case are indicative of the idiopathic form of EM. The differential The aim of this letter is to enhance the suspicion index diagnosis included pharmacodermia, acrocyanosis, of the health care workers about EM; furthermore, more erythrodysesthesia, alcoholism, angiodyskinesia, broad researches should be carried out to better clarify liver insufficiency, lipodermatosclerosis, peripheral its increasing incidence. neuropathy, polycythemia, reflex sympathetic dystrophy, rheumatoid arthritis, and thyrotoxicosis.2 The authors REFERENCES commented on that the prevalence of this scarcely 1. Jha SK, Karna B, Goodman MB. Erythromelalgia. 2020 Nov reported entity may increase following the growth of the 16. In: StatPearls [Internet]. Treasure Island (FL): StatPearls physician’s awareness. Publishing; 2021 Jan-. PMID: 32491719. 2. Modesto dos Santos V, Vieira Brandão B, Mussi P, de Melo Vanwonterghem and Shadid recently reported a Alcântara-Silva S. A 30-year-old healthy man with recent diabetic woman presenting with an accentuated burning onset erythromelalgia: a case report. Iran J Dermatol. sensation, and redness in both legs only relieved by local 2016; 19(1):25-8. cooling.5 The course of diabetes was uncomplicated, 3. Reed KB, Davis MD. Incidence of erythromelalgia: a and she was in regular utilization of simvastatin. She population-based study in Olmsted Country, Minnesota. searched for no specialized outpatient medical attention J Eur Acad Dermatol Venereol. 2008;23:13-5. PMID: and underwent schedule of analgesics and amitriptyline, 18713229. doi: 10.1111/j.1468-3083.2008.02938.x. 4. Sharif S, Haider L, Freeman L, McFarlane IM. Primary without significant improvement of the unbearable erythromelalgia complicated by cellulitis: a case report and symptoms. Worthy of note, her manifestations review of literature. Am J Med Case Rep. 2020;8(6):153-8. disappeared after the empirical discontinuation of PMID: 32490173. Epub 2020 Apr 5. simvastatin. The authors emphasized the lack of suspicion 5. Vanwonterghem Y, Shadid S. Simvastatin-induced about EM, despite typical features, which occasioned erythromelalgia: less is more. Acta Clin Belg. 2021;76(1):58-9. considerable diagnostic delay and prolongation of the doi: 10.1080/17843286.2019.1640929. PMID: 31291834.

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