Mucocutaneous lymphonodular syndrome (Kawasaki syndrome): causes, symptoms, diagnosis, treatment

Mucocutaneous lymphonodular syndrome (acute infantile febrile cutaneous-mucosal-glandular syndrome, Kawasaki disease, Kawasaki syndrome) is an acute systemic disease characterized by morphologically predominant lesions of medium and small arteries with the development of destructive-proliferative vasculitis identical to nodular polyarteritis, and clinically by fever, changes in the mucous membranes, skin, lymph nodes, and possible lesions of the coronary and other visceral arteries.

ICD 10 code

M30.3 Mucocutaneous lymphonodular syndrome (Kawasaki disease).

Epidemiology of Kawasaki syndrome

Kawasaki syndrome is more common than other forms of systemic vasculitis. In Japan, Kawasaki syndrome is more common than in other countries - approximately 112 cases of this disease are registered annually per 100,000 children under 5 years of age, in the USA - 10-22, in Germany, Finland, Sweden - 6.2-9, in Italy - 14.7. Seasonality of the disease is also observed (the peak is in November-February and June-August) with some differences by country. Children are mainly affected, aged from 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 aged 20-30 years.

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Causes of Kawasaki syndrome

The presence of seasonal variability and cyclicity of the disease suggests its infectious nature, but to date this assumption has not been confirmed. Many organisms and toxins have been considered as possible causative agents: viruses (Epstein-Barr, retrovirus, parvovirus B19), streptococcus, staphylococcus, candida, rickettsia, spirochetes, bacterial toxins (streptococcus, staphylococcus), and the formation of a superantigen under the influence of a toxin. Issues of racial predisposition are also discussed in connection with a significantly higher incidence in Eastern countries.

Although the etiologic factor has yet to be identified, it is recognized that immune activation may play a major role in the pathogenesis, as confirmed, in particular, by the detection of immune complex deposits in affected tissues and the development of destructive-proliferative vasculitis. It is assumed that in response to the effect of a toxin or infectious agent, activated T cells, monocytes, and macrophages secrete various cytokines that cause clinical manifestations of the disease.

Symptoms of Kawasaki syndrome

Kawasaki syndrome is characterized by cyclical manifestations, the severity of fever, against the background of which symptoms of damage to the mucous membranes, skin, lymph nodes and various systems, primarily the cardiovascular system, develop.

General manifestations

Kawasaki syndrome begins acutely with an increase in body temperature, usually to high values (39 °C and above). The patient is typically excitable, expressed to a greater extent than in other febrile conditions in children. Patients suffer from high temperatures, often they are tormented by pain in small joints and the abdomen. In the absence of treatment, the fever lasts 7-14 days (sometimes up to 36).

Damage to the mucous membranes. Against the background of high fever, conjunctival hyperemia without pronounced exudative manifestations appears within a few days. Bilateral conjunctivitis persists for 1-2 weeks and disappears. From the first days of the disease, dryness, hyperemia and cracks in the lips, hyperemia of the oral mucosa, swelling of the papillae of the tongue, which becomes "raspberry" in the second week, are observed.

Skin lesions. Shortly after the onset or with the onset of fever, a rash of various types appears on the trunk, limbs, and inguinal areas: irregularly shaped erythematous plaques, scarlet fever-like rash, erythema multiforme. Perineal erythema is possible, which turns into desquamation within 48 hours. A few days after the onset of the disease, erythema and/or thickening of the skin of the palms and soles appears, accompanied by severe pain and limited mobility of the fingers and toes. At the same time, hyperemia of the palms and soles, intense erythema, and dense edema of the hands and feet occur. The rash fades in the second week. After 2-3 weeks, periungual lamellar peeling appears, spreading to the fingers, and sometimes to the entire hand or foot.

Lymph node involvement. Characterized by significant enlargement (at least 1.5 cm in diameter) of one or more cervical lymph nodes.

Cardiovascular system damage. Pathological changes in the cardiovascular system occur in almost half of patients. Cardiac changes are clinically manifested by tachycardia, arrhythmia, gallop rhythm, the appearance of heart murmurs; congestive heart failure may develop. The nature and localization of the pathology are determined using instrumental methods. Most often, this 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 positive dynamics as the patient's condition improves and recovers. At the same time, a distinctive feature of this vasculitis is the risk of rapid development of coronary artery aneurysms. Coronary artery aneurysms usually occur within 1 to 4 weeks from the onset of fever, new lesions are rarely recorded after 6 weeks. Unilateral or bilateral coronary artery damage is represented by vessel dilation, mainly the proximal parts of the vessels are affected.

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

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Other manifestations

Half of patients develop joint pain, 40-45% have gastrointestinal and liver damage, and less frequently, signs of kidney and CNS damage develop. Arthralgia or polyarthritis of the small joints of the hands and feet, followed by damage to the knee and ankle joints, appear in the first week of the disease. Gastrointestinal manifestations include hepatomegaly, gallbladder dropsy, diarrhea, and pancreatitis. Rarely, manifestations such as aseptic meningitis, pulmonary infiltrates, and pleural effusion are encountered. These syndromes and symptoms disappear without a trace after 2-3 weeks.

Flow

Kawasaki syndrome is characterized by a cyclical course with alternating three stages: an acute febrile stage lasting 1-2 weeks, a subacute stage of 3-5 weeks, and recovery after 6-10 weeks from 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 of age and in those who had cardiac manifestations at the onset of Kawasaki syndrome.

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Classification of Kawasaki syndrome

A distinction is made between complete and incomplete Kawasaki syndrome.

