Mucous-cutaneous lymphonodular syndrome (Kawasaki syndrome): causes, symptoms, diagnosis, treatment

Mucous-cutaneous lymphonodular syndrome (acute children's feverish cutaneous mucocutaneous glandular syndrome, Kawasaki's disease, Kawasaki syndrome) is an acute systemic disease characterized by a morphologically predominant lesion of the middle and small arteries with the development of destructive-proliferative vasculitis identical to nodular polyarteritis, and clinically - fever, changes in mucous membranes, skin, lymph nodes, possible damage to coronary and other visceral arteries.

ICD Code 10

M30.3 Mucous-cutaneous lymphonodular syndrome (Kawasaki).

Epidemiology of Kawasaki Syndrome

Kawasaki syndrome occurs more often than other forms of systemic vasculitis. In Japan, Kawasaki syndrome is more common than in other countries - about 112 cases of this disease per 100 000 children under 5 years of age, in the USA - 10-22, in Germany, Finland, 6.2-9, in Italy - 14.7. Seasonality of morbidity is also traced (peak is in November-February and June-August) with some difference in countries. Children suffer mainly from the age of several weeks to 5 years; the ratio of boys to girls is 1.5: 1. In recent years there have been reports of isolated cases of Kawasaki syndrome in adults 20-30 years old.

[1], [2], [3]

Causes of Kawasaki Syndrome

The presence of seasonal variability and cyclicity of the disease suggests its infectious nature, but until now to confirm this assumption was not possible. As possible causative agents, many organisms and toxins were considered: viruses (Epstein-Barr, retrovirus, parvovirus B19), streptococcus, staphylococcus, candida, rickettsia, spirochetes, bacterial toxins (streptococcus, staphylococcus), superantigen formation due to toxin. They also discuss the issues of racial predisposition in connection with a significantly higher morbidity in the countries of the East.

Although the etiological factor has yet to be revealed, it is recognized that immune activation can play a big role in pathogenesis, which is confirmed, in particular, by the detection of the deposits of immune complexes in the affected tissues and the development of destructive-proliferative vasculitis. It is suggested that in response to exposure to a toxin or an infectious agent, activated T cells, monocytes and macrophages secrete different cytokines that cause clinical manifestations of the disease.

Symptoms of Kawasaki Syndrome

The syndrome of Kawasaki is characterized by the cyclicity of manifestations, the severity of the fever, against which the symptoms of the defeat of the mucous membranes, skin, lymph nodes and various systems, especially cardiovascular, develop.

Common manifestations

 Kawasaki syndrome begins acutely with an increase in body temperature, usually up to high figures (39 ° C and above). The excitability of the patient is more typical than in other febrile conditions in children. Patients suffer from high fever, they are often hurt by pain in small joints, abdomen. In the absence of treatment, fever lasts 7-14 days (sometimes up to 36).

Lesion of mucous membranes. Against a background of high fever for several days, hyperemia of the conjunctiva appears without pronounced exudative manifestations. Bilateral conjunctivitis persists for 1-2 weeks and disappears. From the first days of the disease, dryness, flushing and cracking of the lips, hyperemia of the oral mucosa, edema of the papillae of the tongue, which in the second week becomes "crimson".

Defeat of the skin. Soon after the debut or with the onset of fever on the trunk, extremities and inguinal areas, there is a rash in various forms: irregular forms of erythematous plaques, scarlet fever, erythema multiforme. Possible erythema of the perineum, which within 48 hours passes into desquamation. A few days after the onset of the disease, there is erythema and / or condensation of the skin of the palms and soles, accompanied by sharp soreness and restriction of the mobility of the fingers and toes. Simultaneously there are hyperemia of the palms and soles, intense erythema and dense edema of the hands and feet. In the second week the rash fades. After 2-3 weeks, perinopleg flake peeling occurs with spreading to the fingers, and sometimes - to the entire brush or foot.

Lymph node involvement. A significant increase (not less than 1.5 cm in diameter) of one or more cervical lymph nodes is characteristic.

