Immunodeficiencies

Question 0

How can you recognise patients who are immunocompromised?

Answer 0

S - severe ie life threatening
P - persistent
U - unusual - opportunist pathogens
R - recurrent

Question 1

Define immunocompromised

Answer 1

State in which immune system is unable to respond appropriately and effectively to infectious microorganisms

Question 2

Features of a primary immunodeficiency?

Answer 2

Caused by an intrinsic (immune defect)
Congenital or acquired
Relatively rare

Question 3

Features of secondary immunodeficiencies?

Answer 3

Relatively common
Secondary to another condition
Acquired

Question 4

What can a secondary immunodeficiency be caused by?

Answer 4

Infection (HIV)
Malnutrition
Liver disease
Splenectomy 
Drug-induced neutropenia
Lymphoproliferative diseases

Question 5

What is neutropenia?

Answer 5

Abnormally low neutrophils in the blood, leading to increased susceptibility to infection

Question 6

What can cause neutropenia?

Answer 6

Drugs
Autoimmune neutropenia
Bone marrow infiltration with malignancy
B12/folate/iron deficiency 
Chemo-cytotoxic/immunosuppressant
Chemical agents
Radiotherapy

Question 7

Management of suspected neutropenic sepsis?

Answer 7

Treat as acute medical emergency
Empiric antibiotics immediately
Assess risk of septic complications

Question 8

What are asplenic patients more susceptible to? Give examples

Answer 8

Encapsulated bacteria
H influenzae
Streptococcus pneumoniae
N meningitidis

Question 9

What are asplenic patients more at risk of?

Answer 9

Overwhelming post-splenectomy infection

-sepsis and meningitis

Question 10

What do asplenic patients have to have?

Answer 10

Lifelong penicillin prophylaxis
Immunisation against encapsulated bacteria
Medical alert bracelet

Question 11

What does the spleen do?

Answer 11

Immune function against blood-borne pathogens

Antibody production

• acute response: IgM
• long-term protection: IgG

Splenic macrophages

• remove opsonised microbes
• remove immune complexes

Question 12

What can cause loss of catabolism of immune components and the fore secondary immunodeficiency?

Answer 12

Protein losing conditions eg nephropathy, enter ovary

Burns

Question 13

What can primary immunodeficiencies be classified into?

Answer 13

B cell (50%)
Phagocytes (18%)
T cell (30%)
Complement (2%)

Question 14

When are primary deficiencies normally seen?

Answer 14

First few months of life

Question 15

What are the B cell deficiency types?

Answer 15

Common variable immunodeficiency (CVID)
IgA deficiency
Bruton’s disease (X-linked agammaglobulinaemia)

Question 16

What is common variable immunodeficiency?

Answer 16

Inability of B cels to mature into plasma cells.

Low IgG

Question 17

How does IgA deficiency happen?

Answer 17

B cells are unable to switch to IgA

Question 18

What is Bruton’s disease?

Answer 18

Impaired B cell development

Present in first 6 months

Question 19

What are people with Bruton’s disease at increased risk of?

Answer 19

Streptococcus pneumoniae
Mycoplasma amphoriforme
Non-capsulated Haemophilus influenzae

Question 20

What is hyper IgM syndrome?

Answer 20

CD40 ligand on activated T cells prevents them from switching from IgG to IgM
Therefore keep making IgM

Question 21

Presentation and management of patients with primary antibody (B cell?) deficiencies?

Answer 21

Recurrent upper and lower respiratory bacteria infections causing bronchiectasis

GI complications including infections

Anthropathies (joints - including Mycoplasma spp and Ureaplasma spp)

Increased incidence of autoimmune disease

Increased incidence of lymphoma and gastric carcinoma

Question 22

Management of primary antibody deficiencies?

Answer 22

Prompt/prophylactic antibiotics
Immunoglobulin replacement therapy (gold standard)
Management of respiratory function - physiotherapist
Avoid unnecessary exposure to radiation eg CT scan

Question 23

Goal of immunoglobulin replacement therapy?

Answer 23

Serum IgG > 8g/L

Life long

Question 24

What is immunoglobulin replacement therapy given for?

Answer 24

CIVD XLA (Bruton's) Hyper-IgM syndrome

Question 25

What are some clinically important phagocyte deficiencies?

Answer 25

Cyclic neutropenia - cause unknown Leukocyte Adhesion deficiency Chronic granulomatous disease CH syndrome

Question 26

What is leukocyte adhesion deficiency?

Answer 26

Lack of CD18 protein on phagocytes - defects adhesion to endothelium

Question 27

What is chronic granulomatous disease?

Answer 27

Lack of respiratory burst

Question 28

What is CH syndrome?

Answer 28

Failure of phagolysosome formation

Question 29

Presentation of phagocyte deficiencies?

Answer 29

Prolonged and recurrent infection - ulcers - osteomyelitis - deep abscesses - commonly staphylococcal (catalase positive) - invasive aspergillosis - inflammatory problems

Question 30

Management of phagocyte deficiencies?

Answer 30

Prophylactic antibiotics and antifungals Immunisation Surgical management Stem cell transplantation

Question 31

Clinically important T cell deficiencies?

Answer 31

DiGeorge syndrome | Severe combined immunodeficiency

Question 32

What is DiGeorge syndrome caused by?

Answer 32

Defect in thymus embryogenesis and incomplete development

Question 33

Signs and symptoms of DiGeorge syndrome?

Answer 33

``` Cardiac abnormalities Abnormal face (low ears, wide eyes) Thymic hypoplasia Cleft palate Hypocalcaemia ``` 22 - chromosome abnormality

Question 34

Management of DiGeorge syndrome?

Answer 34

Neonatal cardiac surgery Correct hypocalcaemia Low T cell number Bone marrow transplant

Question 35

Presentation of SCID?

Answer 35

``` Failure to thrive Long term antibiotic therapy Deep skin and organ abscesses Low lymphocyte count High susceptibility to fungal and viral infections ```

Question 36

Management of SCID?

Answer 36

Antibiotics and prevention IV Ig Long term - bone marrow/stem cell transplant - gene therapy

Question 37

Where can Aspergillus be found?

Answer 37

Soil | AC systems

Question 38

What can Aspergillus do in immunocompromised patients?

Answer 38

Breathed into upper respiratory tract Causes invasive aspergillosis Starts in lungs and may involve other organs through haematogenous spread

Question 39

Why is Aspergillus difficult to fight?

Answer 39

Combination of low neutrophils (caused by immunodeficiency) and toxic metabolites produced by the fungi

Question 40

Symptoms of Aspergillus?

Answer 40

``` Cough Fever Shortness of breath Pleuritic chest pain Haemoptysis Nasal congestion Pain ```

Question 41

What is Aspergillus treated with?

Answer 41

Amphotericin | Echinocandin derivatives