Primary immunodeficiency

Question 1

What are the types of Primary immunodeficiency in children?

Answer 1

• 2-5 months (T-cell defect) SCID
• 5-7 mon (X-linked agammaglobulinemia)
• The younger the age the more severe the deficiency

Question 2

What are the question marks raised when talking about the family history of PID in children?

Answer 2

1) Family history of maternal male relatives that are affected with (unusual infections) usually can alert the possibility of an X-linked immunodeficiency

2) Relatives with an autoimmune disorder (CVID, & IgA deficiency)

• Not having a family history does not rule out the possibility of this inheritance pattern (X-linked)

Question 3

What sign in a MEDICAL HISTORY might indicate B-cell deficiency?

Answer 3

Adverse reaction to live viral vaccines & paralytic polio (poliovirus attacking brain & spinal cord) has occurred in patients with B-cell deficiency and in combined immunodeficiency patients

Question 4

What are the PHYSICAL EXAMINATIONS done to detect a PID?

Answer 4

• Normal physical examination doesn’t rule out an underlying immunodeficiency
• In X-linked lymphoproliferative disease sign and symptoms does not develop before the Epstein-Barr virus infection develops
• Children with an underlying immunodeficiency appear 1.chronically ill and 2.underweight if it occurs early in life 3.growth & development can be delayed leading to a failure to thrive
• ENT examination (most important system to look for in a PID)
• Lymphoid system examination

Question 5

What does the physical examination do to the ENT system?

Answer 5

• ENT examination (most important system to look for in a PID):
  1) Extensive/persistent candidiasis in the membrane suggests a T-cell defect
  2) Postnasal drainage and purulent nasal discharge are all examined in the pharynx and nasal cavity
  3) Scarred and disfigured tympanic membranes, is a sign of previous and “recurrent infection” of the middle ear

Question 6

How do we examine the lymphoid system for PID patients?

Answer 6

1) Absence of tonsils & lymph nodes, suggest a severe immunodeficiency (XLA or SCID)

• XLA is found in infants that are unable to produce B-cells or immunoglobulins

Question 7

Cervical adenopathy, enlarged liver, or spleen are seen in patients with what type of immunodeficiency?

Answer 7

In patients with B-cell deficiency like CVID (common variable immunodeficiency)

Question 8

Lymphoreticular malignancies occur more commonly in which patients?

Answer 8

patients with primary immunodeficiency like Wiskott-Aldrich syndrome, Ataxia-telangiectasia, and CVID (common variable immunodeficiency)

Question 9

How frequently does IgA deficiency occur?

Answer 9

1:500-700

Question 10

What are the ten warning signs of Primary immunodeficiency (زي اسمك)?

Answer 10

1) 4 or more ear infections within 1 year
2) 2 or more serious sinus infections within a year
3) >=2 months using antibiotics without a result
4) 2 or more pneumonia within a year
5) Failure to gain weight or grow normally in children
6) Recurrent deep skin or organ abscesses
7) Persistent candidiasis after 1Year old
8) The need for an I.V antibiotic to clear an infection
9) 2 or more deep-seated infection
10) A family history of PID

Question 11

In ADULTS the presence of which 2 signs can be caused by PID?

Answer 11

ANY 2 of the following:

1) >= 2 ear infections in one year
2) >= 2 sinus infections in one year in the absence of allergies

3) 1 pneumonia per year for more than one year

4) Chronic diarrhea with weight loss

5) Repeated viral infections (colds, herpes, warts, condyloma)

6) Recurrent need for intravenous antibiotics to clear infections

7) Recurrent deep abscesses of skin or internal organs (ex.: liver, lungs)

8) Persistent thrush (usually in speeds, if seen in adults it would be weird) or fungal infection on the skin

9) Infection with normally harmless tuberculosis-like bacteria

10)Family history of a primary immunodeficiency

Question 12

What are the types of immunodeficiency?

Answer 12

Deficiencies in:
1) B-cell function (Antibodies)
2) T-cell function (Cellular)
3) Combined (B-cell & T-cell functions)
4) Phagocytic cells
5) Complement

Question 13

What are the clinical presentations if a patient is suffering from (a primary defect in antibody production (B-cells)

Answer 13

5-7 months, late childhood and adulthood

• Characterized by:
  1) recurrent infections with encapsulated bacteria
  2) history of failure to respond to antibiotic treatment

Question 14

What are the tests done in the laboratory to detect defects in antibody production?

Answer 14

1) Screening tests:
- IgG, IgM, IgA and IgE levels
- Isohemagglutintin titers (IgG and IgM. Aid in the determination of the relative amount of anti-A or anti-B present in serum to evaluate an individual’s ability to mount an immune response. Most often performed on pediatric patients with recurrent infections)
- Anti-Body response to vaccine antigens (Tetanus diphtheria, pneumococci, & haemophilus influenza)

2) Advanced tests:
- B-cell enumeration (CD19/CD20)
- Antibody response to boosters or new vaccines

Question 15

What are the treatments offered to patients with defective antibody production?

Answer 15

1) Judicious use of antibiotics
2) Regular administration of immunoglobulins
3) Bone marrow transplantation for X-linked agammaglobulinemia (Bruton)

Question 16

What are the findings in patients with X-linked agammaglobulinemia (Bruton)?

