37
Figure 5. Diagnosis of Innate Immune Defects
• 5.1 – A defect of innate immunity is suspected according to one of the
characteristic clinical presentations (Table 1).
• 5.2 – The presentation is principally one of severe recurrent infections of all classes
of pathogens together with ectodermal dysplasia, severe Gram-positive bacterial
infections, or other clinical features suggestive of NF-kB pathway or multiple TLR
signaling defects.
• 5.3 – In the case of 5.2, is TLR function abnormal?
• 5.4 – If yes, consider defects of NF-κB signaling, anhidrotic ectodermal dysplasia
with immunodeficiency, or IRAK-4. If no, go to 5.10.
• 5.5 – The presentation is consistent with HSE.
• 5.6 – In the case of 5.5, pursue a molecular diagnosis, if possible. There are no
routinely available tests of TLR3 function that are informative in this setting.
• 5.7 – If the diagnosis of HSE or CMCC is established, manage as indicated for each
disorder. If not, go to 5.10.
• 5.8 – The presentation is consistent with CMCC.
• 5.9 – In the case of 5.8, pursue a molecular diagnosis, if possible. There are no
routinely available clinical tests that will be informative in this setting. If the
diagnosis is confirmed, proceed as in 5.7. If not, go to 5.10.
• 5.10 – If TLR function is normal or HSE or CMCC diagnoses are not confirmed,
consider the possibility of a CID or primary immunodeficiency syndrome (Figure 2)
or phagocytic cell defect (Figure 4). A syndrome of immune dysregulation can also
be considered (Figure 3). Also consider a cytokine autoantibody (Table 11 and SSs
236 and 237).
5.6
Presentation
consistent with
HSE?
5.9
Presentation
consistent with
CMCC?
5.10
Diagnosis
of CMCC
established?
5.4
Consider EDA-
ID or IRAK4
defect
5.5 Consider
other diagnosis
5.8 Manage as
indicated
YES
YES
NO
5.2
Presentation
consistent with multi-
TLR signaling
defect?
NO
NO YES
YES
NO
NO
YES
NO
5.3 Defective
TLR function?
YES
5.7 Diagnosis
of HSE
established?
5.1 Suspected
innate immune
defect
Defects of Innate Immunity
