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HANDBOOK OF PHYSIOLOGY ^ CIRCULATION II 



vasodilation may be the essential vascular reaction, 

 it alone is not enough to explain the clinical state, 

 since an equivalent degree of vasodilatation may 

 occur in asymptomatic normal subjects in response 

 to warmth or exercise. Thus, he concluded that the 

 essential abnormality was a hypersensitive state of 

 the cutaneous pain fibers to heat or tension (by 

 dilated and engorged vessels), i.e., a "susceptible 

 state" of the skin. Thus, he suggested that a chemical 

 substance liberated into the skin served as the im- 

 mediate stimulus to the nerve endings and supported 

 this by the observation that the pain of the erythro- 

 melalgic skin was prolonged or intensified by arresting 

 the circulation to the part. 



The essential vessels involved in the vasodilatation 

 are not definite, but it seems that all small vessels 

 participate. During a typical attack, the accompany- 

 ing features of vasodilation may be observed. In 

 addition to increased temperature of the skin, there 

 may be increased amplitude of arterial pulsation, 

 throbbing sensations, increased elimination of heat, 

 and increased content of oxygen in the returning 

 venous blood. The affected part assumes a deep, 

 dusky red color. The dusky color of the skin which 

 indicates a low oxygen content of small vessel blood 

 is of interest in light of the high oxygen content of 

 returning venous blood. An explanation offered for 

 this is arteriolar-venous shunting of some of the 

 peripheral flow through open arteriovenous anas- 

 tomoses (91 ). 



Other observations are of interest (3, gi ). If the 

 skin temperature is slightly lower than the critical 

 point, distress may be induced by artificially in- 

 creasing the venous pressure by a proximal constrict- 

 ing blood pressure cuff inflated to a pressure less than 

 arterial pressure or by holding the part below heart 

 level to produce venous congestion. Similarly, 

 symptoms may be lessened if an extremity is elevated 

 even though the skin temperature remains unchanged. 

 In addition, direct pressure on the skin of the in- 

 volved area may cause relief. 



A vasoconstrictor factor has been suspected in 

 some patients during intervals when they are free 

 of the burning distress. This is manifested as local 

 coldness and cyanosis or pallor of the skin during 

 these pain-free periods. Some patients have been 

 reported to suffer from Raynaud's phenomenon when 

 cold and erythromelalgia when warm. 



In diagnosis of erythromelalgia, one must exclude 

 the burning sensations in the extremities of patients 

 who are suffering with peripheral neuritis, occlusive 

 arterial disease, and other states, but who do not 



have erythromelalgia either primary or secondary. 

 In these patients the skin temperature is frequently 

 low (especially in organic vascular disease) or normal, 

 and the intimate relationship of distress to a critical 

 thermal level is not apparent. Further, it should be 

 noted that in organic vascular disease elevation fre- 

 quently accentuates symptoms and causes the in- 

 volved part to assume a pale and waxy color, whereas 

 in erythromelalgia color largely persists on elevation 

 and the symptoms may lie somewhat alleviated. In 

 establishing a diagnosis of erythromelalgia it is es- 

 sential to demonstrate that skin temperature and the 

 distress are related. For this purpose, the patient's 

 reaction and skin temperature are observed while 

 the temperature is raised either by reflex vasodilata- 

 tion or by direct application of heat. 



One other interesting fact bears comment. Acetyl- 

 salicylic acid, in an oral dose of as little as 0.65 g, 

 may produce marked and persistent relief in erythro- 

 melalgia for as long as several days. The mechanism 

 of this response is unexplained, but it may be related 

 to effects on the local release of bradykinin. 



In the pathophysiology of erythromelalgia, al- 

 though the vascular responses to temperature are in 

 part well established, the mechanisms that induce 

 these responses are unknown. Whether the basic 

 defect is in the nervous system or in the blood vessels 

 themselves is not clear. Regardless of the site, the 

 mediators involved need study. Furthermore, it is not 

 known whether or not the disturbance is congenital 

 or acquired. The possible contributions of vasoactive 

 humoral agents and the vasodilator nerves and the 

 mechanisms of their actions are also unknown. It may 

 be worthwhile, however, to direct attention to the 

 renewed interest in vasodepressor polypeptides, in 

 particular bradykinin. Depressor polypeptides have 

 been the subject of a recent review (35) and their 

 possible physiologic functions are covered elsewhere 

 in this volume. Further study might well incriminate 

 bradykinin as an important factor in the patho- 

 physiology of peripheral vascular disease, not only in 

 erythromelalgia, but in numerous other vasodilator 

 reactions. 



Mechanisms in Othc 



n ular Diseases 



In the preceding discussions it was not possible 

 to survey the pathophysiologic mechanisms of many 

 other diseases of the peripheral vascular system. The 

 reader may obtain insight into the scope of the prob- 

 lem by referring to the appendix of this chapter. 



