Approach to the child with immune based and allergic disease

1. Approach to the child
with immune based
and/or allergic disease
Khaled Saad, MD

2. Introduction
Recurrent infections is a common
reason for seeking medical advice in
pediatrics.
This may refer to infections that are:
 great in number
 long lasting
 Very severe
 Associated with unusual complications
 Or fail to resolve with standard therapy

3. Theses children can be grouped into 4
categories:
1. The “normal” child
2. The child with atopic disease
3. The child with another chronic
condition
4. The child with immunodeficiency

4. The “normal” child
 50% of children with recurrent infections
 The average child has (+/-) 4-8 respiratory
infections per year
 The mean duration of viral respiratory
symptoms is 8 days (however can extend
beyond two weeks)
 Normal growth and development
 Respond quickly to treatment, with complete
recovery
 Appear healthy between infections
 Physical examination and lab tests are
normal

5. Child with atopic disease
 Account for 30% of children with
recurrent infection
 Increased susceptibility to URTI
 Usually develop coughing and
wheezing following respiratory
infections (reactive airway
disease/asthma)

6.  Respond well to allergy or asthma
medications
 Growth and development are usually
normal
 Characteristic physical findings
 Elevated serum IgE

7. Child with chronic disease
 10% of children with recurrent
infection
 Cystic fibrosis, GERD, CHD, chronic
aspiration, cerebral palsy
 Increased susceptibilty to infection:
◦ Inadequate clearance of secretions
◦ Increased pulmonary blood flow
◦ FB – artificial cardiac valve, VP shunt,
indwelling catheter

8. Child with immunodeficiency
 Account for 10% of children with
recurrent infection
 PID usually affect B cells
 Secondary immune deficiency usually
affects T cells (aging, malnutrition,
drugs)

9. Types of immunity
A – Innate (natural) immunity 
responds to infection regardless of
previous exposure to the agent
Ex: PNL, phagocytic cells, complement
system
B – Acquired (adaptive) immunity 
develops as a result of exposure to
previous immunogens
Ex: T lymphocytes, B lymphocytes, NK
cells

10. Clinical features suggestive of a
primary immunodeficiency:
 Family history of immunodeficiency
 Failure to thrive
 Need for IV antibiotics and or
hospitalization to clear infection
 4 or more ear infections with in one
year
 2 or more episodes of sepsis or
meningitis in a life time
 2 or more months of antibiotic
treatment with little effect

11.  Recurrent or resistant candidiasis
 Serious infections occuring at unusual
sites (brain, liver abscess)
 Infection with opportunistic organisms
 Complications from live vaccines (rota
virus, varicella)
 Non healing wounds
 Granulomas
 Lymphoma in infancy

12. Features suggestive of PID in
neonates
 Hypocalcemia
 Congenital heart defects (conotruncal
anomalies)
 Absence of thymic shadow in CXR
 Delayed umbilical cord detachment
(>30 days)

13. History
 Birth history – maternal illness, drug intake,
length of gestation, birth weight neonatal
problems, umbilical cord detachment
 Feeding history
 Growth and development
 Immunization history – especially live
vaccines (OPV, rota virus vaccines), vaccine
failure
 Previous illnesses, school abscences
 Family history
 Consanguinity (autosomal recessive
immunodeficiencies)

14. Infection history
1. Age of onset
◦ Birth to 6 months – congenital
neutropenias, leukocyte adhesion
defects, severe combined
immunodeficiency (SCID), and complete
DiGeorge syndrome.
◦ 6 months to 2 years – normal child, child
with allergy. Persistent diarrhea, chronic
cough, or failure to thrive suggests cystic
fibrosis, or PID

15. ◦ 2 to 6 years – children developing
infection in this age group may also fit into
any of the 4 categories.
2ry immunodeficiencies resulting from
malignancy, nephrotic syndrome, or
gastrointestinal problems start at this age
◦ 6 – 18 years – it is unusual for recurrent
infections to first present beyond the age
of six

