- Definition: defect in neutrophil chemotaxis
- Etiology
- Autosomal Dominant mutation in STAT3 gene.
- Defect leads to deficiency in Th17 cells and impaired production of IL-17.
- Consequence: Impaired neutrophil recruitment (chemotaxis) to sites of infection.
- Th17/Th2 Imbalance:
- Th17 cells normally help regulate and suppress excessive Th2 immune responses.
- STAT3 deficiency prevents Th17 differentiation → loss of inhibition on Th2 cells.
- Result is a compensatory skew towards a Th2-dominant response.
- Cytokine Dysregulation:
- Excess Th2 activity leads to overexpression of specific cytokines:
- ↑ IL-4: Drives B-cells to class switch to IgE.
- ↑ IL-5: Stimulates growth, differentiation, and activation of Eosinophils.
- ↑ IL-13: Contributes to IgE production and allergic inflammation (eczema).
- Clinical features
- Mnemonic: FATED
- Facies: Coarse features (broad nose, deep-set eyes, prominent forehead, doughy skin).
- Abscesses: Recurrent “cold” staphylococcal abscesses (lack heat/warmth due to poor neutrophil influx).
- Failure to recruit neutrophils → lack of inflammatory inflammation (heat/redness).
- Teeth: Retained primary teeth (failure to exfoliate), leading to double rows of teeth.
- STAT3 defect → impaired osteoclast function → inability to resorb primary tooth roots.
- Elevated IgE.
- Dermatologic: Severe eczema (atopic dermatitis).
- Th2 cytokines + ↓ antimicrobial peptides (defensins) → barrier breakdown and chronic S. aureus colonization.
- Recurrent Infections: Sinopulmonary infections (pneumonia) often leading to pneumatocele formation.
- Skeletal: Bone fragility, recurrent fractures, scoliosis/hyperextensibility.
- Diagnosis
- ↑ IgE
- (Variable) eosinophilia
- ↓ IFN γ