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Diagnosis of Kawasaki syndrome

To establish a diagnosis of Kawasaki syndrome, 5 of the 6 main criteria must be present, including fever, or 4 main symptoms in combination with coronary aneurysms. With fewer criteria and the presence of signs of heart damage, the condition is classified as incomplete (atypical) Kawasaki syndrome. When assessing symptoms, it is taken into account that the development of these signs cannot be explained by the presence of another disease. The main criteria for Kawasaki disease are:

• increased body temperature for at least 5 days;
• conjunctival hyperemia;
• inflammatory changes in the mucous membrane of the lips and oral cavity;
• palmar and plantar erythema with swelling and subsequent peeling of the skin of the fingers;
• polymorphic rash;
• non-purulent enlargement of the cervical lymph node (more than 1.5 cm in diameter).

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Laboratory diagnostics of Kawasaki syndrome

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

Biochemical blood test. Episodic increase in transaminase activity may be observed; in case of gallbladder hydrops with functional obstruction of the biliary tract, the level of direct bilirubin and urobilinogen may be increased.

Immunological blood test. Characteristically, the content of C-reactive protein is increased.

Urine analysis. Often in the acute phase, slight proteinuria, microhematuria and sterile pyuria are determined.

Lumbar puncture (in meningeal syndrome). The cerebrospinal fluid reveals mononuclear pleocytosis with normal protein and glucose levels.

Instrumental diagnostics of Kawasaki syndrome

ECG. In the acute and subacute stages, one can observe a decrease in the voltage of the R wave, depression of the ST segment, flattening or inversion of the T wave with conduction disturbances - prolongation of the PR or QT intervals.

EchoCG should be performed from the first to second week of Kawasaki syndrome, by the end of the month, and in case of coronary artery disease - every 3 months up to a year and then - once every 6 months. Pericardial effusion, myocardial changes and mitral regurgitation, mainly mild, can be detected.

Coronary angiography reveals not only aneurysms, but also stenosis of any sections of the coronary arteries. It is performed after the patient has recovered during further observation.

Differential diagnosis of Kawasaki syndrome

The clinical picture of Kawasaki syndrome simulates many childhood diseases. Differential diagnostics are carried out with viral infections, toxicosis, scarlet fever, pseudotuberculosis, erythema multiforme, staphylococcal toxicoderma, sepsis, drug disease, the onset of juvenile rheumatoid arthritis, nodular polyarteritis. Diffuse erythema, crusts, petechiae, purpura, the formation of vesicles are not characteristic of Kawasaki syndrome and should raise suspicion of another disease. Taking into account the morphological identity of vascular changes in differential diagnostics, it should be taken into account that in Kawasaki syndrome, unlike nodular polyarteritis, nodules, distal gangrene, arterial hypertension, appendicular arteritis, multiple asymmetric mononeuritis are not found.

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Indications for consultation with other specialists

• Rheumatologist - to diagnose Kawasaki syndrome if the child is hospitalized in an infectious diseases hospital.
• Infectious disease specialist - to rule out an infectious disease if the child is hospitalized in the rheumatology or somatic department.
• Cardiac surgeon - in case of development of coronary artery stenosis, as well as in case of repeated episodes of coronary ischemia, to decide on surgical treatment.

Treatment of Kawasaki syndrome

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

Drug treatment of Kawasaki syndrome

Since the etiology is unknown, therapy is non-specific. It is aimed at modulating the immune response and inhibiting platelet activation to prevent coronary aneurysms. The main treatment method is a combination of acetylsalicylic acid with IVIG; the use 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). A meta-analysis has shown that a single administration of IVIG at a dose of 2 g/kg is more effective in preventing the formation of coronary aneurysms than daily use of 0.4 g/kg for 5 days. The drug should be administered at a rate of no more than 20 drops per minute, the patient should be observed during the infusion and for 1-2 hours after its completion. IVIG is used in combination with acetylsalicylic acid, which is prescribed at a daily dose of 50-80 mg/kg until the elevated body temperature decreases and at a dose of 3-5 mg/kg per day for 6 weeks in the absence of coronary artery damage. In the presence of coronary artery aneurysms, acetylsalicylic acid is prescribed until they disappear (12 months or more). Approximately 10% of patients have resistant or recurrent fever despite IVIG treatment. In this case, a second course of IVIG at a dose of 1 g/kg per day may help, but it is unknown whether it prevents aneurysms. Some patients are resistant to IVIG. They have the highest risk of developing aneurysms and prolonged disease. There are reports that pulse therapy of PS can be used in some patients resistant to IVIG.

Long-term management of patients with aneurysms who have had Kawasaki syndrome should be aimed at preventing coronary heart disease and atherosclerosis (long-term use of acetylsalicylic acid, correction of hyperlipidemia, etc.).

Surgical treatment of Kawasaki syndrome

In the development of coronary artery stenosis, as well as repeated episodes of coronary ischemia (or after myocardial infarction) associated with a coronary artery aneurysm, in individuals who have had Kawasaki syndrome, aortocoronary bypass grafting, angioplasty or stenting are performed.

Prevention of Kawasaki syndrome

Primary prevention has not been developed. Secondary prevention of coronary artery thrombosis is carried out in the case of coronary artery aneurysm.

Prognosis for Kawasaki syndrome

The prognosis is usually favorable. Most patients recover. Recurrent relapses 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 the subacute period - rupture of a coronary aneurysm or acute cardiovascular failure due to coronary thrombosis, in the convalescence period - myocardial infarction. The long-term prognosis of Kawasaki syndrome is still unclear. The dynamics of coronary aneurysms has been tracked in several studies. In almost half of the cases, coronary aneurysms regress within 2 years. However, there are reports of young adults who suffered from myocardial infarction decades after the disease.