Neutropenia in children

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

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Causes of Neutropenia in Children

The causes of neutropenia are divided into 3 main groups.

• Impaired production of neutrophils in the bone marrow due to defects in progenitor cells and/or microenvironment or impaired migration of neutrophils to the peripheral circulation - mainly hereditary neutropenia and neutropenia syndrome in aplastic anemia.
• Violation of the ratio of circulating cells and the parietal pool, 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 during infections, the impact of other factors.

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

Cyclic neutropenia. A rare (1-2 cases per 1,000,000 population) autosomal recessive inherited disease. Familial variants of cyclic neutropenia have a dominant type of inheritance and debut, as a rule, in the first year of life. Sporadic cases occur at any age.

Cyclic neutropenia is based on a violation of granulopoiesis regulation with a normal, even increased content of colony-stimulating factor during the period of recovery from the crisis. In patients with cyclic neutropenia, a mutation of the neutrophil elastase gene has been described, but in general, the mechanism of development of cyclic neutropenia is heterogeneous.

Chronic genetically determined neutropenia with impaired neutrophil release from the bone marrow (myelocachexia). Autosomal recessive inheritance is assumed. Neutropenia is caused by 2 defects: shortened lifespan of neutrophils, their accelerated apoptosis in the bone marrow and decreased chemotaxis. In addition, the phagocytic activity of granulocytes is reduced. Changes in the myelogram are typical: the bone marrow is normo- or hypercellular, the granulocytic series is increased with a normal ratio of cellular elements and a predominance of mature cells. Hypersegmentation of the nuclei of segmented neutrophils in the bone marrow and vacuolization of the cytoplasm are observed, the number of granules in it is reduced. In the peripheral blood - leuko- and neutropenia in combination with monocytosis and eosinophilia. The pyrogenal test is negative.

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Symptoms of Neutropenia in Children

The clinical picture of neutropenia is determined primarily by the severity of neutropenia, and the course of the disease depends on its cause and form. Mild neutropenia may be asymptomatic or patients may develop frequent acute viral and localized bacterial infections that respond well to standard treatment methods. Moderate forms are characterized by frequent relapses of localized purulent infection and acute respiratory viral infections, recurrent oral infections (stomatitis, gingivitis, periodontosis). 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 and high mortality 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 background of bacterial complications, neutrophilic leukocytosis occurs, which after 2-3 days is replaced by leukopenia.

Diagnosis of neutropenia

Diagnosis of neutropenia is based on the disease history, assessment of family history, clinical picture, hemogram indicators in dynamics. Additional studies that allow diagnosing the etiology and forms of neutropenia include:

• clinical blood test with platelet count 2-3 times a week for 6 months;
• examination of bone marrow puncture in severe and moderate neutropenia; special tests (cultural, cytogenetic, molecular, etc.) are performed as indicated.
• determination of serum immunoglobulin content;
• study of the titer of antigranulocyte antibodies in the patient's blood serum with the determination of antigranulocyte antibodies to the membrane and cytoplasm of neutrophils using monoclonal antibodies - as indicated (typical for virus-associated forms).

General diagnostic criteria for genetically determined neutropenias are aggravated heredity, 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 the cases - with eosinophilia in the peripheral blood. Antigranulocyte antibodies are absent. 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 tests 2-3 times a week for 6 weeks; a myelogram is not required.

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Treatment of neutropenia in children

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

The main method of treating cyclic neutropenia is granulocyte colony-stimulating factor (filgrastim or lenograstim) in a daily dose of 3-5 mcg/kg subcutaneously. The drug is administered 2-3 days before the crisis and continues until blood counts return to normal. Another tactic is continuous treatment with granulocyte colony-stimulating factor daily or every other day 2-3 mcg/kg subcutaneously. This is enough to maintain the neutrophil count above 0.5/mcl, which ensures a satisfactory quality of life for patients. In the event of infections, antibacterial and local therapy is used. The risk of leukemia is not increased.

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