systematic stepwise approach to primary immunodeficiency in children

1. Approach to primary
immunodeficiency in children
Dr.Sachin subhash wagh

2. When to suspect immunodeficiency
Unusual, chronic,or recurrent infections such as:
• >1 systemic bacterial infection( seosis, meningitis)
• >2 serious respiratory or documented bacterial
infection(cellulitis, abscesses,draining otitis
media,pneumonia) within 1 yr
• Serious infection occuring at unusual sites(liver,
brain abscess)
• Infection unusual pathogen
• Infection with common childhood pathogen but
of unusual severity

3. • Family history of early infant death or a
known immunodeficiency disorder
• Additional clues-
FTT with or without chronic diarrhea
Persistent infection after receiving live
vaccine
Chronic oral or coetaneous moniliasis

4. WHY DIAGNOSIS IS DIFFICULT
Extensive use of antibiotics
may mask the classic
presentation
Immunodeficiency diseases
are not screened for at any
time during life
Most affected do not
have abnormal physical
feature

5. CLASSIFICATION OF IMMUNODEFICIENCY
PRIMARY IMMUNODEFICIENCY
• Predominant antibody
defect
• Combined T and B cell
defect
• Other cellular
immunodeficiency
• Complement defect
• Phagocytic defect
• Disease of immune
dysregulation
SECONDARY
IMMUNODEFICIENCY
• Systemic disorders-
diabetes,HIV, Undernutrition
• Immunosuppressive Tt:
cytotoxic chemotherapy ,
bone marrow transplant,
Radiation Therapy,
corticosteroids, etc
• Prolonged serious illness (
critically ill, hospitalized
patients)

6. Predominant T cell def
• Severe combined
immunodeficiency(SCID)
• Omenn syndrome
• Combined immunodeficiency
Predominant B cel def
MOST COMMON PIDs:
• XL
agammaglobulinemia(bruto
n agammaglobulinemia)
• AR agammaglobulinemia
• Common variable
immunodeficiency(CVID)
• Selective IgA deficiency
• Hyper – IgM syndromes
• Ig heavy – chain deletions-
AR
Primary immunodeficiency

7. COMPLEMENT DISORDERS
• C1q , C1r, C2-C9 deficiency
• C1 inhibitor
• Factor I Deficiency
• Factor H deficiency
• Factor D deficiency
• Properdin deficiency
PHAGOCYTE DISORDERS
• Chronic granulomatous
disease
• Leukocyte adhesion defect
• Chediac- Higashi syndrome
• Myeloperoxidase deficiency
• Cyclic neutropenia(elastase
defect)
• Neutrophil G6PD deficiency

8. OTHER CELLULAR IMMUNODEFICIENCY
• Wiskott- Aldrich syndrome
• Ataxia – telengectasia(AT)
• DiGeorge anomaly
• Hyper IgE syndrome (HIGE)

9. Disease of immune dysregulation
• Familial hemophagocytic
lymphohistocystosis(FHLH)
• Autoimmune lymphoproliferative
syndrome(ALPS)

10. PREDOMINAT T CELL DEFECT
AGE AT ONSET SPECEFIC
PATHOGEN
AFFECTED ORGAN SPECIAL FEATURE
Early age
2-6 months
Bacteria- gram +ve
and gram –ve
Mycobacteria
Virus- CMV,
EBV,VARICELLA,
Adenovirus
Fungus- candida ,
pnemocystis
jiroveci
-Extensive
mucocutaneous
candidiasis
-Lungs
-GI
•FAILURE TO THRIVE
•Protracted
diarrhoea
•Post vaccination
desseminated BCG
OR VARICELLA
•Hypocalcemic
tetany in infancy
• graft vs host
disease

11. PREDOMINANT B CELL DEFECT
AGE AT ONSET SPECIFIC
PATHOGEN
AFFECTED ORGAN SPECIAL FEATUREES
After maternal
antibody diminish,
usually after 5- 7
months of age
Bacteria-
pneumococci,
streptococci,
staphylococci.myco
plasma
Virus- enterovirus
parasite-
giardia,cryptosporid
ia
•Recurrent
sinopulmonary
infection
•Chronic GI
symptoms,
malbabsorption
•Arthritis
•Enteroviral
meningoencephaliti
s
• autoimmunity
•Post vaccination
paralytic polio
•Lymphoreticular
malignancy
•Lymphoma
•thymoma

12. PHAGOCYTE DEFECT
Age at onset Specific pathogen Affected organ Specific features
Early onset Bacteria: staph,
pseudomonas,
klebsiella,
salmonella
Fungi: candida,
nocardia,
aspergillus
Skin: abscess,
impetigo, cellulitis,
Lymphnode:
suppurative
addenitis
Oral cavity:
gigngivitis, mouth
ulcer
Prolonged
attachment of
umbilical cord. Poor
wound healing.

