The Prostaglandin E1 Analog Misoprostol Reduces Symptoms and Microvascular Arteriovenous Shunting in Erythromelalgia—A Double-Blind, Crossover, Placebo-Compared Study

Abstract

Based on previous experience with parenteral prostanoids, we studied the effect of misoprostol treatment, an orally administered prostaglandin E1 analog, in patients with erythromelalgia. Treatment with placebo was followed by treatment with misoprostol (0.4-0.8 mg per d), both for 6 wk. The patients (n=21) and a study nurse who administered the trial were blinded. The endpoints were change in pain and need for cooling and global assessment of the treatment. Following central body heat provocation, global skin perfusion, capillary morphology, and change in pain were also recorded before and after each treatment period. Results were compared with data from healthy control subjects (n=11) that did not undergo treatment. Clinical safety and tolerability evaluation included physical examinations, clinical laboratory tests, and monitoring of adverse events. All clinical outcome measures were significantly better after treatment with misoprostol (p<0.01) as compared with placebo treatment and after a 3- mo follow-up without treatment. The heat-induced increase in global perfusion after misoprostol treatment was similar to the control group and significantly lower when compared with baseline (p<0.01) and placebo treatment (p<0.05), respectively. This study demonstrates that misoprostol is clinically superior to placebo in patients with erythromelalgia. The results of the perfusion studies may imply that the mechanism of action of the beneficial effect of misoprostol is reduced microvascular arteriovenous shunting in affected skin.

Eritromelalgia primária: relato de caso

“…Mork et al, in a double-blind controlled placebo prospective study in 21 patients observed that the analogue of oral PGE1, misoprostol, given on a 0,4 a 0,8 mg/day for 6 weeks , determined a significant reduction of the pain symptoms and local erythema but this decrease did not persist and after three months of treatment no further continuation was required. 3 As the responses for the current available treatments varies a lot, it was chosen as a more conservative treatment for our patient who had been presenting long periods between the crises (5 years) and limited duration (two weeks) of the symptoms. …”

“…1 Heat exposure, physical exercises, gravity and the use of stockings/socks and gloves can act as triggers of the symptoms or intensify the discomfort while cold causes discomfort relief. [3][4][5] The disease takes typically a chronic course and it is associated with a decrease in the quality of life and considerable morbidity. It differs from Lane's palmoplantar erythema or red palms syndrome -a congenital, familial and hereditary dysplasia characterized by persistent and symmetric redness, without subjective manifestations -due to the intermittent nature of the symptoms.…”

“…7 Etiopathogenesis of erythromelalgia is not known yet but it is admitted the existence of primary or secondary vascular abnormalities that result in endothelial edema, with increase in temperature and blood flow, hypoxia, platelet aggregation and activation, with release of prostaglandins which produces erythema and pain. [3][4][5] It was also observed the presence of small-fiber neuropathy. 9 Its treatment includes drugs that act in the neuropathy such as gabapentin, tricyclic antidepressants and selective inhibitors of serotonin reuptake, and, in vasculopathy, drugs like acetylsalicylic acid, ‚-blockers and calcium channel antagonists.…”

Current pain management strategies for patients with erythromelalgia: a critical review

“…Prostaglandin and prostacyclin analogs with vasodilatory effects have been the subjects of two small RCTs in EM treatment of pain (n=12–21). Findings were that iloprost and misoprostol were associated with a reduction in symptoms and sympathetic dysfunction 7,34,35…”

Erythromelalgia

“…A study by Mork et al [6] is the only double-blind, crossover, placebo-compared study of a drug in erythromelalgia. A study by Mork et al [6] is the only double-blind, crossover, placebo-compared study of a drug in erythromelalgia.…”