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MBBS IV - Junior Clerkship WCS > JC118 (Paediatrics) - Immunodeficiency in children > Flashcards

JC118 (Paediatrics) - Immunodeficiency in children Flashcards

1
Q

Features suggestive of allergy instead of infection

A

 Symptoms (e.g. runny nose, cough) without the presence of fever
 Seasonal/ exposure pattern
 Poor response to antibiotics
 Good response to antihistamine/ bronchodilators
 Prior history of eczema/ food allergy/ other allergic symptoms
 Positive family history of allergy

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2
Q

Outline the causes of immunodeficiency in children **

A
  1. Non-immunologic defects
    - Obstruction to flow
    - Damaged barrier
    - Foreign bodies infection
  2. Primary immunodeficiencies: main groups:
    - Antibody deficiency
    - Cellular deficiencies
    - Combined immunodeficiencies
    - Phagocytic defect
    - Complement deficiencies
  3. Secondary immunodeficiencies
    - Iatrogenic immunosuppressants/ drugs
    - Malignancies
    - Malnutrition (zinc)
    - HIV/AIDS
    - DM
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3
Q

All causes of Non-immunologic defects and associated infections in children

A

Obstruction to flow:

  • Bronchial obstruction (congenital) - recurrent pneumonia of same lobe
  • Eustachian tube obstruction - Recurrent otitis media
  • Urinary tract obstruction - Recurrent UTI

Damaged barriers:

  • Burns, sinus tracts, open fractures - localized pyogenic infection
  • Mid-line defects (e.g. neural tube), middle ear defects (continued with CNS) - Recurrent meningitis
  • Primary ciliary dyskinesia (clears bronchi) - Bronchiectasis, situs inversus

Foreign bodies
- Ventriculoperitoneal shunts, prosthetic valves, central lines - recurrent infection

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4
Q

Most common types of primary immunodeficiency in children

Less common types of PID

A 
Most common:
• B cell deficiency (antibody) (65%)
• T cell deficiency (5%)
• Combined B and T cell deficiency (15%)
• Phagocytic deficiency (10%)
• Complement/ Other innate deficiency (5%)

Less common:
 Combined immunodeficiencies with associated/ syndromic features (15.2%)
 Diseases of immune dysregulation (3.2%)
 Defects in intrinsic and innate immunity (4.9%)
 Bone marrow failure
 Phenocopies of PID

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5
Q

Various possible presentations of PID

A 
 Infections
 Autoimmune phenotypes
 Autoinflammatory phenotypes (5.7%)
 Hemophagocytosis
 Lymphoid cancer
 Allergy
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6
Q

Outline history taking questions for immunodeficiency in children

A
  1. Document recurrent infections
  2. General health history: Past medical health, past medication and immunosuppression, Transfusion history
  3. Birth history, immunization history and reaction to vaccines
  4. Family history of allergies, immunodeficiencies, autoimmune syndromes; unexplained death in siblings or young relatives
  5. Social history
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7
Q

Define the vaccinations that are intolerable to children with primary immunodeficiency

A

Intolerable conditions:

BCG vaccine:
SCID, Chronic granulomatous disease, MSMD (Mendelian susceptibility to mycobacterial disease)// STAT1

Oral polio vaccine:
SCID, XLA (X-linked agammaglobulinemia)

Rota V: SCID

Rubella V: Chronic skin granuloma in primary T-cell deficiency

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8
Q

Warning signs/ red flag signs suggestive of PID

A

Infections:
 >8 new ear infections within 1 year
 >2 serious sinus infections within 1 year (CT scan)
 >2 pneumonias within 1 year
 >2 deep-seated infections
 Recurrent, deep skin/ organ abscesses(e.g. HIES, CGD)
 Recurrent/chronic diarrhea (e.g. CVID, Wiskott-Aldrich syndrome, SCID)

Bad reaction to vaccine:
 Vaccine-associated paralytic polio
 Disseminated BCG infection

Poor antibiotic function:
 >2 months on antibiotics with little effect
 Need for iv antibiotics to clear infections

Family history of PID easiest way to Ix and Dx

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9
Q

Signs of PID on physical exam

Growth, skin/ barriers, lungs, musculoskeletal, lymphatic system, neurological …

A

Failure to thrive (weight below 3rd centile)

Mucocutaneous surfaces: Persistent thrush, Candidiasis

Nails: Dyskeratosis (bone marrow failure)/ Candidiasis

Skin: Poor wound healing/ scar, infection

Lung: Bronchiectasis and ILD (antibody deficiency)

