The European Society for Immunodeficiencies (ESID) clinical guidelines grouping by clinical patterns of presentation (modified from de Vries E17)
| Presentation | Possible further clues (adapted from 17) | Possible immune deficiency | Differential |
|---|---|---|---|
| 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 HIV 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 infancy | Particularly when associated with chronic diarrhoea, rash, Candida | T-lymphocyte deficiency (SCID) HIV | Wide variety |
| Recurrent pyogenic infections | Including 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 defects | Skin barrier breach, for example, eczema Staph aureus carriage, especially if PVL toxin positive Neutropenia Malignancy |
| Unusual infections or unusually severe course of infections | Invasive 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) HIV Wiskott-Aldrich Syndrome Defects of innate immunity | Secondary immunodeficiency Malignancy, malnutrition, chronic disease, immunosuppressive disease |
| Recurrent infections with the same type of pathogen | Recurrent 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 disease | Increasingly recognised as a feature of PID | Common variable immunodeficiency (CVID) Haemophagocytic lymphohistiocytosis (HLH) | Other auto-immune disease Systemic Lupus erythematosus |
| Syndrome characteristic combinations of clinical features | PID is increasingly being diagnosed in more genetically determined diseases | DNA 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.