Neutropenia in children

Neutropenia occurs as a syndrome or is diagnosed as a primary disease of neutrophilic leukocytes and / or their precursors. The criterion of neutropenia in children older than one year and adults is the decrease in the absolute number of neutrophils (stab and segmented) in peripheral blood to 1.5 thousand in 1 μl of blood and lower, in children of the first year of life - up to 1 thousand in 1 μl and lower.

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Causes of neutropenia in children

The causes of neutropenia are divided into 3 main groups.

• Violation of the production of neutrophils in the bone marrow due to defects in precursor cells and / or microenvironment or disturbance of neutrophil migration to the peripheral channel - mainly hereditary neutropenia and neutropenia syndrome in aplastic anemia.
• Violation of the ratio of circulating cells and parietal pool, the accumulation of neutrophils in the foci of inflammation - redistribution mechanism.
• Destruction in the peripheral bloodstream and in various organs by phagocytes - immune neutropenia and hemophagocytic syndromes, sequestration in infections, the impact of other factors.

Combinations of the above-mentioned etiological factors are possible. Neutropenia syndromes are characteristic for many blood diseases [acute leukemia, aplastic anemia, myelodysplastic syndrome], connective tissue, primary immunodeficiency states, viral and some bacterial infections.

Cyclic neutropenia. A rare (1-2 cases per 1,000,000 population) is an autosomal recessively inherited disease. Family variants of cyclic neutropenia have a dominant type of inheritance and debut, as a rule, in the first year of life. Meet sporadic cases at any age.

At the heart of cyclic neutropenia is a disruption in the regulation of granulopoiesis with a normal, even elevated, colony-stimulating factor in the period of emergence from the crisis. In patients with cyclic neutropenia, a mutation of the neutrophil elastase gene is described, but in general the mechanism of cyclic neutropenia development is heterogeneous.

Chronic genetically determined neutropenia with impaired neutrophil output from the bone marrow (myelocaecia). An autosomal recessive type of inheritance is assumed. Neutropenia is caused by 2 defects: a shortened life of neutrophils, their accelerated apoptosis in the bone marrow and a decrease in chemotaxis. In addition, the phagocytic activity of granulocytes is reduced. Typical changes in the myelogram: bone marrow normo- or hypercellular, increased granulocyte series with a normal ratio of cellular elements and the predominance of mature cells. There is a hypersegmentation of the nuclei of segmented neutrophils of the bone marrow and vacuolization of the cytoplasm, the number of granules in it is reduced. In peripheral blood - leuko- and neutropenia in combination with monocytosis and eosinophilia. The pyrogenic test is negative.

[2], [3], [4],

Symptoms of neutropenia in children

The clinical picture of neutropenia is caused, first of all, by the severity of neutropenia, and the course of the disease depends on its cause and form. Light neutropenia can occur asymptomatically or in patients there are frequent acute viral and localized bacterial infections that respond well to standard methods of treatment. Moderately severe forms are characterized by frequent relapses of localized purulent infection and acute respiratory infections, recurrent oral infections (stomatitis, gingivitis, periodontitis). There may be an asymptomatic course, but with agranulocytosis. Severe neutropenia is characterized by a general severe condition with intoxication, fever, frequent severe bacterial and fungal infections, necrotic lesions of the mucous membranes, less often the skin, destructive pneumonia, a high risk of sepsis development and high lethality with inadequate treatment.

Clinical symptoms of chronic genetically determined neutropenia - recurrent localized bacterial infections, including pneumonia, recurrent stomatitis, gingivitis, - appear in the first year of life. Against the backdrop of bacterial complications, there is neutrophilic leukocytosis, which after 2-3 days is replaced by leukopenia.

Diagnosis of neutropenia

Diagnosis of neutropenia is based on the history of the disease, evaluation of the family history, clinical picture, hemogram indices in the dynamics. Additional studies to diagnose the etiology and forms of neutropenia include:

• the clinical analysis of blood with calculation of the number of thrombocytes 2-3 times per week for 6 months;
• examination of bone marrow puncture in severe and moderate neutropenia; according to the indications, special tests are carried out (culture, cytogenetic, molecular, etc.).
• determination of serum immunoglobulin content;
• study of the titer of anti-granulocyte antibodies in the patient's serum with the determination of anti-granulocyte antibodies to the membrane and neutrophil cytoplasm using monoclonal antibodies - according to indications (typical for virus-associated forms).

General diagnostic criteria for genetically determined neutropenia is a hereditary burden, a manifest clinical picture from the first months of life, constant or cyclic neutropenia (0.2-1.0x10 ⁹ / L neutrophils) in combination with monocytosis and in half of cases with eosinophilia in peripheral blood. There are no anti-granulocyte antibodies. Changes in the myelogram are determined by the form of the disease. Molecular biological methods can reveal a genetic defect.

The diagnosis of cyclic neutropenia is documented by blood test results 2-3 times per week for 6 weeks, the myelogram study is not required.

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

Treatment of neutropenia in children

For patients with an absolute neutrophil count of <500 / μL and fever, regardless of the suspected cause of neutropenia, immediately begin empirical antibiotic treatment that is effective against pathogens that most often cause infections in these patients (including chemotherapy, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp.). Further tactics are determined by the nature and course of neutropenia.

The main method of treatment of cyclic neutropenia is a granulocyte colony-stimulating factor (filgrastim or lenograstim) in a daily dose of 3-5 μg / kg subcutaneously. The administration of the drug is started 2-3 days before the crisis and continues until the blood values are normalized. Another tactic is the continuous treatment with granulocyte colony-stimulating factor daily or every other day 2-3 μg / kg subcutaneously. This is sufficient to maintain the number of neutrophils more than 0.5 / μl, which ensures a satisfactory quality of life for patients. At development of infections - antibacterial and local therapy. The risk of leukemia is not elevated.

Active treatment of chronic genetically determined neutropenia is carried out during an acute bacterial infection with the use of broad-spectrum antibiotics. In severe cases, a granulocyte colony-stimulating factor is prescribed, and donor granulocytes are transfused.