16. Infection history (cont’d)
2. Sites of infection:
 Upper respiratory tract
 Most common site, usually viral
 Chronic purulent nasal discharge and cough
 chronic siusitis
 Chronic or seasonal clear nasal discharge,
congestion, itchy eyes, nocturnal cough 
allergic disease
 Recurrent oral thrush, stomatitis, gingivitis, 
t-cell and phagocytic cell disorder
 Recurrent pharyngitis, or tonsillitis usually not
associated with immunodeficiency

17. Lower respiratory tract
 Recurrent pneumonia is rare in normal children
or children with allergic disease
 Suggest chronic cardiopulmonary disease or
immunodeficiency
 Recurrent pneumonia limited to a particular
anatomic region  local anatomical
abnormality

18. Blood and brain
Bacterial meningitis and sepsis suggest
antibody deficiency or complement defect
Chronic enteroviral encephalomyelitis occurs in
patients with profound antibody deficiency and
commonly follows OPV

19. Other
 Recurrent and or chronic GIT infections
occur in patients with IgA deficiency
 Recurrent UTI is uncommon in
immunodeficiency and suggests
structural abnormality
 Abscesses of the skin, intestine, or LN
suggest phagocytic or antibody
deficiency

20. 3. Isolated organisms
 Recurrent sinopulmunary infections with
encapsulated organisms  B cell
abnormalities
 Pneumocystis carnii is the hallmark of SCID
and other T cell defects
 Enteroviral meningoencephalitis  x-linked
agammaglobulinemia
 Recurrent staph infections 
hyperimmunoglubulin E syndrome
 Severe candidiasis  abnormal t cell
immunity

21. Physical Examination
 General appearance, dysmorphic
features
 Failure to thrive (growth charts)
 Discharging ears, perforated
tympanic membrane suggest
immunodeficiency
 Pallor without anemia, allergic
shiners, conjunctivitis, transverse
nasal crease, clear nasal
discharge, suggest allergy

22.  Mouth ulcers, gingivitis, oral thrush,
poor dentition, suggest
immunodeficiency
 Atopic dermatitis (eczema) suggest
allergic disease.
 Immunodeficiencis associated with
eczema: wiskott-aldrich, hyper IgE,
SCID, omenn syndrome

23.  Diminished or absent tonsils and
cervical lymph nodes in the presence
of recurrent respiratory infections
suggest antibody deficiency
 Absence of lymphoid tissue suggest
SCID or x – linked
agammaglobulinemia
 Adenopathy and HSM can be seen in
IgA deficiency, common variable
immunodeficiency, and HIV infection.

24. Clinical patterns of
immunodeficiency
 Wiskott – aldrich syndrome :
petechiae, easy bleeding, eczema,
chronic draining ears
 Ataxia – telangiectasia: ataxia,
telangiectasia, developmental
delay
 Warts hypogammaglobulinemia
infections myelokathexis (WHIM)
syndrome : extensive warts or
molluscum contagiosum

25.  Hyper IgE syndrome: coarse
features, chronic infected
eczema, deep seated
abscesses
 DiGeorge syndrome: short
stature, CHD, developmental
delay, low set ears,
downturning eyes,
micrognathia
 Chediak Higashi disease:

26. Laboratory Evaluation
Initial tests (screening evaluation) –
should be done for all children with
recurrent infections
Abnormalities of these initial tests may
suggest allergy, immunodeficiency or
a chronic illness, and will need further
investigations
If screening tests are normal, the
patient’s family can be reassured that
a serious disorder has been excluded.

