Agammaglobulinemia is a hereditary disease in which severe primary immunodeficiency develops (a defect in the body’s immune defense) with a marked decrease in the level of gamma globulins in the blood. The disease usually manifests itself in the first months and years of a child’s life, when repeated bacterial infections begin to develop: otitis, sinusitis, pneumonia, pyoderma, meningitis, sepsis. During examination, serum immunoglobulins and B-cells are practically absent in peripheral blood and bone marrow. Treatment of agammaglobulinemia consists in lifelong replacement therapy
ICD 10
D 80 – Immunodeficiency with predominant deficiency of antibodies
General information
Agammaglobulinemia (hereditary hypogammaglobulinemia, Bruton’s disease) is a congenital defect of humoral immunity caused by mutations in the genome of cells, which leads to insufficient synthesis of B-lymphocytes. As a result, the formation of immunoglobulins of all classes is disrupted, and their content in the blood decreases sharply until complete absence, primary immunodeficiency develops. Low reactivity of the immune system leads to the development of severe repeated purulent-inflammatory diseases of the ENT organs, bronchi and lungs, gastrointestinal tract and meninges. Bruton’s disease occurs exclusively in boys and is observed in about 1-5 people out of a million newborns, regardless of race and ethnic group.
Causes
The X-linked form of hereditary agammaglobulinemia occurs due to damage to one of the genes of the X chromosome (located on Xq21.3-22.2). This gene is responsible for the synthesis of the enzyme tyrosine kinase involved in the formation and differentiation of B cells. As a result of mutations of this gene and blocking the synthesis of Brutonian tyrosine kinase, the formation of humoral immunity is disrupted. In agammaglobulinemia, young forms (pre-B cells) are present in the bone marrow, and their further differentiation and entry into the bloodstream is disrupted.
Accordingly, the production of all classes of immunoglobulins is practically not produced, and the child’s body becomes defenseless when pathogenic bacteria enter (most often streptococci, staphylococci and Pseudomonas aeruginosa). A similar mechanism of disorders is noted in the case of another form of hereditary agammoglobulinemia – linked to the X chromosome and growth hormone deficiency. The autosomal recessive form develops as a result of mutation of several genes (µ-heavy chains, the λ5/14.1 gene, the adaptive protein gene and the IDA signaling molecule gene).
Classification
There are three forms of hereditary agammaglobulinemia:
- X-linked (85% of all cases of congenital hypogammaglobulinemia, only boys suffer)
- autosomal recessive sporadic Swiss type (found in boys and girls)
- X-linked and growth hormone deficiency agammaglobulinemia (extremely rare and only in boys)
Symptoms
Reduced reactivity of humoral immunity in agammaglobulinemia leads to the development of repeated purulent-inflammatory diseases already in the first year of a child’s life (as a rule, after the cessation of breastfeeding – at 6-8 months). At the same time, protective antibodies from the mother no longer enter the child’s body, and their immunoglobulins are not produced. By the age of 3-4, inflammatory processes turn into a chronic form with a tendency to generalization. Purulent infection with agammaglobulinemia can affect various organs and systems.
From the ENT organs, purulent sinusitis, ethmoiditis, otitis are not uncommon, and purulent otitis develops more often in the first year of a child’s life, and sinusitis – in 3-5 years. Of the diseases of the bronchopulmonary system, repeated bronchitis, pneumonia, lung abscesses are observed. Often there is a lesion of the gastrointestinal tract with persistent diarrhea (diarrhea) caused by chronic infectious enterocolitis (the main pathogens are campylobacteria, giardia, rotavirus). Impetigo, microbial eczema, recurrent furunculosis, abscesses and phlegmons are found on the skin.
Eye damage (purulent conjunctivitis), oral cavity (ulcerative stomatitis, gingivitis), musculoskeletal system (osteomyelitis, purulent arthritis) is not uncommon. In general, the clinical picture of agammaglobulinemia is characterized by a combination of common symptoms observed in purulent infection (high body temperature, chills, muscle pain and headache, general weakness, sleep and appetite disorders, etc.) and signs of damage to a particular organ (cough, shortness of breath, difficulty nasal breathing, purulent discharge, diarrhea, etc.).
Complications
Any infectious and somatic disease in a patient with immunodeficiency proceeds heavily, for a long time and is accompanied by complications. Severe course of agammoglobulinemia may be complicated by the development of meningitis, viral encephalomyelitis, post-vaccination paralytic polio, sepsis. Against the background of the disease, the likelihood of developing autoimmune and oncological diseases is increased. The death of patients often comes from infectious and toxic shock.
Diagnostics
During a clinical examination of the patient by an allergist-immunologist, signs of purulent-inflammatory lesions of an organ (tissue) and symptoms confirming reduced reactivity of the immune system are revealed: hypoplasia of the tonsils, a decrease in peripheral lymph nodes. There are also signs of lag in the physical development of the child.
Laboratory blood test reveals a marked decrease in the level of immunoglobulins in the immunogram (IgA and IgM
Differential diagnosis of hereditary agammaglobulinemia is carried out with other primary and secondary immunodeficiency conditions (genetic disorders, HIV and cytomegalovirus infection, congenital rubella and toxoplasmosis, malignant neoplasms and systemic disorders, immunodeficiency due to drug intoxication, etc.).
Treatment
Lifelong replacement therapy with antibody-containing drugs is necessary. Intravenous immunoglobulin is usually used, and in its absence, native plasma from healthy permanent donors is used. With the first diagnosis of agammaglobulinemia, substitution treatment is carried out in saturation mode until the level of IgG immunoglobulin is above 400 mg / dl, after which, in the absence of an active purulent-inflammatory process in organs and tissues, it is possible to proceed to maintenance therapy with the introduction of preventive doses of drugs containing immunoglobulins.
Any episode of bacterial purulent infection, regardless of the localization of the inflammatory process, requires adequate antibacterial therapy, which is performed simultaneously with substitution treatment. More often, with agammaglobulinemia, antibacterial agents from the group of cephalosporins, aminoglycosides, macrolides, as well as penicillin antibiotics are used. The duration of treatment is several times longer than the standard for this disease.
Symptomatic treatment is carried out taking into account the specific lesion of a particular organ (washing the paranasal sinuses with antiseptics, performing vibratory chest massage and postural drainage for bronchitis and pneumonia, etc.).
Forecast
If agammaglobulinemia is detected at an early age before the onset of severe complications, and replacement therapy adequate to the patient’s condition is started in a timely manner, it is possible to maintain a normal lifestyle for many years. However, in most cases, the diagnosis of hereditary disorders of humoral immunity is carried out too late, when irreversible chronic purulent-inflammatory diseases of organs and body systems have already developed. In this case, the prognosis for agammaglobulinemia is unfavorable.
Literature
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