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Editors

KaarinaHeiskanen
PetriS.Mattila

Recurrent Infections and Immunodeficiencies in Children

Essentials

  • ”Recurrent infections in a child” usually refers to frequent infections of the respiratory tract.
  • A child will normally have 6-10 respiratory tract infections in one year.
  • An overwhelming majority of children suffering from recurrent infections have a normal immune system. The following features are suggestive of a normally functioning immune system:
    • the onset of recurring infections coincides with the child starting to attend a child care facility
    • the infections only affect the respiratory tract
    • the infections are caused by viruses
    • the recovery from individual infections is normal
    • the child's growth and development are normal
    • normal physical status (and chest x-ray, see below)
    • no family history of increased predisposition to infections.

Aetiology of recurrent infections

Related to the child

  • Due to genetic factors, there are differences between children regarding their susceptibility to infections. Boys are more likely to have infections than girls.
  • Some children have dysfunctional problems of the middle ear or the Eustachian tube.
  • Children who have problems with gastro-oesophageal reflux tend to have more frequent infections of both upper and lower respiratory tract.
  • Atopy as such does not predispose to infections, and antimicrobials should not be prescribed to an atopic child with less strict criteria than to any other child. Due to the prolonged cough and rhonchi in a child with airway hyperreactivity, it is easy to misdiagnose such a child as having recurrent infections.
  • Periodic fever syndrome may be the aetiology behind recurrent fever in a child; some cases are hereditary.
  • Congenital immunodeficiencies are rare.

Environmental factors

  • Frequent contact with infections
  • Small children attending a child care facility have 1.5-3 times more infections than children cared for at home.
  • Passive smoking
  • Smoking indoors at home may double the number of infections.

Investigations in recurring cycle of infections

  • In order to obtain a proper overall picture and provide support for the family, the care of a child with recurrent infections should be dedicated to one physician.

History

  • The age of the child at the onset of recurrent infections (compare with the age when started to attend a child care facility)
  • The number and duration of infections (6-10 infections a year with symptoms for 2-4 months may often be considered normal in children aged less than 3 years)
  • The type of infections (deep/severe), the number of antimicrobial courses and/or hospital admissions
  • Recovery from infections (complications?) and health between infections
  • Gastrointestinal and skin symptoms (diarrhoea, eczema, abscesses)
  • Atopic symptoms, signs of respiratory tract obstruction, signs of gastro-oesophageal reflux
  • The child's other illnesses, medication (immunosuppressive)
  • Family history: atopy, asthma, abnormalities in growth, susceptibility to infections, failure to thrive in infancy, deaths through infection
  • Type of day care (size of the group)
  • Passive smoking

Status

  • The consistency of growth and development should be checked (growth charts!).
  • Ear examination with a pneumatic otoscope or a tympanometer (focus of infection)
  • Heart and lung auscultation (focus of infection, also to rule out a heart defect)
  • Abdominal palpation (to rule out organomegaly)
  • The condition of skin, nails, hair, teeth and mucous membranes (hypoplasia, rash, abscesses, chronic thrush)

Primary investigations

  • A child with recurrent infections should have his/her basic blood count with differential white cell count and ESR (during an infection free period) checked once in primary care. If considered necessary, plasma IgG, IgA and IgM (note age-related variation) and HIV antigen and antibodies are examined.
  • The size of the adenoids may be deduced from mouth breathing and snoring. An x-ray is not indicated.
  • An x-ray is not usually needed because little information can be gathered from an isolated chest or sinus x-ray taken during a recovery period, particularly in children aged less than 4 years.
  • An x-ray is warranted during an acute infection if recurring pneumonia is suspected (focus of infection, atelectasis, suspicion of a foreign body or structural anomaly, is the thymic shadow visible?)

Treatment

ENT consultation

  • Indications for consultation
    • Recurrent acute otitis media
    • Glue ear
    • Mouth breathing, snoring and disturbed sleep
    • Persistent rhinitis or cough
  • Tympanostomy should be considered after more than 3 documented episodes of acute otitis media in 6 months, or more than 4 episodes in one year, or if the child has glue ear. Adenoidectomy for Otitis Media in Children
  • Adenoidectomy alone, or in combination with tympanostomy, as the primary intervention does not offer additional benefit as regards the prophylaxis of recurrent acute otitis media.
  • The adenoids of a child grow as a result of common respiratory infections, but usually they do not completely obstruct the nasopharynx.
  • Sometimes the adenoids obstruct the whole nasopharynx causing mouth breathing and snoring. Prolonged mouth breathing may lead to malocclusion of the teeth. Persistent mouth breathing is an indication for adenoidectomy.
  • Defining the size of the adenoids in advance, for example with an x-ray, is not indicated.
  • Adenoidectomy can be considered in the treatment of glue ear, if the glue ear recurs despite tympanostomies.
  • Chronically inflamed adenoids may act as a bacterial reservoir during viral infections, thus increasing the risk of complications of respiratory tract infections.