Lymphatic tissue: Too much (e.g. CGD, CVID, WAS)/ too little (SCID, XLA)

Abdomen Hepatosplenomegaly

MSS: Arthritis

Neurological: Ataxia-telangiectasia (DNA repair defect)

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10
Q

Which types of PID is predisposed to recurrent bacteria infection
Specify which bacteria

A

Antibody (e.g. X- linked agamma- globulinemia (XLA))

  • susceptible to encapsulated bacteria: Pneumococcus, Haemophilus influenzae
  • Mycoplasma

Neutrophil defect:
- Staphylococcus, Pseudomonas, Salmonella

T-helper type-1 cytokines (IL-12, INF-γ)
- Salmonella, mycobacteria (typical, atypical)

Complement defect: Meningococcus

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11
Q

Which types of PID is predisposed to recurrent viral infection
Specify which viruses

A

Antibody (e.g. X- linked agamma- globulinemia (XLA))
- Enteroviruses (poliovirus, echovirus)

T-cell defect (e.g. SCID)
- Herpes virus (EBV, CMV)

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12
Q

Which types of PID is predisposed to recurrent fungi infection
Specify which fungi

A

T-cell (e.g. SCID): Candida albicans, Pneumocystis jiroveci

CD40 ligand deficiency: Pneumocystis

Neutrophil defect: Candida albicans, Aspergillus

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13
Q

Which types of PID is predisposed to recurrent protozoa infection
Specify which protozoa

A

Antibody (e.g. X- linked agamma- globulinemia (XLA))
- Giardia lamblia

T-cell defect (e.g. SCID)
- Cryptosporidium

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14
Q

List types of primary humoral/ antibody deficiency and their related molecular defect

A

X-linked agammaglobulinemia (XLA) - Btk protein***

Autosomal recessive hyper-IgM syndrome - CD40***

Common variable immunodeficiency (CVID) - ICOS, CD19

Selective IgA deficiency - (unknown defect)

IgG subclass deficiency (+/- IgA deficiency) - (unknown defect)

Transient hypogammaglobulinemia of infancy - (unknown defect)

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15
Q

X-linked agammaglobulinemia (XLA)

  • Molecular defect
  • Types of recurrent infection/ presentation
  • Confirmatory Tx
  • Tx
A
  • Molecular defect = Btk protein
  • Types of recurrent infection/ presentation: Respiratory tract infection, meningitis, diarrhea, bronchiectasis
  • Confirmatory Tx: Panhypogammaglobulinemia, no B cells in peripheral blood
  • Tx: Regular IVIg (regardless of IgG titer)
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16
Q

Common variable immunodeficiency (CVID)

  • Molecular defect
  • Presentation/ types of recurrent infection
  • Confirmatory Ix
  • Tx
A
  • Molecular defect: ICOS, CD19
  • Presentation/ types of recurrent infection: Recurrent respiratory tract infection, autoimmune diseases, granulomatous diseases, Lymphoma (polyclonal lymphoproliferation)**
  • Confirmatory Ix: Low serum IgG, IgA, IgE + poor antibody response to vaccines
  • Tx: BM transplant

** Diagnosis after age 4 and exclusion of T-cell deficiency/ secondary causes of hypogammaglobulinemia)

17
Q

Long-term lung diseases caused by primary antibody/ humoral deficiencies

A

Granulomatous lymphocytic interstitial lung disease
e.g. Concurrent T cell dysfunction, HyerIgM syndrome …etc

Bronchiectasis
e.g. recurrent infection, Low IgA. MBL deficiency …etc

18
Q

Name one PID with impaired T cell immunity

  • Presentation
  • Ix
  • Tx
A

DiGeorge’s syndrome:

Presentation:
 Neonatal hypoglycemia
 Failure to thrive; psychiatric & learning issues
 Chronic diarrhea; thrush; viral, fungal opportunistic infections
 Abnormal facies: prominent ears, small chin, short philtrum

Ix: no thymus, no T cell, conotruncal defect

Diagnosis by FISH: chromosome 22q deletion

19
Q

Wiskott-Aldrich syndrome (WAS)

  • Presentation
  • Associated diseases/ phenotypes
  • Tx
A

Wiskott-Aldrich syndrome (WAS) = combined immunodeficiency

Presentation: HSV otitis, EBV lymphoma, complicated with inflammatory bowel disease***

