Erythromelalgia: causes, symptoms, diagnosis, treatment

Erythromelalgia is a rare disease. The syndrome was first mentioned in 1943, when Graves described paroxysms of sudden pain and heat in the feet. The first description of erythromelalgia as an independent disease was given in 1872 by Weir Mitchell.

Erythromelalgia is a disturbing paroxysmal dilation of the vessels (small arteries) in the legs and arms, less often in the face, ears or knees. It causes acute pain, increased skin temperature and redness.

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

Currently, erythromelalgia is distinguished as an independent disease and as a syndrome in various primary diseases:

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

Secondary erythromelalgia syndrome is somewhat more common and in a mild form can accompany endarteritis, phlebitic conditions, diabetes and many other, mainly vascular diseases, as well as the third phase of Raynaud's disease.

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Causes and pathogenesis of erythromelalgia

Peripheral neuritis was considered a possible cause of the disease, in connection with which impulses from the affected nerve endings were eliminated in some patients by resection of peripheral nerves. A similar erythromelalgic phenomenon was observed in patients with damage to the median nerve. In contrast to the point of view on the peripheral origin of the disease, K. Degio believed that this disease has a central spinal origin. Other researchers shared a similar opinion. According to their ideas, erythromelalgia is based on a 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 of the development of erythromelalgic syndrome in patients with various lesions of the spinal cord.

The phenomenon of erythromelalgia is explained by damage to the centers of the diencephalic (thalamic and subthalamic) region and the region around the third ventricle based on observations of patients with pathology of the corresponding areas of the brain who developed erythromelalgia-like syndrome.

The disease is also associated with damage to various levels of the sympathetic nervous system. The connection between the manifestations of erythromelalgia and Raynaud's disease is emphasized. These assumptions are confirmed by observations of a favorable outcome of the erythromelalgic phenomenon that developed in the picture of the third phase of the Raynaud's phenomenon, which arose after sympathectomy.

Denying the damage of the nervous system in erythromelalgia, some authors considered various changes in the arterial wall as the cause of the disease. A combination of erythromelalgia with Osler-Rendu disease (hereditary hemorrhagic telangiectasia) has been described. It has been shown that other diseases with primary damage to the vascular walls often lead to erythromelalgic attacks. Cases of combined erythromelalgia with polycythemia (Vaquez disease) have been described.

There is also an opinion that erythromelalgia is a vasomotor neurosis and can occur in people with mental disorders. The development of erythromelalgia in children suffering from psychosis has been observed. Some humoral aspects of the theory of erythromelalgia pathogenesis have also developed. The occurrence of the disease is associated with a violation of serotonin metabolism, as indicated by the relief of the patient's condition after taking reserpine and the appearance of erythromelalgic syndrome in serotonin-producing tumors.

The 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 bed, especially through arteriovenous anastomoses. The flow of arterial blood through microscopic arteriovenous connections at the precapillary-venule level is many times more powerful in volume than through 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 by increased blood flow irritates the receptor field, which may explain the burning pain. As a result, physiological impulses from angioreceptors do not arise, vasospastic reactions are inhibited, which is possibly due to damage to sympathetic formations. At the same time, increased sweating occurs in the affected areas, associated with both an increase in temperature and a disruption of sympathetic innervation.

According to these concepts, vasodilation occurs actively, not passively. Cold is a natural stimulant of vasoconstrictors. Therefore, the use of a cold stimulus stops this attack again by actively stimulating vasoconstrictors. Finger plethysmography and nail bed capillaroscopy reveal an increase in blood flow in the affected limb by 20-25%, and when the healthy and affected limbs are cooled, the difference in blood flow becomes even more pronounced. This also indicates increased blood flow through arteriovenous anastomoses. Significantly greater oxygenation of venous blood was found in the affected limb. Blood composition studies often reveal an increase in the content of erythrocytes and hemoglobin.

Pathological anatomical studies of 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 posterior horn and minor changes in the posterior roots. Changes in the cells of the lateral horns of the I-III thoracic segments (thickening of cells, swelling of the capsules, displacement of their nuclei to the periphery) served as the basis for the identification of so-called lateral (vegetative) poliomyelitis.

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Symptoms of Erythromelalgia

Acute pain, localized temperature increase, redness of the legs or arms last from several minutes to several hours. In most patients, symptoms are caused by minor overheating (exposure to a temperature of 29-32 °C) and usually decrease when the limbs are immersed in ice water. Trophic changes do not occur. Symptoms may remain moderate for many years or worsen, leading to disability. Generalized vasomotor dysfunction is often noted, and Raynaud's phenomenon is possible.

The main clinical symptom of primary erythromelalgia is paroxysms of burning pain that worsen in the summer, hot weather, at night from being in a warm bed. At first, the pain occurs only in the evenings and continues all night, later it can last for 24 hours. Usually the big toe or heel is affected, then the pain spreads to the sole, the back of the foot and even the shin. The disease can also affect other parts of the body (earlobe, tip of the nose, etc.). The longer the anamnesis, the larger the affected area. Primary erythromelalgic phenomenon is almost always bilateral, symmetrical, although the process can begin with one limb, then spreading to the other. An objective examination reveals sensory disorders, most often in the form of local areas of hyperesthesia.

The course of erythromelalgia

The course of erythromelalgia is characterized by painful attacks (erythromelalgic crisis), which last from several hours to several days. The excruciating burning pain during an attack is so intense that it can drive the patient to despair. The affected limb sharply turns red, acquires a cyanotic hue, becomes hot to the touch and damp with sweat, in rare cases an urticarial rash appears. In addition, moderate swelling of the affected areas is usually noted, in advanced stages there may be necrosis. In this case, the fingers thicken like a flask, thickening or atrophy of the skin, brittleness and clouding of the nails with disfigurement of the limb appear.

