| 1. |
- Asker, Claes, et al.
(författare)
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Computer assisted evaluation of skin capillary density supports the hypothesis of microvascular shunting in erythromelalgia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Erythromelalgia subjects often suffer from burning pain in distal parts of the extremities, aggravated by warmth and relieved by cooling. Affected skin is hyperemic and has an increased skin temperature. The shunting hypothesis for the pathogenesis of erythromelalgia, postulates maldistribution of skin microvascular blood flow with increased thermoregulatory flow through arteriovenous shunts and an inadequate nutritive perfusion with a corresponding tissue hypoxia. Our aim was to characterize recruitment and steal distribution changes in affected skin with the aid of an enhanced technique of computer-assisted analysis of capillary beds. This method was used to determine the capillary density before and after central body heating in 14 patients with erythromelalgia and 10 controls. Symptoms were induced in 8 patients and their skin temperature became higher (p<0.05) after central body heating, but the number of visible or active capillaries in the dorsal aspect of the foot decreased significantly, as compared to asymptomatic patients and controls. Since the increased temperature should, normally induce capillary recruitment, and other studies using laser Doppler techniques have shown an increase in global skin perfusion during EM attacks, we conclude that the reduced capillary density shown in this study, is compatible with the hypothesis of blood shunting through AV anastomoses, deep in the dermis.
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| 2. |
- Mørk, Cato, et al.
(författare)
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Combined computer assisted capillary microscopy and laser Doppler imaging used to assess redistribution changes in skin of erythromelalgic patients during treatment with misoprostol
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Erythromelalgia is a rare condition defined by red, hot and painful extremities. Warmth intensifies the discomfort while cold provides relief. The clinical picture is heterogeneous with respect to aetiology and severity. We have previously postulated arteriovenous shunting in the skin as a common pathogenetic mechanism. Defects in prostaglandin synthesis, metabolism or functional response have been implicated in the pathogenesis of erythromelalgia. In this pilot study we wanted to describe the skin microcirculation before and after misoprostol treatment, an oral PGE1 analogue.A non-randomised, placebo-compared study investigating the effect of misoprostol on the skin microcirculation in patients with erythromelalgia using Laser Doppler Perfusion Imaging (LDPI) and Computer Assisted Capillary Microscopy (CACM).EM was treated with placebo for six weeks followed by misoprostol for the next six weeks. Cutaneous microcirculation was evaluated as determined by the analysis of laser Doppler perfusion imager (global skin perfusion) and computer assisted capillary microscopy (capillary perfusion) before and after whole body heating at baseline, after placebo and misoprostol treatment.There were a significant increase in skin temperature, global perfusion and reduction in capillary density in non-treated erythromelalgia patients. After misoprostol treatment the changes in the microcirculation are reduced.The results are consistent with earlier findings of increased global perfusion and reduced capillary density during central body heating. The microcirculatory changes after misoprostol treatment indicate reduced arteriovenous shunting and increased nutritive perfusion.
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| 3. |
- Mørk, Cato, et al.
(författare)
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Microvascular arteriovenous shunting is a probable pathogenetic mechanism in erythromelalgia
- 2000
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 114:4, s. 643-646
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Tidskriftsartikel (refereegranskat)abstract
- Erythromelalgia is a condition consisting of red, warm, and burning painful extremities. Symptoms are relieved by cold and aggravated by heat. A wide variety of etiologic conditions can cause erythromelalgia, but one common pathogenetic mechanism, microvascular arteriovenous shunting, has been hypothesized. The aim of this study was to test this hypothesis. Quantification of skin microvascular perfusion using laser Doppler perfusion imaging and skin temperature at rest and after central body heating was performed in 14 patients with erythromelalgia and 11 controls. Attacks of erythromelalgia were induced in eight patients after heat provocation. In the plantar region of the foot, the location of numerous anatomical arteriovenous shunts, these patients significantly increased the skin perfusion as compared with asymptomatic patients with erythromelalgia and controls. In the dorsal region with few arteriovenous shunts no significant differences between the groups were demonstrated. The results show a relation between clinical symptoms and increased perfusion in the region of numerous anatomical arteriovenous shunts, and support the hypothesis of increased thermoregulatory arteriovenous shunt flow during attacks in primary erythromelalgia.
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| 4. |
- Mørk, Cato, et al.
(författare)
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Reduced Skin Capillary Density During Attacks of Erythromelalgia Implies Arteriovenous Shunting as Pathogenetic Mechanism
- 2002
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Ingår i: Journal of Investigative Dermatology.
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Tidskriftsartikel (refereegranskat)abstract
- Erythromelalgia is characterized by burning pain, erythema, and increased temperature in acral skin. The pain is aggravated by warming and relieved by cooling. Increased microvascular arteriovenous shunting in deep dermal plexa has been hypothesized as the pathogenetic mechanism of pain in affected skin, inducing hypoxia during pain attacks. The aim of this study was to quantify skin capillary density in erythromelalgic patients before and after heat provocation, as increased skin temperature should increase the need for nutritive blood supply by the capillaries. Fourteen patients and 10 healthy control subjects were studied using an enhanced technique of computer-assisted analysis of capillary bed morphology and temperature measurements before and after central body heating. The increase in acral skin temperature was significantly higher (p < 0.05) in the eight patients where symptoms were induced after heat provocation, compared to asymptomatic patients and healthy control subjects. The number of visible capillaries in a field of view (1.7Êmm 2) decreased significantly (p = 0.01) in erythromelalgia patients from 105 (62-137) (median with total range) to 89 (49-118) after warming in areas with numerous arteriovenous anastomoses (nail bed region). In symptomatic patients an even more significant reduction was observed (p = 0.01). The capillary size was also significantly reduced (p < 0.05) from 41.0 (31.5-50.5) (arbitrary units) to 37.3 (33.0-46.0) in symptomatic patients. The change in capillary density in the nail bed area was significantly larger in erythromelalgia patients 17 ( 49 to 39) compared to controls 0 ( 47 to 13) (p < 0.05), and in symptomatic patients 19 ( 49 to 12) compared to asymptomatic patients 8 ( 48 to 39) (p < 0.05) and controls (p < 0.01). The reduced skin capillary density after heating is compatible with increased microvascular arteriovenous shunting of blood and a corresponding relative deficit in nutritive perfusion (steal phenomenon) with skin hypoxia, causing the symptoms in erythromelalgia
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| 5. |
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| 6. |
- Mørk, Cato, et al.
(författare)
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The Prostaglandin E1 Analog Misoprostol Reduces Symptoms and Microvascular Arteriovenous Shunting in Erythromelalgia : A Double-Blind, Crossover, Placebo-Compared Study
- 2004
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Ingår i: Journal of Investigative Dermatology. - : Nature Publishing Group. - 0022-202X .- 1523-1747. ; 122:3, s. 587-593
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Tidskriftsartikel (refereegranskat)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.
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