Erythromelalgia: causes, symptoms, diagnosis, treatment

Erythromelalia refers to rare diseases. The first mention of the syndrome refers to 1943, when Graves described the paroxysms of sudden pain and heat in the feet. The first description of erythromelalgia as an independent disease is given in 1872 by Weir Mitchell.

Erythromelalgia is a paroxysmal dilating of the vessels (small arteries) disturbing the patient in the legs and hands, less often on the face, ears or knees. It causes severe pain, an increase in skin temperature and redness.

This rare disease can be primary (cause unknown) or secondary to myeloproliferative diseases (eg, true polycythemia, thrombocythemia), arterial hypertension, venous insufficiency, diabetes mellitus, SLE, RA, scleroderma, gout, spinal cord injury or multiple sclerosis.

At present, erythromelalgia is isolated as an independent disease and as a syndrome in various primary diseases:

1. neurologic - syringomyelia, dorsal arteries, multiple sclerosis, deforming spine diseases, neurovascular manifestations of spinal osteochondrosis, consequences of traumatic injuries;
2. somatic hypertension, myxedema, blood diseases, chronic arterial occlusions;
3. as a result of injuries, frostbite, overheating.

Secondary erythromelalgia syndrome occurs more often and can accompany endarteriitis, phlebitis, diabetes and many others, mainly vascular diseases, as well as the third phase of Raynaud's disease.

[1], [2], [3]

Causes and pathogenesis of erythromelalgia

A possible cause of the disease was considered peripheral neuritis, in connection with which in some patients by resection of the peripheral nerves the impulses from the affected nerve endings were eliminated. Similarity of erythromelagic phenomenon was observed in patients with median nerve damage. In contrast to the point of view about the peripheral origin of the disease, C. Degio believed that this disease has a central spinal origin. A similar opinion was shared by other researchers. According to their ideas, at the heart of erythromelalgia lies the change in the gray matter of the lateral and posterior horns of the spinal cord, accompanied by paralysis of the vasomotor fibers. This was confirmed by observations on the development of erythromelagic syndrome in patients with various spinal cord lesions.

The phenomenon of erythromelalgia is explained by the defeat of the centers of the diencephalic (thalamic and subthalamic) region and the area around the third ventricle on the basis of observation of patients with pathology of the corresponding regions of the brain in which erythromelalgic syndrome developed.

The disease is also associated with the defeat of various levels of the sympathetic nervous system. At the same time, the connection between the manifestations of erythromelalgia and Raynaud's disease is emphasized. These assumptions are confirmed by observations of the successful outcome of the erythromelagic phenomenon, which developed in the picture of the third phase of the Reino phenomenon, which arose after sympathectomy.

Denying the defeat of the nervous system with erythromelalgia, some authors considered the cause of the disease to be various changes in the arterial wall. A combination of erythromelalgia with Osler-Randu disease (hereditary hemorrhagic telangiectasia) is described. It is shown that other diseases with primary lesion of the vascular walls often lead to erythromelalgic attacks. The cases of combined erythromelalgia with polycythemia (Vakez disease) are described.

There is an opinion that erythromelalgia is a vasomotor neurosis and can occur in persons with mental characteristics. The development of erythromelalgia in children suffering from psychosis was observed. There were also some humoral aspects of the theory of the pathogenesis of erythromelalgia. The occurrence of the disease is associated with a violation of serotonin metabolism, as indicated by the relief of patients after taking reserpine and the appearance of erythromelagic syndrome in serotonin-producing tumors.

Primary disease has an independent pathogenesis. It has now been established that the pathophysiological mechanism leading to angiopathic disorders in erythromelalgia is associated with increased blood flow through the microcirculatory pathway, especially through arteriovenous anastomoses. The flow of arterial blood through microscopic arteriovenous connections at the level of precapillary - venules is much more powerful by volume than by capillary tubes. As a result, there is a significant increase in tissue temperature. The skin becomes hot to the touch and red. Arteriovenous anastomoses are richly innervated by sympathetic nerves. Their stretching with a strengthened blood stream irritates the receptor field, which can serve as an explanation for burning pain. As a result, physiological impulses from angioreceptors do not arise, vasospastic reactions appear to be inhibited, which may be due to sympathetic lesions. At the same time, intense sweating occurs in the affected areas, associated with both increased temperature and sympathetic innervation.