Defeat of the cardiovascular system. Pathological changes in the cardiovascular system occur in almost half of the patients. Cardiac changes are clinically manifested by tachycardia, arrhythmia, gallop rhythm, the appearance of cardiac murmurs; can develop congestive heart failure. The nature and localization of pathology is determined using instrumental methods. More often it is pericardial effusion, myocardial changes and mitral regurgitation. Changes in the membranes of the heart accompany the acute phase of the disease and usually have a positive dynamics with the improvement of the patient's condition and recovery. At the same time, the distinctive feature of this vasculitis is the risk of rapid development of coronary artery aneurysms. Aneurysms of the coronary arteries usually occur within a period of 1 to 4 weeks from the onset of fever, new lesions can rarely be detected after 6 weeks. One- or two-sided lesions of the coronary arteries are represented by the dilatation of the vessel, mainly the proximal parts of the vessels are affected.

In addition to coronary arteries, other vessels may be involved, including the abdominal aorta, the superior mesenteric, axillary, subclavian, brachial, iliac and renal arteries with distal ischemia and necrosis as a result of active vasculitis.

[4], [5], [6], [7], [8], [9]

Other manifestations

Half of the patients have joint pain, 40-45% have gastrointestinal and liver damage, and the signs of kidney damage and CNS are less common. Arthralgia or polyarthritis of small joints of hands and feet, with subsequent damage to the knee and ankle joints appear in the first week of the disease. Gastrointestinal manifestations include hepatomegaly, gall bladder edema, diarrhea and pancreatitis. Seldom occur such manifestations as aseptic meningitis, pulmonary infiltrates and pleural effusion. These syndromes and symptoms pass without a trace in 2-3 weeks.

Flow

Kawasaki syndrome differs cyclic course with alternation of three stages: acute febrile stage lasting 1-2 weeks, subacute stage - 3-5 weeks, recovery - 6-10 weeks after the onset of the disease. In some cases (3%), relapses are possible, which usually develop within 12 months, more often in children under 3 years old and in those who have had cardiac manifestations in the onset of Kawasaki syndrome.

[10], [11], [12], [13], [14], [15]

Classification of Kawasaki syndrome

There is a complete and incomplete Kawasaki syndrome.

[16], [17], [18], [19], [20], [21], [22]

Diagnosis of Kawasaki Syndrome

To establish the diagnosis of Kawasaki syndrome, 5 of the 6 main criteria, including including fever, or 4 main symptoms in combination with coronary aneurysms, should be present. With fewer criteria and signs of heart disease, the condition is classified as incomplete (atypical) Kawasaki syndrome. When assessing the symptoms, it is considered that the development of these symptoms can not be explained by the presence of another disease. Key criteria for Kawasaki disease:

• increase in body temperature for at least 5 days;
• hyperemia of the conjunctiva;
• inflammatory changes in the mucous membrane of the lips and oral cavity;
• palmar and plantar erythema with edema and subsequent peeling of the skin of the fingers;
• polymorphic rash;
• a nasal enlargement of the cervical lymph node (more than 1.5 cm in diameter).

[23], [24], [25], [26], [27], [28]

Laboratory Diagnosis of Kawasaki Syndrome

General blood analysis. In the early stages of the disease, leukocytosis is detected, a significant increase in ESR, often normochromic anemia and thrombocytosis. In the subacute stage of the disease, the number of platelets increases and often reaches 1000x10 ⁹ / l or more at week 3 of the disease.

Blood chemistry. An episodic increase in the activity of transaminases may be noted, with a drop of the gallbladder with functional obstruction of the biliary tract, the level of direct bilirubin and urobilinogen may be increased.

Immunological analysis of blood. Characteristically, an increase in the content of C-reactive protein.

Analysis of urine. Often in the acute phase, a small proteinuria, a microhematuria and a sterile pyuria are detected.

Lumbar puncture (with meningeal syndrome). In the cerebrospinal fluid, mononuclear pleocytosis is detected with normal protein and glucose content.

Instrumental Diagnosis of Kawasaki Syndrome

ECG. In acute and subacute stages, a decrease in the voltage of the R wave, ST segment depression, flattening or inversion of the T wave in conduction disturbance, prolongation of the PR or QT intervals can be observed.

Echocardiography should be performed from the first or second week of Kawasaki syndrome, by the end of the month and in case of coronary artery disease - every 3 months to one year and then - once every 6 months. Pericardial effusions, changes in the myocardium and mitral regurgitation can be detected, mostly of mild degree.

Coronary angiography reveals not only aneurysms, but also stenoses of any parts of the coronary arteries. It is carried out after recovery of the patient with further observation.