13. COMPLEMENT DEFECT
Age at
onset
Specific pathogen Affected organ Special features
Any age Bacteria: Pneumococci,
Neisseria
Infection:
meningitis, arthritis,
septicemia,
recurrent
sinopulmonary
infections
Autoimmune
disorder: SLE,
Vasculitis,
svcleroderma,
dermatomyositis,
glomerulonephritis.

14. APPOROACH TO CHILD WITH
IMMUNODEFICIENCY
• HISTORY(symptoms , age of onset)
• Physical examination
• Investigation
• treatment

15. THE EUROPEAN SOCIETY OF
IMMUNODEFICIENCY
10 WARNING SIGNS FOR SUSPICION OF PID
• 4 or more new ear infections within 1 year
• 2 or more serious sinus infections within 1
year
• 2 or more pneumonias within 1 yr
• 2 or more deep- seated infections including
septicemia

16. • 2 or more months on antibiotics with little effect.
• Failure to gain weight or grow normally
• Recurrent , deep skin or organ abscesses
• Persistent thrush in mouth or fungal infection on
skin
• Need for intravenous antibiotics to clear infection
• A family history of PID

17. OCCASIONALLY PRESENT:
• Lymphadenop[athy
• Hepatosplenomegaly
• Recurrent meningitis
• Pyoderma
• Deep infections: osteomylitis, cellulitis

18. Age at presenatation
New born and young
infant (0-6 months)
In infant and young
children (6 months- 5
years)
In children (>5 years ) and
adults
•SCID
•LAD
•DiGeorge anomaly
•Wiskott Aldrich Syndrome
•X-linked hyper IgM
syndrome.
•CGD
•Hyper IgE syndrome
•Chediak-Higashi undrome
•Chronic mucocutaneous
candidiasis
•X-linlked
lymphopriliferative
syndrome.
•X linkede
agmmaglobulinemia
•Ataxia telangectasia
•Common varialble
immunodeficiency

19. Physical examination
Clinical feature Disorder
Skin
Vitiligo
Alopecia
B- cell defetct
Oculocutaneous albinisim
Spares or hypopigmented hairs
Chediak-Hiogashi syndrome, Griscelli
syndrome.
Eczema Wiskott-Aldrich syndrome, Hyper IgE
syndrome, IgA deficiency
Severe dermatitis, erythrodrma Omenn syndrome.
Recurrent abscess with pulmonary
pneumatocele
Hyper IgE syndrome
Recurrent abscess or celllulitis Hyper IgE syndrome chronic
Granulomatous disease, Leukocyte
adhesion defect.

20. Mouth
Oral ulcer CGD, SCID, Congenital neutopenia
Oral & nail candidiasis T cell defect, SCID
Periodonitis, gigngivitis, stomatitis Neutrophil defect
Extremities
Cluubing nails Chronic lung diseases due to antibody
defect
Arthritis Antibody defect, WAS, hyper IgM
syndrome
Endocrinologic
Hypoparathyroididsm DiGeorge syndrome, mucocutaneous
syndrome.
Growth hormone deficicency X- linked agammaglobulinemia.
Heamtological
Hemolytic anemia B & T cell defect, ALPS
Thrombocytopenia WAS
Neutropenia Hypr IgM syundrome,WAS, CGD

21. Screening immunologic testing in child
with recurrent infection
• CBC with DLC & ESR
Absolute neutrophil count Normal result rule out
Congenital or acquired neutropenia
Leukocyte adhesion defect
Absolute lymphocyte count Normal result rule out T cell defect
Platelet count Normal result rule out WAS
ESR Normal result rule out bacterial or fungal
infection

22. Screening test for T-cell defect
• Absolute lymphocyte count – normal result
rule out T cell defect
• Flow cytometry- to check for naïve T cells
Screening test for B cell defect
• IgA- if normal measure IgM, IgG
Screening test for phagocytic cell disorder
• Absolute neutrophil count
• Respiratory burst assay

23. Treatment
• Primary antibody production(B-Cell) defect:
Antibody for documentation
Regular IVIG (approx 400mg/kg per month)
• Primary T-cell defect: cultured unrelated
thymic tissue transpalnt or stem cell
transplant

24. Take home message
• Require high index of suspicion
• Do screening tests and appropriate additional
testing as required
• Early diagnosis and prompt teratment could
be life saving
• Teach patients how to avoide infections, and
do required preventive measures

25. • THANK YOU