Answer 16

Profound defect in B lymphocyte development resulting in:

1) severe hypogammaglobulinemia (in males “low-level of antibodies”)
2) absence of circulating B cells
3) small to absent tonsils
4) no palpable lymph nodes

Question 17

Describe the presentations in T-cell defects

Answer 17

1) Early onset

2) 2-6 months of age

3) Specific pathogens are involved:
- Bacteria: (Mycobacteria)
- Viruses: (CMV, EBV, Varicella, & enterovirus)
- Fungi: (Candida, PCP)

4) Affected organs:
- Failure to thrive
- Protracted diarrhea
- Extensive mucocutaneous candidiasis

5) Special features:0
- Graft vs Host disease (GvHD) to maternal antibodies/ non-irradiated blood
- Post-vaccination disseminated BCG or Paralytic polio
- Hypocalcemic tetany in infants

Question 18

What are the characteristic features of DiGeorge syndrome?

Answer 18

1) Posteriorly rotated, Low-set ears
2) Ocular hypertelorism
3) Bulbous nasal tip
4) Thymic hypoplasia
5) Underdevelopment of the parathyroid gland (hypocalcemia “develops seizures””)
6) Congenital heart defects (we hear murmur)
7) Increased susceptibility to infections

Question 19

What causes DiGeorge Syndrome?

Answer 19

heterozygous chromosomal deletion of 22q11.2

Question 20

How to treat DiGeorge syndrome?

Answer 20

1) Thymic tissue transplants
2) HLA- identical sibling bone marrow transplant

Question 21

What are the types of Primary combined immunodeficiency?

Answer 21

1) SCID (Severe combined immunodeficiency)

2) WISKOTT-ALDRICH SYNDROME (Immunodeficiency with thrombocytopenia and eczema)

3) Ataxia-telangiectasia (imbalance, inherited neurological disorder that affects part of the brain which controls the movement)

Question 22

Describe SCID

Answer 22

• Patient fails to survive and has repeated infections (oral thrush)
• Occurs once every 100,000 Birth
• 50% of cases are X-linked, the other 50% are from various Autosomal recessive forms

Question 23

What is the typical finding in the history of a SCID patient?

Answer 23

1) Consanguinity
2) Sibling death in infancy/miscarriages
3) Family history of SCID
4) Poor feeding and weight gain
5) Chronic diarrhea
6) Previous infection (especially pneumonia)
7) Eczema (Omenn syndrome)

Question 24

What are the findings of the clinical examination in SCID patients?

Answer 24

1) No lymphadenopathy and there is no increase in tonsillar tissue despite serious infection

Question 25

Describe Omenn syndrome

Answer 25

An autosomal recessive form of severe combined immunodeficiency (SCID) characterized by erythroderma, desquamation, alopecia (hair loss), chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly

Question 26

What are the usual pathogens that causes recurrent infections in SCID?

Answer 26

1) Pneumocystis carinii pneumonia
2) Atypical mycobacterium
3) Herpes viruses
4) Candidiasis and other systemic fungus
5) Cryptosporidium
6) Pneumococcus and other common bacteria

Question 27

What are the lab findings in SCID?

Answer 27

1) Detects lymphopenia
2) Draw lymphocyte markers at the same time as the CBC count to obtain percentages and absolute counts of CD3+, CD4+ T cells, CD8+ T cells, CD19+ B cells, and NK cell markers (CD16 and CD56)
3) Overall decrease in total serum immunoglobulin levels of (IgG, IgA, IgM & IgE, “test lymphocyte function, look for antibodies produced by the standard vaccines’ protein (eg, diphtheria and tetanus); Patients with SCID essentially have no antibody formation and have very poor proliferation of lymphocytes”)
4) Candida albicans skin testing antigen for intradermal injection which assess cell-mediated hypersensitivity to candida albicans

Question 28

Without treatment, SCID can lead to death in?

Answer 28

the first two years

Question 29

What are the different treatments offered to treat SCID?

Answer 29

1) Intravenous immunoglobulin (IVIG) replacement therapy

2) Prophylaxis for PCP (Pneumocystis carinii pneumonia ) Trimethoprim-sulfamethoxazole

3) Live Vaccines (e.g. BCG, MMR, oral rotavirus should not be given)

4) Hematopoietic cell transplantation (HCT)

5) Gene therapy is successful especially if no donor is available

Question 30

Describe wiskott-Aldrich syndrome

Answer 30

1) X-linked
2) Recurrent infections
3) Eczema
4) Thrombocytopenia and small platelet size
5) Increases the risk of malignancies (leukemia and lymphoma)
and autoimmune disorders (neutropenia)

Question 31

Describe Ataxia-telangiectasia

Answer 31

1) Facial cellulitis
2) Periorbital telangiectasias (dialated BV of eyes)
3) Neurological manifestations (choreoathetosis “hand-writing movements” & cerebellar ataxia)
4) Susceptibility to malignancies

Question 32

PID in simple words

Answer 32

Primary immunodeficiency disorder (PID) refers to a heterogeneous group of disorders characterized by poor or absent function in one or more components of the immune system which predisposes affected individuals to increased frequency and severity of infection, autoimmunity, and aberrant inflammation and malignancy.