Differential Diagnosis of Kawasaki Syndrome

The clinical picture of Kawasaki syndrome simulates many childhood diseases. Differential diagnosis is carried out with viral infections, toxicosis, with scarlet fever, pseudotuberculosis, erythema multiforme, staphylococcal toxicosis, sepsis, drug disease, debut of juvenile rheumatoid arthritis, nodular polyarteritis. Diffuse erythema, crusts, petechiae, purpura, the formation of vesicles are not characteristic of Kawasaki syndrome and should cause suspicion of another disease. Given the morphological identity of vascular changes in differential diagnosis, it should be borne in mind that in Kawasaki syndrome unlike nodular polyarteritis there are no nodules, distal gangrene, arterial hypertension, appendicular arteritis, multiple asymmetric mononeuritis.

[29], [30], [31], [32], [33], [34], [35]

Indications for consultation of other specialists

• Rheumatologist - for the diagnosis of Kawasaki syndrome, if the child is hospitalized in an infectious hospital.
• Infectionist - to exclude an infectious disease, if the child is hospitalized in a rheumatological or somatic department.
• Cardiosurgeon - in case of development of stenosis of the coronary artery, as well as with repeated episodes of coronary ischemia to address the issue of surgical treatment.

Treatment of Kawasaki Syndrome

Indications for hospitalization are debut, relapse of the disease, myocardial infarction, the need for coronary angiography in a child, the need for surgical intervention on the coronary arteries, an examination to determine the protocol of treatment during remission.

Medical treatment of Kawasaki syndrome

Since the etiology is unknown, the therapy has a nonspecific character. It is aimed at modulating the immune response and inhibiting the activation of platelets to prevent coronary aneurysms. The main method of treatment is the combination of acetylsalicylic acid with IVIG; application of the latter reduces the risk of coronary artery damage from 25 to 5% or less.

IVIG is used in a course dose of 2 g / kg (preferably in the first 10 days of the disease). In the carried out metanalysis it was proved that the introduction of IVIG at a dose of 2 g / kg once more effectively prevents the formation of coronary aneurysms than the daily use of 0.4 g / kg for 5 days. The drug should be administered at a rate of not more than 20 drops per minute, monitor the patient during infusion and 1-2 hours after its termination. IVIG is used in combination with acetylsalicylic acid, which is prescribed in a daily dose of 50-80 mg / kg to reduce the elevated body temperature and at a dose of 3-5 mg / kg per day for 6 weeks in the absence of coronary artery disease. In the presence of coronary artery aneurysms, acetylsalicylic acid is prescribed until they disappear (12 months or more). Approximately 10% of patients, despite IVIG treatment, have a resistant or repeated fever. In this case, a repeated course of IVIG at a dose of 1 g / kg per day may help, but it is not known whether it prevents aneurysms. Some patients are resistant to IVIG. They have the greatest risk of aneurysms and a prolonged course of the disease. There are reports that in some patients resistant to IVIG, the use of PS-pulse therapy is possible.

Long-term management of patients suffering from Kawasaki syndrome with aneurysms should be aimed at the prevention of coronary heart disease and atherosclerosis (long-term intake of acetylsalicylic acid, correction of hyperlipidemia, etc.).

Surgical treatment of Kawasaki syndrome

With the development of coronary artery stenosis, as well as repeated episodes of coronary ischemia (or after myocardial infarction) associated with an aneurysm of the coronary artery, patients undergoing Kawasaki syndrome undergo coronary artery bypass grafting, angioplasty, or stenting.

Prevention of Kawasaki Syndrome

Primary prevention is not developed. Secondary prophylaxis of coronary artery thrombosis is performed in the presence of an aneurysm of the coronary arteries.

Prognosis for Kawasaki syndrome

The forecast is more often favorable. Most patients recover. Repeated recurrences of Kawasaki syndrome are rare and their risk is higher in the first 12 months after the first episode of the disease. Mortality is 0.1-0.5%. The immediate cause of death in the acute period of the disease is myocarditis or arrhythmia, in subacute - a rupture of coronary aneurysm or acute cardiovascular insufficiency as a result of coronary thrombosis, in the period of convalescence - myocardial infarction. A distant prognosis of Kawasaki syndrome is still not clear. The dynamics of coronary aneurysms has been traced in several studies. In almost half the cases, coronary aneurysms regress within 2 years. However, there are reports of young adults affected by myocardial infarction decades after the disease.