Indications for special investigations in suspected immunodeficiency

Primary immunodeficiencies

  • Primary immunodeficiency (PID) refers to a congenital disorder of the immune system caused by a genetic alteration. It leads to impaired infection defence and an increased risk of immunological diseases.
  • The prevalence in Finland is > 15/100 000. More than 320 monogenic conditions that manifest as disturbance of the immune defence system are known so far.
  • Isolated immunodeficiencies are rare, but more common than thought due to underdiagnosis.
  • Congenital immunodeficiencies are classified as deficiencies of B cells or T cells, combined T and B cell defects, phagocytic cell defects, and defects in innate immunity.
    • The majority (> 50-80%) are B-cell deficiencies, i.e. deficiencies in the humoral immunity, manifested mainly as hypogammaglobulinaemia (plasma IgG, IgA, IgM < -2 SD).
  • Deficiency or a functional defect of B-cells may predispose the child to recurrent infections caused by extracellular bacteria, particularly to infections by polysaccharide-encapsulated bacteria
    • The aetiologies of hypogammaglobulinaemia include:
      • transient hypogammaglobulinaemia of infancy (1/16 000)
      • common variable immunodeficiency (CVI; 7.7/100 000)
      • X-linked agammaglobulinaemia (XLA; 1/150 000)
      • CSR deficiency (hyper-IgM syndrome, HIGM; 1/150 000).
  • IgG subclass deficiencies, specific inability to form polysaccharide antibodies and certain complement deficiencies also increase the risk of infections caused by polysaccharide encapsulated bacteria.
  • Patients with cell-mediated immunodeficiency, i.e. decreased number or deficient functioning of T-cells, are at an increased risk of infections caused by intracellular pathogens (viruses, Pneumocystis jirovecii, mycobacteria, fungi).
  • If the immunodeficiency is caused by a disturbed co-operation between B-cells and T-cells (CVI and CSR deficiency), the patient will be prone to infections caused by both extracellular and intracellular pathogens.
  • Severe combined immunodeficiency (SCID) is a rare condition affecting both the humoral and cell-mediated immune response. The condition becomes manifest in early infancy and is characterized by failure to thrive, chronic diarrhoea, skin changes and severe or chronic viral, fungal or opportunistic infections. The afore-described clinical picture and/or low absolute lymphocyte count (< 2.0 × 109 /l) and/or weak or absent mitogen responses of lymphocytes in an infant raise the suspicion of severe immunodeficiency that immediately requires further investigations.

Other biochemical abnormalities predisposing to infections

  • Cystic fibrosis Cystic Fibrosis (CF)
    • Exocrine pancreatic insufficiency, lung infections
  • Alfa-1-antitrypsin deficiency
    • PiZZ phenotype (the most severe homozygous type), 1/1 500-2 000
    • The symptoms, which affect the lungs and liver, usually do not become manifest until adulthood
  • Shwachman syndrome
    • Growth failure, neutropenia, thrombocytopenia, eczema, predisposition to infections
  • Cartilage-hair hypoplasia
    • Severe growth retardation, varying immunodeficiency
  • Wegener's granulomatosis
    • Recurrent sinusitis and lung infections
  • Immotile cilia syndrome
    • Sinusitis, lung infections, treatment-resistant asthma

Investigations in suspected immunodeficiency

  • In primary health care, the susceptibility to infections is documented (infection diary), and complete blood count (note particularly neutropenia, lymphopenia) and immunoglobulins (plasma IgA, IgG, IgM, serum IgE; note concentrations < -2 SD of the age-adjusted reference values) are examined. HIV antigen and antibody assay as considered necessary.
  • If immunodeficiency is suspected on the basis of the symptoms and signs listed above (history and/or laboratory findings), the child should be referred to a paediatric unit for further investigations.
  • Suspicion of severe combined immunodeficiency (SCID) is an emergency requiring immediate or urgent assessment.
  • Specialist intervention is needed to decide on individual treatment management which should be based on the child's age at symptom onset, character of the symptoms, the health of body systems, the type of infections and the causative agents.

References

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Evidence Summaries ⬆