27. General screening tests
Include:
 CBC with differential count
 Electrolytes, glucose, KFT, albumin
 Urine analysis
 ESR
 CRP
 CXR

28.  CBC
◦ With special attention paid to the total
absolute lymphocyte count: lymphopenia
<1500cells/uL in patients over 5 years or
<2500 cells/uL in younger children
◦ Eisinophilia suggests allergy
◦ Thrombocytosis suggests chronic
inflammation

29.  ESR, CRP, appropriate cultures
should be done for evaluation of
infection
 CXR should be done if the child has
chronic cough or other features
suggesting lung problems
it should also be done in newborns
presenting with recurrent infections for
assessment of thymic size

30. Other initial investigations:
 Immunoglobulin levels:
Antibody defeciency is suggested by:
◦ IgG <200 mg/dL
◦ Total Ig (M + G + A) <400 mg/dL
◦ Complete absence of IgM or IgA
An elevated IgE (>100mg/dL) suggests
allergy, eczema, or chronic skin infections
or may be found in hyper IgE syndrome,
phagocytic disorders

31. Intermediate tests for
immunodeficiency
These tests are indicated when the
screening tests are abnormal or the
clinical picture is highly suggestive for
an immunodeficiency.
 Antibody titres: The function of the
antibody system is best assessed by
checking antibody titres to previously
administered vaccines (tetanus,
diphtheria, and hemophilus influenza
type b.

32.  Complement activity- should be
assessed in patients with recurrent
sepsis of neisserial infection. A
normal level of CH50 excludes nearly
all hereditary complement
deficiencies. Levels of individual
complement componenets are
measured of the CH50 is significantly
reduced or zero.

33. Diagnostic tests
Should be done when previous tests
are abnormal or if there is a
convincing history of
immunodeficiency.
 Lymphocyte subset analysis: done by
flow cytometry including CD3 (total T
cells), CD4 (T helper), CD8
(cytotoxic), CD19 or CD20 (B cells)
and CD16/56 (natural killer cells) is
done when B or T cell defect is
suspected

34. Lymphocyte subset analysis
 CD4 is the most valuable reflection of
the cellular immune system
 CD19 (B cell) count <100 cells/uL
suggests hereditary
agammaglobulinemia
 A low CD16/56 count suggests a NK
cell deficiency

35. Vaccine challenge
Vaccine responsiveness is used to
further assess the antibody system.
A killed vaccine that has not been
administered previously is given and
titres are measured before and 6
weeks after vaccination.

36. Other tests
 HIV Testing should be done in any
patient suspected of a T cell deficiency
 Lymphoproliferative Assays these are in
vitro assays used to further assess the
cellular immune system. The ability of
lymphocytes to proliferate to mitogens,
stimulatory monoclonal antibodies, or
allogenic cells indicates intact
lymphocyte activation to nonspecific
stimuli. However, diminished or absent
proliferation indicates derangement in T
cell function

37. Management of the child with
recurrent infection
1. Infections should be promptly
recognized and treated with emperic
antibiotic therapy until appropriate
culture results are available
2. Prophylactic antibiotics may be
administered
3. Live – virus vaccines and live BCG
vaccines must not be administered to
the child

38. 4. Only irradiated, leukocyte - poor,
virus free should be used if blood
transfusion is necessary
5. IVIG should not be administered until
there has been a thorough evaluation
of the childs immune system.
(expensive, side effects)

39. Summary and
Recommendations
 The majority of children who present with
recurrent infections, have increased
exposure, allergy, or an anatomic
problem rather than an
immunodeficiency
 Primary immunodeficiency should be
considered in children who have
recurrent and/or complicated bacterial
infections; persistent oral candidiasis;
infection with opportunistic, unusual, or
"signature" organisms; failure to thrive;
or a family history of immunodeficiency

40.  B cell and combined B and T cell
abnormalities account for nearly three-
fourths of the primary
immunodeficiencies and should be
considered initially. Isolated T cell,
phagocytic, and complement defects
are rare.

41.  Screening tests may include a complete
blood count with differential, chemistry
studies, urinalysis, sedimentation rate or
CRP, appropriate cultures, radiologic
imaging of the infection site,
immunoglobulin levels, antibody titers to
vaccine antigens, and complement
activity.
 Definitive diagnostic testing should be
performed if the initial screening
evaluation is abnormal, and should be
done in consultation with a pediatric
immunologist.