Painful sensations may subside in a horizontal position and when applying cold, so patients try to reduce the pain by taking off shoes and warm clothes or raising their limbs up. And vice versa, when standing and walking, lowering the legs, from heavy shoes, the pain intensifies. An attack of pain can be provoked by reactive hyperemia, which occurs when walking, so even in the initial forms of the disease, patients often have a desire to take off their shoes while walking and go barefoot.

Outside of an attack, the patient does not feel completely healthy, since excruciating pain during an attack is accompanied by pronounced emotional disorders. Erythromelalgia as an idiopathic form is somewhat more often observed in men than in women; mainly young people are affected. In rare cases, a stationary type of the disease course occurs.

The secondary syndrome of erythromelalgia is characterized by a milder course. The intensity of peripheral vascular disorders may vary: from a periodically felt feeling of heat in the extremities with transient hyperesthesia and increased skin temperature to the development of classic erythromelalgic crises. Trophic disorders, as a rule, are not as pronounced as in the primary form of the disease. The course of the erythromelalgic phenomenon depends on the course of the underlying disease.

Diagnosis and differential diagnosis of erythromelalgia

The diagnosis is made clinically. Research is conducted to identify the causes. Since erythromelalgia may precede myeloproliferative disease by several years before its onset, repeat blood tests are prescribed. Differential diagnostics include post-traumatic reflex dystrophies, brachiocephalic syndrome, peripheral neuropathy, causalgia, Fabry disease, and bacterial panniculitis.

Clinical diagnosis of erythromelalgia should be based on the following symptoms: a) complaints of paroxysmal pain; the pain is pulsating, burning, duration of attacks from several minutes or hours to several days, interictal periods from 10-15 minutes to several weeks or more, sometimes with a constant increase in the duration of the attack; dependence of a pain attack on the season, time of day (usually in the evening, at night), ambient temperature, wearing warm shoes, physical exertion, position of the limb. Pain subsides from walking on wet sand, snow, cold compresses with ice, etc.; b) initial localization of pain: in the 1st toe, sole, heel, followed by spreading to the entire foot and further; c) symmetry of the lesion: most often the lower limbs are affected, sometimes all four limbs, less often only the upper limbs, rarely other localizations; d) local changes: local hyperemia, sometimes with edema, hyperhidrosis; The skin color is most often bluish, may have cyanotic spots, sometimes marbled. There are never trophic ulcers. In some cases, hyperkeratosis, lamellar layering of the epidermis with deep cracks, is observed.

When making differential diagnoses between primary and secondary forms of the disease, the following should be taken into account:

• In the secondary form:
  • erythromelalgic crises are not so pronounced;
  • as a rule, the medical history is shorter and the patients are older;
  • unilateral lesions are more common;
  • the pain and area of the lesion are stationary and do not progress over time;
  • It is possible to identify the underlying cause, the treatment of which leads to a significant reduction in the manifestations of erythromelalgia.
• In the primary form:
  • the symptoms are more acute;
  • age is younger, the medical history may be long;
  • over time, the symptoms increase and the area of damage increases;
  • most often the lesion is symmetrical;
  • Even the most thorough clinical examination fails to reveal a disease that could cause the manifestations of erythromelalgia.

There are diseases of the peripheral circulation that manifest themselves in attacks similar to erythromelalgia. To some extent, the clinical picture of erythromelalgia and Raynaud's disease are opposite. In Raynaud's disease, attacks occur in cold weather, and erythromelalgic crises - in hot weather; Raynaud's disease is manifested by vascular spasms, pallor, coldness and numbness of the fingers, erythromelalgia - by active expansion of blood vessels, their overflow with blood, resulting in fever and burning pain in the fingers.

There are also other phenomena accompanied by pathological vasodilation. The mildest of them are erythroses, which are manifested by a tendency to skin reddening. V. M. Bekhterev described acroerythroses - painless reddening of the distal parts of the hands.

The occurrence of pain when walking often serves as a reason for diagnosing endarteritis. It should be taken into account that erythromelalgia is a symmetrical lesion that occurs in young people, while the pulsation of the arteries is preserved and there are no symptoms of intermittent claudication.

Feverish conditions, a significant increase in the temperature of the affected areas of the extremities, as well as changes in the blood picture are not characteristic of this disease. This is how it differs from erysipelas and phlegmon. Erythromelalgia differs from acute limited edema of the Quincke type by sharp pain and reddening of the skin.

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Treatment of erythromelalgia

Treatment involves avoiding overheating, rest, elevating the limbs, and keeping the area cool. In primary erythromelalgia, gabapentin and prostaglandin analogues (eg, misoprostol) may be effective. In secondary erythromelalgia, treatment is directed at the underlying pathology; aspirin may be used if myeloproliferative disease develops.

Treatment of erythromelalgia should be comprehensive, taking into account all etiologic factors and their possible elimination. Even in the primary disease, along with its treatment, the use of vasoconstrictors, vitamin B12, histamine therapy, novocaine administration, prescription of various types of physiotherapy (galvanic collar according to Shcherbak, galvanization of the sympathetic ganglia area, alternation of warm and cold baths, two-chamber baths - sulfide, radon, mud applications on segmental zones, ultraviolet irradiation of paravertebral areas DI, DXII) have not lost their significance, novocaine blockades of nodes DII - DIV are indicated in case of damage to the upper limbs, LI - LII - lower. Acupuncture, deep X-ray therapy on the spinal cord area are quite effective. Patients should wear light shoes, avoid overheating.

In severe cases, surgical intervention is used (periarterial, preganglionic sympathectomy). In the idiopathic form of the disease, accompanied by severe pain syndrome, stereotactic surgery on the basal ganglia gives a significant effect [Kandel E. I., 1988].