Associated diseases - one gene multiple diseases and phenotypes:
 Missense correlated with XLT (X-linked thrombocytopenia) phenotype (little infection, no eczema)
 X-linked neutropenia

Tx: donor transplant, prednisolone, methotrexate, gene therapy

20
Q

2 examples of combined immunodeficiencies with syndromic features*

A

Wiskott-Aldrich syndrome (WAS)

Hyper-IgE syndrome (HIES)

21
Q

Hyper-IgE syndrome

  • Genetic defect
  • Unique clinical features
A

Autosomal dominant (e.g. STAT3 loss of function)

Distinctive features:
 Characteristic facial appearance: coarse facial features
 Retained primary teeth, poor dentition
 Minimal trauma fractures, scoliosis
 Pneumatoceles (cavity in lung parenchyma) with secondary infections
 Prolonged bronchopleural fistulae after lung resection
 Mucocutaneous candidiasis
 Less allergies and anaphylaxis than expected for level of serum IgE

22
Q

Severe combined immunodeficiencies (SCID)

  • Modes of inheritance
  • Clinical features
  • Confirmatory Ix
  • Tx
A
  • Modes of inheritance: X-linked (IL2R common gamma chain defect), AR (various defects…)
- Clinical features:
Failure to thrive 
Chronic diarrhea 
PCP 
Recurrent oral candidiasis
BCG abscess and disseminated skin lesions 
- Confirmatory Ix:
T-B+ or T-B- lymphopenia
Hypogammaglobulinemia
Absent thymic shadow
Whole exome sequencing: e.g. heterozygous RAG1 gene mutation
  • Tx
    XL: Bone marrow transplant (HSCT)
    ADA-SCID (special type): HSCT/ gene therapy/ PEG-ADA
23
Q

Phagocyte defect in PID

  • Examples of disease entities
  • Types of infections
A 
Entities:
 Severe congenital neutropenia
 Asplenia
 Chronic granulomatous disease (CGD): NADPH oxidase in respiratory burst
 Leucocyte adhesion deficiency (LAD)

Types of infections:
recurrent pyogenic infections, staphylococcal; skin infections

24
Q

Chronic granulomatous disease

  • Mode of inheritance
  • Molecular defect
  • Types of infections/ presentation
A

Inheritance: X-linked or AR

Defect: gp22 phox, gp47 phox

Clinical features:
 Skin abscesses, perianal abscesses/ scars
 Lymphadenitis
 TB, BCG dissemination
 Rheumatological disease (e.g. arthritis, iritis, dactylitis)

25
Q

Leucocyte adhesion deficiency (LAD)

  • Mode of inheritance
  • Molecular defect
  • Clinical features
  • Confirmatory Ix
  • Tx
A

Inheritance: AR

Molecular defect: CD18 (beta-integrin)

Clinical features:
 Poor wound healing (papery thin scar), skin abscess
 Chronic periodontitis
 Omphalitis

Ix: Peripheral blood neutrophil count extremely high

Tx: Marrow transplant

26
Q

Complement deficiencies

  • Types of complement defect
  • Mode of inheritance
  • Types of infections/ presentation
A

Abnormalities:
 C5-C9 deficiency (terminal pathway)
 C3 deficiency (key for all 3 pathways)

Inheritance: AR

Infections:

  • Pyogenic infection esp. encapsulated bacteria
  • Neisserial infections
  • SLE, RA
27
Q

First-line investigations for PID

A

Blood counts (CBP and differentials)

All Ig: IgGAME (XLA, hyper-IgM, hyper-IgE, CVID)

IgG subclasses and functional Abs (CVID)

Lymphocyte subsets and proliferation (SCID)

Nitroblue tetrazolium test and dihydrorhodamine (CGD)

Flow cytometric analysis of CD18 (LAD), CD40L and CD40 (hyper-IgM)

28
Q

Management of a child with PID

A 
1. Optimal management:
 IVIG
 Stem cell transplant (e.g. SCID)
 Gene therapy 
 Appropriate prophylaxis
 Advice on vaccination (e.g. T cell defect C/I all live vaccines (polio, MMR))
  1. Genetic counselling
  2. Prenatal diagnosis
29
Q

Describe the Ig count changes in neonates

A

 Maternal IgG contribution before birth

 Trough at 3-4 months of age before newborn IgG takes over

MBBS IV - Junior Clerkship WCS (131 decks)

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