Table 2

The European Society for Immunodeficiencies (ESID) clinical guidelines grouping by clinical patterns of presentation (modified from de Vries E17)

PresentationPossible further clues (adapted from 17)Possible immune deficiencyDifferential
Recurrent ENT and airway infection (majority of cases)Bronchiectasis particularly associated with antibody deficiency.18
Single isolated episodes of bacterial rhinosinusitis in children do not require screening for PID.19
Antibody deficiency
Phagocyte deficiency
Wiskott-Aldrich Syndrome
Complement deficiency
Normal child (majority of cases)
Asthma, allergy
Adenoidal hypertrophy
Gastro-oesophageal reflux
Inhaled foreign body
Cystic fibrosis
Ciliary dyskinesias
Failure to thrive from early infancyParticularly when associated with chronic diarrhoea, rash, CandidaT-lymphocyte deficiency (SCID)
Wide variety
Recurrent pyogenic infectionsIncluding granulomatous inflammation and poor wound healing
Invasive Aspergillus or Burkholderia raises possibility of chronic granulomatous disease (CGD)
May be associated with inflammatory bowel disease (CGD)
Neutrophil defectsSkin barrier breach, for example, eczema
Staph aureus carriage, especially if PVL toxin positive
Unusual infections or unusually severe course of infectionsInvasive pneumococcal disease when isolated from CSF or a serotype covered by the vaccine
A single episode of Herpes Simplex Encephalitis in a child should be investigated for innate immune defect (TLR3)20
T-lymphocyte deficiency (SCID)
Wiskott-Aldrich Syndrome
Defects of innate immunity
Secondary immunodeficiency
Malignancy, malnutrition, chronic disease, immunosuppressive disease
Recurrent infections with the same type of pathogenRecurrent episodes meningococci or other encapsulated bacteria or infection with uncommon serotype (W135 or Y in UK).Encapsulated—antibody deficiency or complement deficiency
Candida—T-lymphocyte deficiency
Mycobacteria—macrophage–T-cell interaction problem
Increased exposure
Inadequate first-line treatment or drug resistance
Anatomical defects, for example, recurrent aspiration, blocked Eustachian tube or CSF fistula
Autoimmune or chronic inflammatory diseaseIncreasingly recognised as a feature of PIDCommon variable immunodeficiency (CVID)
Haemophagocytic lymphohistiocytosis (HLH)
Other auto-immune disease
Systemic Lupus erythematosus
Syndrome characteristic combinations of clinical featuresPID is increasingly being diagnosed in more genetically determined diseasesDNA repair defects
Hyper IgE syndrome
Microdeletion 22q11 (DiGeorge)
  • CSF, cerebrospinal fluid; ENT, ear, nose and throat; PIDs, primary immune deficiencies; PVL, Panton-Valentine leukocidin; SCID, severe combined immune deficiency; SLE, systemic Lupus erythematosus.