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LeenaKainulainen

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 diagnosed immunodeficiencies.

Aetiology

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.
  • Periodic fever syndrome may be the aetiology behind recurrent fever in a child; some cases are hereditary.
  • Congenital immunodeficiencies are rare, but remember to consider these.

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 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
  • Vaccinations

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, onychomycosis, chronic thrush)
  • Size or possible absence of palatine tonsils
  • Palpation of the lymph node areas

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.
  • In an acute infection, an x-ray is warranted if recurring pneumonia is suspected.

Treatment

ENT consultation

  • Indications for consultation
    • Recurrent acute otitis media
    • Glue ear
    • Mouth breathing, snoring and disturbed sleep
  • 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.

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 incidence of PID is about 1/10 000 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987400/. More than 500 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
  • 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) http://www.orpha.net/en/disease/detail/183660 is a very rare condition. It is an immunological emergency leading to death, unless a stem cell transplantation is performed in time. T cells are absent leading to a low absolute lymphocyte count (< 2.0 × 109 /l) in the infant. Additionally, also B cells and/or NK cells may be absent. Nowadays the disease is screened in newborn babies with TREC (T cell receptor excision circles) test in many countries.

Other biochemical abnormalities predisposing to infections

  • Cystic fibrosis Cystic Fibrosis (CF)
    • Troublesome production of sticky mucus
    • Exocrine pancreatic insufficiency, lung infections
    • CFTR gene mutation
  • Shwachman syndrome http://www.orpha.net/en/disease/detail/811
    • Growth failure, neutropenia, thrombocytopenia, eczema, predisposition to infections
  • Cartilage-hair hypoplasia http://www.orpha.net/en/disease/detail/175
    • Mutation in RMRP gene
    • Severe growth retardation, thin hair, varying immunodeficiency
  • Chronic granulomatous disease http://www.orpha.net/en/disease/detail/379
    • Oxidation disturbance in neutrophils
    • Recurrent bacterial infections (staphylococci, Serratia, Burkholderia), deep abscesses, fungal infections (Aspergillus, Nocardia)
  • Primary ciliary dyskinesia (formerly immotile cilia syndrome)
    • Middle ear infections (otitis media), sinusitis, lung infections, treatment-resistant asthma
    • Bronchiectasis
    • Situs inversus (50%)

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.
  • 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.

Disability benefit

  • A child with recurrent respiratory infections or ear infections may be entitled to disability benefit or other types of social support. Find out about local policies and practices and make the necessary medical certificates.

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