According to these ideas, vasodilatation occurs actively, and not passively. Cold is a natural causative agent of vasoconstrictors. Therefore, the use of a cold stimulus will arrest this attack again with active excitation of vasoconstrictors. Conducting finger plethysmography and capillaroscopy of the nail bed reveals an increase in blood flow in the affected limb by 20-25%, and when the healthy and affected limb is cooled, the difference in blood flow becomes even more pronounced. This also indicates increased blood flow through arteriovenous anastomoses. On the affected extremity, a much greater oxygenation of the venous blood was detected. Studies of the composition of the blood often show an increase in the content of erythrocytes, hemoglobin.

Pathoanatomical studies with erythromelalgia are few. Changes were found in the cells of the lateral horns of the thoracic spinal cord, partly in the cells of the base of the horn and slight changes in the posterior roots. Changes in the cells of the lateral horns of I-III thoracic segments (thickening of cells, puffiness of capsules, displacement of their nuclei to the periphery) served as the basis for isolating the so-called lateral (vegetative) poliomyelitis.

[4], [5], [6], [7]

Symptoms of erythromelalgia

Acute pain, local fever, redness of the feet or hands last from several minutes to several hours. In most patients, the symptoms are caused by a slight overheating (temperature effect of 29-32 ° C) and usually decreases when immersed in ice water. Trophic changes do not occur. Symptoms can remain mild for years or worsen, leading to disability. Often noted generalized vasomotor dysfunction, the phenomenon of Raynaud is possible.

The main clinical symptom of primary erythromelalgia are paroxysms of burning pains that are aggravated in the summer, hot weather, at night from being in a warm bed. In the beginning, pain occurs only in the evenings and lasts all night, afterwards it can last for a day. Usually the thumb or heel is affected, then the pain extends to the sole, the rear of the foot and even the shin. The disease can affect other parts of the body (earlobe, tip of the nose, etc.). The longer the anamnesis, the greater the lesion area. The primary erythromelalgic phenomenon is almost always bilateral, symmetrical, although the process can begin with one limb, spreading then to the second one. In an objective study, sensitive disorders are found more often in the form of local areas of hyperesthesia.

The course of erythromelalgia

The course of erythromelalgia is characterized by painful attacks (erythromelagic crisis), which last from several hours to several days. An excruciating burning pain during an attack is so intense that it can bring the patient to despair. The affected limb turns red, acquires a cyanotic shade, becomes hot to the touch and damp from sweat, in rare cases, a urticaria rash appears. In addition, there is usually a moderate swelling of the affected areas, in far-reaching stages there may be necrosis. In this case, the fingers bulb thicken, thicken or atrophy of the skin, fragility and turbidity of the nails with disfigurement of the limb.

Painful sensations can subside in the horizontal position and with the application of cold, so patients try to reduce pain by removing shoes and warm clothes or lifting their limbs upwards. Conversely, when standing and walking, lowering the legs, from heavy shoes, the pain intensifies. A painful attack can be triggered by reactive hyperemia that occurs when walking, so even with the initial forms of the disease, patients often want to walk off their shoes and walk barefoot while walking.

Outside the attack, the patient does not feel completely healthy, as painful pain during the attack is accompanied by severe emotional disorders. Erythromelalgia as an idiopathic form is somewhat more common in men than in women; mostly young people are ill. In rare cases, there is a steady-state type of disease course.

The secondary syndrome of erythromelalgia is characterized by a lighter course. The intensity of peripheral vascular disorders can be different: from a periodically felt feeling of heat in the extremities with transient hyperesthesia and an increase in skin temperature until the development of classical erythromelalgic crises. Trophic disorders, as a rule, are not as pronounced as in the primary form of the disease. The course of erythromelagic phenomenon in this case depends on the course of the underlying disease. 

Diagnosis and differential diagnosis of erythromelalgia

The diagnosis is made clinically. Studies are conducted to identify the causes. Because erythromelalgia may precede myeloproliferative disease a few years before its debut, repeat blood tests are prescribed. Differential diagnosis includes posttraumatic reflex dystrophy, brachiocephalic syndrome, peripheral neuropathy, causalgia, Fabry's disease and bacterial panniculitis.

