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Kalgaard OM, Clausen OP, Mellbye OJ, Hovig T, Kvernebo K
Archives of dermatology •
To report on the histopathologic findings of affected skin in consecutively collected biopsy specimens from 49 patients with erythromelalgia (EM). Skin biopsy specimens were obtained from the foot arch and analyzed by light microscopy, immunofluorescence microscopy, and electron microscopy. Oslo University Hospital-Gaustad, University of Oslo, Oslo, Norway. Thirty-one patients had primary EM, 17 patients had secondary EM, and 1 patient had erythromelalgic syndrome. Evidence of microvascular abnormalities in skin biopsy specimens. Light microscopy showed evidence of capillary proliferation in 10 of 31 patients with primary EM and in 1 of 17 patients with secondary EM. The biopsy specimen from the patient with erythromelalgic syndrome showed numerous capillary nests with endothelial cell defects and a slight perivascular inflammatory reaction. Among the 17 secondary EM cases, sparse perivascular lymphocyte infiltrations were observed in the biopsy specimens from 2 patients with chronic myelogenous leukemia and 1 patient with diabetes mellitus. Eleven patients also had signs of vasculopathy based on findings of immunodeposits of C3 and fibrin. Six of 30 patients with primary EM showed endothelial abnormalities on electron microscopy. All 3 investigations showed unremarkable biopsy results in 16 cases. Histopathologic analysis is not useful as a routine diagnostic tool in EM because no morphological changes are specific to EM. The capillary proliferation and vasculopathy are assumed to be a consequence of intermittent skin hypoxia (vascular hypothesis of pathogenesis). Whether the proliferation is a consequence of EM or a pathogenic factor in the development of the disease is uncertain.
Sympathetic dysfunction and skin microvascular arteriovenous shunting with insufficient nutritive perfusion and tissue hypoxia have been reported in patients with erythromelalgia. The objective of this study was to determine whether iloprost, a synthetic prostacyclin analogue--primarily a vasodilator and inhibitor of platelet activation--improves symptoms and sympathetic function in patients with erythromelalgia. Erythromelalgia is a rare condition, but we managed to collect 12 primary cases for a double-blind, randomized, parallel-group pilot trial evaluating the effect of iloprost (n = 8) and placebo (n = 4). The treatment effect was determined by the need for cooling of affected skin and by vasoconstrictor tests following Valsalva's manoeuvre and contralateral cooling. The results show a significant reduction in symptoms (p < 0.05) and sympathetic dysfunction (p < 0.05) in the iloprost group. Further studies with oral prostacyclins or analogues are suggested.
Erythromelalgia is a clinical diagnosis characterized by erythema, increased temperature and burning pain in acral skin. The pain is relieved by cooling and aggravated by warming. The symptoms have been hypothesized to be caused by skin hypoxia due to increased arteriovenous shunting. We examined skin microvascular perfusion in response to vasoconstrictory and vasodilatory stimuli, to characterize local and central neurogenic reflexes as well as vascular smooth muscle and vascular endothelial function, using laser Doppler perfusion measurements in 14 patients with primary erythromelalgia and healthy control persons. Skin perfusion preceding provocative stimuli was significantly reduced in patients with erythromelalgia (p < 0.01). The laser Doppler flowmetry signal after sympathetic stimulation of reflexes mediated through the central nervous system, was significantly diminished in patients with erythromelalgia as compared with healthy controls (Valsalva's maneuver p < 0.01; contralateral cooling test p < 0.05). Local neurogenic vasoconstrictor (venous cuff occlusion and dependency of the extremity) and vasodilator reflexes (local heating of the skin), as well as tests for vascular smooth muscle and vascular endothelial function (postocclusive hyperemic response) were maintained. These results indicate that postganglionic sympathetic dysfunction and denervation hypersensitivity may play a pathogenetic role in primary erythromelalgia, whereas local neurogenic as well as endothelial function is unaffected.
Journal of the European Academy of Dermatology and Venereology : JEADV •
Erythromelalgia is a clinical syndrome characterized by burning pain in the extremities together with erythema and increased skin temperature. Typically, the patients experience relief from cold, and aggravation from warmth. Symptoms are hypothesized to be caused by arteriovenous shunting and reduced nutritive skin capillary perfusion with corresponding tissue hypoxia. Erythromelalgia is most often primary, but may be secondary to a wide variety of diseases. We report erythromelalgia in a patient with acquired immune deficiency syndrome (AIDS). At peak pain intensity he actively cooled hands and feet for more than 12 h/day. Many doctors handling human immunodeficiency virus/AIDS patients are unfamiliar with erythromelalgia, and the condition can easily be overlooked, especially the more common milder cases.