Otis is a 3yr old boy presenting to the emergency department with fever, and purulent discharge from his left ear. He otherwise looks well, however, his mother mentions this is his third ear infection since he was born, and he always seems to have a cough and a cold. She asks you if there could be a problem with his immune system?
Some children seem to have constant ear, nose or throat infections during childhood. We know that for a small, but important minority of children this may be the presenting feature of a primary immunodeficiency. Let’s look at how these may present, when to think of it, and what to do about it.
Primary immunodeficiency is rare
It’s worth stating from the outset, that the majority of children with recurrent ENT infections will not have a primary immunodeficiency. There is a relatively common phenomenon called “physiological immunodeficiency of infancy”, where-by there is a natural nadir in immunoglobulin levels as maternal immunoglobulin fades, and the child’s own immune system has only just become able to produce immunoglobulin for itself. This is at its lowest between 3-6 months and normally resolves by age 1. However, fully developed protection against encapsulated organisms doesn’t reach maturity until between 2-5 years, and IgA production doesn’t reach adult levels until adolescence. It can be completely normal for young children to suffer 4-11 respiratory infections a year (depending on exposure, e.g. siblings, nursery, etc.)
When should I suspect immunodeficiency?
When considering the characteristics of infections that should trigger suspicion for immunodeficiency, we should be thinking about:
More severe infections than is usual
Combined immunodeficiency disorders (affecting both cellular and humoral immunity), such as severe combined immunodeficiency (SCID), present in the first 3-6 months with severe, life-threatening infection. Unusually aggressive infections should prompt further investigation
Infections with unusual organisms
Infections with certain pathogens can point towards specific diagnoses, including respiratory infections with Pseudomonas aeruginosa (think cystic fibrosis or primary ciliary dyskinesia), oral/oesophageal candidiasis (think HIV or chronic granulomatous disease), upper respiratory infections with Pneumocystis carinii (think HIV or other T cell deficiencies) or recurrent otitis/sinusitis with Neisseria meningitidis (think complement deficiency).
Finally, to a lesser extent:
Frequency of infection
This is the least predictive of immunodeficiency, given the discussion above. Very frequent sinopulmonary infections in younger children with encapsulated bacteria can be the presenting feature of the rare condition X-linked agammaglobulinaemia (XLA: boys who produce no immunoglobulins). In late childhood and adolescence, the same presentation in a milder form may be a sign of combined, variable immunodeficiency (CVID), which is a heterogeneous group of disorders of antibody production.
Other, rare conditions include chronic granulomatous disease (CGD) which may present with deep abscesses of the outer ear or mastoid, or HIV presenting with recurrent otitis media (normally with other associated features)
When to refer
Some general guidelines have been produced by the Jeffrey Modell foundation for when to consider referral for immunodeficiency workup:
- Four of more new ear infections within 1 year
- Two or more serious sinus infections within 1 year
- Two or more months on antibiotics with little effect
- Two or more pneumonias within 1 year
- Failure of an infant to gain weight or grow properly
- Recurrent, deep skin or organ abscesses
- Persistent thrush in the mouth or fungal infection on skin
- Need for intravenous antibiotics to clear infections
- Two or more deep-seated infections including septicaemia
- A family history of primary immunodeficiency
Although having a low specificity, they provide a useful framework when thinking of children with more severe infections than usual.
Should I do some tests?
If considering referral, there are definitely some basic tests are useful to do first (if the child is severely unwell, don’t wait for tests to refer).
Full blood count
This is useful for ANY suspected immunodeficiency. Persistent lymphopaenia in a child <2yrs should prompt screening for SCID.
NB: It can be normal to have transient lymphopaenia or neutropaenia in isolation in young children following a viral illness. Incidental neutropaenia does not need repeat testing if there are no concerns about underlying immunodeficiency.
IgG, IgM and IgA levels are useful to investigate children with recurrent ENT/airway infections.
It is also worth considering an HIV test if symptoms are consistent, but ensure you have a discussion with parents before testing.
If both FBC and immunoglobulins are normal in the setting of recurrent infections, it is perfectly acceptable to wait for 3 -6 months to see if the condition improves before referral.
- Primary immunodeficiencies are rare but important, and ENT infections may be the presenting feature
- The severity of infection and presence of opportunistic pathogens are a much stronger predictor than the frequency of infections
- Basic tests such as FBC and Immunoglobulins should be performed in children prior to/pending referral if they are not severely unwell
- Consider investigation and referral for primary immunodeficiency early in children with severe infections and failure to thrive, or those with family history
Further reading: https://www.entmasterclass.com/ENT_Journal_2019_Interactive.pdf page 9