Clinical diagnosis of erythromelalgia should be based on the following symptoms: a) complaints of paroxysmal pain; the nature of the pain is pulsating, burning, the duration of seizures from several minutes or hours to several days, interictal periods from 10-15 minutes to several weeks and more, sometimes with a constant increase in the duration of the attack; the dependence of the pain attack on the time of the year, the time of day (often in the evening, at night), the surrounding temperature, wearing warm shoes, physical stress, limb position. Stimulation of pain from walking on wet sand, snow, cold lotions with ice, etc .; b) the initial localization of pain: in the first finger, sole, heel, followed by spreading to the entire foot and beyond; c) symmetry of the lesion: the lower limbs are more often affected, sometimes all four limbs, rarely only the upper limbs, rarely other localizations; d) local changes: local hyperemia, sometimes with edema, hyperhidrosis; Skin coloration is most often cyanotic, can be with cyanotic spots, sometimes marble. There are never any trophic ulcers. In some cases hyperkeratosis, lamellar layering of the epidermis with deep cracks is observed.

In the differential diagnosis of primary and secondary forms of the disease, the following should be considered:

• In the secondary form:
  • erythromelalgic crises are not so pronounced;
  • as a rule, the anamnesis of the disease is shorter, and the age of the patients is older;
  • more often there are unilateral defeats;
  • pain and lesion area are stationary and do not progress with time;
  • it is possible to identify the main suffering, the treatment of which leads to a significant decrease in the manifestations of erythromelalgia.
• With the primary form:
  • Symptoms are more acute;
  • age is younger, the history of the disease can be prolonged;
  • with the passage of time the symptomatology grows and the area of the lesion increases;
  • more often symmetrical lesions;
  • with the most thorough clinical examination it is not possible to identify a disease that can cause manifestations of erythromelalgia.

There are diseases of peripheral blood circulation, manifested by attacks similar to erythromelalgia. To a certain extent, the clinical picture of erythromelalgia and Raynaud's disease is opposite. With Raynaud's disease, seizures occur in cold weather, and erythromelalgic crises occur in hot weather; Raynaud's disease is manifested by vascular spasms, paleness, cooling and numbness of the fingers, erythromelalgia - active expansion of blood vessels, overfilling with blood, resulting in fever and burning pain in the fingers.

There are other phenomena accompanied by abnormal vasodilation. The easiest ones are erythrose, which shows a tendency to reddening the skin. VM Bekhterev described acroerythrosis - painless reddening of the distal parts of the hands.

The appearance of pain during walking often serves as an excuse for the diagnosis of endarteritis. It should be borne in mind that erythromelalgia is a symmetrical lesion that occurs in young people, with the pulsation of the arteries being preserved and no symptoms of intermittent claudication.

Febrile conditions, a significant increase in the temperature of the affected limbs, as well as a change in the blood picture are not characteristic for this disease. This is different from erysipelas and phlegmon. With sharp pain and reddening of the skin, erythromelalgia differs from an acute limited edema of the Quincke type.

[8], [9]

Treatment of erythromelalgia

Treatment involves the exclusion of overheating, rest, giving the limbs an elevated position and a cold place. With primary erythromelalgia, gabapentin and prostaglandin analogues (eg, misoprostol) can be effective. With secondary erythromelalgia treatment is directed to the main pathology; it is possible to use acetylsalicylic acid if a myeloproliferative disease develops.

Treatment of erythromelalgia should be comprehensive, taking into account all etiological factors and possible their elimination. Even with the primary disease, along with his treatment, values were not lost, as in the idiopathic form of erythromelalgia, the use of vasoconstrictors, vitamin B12, histamine therapy, the administration of novocain, the appointment of various types of physiotherapy (galvanic collar in the Shcherbak, galvanization of the sympathetic area, alternation of warm and cold baths, two-chamber baths - sulphide, radon, mud applications for segmental zones, ultraviolet irradiation of paravertebral regions of DI, DXII), new kain blocks hells DII nodes - DIV with the defeat of the upper extremities, LI - LII - lower. Sufficiently effective is the use of acupuncture, deep X-ray therapy on the area of the spinal cord. Patients should wear light shoes, avoid overheating.

In severe cases, resort to surgery (periarterial, preganglionic sympathectomy). In the idiopathic form of the disease, accompanied by a marked pain syndrome, a significant effect is produced by a stereotaxic operation on the basal ganglia [Kandel EI, 1988].