Immunodeficiencies (overview) D84.9

Disturbance of the immune system leading to a pathological response of the organism when exposed to an immunogenic stimulus.

A distinction is made between primary (congenital) and secondary (acquired) disorders of the immune system's defense function. The term "primary immunodeficiencies" (synonym: PID/immune deficiency syndromes) covers numerous congenital (>300 entities) diseases of the immune system, which are characterized by a passive or irreversible disturbance of the immune function. Primary diseases (PID) are those in which immunodeficiency is congenital, familial and/or inherited.

The PID group is contrasted with diseases and referred to by the generic term "secondary immunodeficiencies" in which the immunodeficiency is acquired. The best-known example of this is AIDS (acquired immune deficiency syndrome).

Immunodeficiencies, primary congenital (Hereditary immunodeficiencies (detailed overview and classification see below. Immunodeficiencies primary, classification):

• Antibody deficiency (D80.9) (50-60% of primary immunodeficiencies).
  • reduction of all Ig isotypes with reduced or absent B cells
    • Agammaglobulinemia congenital type Bruton (D80.0) x-linked inheritance with mutation in Bruton tyrosine kinase gene (Btk gene)
    • Agammaglobulinemia congenital type with autosomal recessive inheritance
    • Reduction of at least 2 Ig isotypes with normal or slightly reduced B lymphocyte counts
    • Immunodeficiency syndrome variables (Common variable Immunodeficiency - CVID- D83.9)
    • Combined IgA and IgG deficiency with normal or slightly increased IgM and normal B lymphocyte counts (D80.5)
    • Isotype and light chain deficiency with normal B lymphocyte counts
      • Isolated IgG subclass deficiency (D80.3)
      • IgA with IgG subclass deficiency (D80.3)
      • Selective IgA deficiency syndrome (D80.2), most common primary immunodeficiency
  • Deficiencies of other Ig isotypes
    • Agammaglobulinemia acquired
• Immunodeficiencies, combined (T and B cell) dysfunction(SCID):10-20% of primary immunodeficiencies. The classification of these immunodeficiency syndromes is initially based predominantly on clinical findings and immunologic abnormalities specific to the disease, including morphologic, functional, and phenotypic studies of the lymphatic system. The possibility of defining the underlying defects at the molecular level increasingly allows a classification according to pathogenetic aspects. For details see below. SCID (OMIM: 304400). S.a. primary T-cellular immunodeficiencies.

Immunodeficiencies secondary (acquired):

The following conditions may indicate a secondary immunodeficiency:

• Bronchial asthma , for example, is associated with an increased frequency of pneumonia.
• Diabetes mellitus or heart disease, obesity, or chronic smoke exposure predispose to increased susceptibility to infection.
• Congenital conditions with increased susceptibility to infection include cystic fibrosis and primary ciliary dyskinesia (Kartagener syndrome (Bush A et al.2007).
• Unusually progressing mycotic or bacterial diseases such as botryomycosis, actinomycosis, infections caused by atypical mycobacteria.
• AIDS: A serious acquired secondary immunodeficiency is AIDS caused by HIV infection.
• Secondary antibody deficiency e.g. due to chronic enteric or renal loss, drug use (e.g. some antiepileptic drugs, antimalarial drugs, immunosuppressants or chemotherapies) or malignancies, especially lymphomas and leukemias can lead to pathological susceptibility to infection. Patients with acquired or functional asplenia show particular susceptibility to infection by encapsulated pathogens.

Primary immunodeficiencies are among the rare diseases, and precise data on the prevalences of the now almost 300 different immunodeficiencies, mostly defined by molecular genetics, are lacking. From data in the USA, the prevalence for a clinically relevant immunodeficiency is estimated to be between 1:1200 and 1:2000.

In the case of hereditary immunodeficiencies, the family history is particularly important. It is important to determine whether unusual infections have occurred, whether a family member died suddenly in early life due to an infection, or whether autoimmune diseases have been diagnosed in the family.

Further clues are provided by possible vaccination complications, inflammation during teething and omphalitis in the newborn. Thus, the healing of the umbilicus is considered one of the first tests for the immune system. If omphalitis occurs when the umbilicus heals or if it falls off very late, this could be a first indication of granulocyte dysfunction.

As an orienting basic diagnosis, a differential blood picture should be taken. be taken. It is important to also record the absolute numbers of the different cell populations. Furthermore: recording of the immunoglobulin levels (IgA, IgM, IgG, IgE). IgE is a sensitive parameter to detect immune dysregulation.

Furthermore, vaccine antibodies are considered very good surrogate markers to further determine the B-cell axis of the humoral immune system. If a primary immunodeficiency is suspected, further diagnostics must be performed.

The following acronyms stand for susceptibility to infection or immune dysregulation.

"ELVIS" (pathological susceptibility to infection).

• Pathogen
• Localization
• Course
• Intensity

"GARFIELD" (immune dysregulation)

• Granulomas
• Autoimmunity
• Recurrent fever
• Fever
• Eczema
• Lymphoproliferation
• Chronic intestinal inflammation