Erythromelalgia: a cutaneous manifestation of neuropathy?

Abstract

The low prevalence of erythromelalgia, classified as an orphan disease, poses diagnostic and therapeutic difficulties. The aim of this review is to be an update of the specialized bibliography. Erythromelalgia is an infrequent episodic acrosyndrome affecting mainly both lower limbs symmetrically with the classic triad of erythema, warmth and burning pain. Primary erythromelalgia is an autosomal dominant inherited disorder, while secondary is associated with myeloproliferative diseases, among others. In its etiopathogenesis, there are neural and vascular abnormalities that can be combined. The diagnosis is based on exhaustive clinical history and physical examination. Complications are due to changes in the skin barrier function, ischemia and compromise of cutaneous nerves. Because of the complexity of its pathogenesis, erythromelalgia should always be included in the differential diagnosis of conditions that cause chronic pain and/or peripheral edema. The prevention of crisis is based on a strict control of triggers and promotion of preventive measures. Since there is no specific and effective treatment, control should focus on the underlying disease. However, there are numerous topical and systemic therapies that patients can benefit from.

Review of primary and secondary erythromelalgia

“…Diagnosis of erythromelalgia is based on clinical criteria and exclusion of differential diagnoses, including peripheral neuropathies, vasculitis, the redness phase of RP, acrocyanosis and Fabry disease . Strict application of the criteria proposed by Thompson et al .…”

A case of sporadic erythromelalgia presenting with small fibre neuropathy

“…Approaching EM with agents that would regulate the function of mutated sodium channels is considered one of the optimal ways of treating this condition. Several types of pharmacological agents, including anaesthetics, antiarrhythmic drugs and anticonvulsants, can play a role in systemic regulation of sodium channels and improvement in patient symptoms 4…”

“…These tests are helpful, but are unable to detect small fibre neuropathy, which limits their utility, but does help narrow the differential in the sense that it rules out conditions related to large fibre neuropathy or another specific neuromuscular disease. Further diagnostic studies involving nerve biopsy had to be performed in order to evaluate for small fibre neuropathy, which in concordance demonstrated findings consistent with decreased nerve fibre density This is something important to keep in mind when ruling out secondary causes of this condition, especially in view of the limitations and mimics of clinical examination 4 5…”

Erythromelalgia successfully treated with sulodexide

“…The vascular theory of secondary erythromelalgia proposes the existence of primary or secondary vascular abnormalities that result in an abnormal distribution of the microvascular flow through arteriovenous precapillary shunts, causing a decrease in capillary circulation and producing endothelial oedema, hypoxia, platelet aggregation and activation, with the release of prostaglandins …”

“…The vascular theory of secondary erythromelalgia proposes the existence of primary or secondary vascular abnormalities that result in an abnormal distribution of the microvascular flow through arteriovenous precapillary shunts, causing a decrease in capillary circulation and producing endothelial oedema, hypoxia, platelet aggregation and activation, with the release of prostaglandins. 4 Several treatment options, including drugs acting on vasculopathy (acetylsalicylic acid, misoprostol), neuropathy (gabapentin, amitriptyline and sertraline) and pain (lidocaine and mexiletine) have been used with moderate effect in erythromelalgia. 1,3 Sulodexide is a drug compounded of a heparin fraction (80%) with affinity for antithrombin III and a dermatan sulfate fraction (20%) with affinity for heparin cofactor II.…”