Immunodeficiency in children

2. Outlines
• Introduction.
• Immunity to infection.
• Types of primary immunodeficiency
• Clinical approach to the child with recurrent
infections.
• History & Examination.
• Investigations.
• Treatment

3. Immunology
• Definition: Study of the immune system, both
in wellness and disease
• - Infectious disease
• - Autoimmune disease
• - Allergic disorder
• - Oncology

6. Immunity to infection
• The different areas of the immune system to
be consider are:-
• Humoral immunity(B-cells and IG production)
• Cell-mediated immunity(T-cells) ;
granulocytes(neutrophils , polymorphs).
• Complement cascade.

7. Microorganism
• Invading organisms can be divided into
intracellular and extracellular.
• Extracellular organisms are mainly bacteria, and
are predominantly cleared by phagocytic
cells,aided by opsonization with
antibody(produced by B-cells) and complement.
• Intracellular organisms such as viruses,
Mycobacterium tuberculosis and listeria, they
are hidden from extracellular defenses, and the
immunological response against these organisms
is predominantly mediated by cellular immunity.

8. INTRODUCTION
• Immunodeficiency is a state in which the immune system’s
ability to fight infectious disease is either compromised or is
completely absent.
• Two Types:-
• Primary Immunodeficiency :Usually congenital, resulting
from genetic defects in some components of the immune
system.
• Secondary (Acquired):as a result of other diseases or
conditions such as:
• DRUGS
• INFECTIONS
• Malnutrition

9. Incidence
• Exact incidence is not known but it is
estimated to be 1:10000

10. Types of primary immunodeficiency
• B- cell (humoral) defects: 50%
• T- cell (cellular immunity) defects (includes
combined T & B cell defects): 30%
• Phagocytic system defects: 15-20%
• Complement defects: 1-2%

11. Classification
T cell disorders B cell defects
-Severe combined immunodeficiency
-Wiskott aldrich syndrome(Xp11)
-Ataxia telengectiasia(11q)
-Digeorge anomaly
-XL agammaglobulinemia
-Common variable immunodeficiency
-Selective IgA deficiency
-AR agammaglobulinemia
-Hyper-IgM syndromes- XL
Phagocyte disorders Complement disorders
-Chronic granulomatous disease
-Leukocyte adhesion defect
-Chediac higashi syndrome
-Myeloperoxidase deficiency
-Cyclic neutropenia (elastase defect)
-C1q deficiency
-Factor I deficiency
-Factor H deficiency
-Factor D deficiency
-Properdin deficiency

13. Major pattern of organism causing
diseases in Immunodeficiency
Immune
Deficiencies
Bacterial
Infection
Viral
Infection
Fungal
Infection
Protozoan
Infection
B cell defects +++ + - +++
T cell disorders
or combined T &
B cell defects
+++ +++ +++ +++
Complement
disorders
+++ - - -
Phagocyte
disorders
+++ - +++

14. Why diagnosis is difficult
Primary immunodeficiency
diseases are not screened for at any
time during life
Most affected do
not have abnormal
physical features
Extensive use of
antibiotics may mask
the classic
presentation.

15. Clinical features which may indicate immune
deficiency
• Three ore more episodes of otitis media in 6 months
or 4 in a year.
• Persistent purulent ear discharge.
• Two or more serious sinus infection within one year.
• Two or more episodes of pneumonia within one year.
• Failure to thrive.
• Recurrent deep skin or organ abscesses.
• Persistent or recurrent candidiasis.
• Two or more deep tissue or sterile site infections:e.g.
pneumonia,meningitis,osteomyelitis,deep abscesses.
• A family history of primary immunodeficiency.

16. Diagnostic approach- history
• Whether patients have a history of risk factors for
infection
• Symptoms and risk factors for secondary
immunodeficiency disorders
• Family history is important

17. Age of presentation
• Onset before age 6 mo suggests a T-cell defect
• Onset between the age of 6 and 12 mo may suggest
combined B- and T-cell defects or a B-cell defect
• Later than 12 mo usually suggests a B-cell defect or
secondary immunodeficiency

18. Characteristic features
Predominant T cell
Early onset (2-6 months) Gram positive and neg
bacteria,
mycobacteria,CMV, EBV,
and fungi –candida
Lungs and GI tract
Predominant B cell
Onset after 5-7 months of
age
Pneumococci, staph,
strepto,enteroviruses,giar
dia
Sinopulmonary, GI
infections
Phagocytic defect
Early onset • Staph, pseudomonas,
• candida, nocardia
Skin abscess, LN
suppuration,oral cavity
infections
Compliment defect
Onset at any age Pneumococci and
neiserria
Meningitis
,arthritis,sepsis

19. Physical examination
Common clinical features
Usually present Recurrent URTI
Severe bacterial infections
Not responding to treatment
Often present Failure to thrive
Recurrent pneumonia
Diarrhoea and malabsorption
Occasionaly seen LN pathy
HS megaly
Recurrent meningitis
Chronic encephalitis

20. Clinical pattern according to age
Infants 0-6 months
Hypocalcemia, unusual facies and ears,
heart disease
DiGeorge anomaly
Delayed umbilical cord detachment,
leukocytosis, recurrent infections
Leukocyte adhesion defect
Persistent thrush, failure to thrive,
pneumonia, diarrhea
Severe combined immunodeficiency
Bloody stools, draining ears, atopic
eczema
Wiskott-Aldrich syndrome
Pneumocystis jiroveci pneumonia,
neutropenia, recurrent infections
X-linked hyper-IgM syndrome

21. Clinical pattern according to age
6 months to 5 years
Severe progressive infectious
mononucleosis
X-linked lymphoproliferative
syndroem
Recurrent staphylococcal infections Hyper-IgE syndrome
Persistent thrush, nail dystrophy,
endocrinopathies
Chronic mucocutaneous candidiasis

22. Clinical pattern according to age
More than 5 years and adults
Progressive dermatomyositis with
chronic enterovirus encephalitis
X-linked agammaglobulinemia
Recurrent neisserial meningitis C6, C7, or C8 deficiency
Sinopulmonary infections,
neurologic deterioration,
telangiectasia
Ataxia-telangiectasia

23. When to do screening labs
• Infections with unusual organisms (e.g.
Aspergillus)
• Infections of unusual severity (e.g. varicella
complicated by pneumonia)
• Infections occurring at unusual sites (e.g. liver
abscess)
• Clinical manifestations of a specific immune
disorder (e.g., DiGeorge anomaly)
• Family history of immunodeficiency
• Recurrent infections

31. Key Points
• High index of suspicions
• Thorough history and complete physical
examination is must
• Begin with screening tests and approperiate
additional testing as required
• Teach patients how to avoid infections ,and
do required preventive measures
• Early diagnosis and prompt treatment could
be life saving

32. References
• Nelsons textbook of pediatrics 19 th ed
• Diagnostic Approach to Primary
Immunodeficiency Disorders; indian
pediatrics,june 2013
• Approach to the Patient With Suspected
Immunodeficiency: Immunodeficiency
Disorders: Merck Manual
• TUTORIALS in Paediatric Differential
Diagnosis.
• www.uptodate.com

33. THANKS FOR YOUR
PATIENCE….