See also
Febrile child
Community acquired pneumonia
Pleural effusion and empyema
Meningitis and encephalitis
Key points
- Primary immunodeficiencies (PIDs) present with a variety of symptoms depending on which part of the immune system is affected
- Careful stepwise investigation in consultation with specialists allows for accurate diagnosis and prompt management
- Most young children with recurrent minor infections do not have a PID
Background
Primary immunodeficiencies:
- Are a diverse group of genetically determined defects that can occur across all parts of the immune system
- Lead to an increased risk of bacterial, fungal and/or viral infections
- In severe PIDs, early diagnosis can prevent complications from infections and allows for curative treatment
Assessment
Early identification relies on a high index of suspicion.
PIDs should be considered in all children with:
- severe infection
- infection with unusual or opportunistic organisms
- recurrent infection - more than expected for age (eg healthy toddlers may have 5-10 minor infections per year, often more if attending childcare)
- recurrent infection at the same site may also be due to an anatomical abnormality (eg meningitis and anatomical defects in the blood-brain-barrier)
PIDs can be categorised into six main types:
|
Type of PID
|
Examples
|
Clinical features
|
|
Antibody deficiency
|
- X-linked agammaglobulinemia (XLA)
- Common variable immunodeficiency (CVID)
- Specific antibody deficiency
|
- Poor growth
- Chronic diarrhoea and/or malabsorption
- Recurrent/severe sinusitis or otitis media
- Meningitis
- Sepsis
|
|
Combined immunodeficiency
|
- Severe combined immunodeficiency (SCID)
- 22q11 deletion (DiGeorge syndrome)
- X-linked Hyper-IgM
- Wiskott-Aldrich syndrome
|
- Poor growth
- Absence of thymus
- Chronic diarrhoea
- Recurrent/severe sinusitis or otitis media
- Severe eczema or nappy rash
- Severe oral candidiasis
- Severe or chronic viral infections eg EBV
- DiGeorge syndrome: Congenital heart disease and/or characteristic facial features
- Ectodermal dysplasia: absence of nails, thin hair, reduced sweating
|
|
Phagocytic cell deficiency
|
- Chronic granulomatous disease (CGD)
- Leukocyte adhesion defect (LAD)
- Chediak Higashi syndrome
- Cyclic neutropenia
|
- Recurrent skin or deep organ abscesses
- Gingivitis
- Osteomyelitis
- Severe or recurrent pneumonia
|
|
Complement deficiency
|
- Hereditary angioedema
- Specific complement deficiency
|
- Meningitis or sepsis due to encapsulated bacteria (Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type B)
- Recurrent angioedema
|
|
Immune dysregulation
|
- Autoimmune lymphoproliferative syndrome (ALPS)
- Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX)
- Autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy (APECED)
- Familial hemophagocytic lymphohistiocytosis (FHL) syndromes
|
- Endocrine disorders
- Chronic diarrhoea
- Lymphadenopathy
|
|
Autoinflammatory disorders
|
- Familial Mediterranean Fever (FMF)
- Chronic Recurrent Multifocal Osteomyelitis (CRMO)
- Inflammatory bowel disease
- Other autoinflammatory disorders
|
- Recurrent fevers
- Inflammatory arthritis or peritonitis
- Rash
- Splenomegaly
|
History
There are a broad range of symptoms and signs of PIDs, including:
- Poor growth (especially
slow to gain weight)
- Persistent lymphopenia (especially lymphocyte count
<1 x 109/L in children <1 yo)
- Chronic diarrhoea
- Four or more middle ear infections within one year
- Two or more serious sinus infections within one year
- Recurrent deep skin or organ abscesses
- Persistent thrush in the mouth, skin or elsewhere after 1 yo
- Inadequate response to antibiotics (two or more months of antibiotics with little effect)
- Repeat hospital admission for intravenous antibiotics
- Invasive pneumococcal or meningococcal disease
- Recurrent, severe or prolonged infections with common pathogens, eg adenovirus
- Family history of immunodeficiency, previous sibling death (unexplained or due to infection), parental consanguinity
Examination
- Persistent lymphadenopathy
- Oral candidiasis
- Gingivitis
- Severe or chronic otitis media or sinusitis
- Skin abscesses
- Digital clubbing
- Severe eczema or eczema-like rashes
- Splenomegaly
- Poor muscle bulk, fat stores or signs of nutritional deficiency
Management
Investigations
First-line investigations include:
- FBE and differential (compare with previous results)
- Blood film (to assess for presence of Howell Jolly bodies)
After specialist consultation, consider:
- Total serum immunoglobulins G/A/M (IgG subclass should not be routinely measured)
- Lymphocyte subsets – CD3/CD4/CD8/CD19/CD16/56
- If SCID is suspected assessment of naïve T cells (CD45RA/RO) is required as CD4/CD8 numbers may be in the normal range
- HIV antibody
- An abdominal ultrasound to confirm presence of a spleen and complement studies (eg CH50) in children with invasive meningococcal or pneumococcal disease
Children aged >2 years presenting with invasive pneumococcal disease (sepsis, meningitis, complicated pneumonia or septic arthritis) with no clear predisposing condition, and all children with recurrent IPD should be investigated for immunodeficiency
Any child with normal first-line investigations but high suspicion of PID should be referred to a paediatric immunologist for evaluation and consideration of second-line testing
Children with suspected PID should not be administered live vaccines (this includes varicella, MMR, rotavirus and BCG vaccine)
Consider consultation with local paediatric team when
- Any child with severe infection or poor response to therapy
- Any child with known or suspected primary immunodeficiency with fever
- Unclear whether investigation and follow-up for suspected PID is required
- Any child suspected of having SCID should be immediately discussed with a paediatric immunologist
Consider transfer when
Child requiring care above the level of comfort of the local hospital
For emergency advice and paediatric or neonatal ICU transfers, see Retrieval Services
Consider discharge when
Child is well, has clear management plan in place and family are aware when to return for review
Parent information
ASCIA immunodeficiencies
Immune deficiencies Foundation Australia
Additional notes
The Australasian Society of Clinical Immunology and Allergy (ASCIA) provides free primary immunodeficiency e-training for health professionals-
https://immunodeficiency.ascia.org.au/
Last updated March 2021