ERYTHROMELALGIA - A CONDITION CAUSED BY MICROVASCULAR ARTERIOVENOUS SHUNTING

Definition Erythromelalgia (EM) is a rare disorder of unknown etiology characterized by intense burning extremity pain associated with eryth ema and increased skin temperature. Warmth intensifies the discomfort while cold provides relief. The condition was first described by Grave s in 1834. The clinical entity of EM has been questioned by some autho rs, but is accepted by the leading textbooks. The clinical manifestati ons varies considerably from patient to patient, both with regards to the time course and severity of the burning pain. The age at onset can vary from childhood to old age. In some cases inheritance seems to be one etiological factor. In other cases the condition is idiopathic or secondary to another primary disease. In the literature no proposed c lassification takes all these variables into account. This monograph t herefore proposes based on experiences with 40 patients seen by the au thor, a new classification system. In this system EM can be a syndrome (ES, inheritance as an etiological factor, and structural abnormaliti es found in the microvasculature of affected skin areas) or a phenomen on with intermittent attacks. Cases with erythromelalgic phenomena (EP ) can be primary (EPP) or secondary (EPS), and both these groups can a gain be acute (EPPA and EPSA) or chronic (EPPC and EPSC). The severity and duration of the burning pain also varies considerably and a sever ity group scale is proposed on the basis of the patients subjective fe eling of pain combined with the amount of active cooling. On the basis of the 40 cases described in Norway, a country with a population of 4 ,5 million inhabitants, a prevalence of 2/100 000 and an incidence of 0,25/100 000 is estimated. In the present material one patients is tho ught to have an erythromelalgic syndrome, 27 a primary phenomenon (EPP ), while 12 have secondary phenomena (EPS). A wide range of conditions is thought to be the primary disease in cases with EPS. All primary c onditions, however, may influence either blood rheology (like polycyth emia), the vessel wall of nutritional capillaries with increased blood /tissue diffusion barrier (like systemic lupus erythematosus) or the d istribution of microvascular skin perfusion (like cholesterol emboli s yndrome). Histopathology EM is in the authors opinion not one defined disease, but a symptom complex. It is therefore not surprising that th ere were no consistent histopathological findings in skin biopsies fro m six of the patients in the present material. Physiology The circulat ion in affected skin and extremities was examined with laser Doppler f lowmetry (LDF), transcutaneous oxygen tensiometry (TCpO2) and ultrasou nd ankle blood pressure measurements, and ultrasound flow velocity pro files were described. Affected skin was hyperemic as assessed by LDF, without normal ability to postocclusive hyperemia. This finding coinci ded with hyperemic flow velocity profiles in the arteries supplying th e affected skin areas. The perfusion in muscle underlying affected ski n seemed to have a normal physiological response to occlusion, implyin g that EM is a circulatory abnormality confined to skin microcirculati on. TCpO2 measurements implied that at least some patients with EM hav e hypoxia in affected skin areas. This finding is compatible with the clinical observation of skin ulcers in some patients with severe EM. P athogenesis Based on the clinical, etiological and physiological findi ngs in the present material, a theory of pathogenesis is proposed. The author believes that local skin hypoxia is existing in affected skin. The hypoxia is caused by maldistribution of skin perfusion, leading t o increased thermoregulatory and decreased nutrition perfusion. The ma ldistribution can be caused by opening of physiological AV anastomosis in hands and feet, by shunting through proliferated microvessels or b y shunting through capillaries serving physiologically as ''thorough - fare'' channels. A consequence of the hypoxia is arteriolar dilatatio n, and thereby chronic hyperemia (which is maldistributed) in the rela ted microvessels. The hyperemia increases skin temperature, skin metab olism and tissue oxygen consumption, causing a further increase in tis sue hypoxia. A vicious circle is created and is maintained by the mald istribution of the perfusion. Therapy The therapeutic consequence of t he pathogenetic theory, must be to try to increase tissue oxygen suppl y. This can be achieved by decreasing the oxygen consumption of the sk in, for example by cooling the tissue (which is what all patients with EM intuitively do). The factors causing maldistribution of perfusion should also be attacked if possible. In patients with secondary EM, ag gressive treatment of the primary condition may achieve this goal (for example reduction of hematocrit in patients with polycythemia). In pa tients with maldistribution caused by opening of AV anastomosis, where a steal mechanism from nutritional to thermoregulatory AV flow is bel ieved to be the case, vasodilator treatment could be tried to also ope n up nutritional capillaries. In two children with severe EM, life thr eatening in one of the cases, this approach was used by the author. On e was given sodium nitroprusside and the other prostaglandin El. The e ffect was documented by the clinical course, the reduction in the use of cooling and by laser Doppler perfusion assessments. Over a period o f 3-5 days, gradually the skin hyperemia became reduced, together with less need for skin cooling. At the end of the week there was no more signs of active EM, the vicious circle was broken. These patients have later been observed several years without further signs of EM or othe r severe disease. EM is a rare condition. It is the authors belief, ho wever, that the condition can serve as a model for the mechanisms of m icrovascular shunting, and also show some of the consequences. I also believe that these mechanisms will be focused in the future approach t o treatment of conditions like septicemia, and complications to diabet es mellitus, severe atherosclerosis and venous leg ulcers.