STEPTRACKERGENERAL PRINCIPLES | IMMUNOLOGY + PATHOLOGY | HIGH-YIELD REVIEW

Phagocyte Defects

When neutrophils can't leave the vessel, fuse their granules, make bleach — or simply aren't there.

FOCUS ON
Each disease blocks one step: exit (LAD), granule fusion (Chédiak-Higashi), respiratory burst (CGD), bleach (MPO deficiency). The organism list and one buzzword usually name the defect: delayed cord separation, giant granules, catalase-positive infections.
DISORDER
DEFECT · INHERITANCE
PRESENTATION
DIAGNOSTIC CLUE
LAD type 1
can't exit vessels
CD18 (β₂ integrin) defect → no firm adhesion · autosomal recessive
Delayed umbilical cord separation (> 30 days), omphalitis, recurrent skin and gum infections without pus, poor wound healing
Marked neutrophilia; ↓ CD18 on flow cytometry
LAD type 2
can't roll
Fucosylation defect → no sialyl Lewis X for selectins · autosomal recessive
Milder infections, intellectual disability, short stature
Bombay (hh) blood group
Chédiak-Higashi
can't fuse granules
LYST mutation → microtubule/trafficking defect → phagolysosome fails · autosomal recessive
Recurrent pyogenic infections (S aureus, strep), partial albinism, peripheral neuropathy, easy bleeding, pancytopenia
Giant granules in neutrophils and platelets
Chronic granulomatous disease
no respiratory burst
NADPH oxidase defect · X-linked (gp91phox) most common; AR forms exist
Recurrent infections and granulomas from catalase-positive organisms: lung, skin, liver abscess, osteomyelitis
Abnormal DHR flow test; NBT stays colorless
MPO deficiency
no HOCl
Myeloperoxidase absent → H₂O₂ not converted to bleach · autosomal recessive
Usually asymptomatic; ↑ Candida infections, especially with diabetes
NBT normal (burst intact)
Hyper-IgE (Job) syndrome
poor recruitment
STAT3 loss → no Th17 → poor neutrophil recruitment · autosomal dominant
"Cold," non-inflamed staph abscesses, eczema, retained primary teeth, coarse face, fractures
Very high IgE, eosinophilia
Congenital / cyclic neutropenia
too few cells
ELANE (neutrophil elastase) mutations most often
Recurrent bacterial and fungal infections, mouth ulcers; cyclic form recurs about every 3 weeks
ANC < 500; serial counts for cycling

Mechanism — where each defect blocks

Exit vesselLAD 1, LAD 2
→
Reach siteHyper-IgE (Th17)
→
Fuse lysosomeChédiak-Higashi
→
Respiratory burstCGD
→
Make HOClMPO deficiency

Why catalase matters in CGD: catalase-negative bacteria leave their own H₂O₂ behind, and the neutrophil uses it. Catalase-positive organisms destroy that H₂O₂, so they survive.

Tests and organisms

TEST
WHAT IT SHOWS
ABNORMAL IN
DHR flow cytometry
Burst oxidizes DHR to fluorescent dye
CGD (↓ fluorescence)
NBT test
Burst turns yellow dye blue
CGD (stays colorless)
CD18 flow
Integrin expression
LAD type 1
Blood smear
Granule morphology
Chédiak-Higashi (giant granules)
Serum IgE
Th2 skew
Hyper-IgE syndrome
CGD organisms (catalase +)
S aureus · Burkholderia cepacia · Serratia · Nocardia · Aspergillus
CGD care
TMP-SMX + itraconazole prophylaxis; IFN-γ; stem cell transplant

How it's tested

COMMON CONFUSIONLAD 1 has a very high blood neutrophil count with no pus at infected sites. The cells exist but can't leave the vessels.
THE TRAP"Nitroblue tetrazolium remains yellow" or "DHR shows no fluorescence" is CGD stated without the name.
YOUR APPROACHUse the organism and one physical clue (cord, albinism, teeth/eczema) to pick the step that failed, then confirm with the matching test.

If you see… think…

Cord still attached at 6 weeks, infections without pus → LAD type 1 (CD18)
Silvery hair, light skin, recurrent staph, neuropathy → Chédiak-Higashi (LYST)
Boy with Aspergillus pneumonia and staph liver abscess → X-linked CGD
Burkholderia cepacia or Serratia infection in a child → CGD
Diabetic with recurrent candidiasis, burst test normal → MPO deficiency
Cold abscesses, eczema, retained baby teeth, IgE in thousands → STAT3 hyper-IgE
Mouth ulcers and fevers every 21 days → cyclic neutropenia (ELANE)
Bombay blood type + recurrent infections → LAD type 2
Prophylaxis for CGD → TMP-SMX, itraconazole, IFN-γ