Primary Immune Deficiency

Question 1

What is PID?

Answer 1

Inherited defects in innate or acquired immune system.

Question 2

Which parts of the immune system are affected by PID?

Answer 2

Innate
Humoral
Cell mediated

Question 3

What are the innate syndromes of PID?

Answer 3

· Neutropenia NP

· Chronic granulomatous disease CGD – 0.2/100k.

· Complement deficiency cD – 1/10k.

Question 4

What are the humoral syndromes of PID?

Answer 4

· IgA deficiency (common) IgAD – 2/1k

· Transient hypogammaglobuminaemia of infancy THI

· X linked agammaglobulinaemia XLAG

· Common variable immunodefieicncy CVD

Question 5

What are the cell mediated syndromes of PID?

Answer 5

· Severe combined immunodefieicncy (Reticular dysgenesis/leukocyte adhesion) – 1/75k. Very severe.

· Wiskott-Aldrich WA - 0.15/100k.

· DiGeorge DiG – 1/5k.

Question 6

What is the aetiology of the innate PID?

Answer 6

NP: congenital (Kostmanns) cyclical or secondary to chemotherapy.

CGD: X linked or AR.

CD: AR or due to consumption (SLE)

Question 7

What is the aetiology of the humoral PID?

Answer 7

SigAD: AD or after viral infection.

CVID: gene environment interaction.

XLAG: X linked TK gene in early B lymphocytes.

Question 8

What is the aetiology of the cell mediated PID?

Answer 8

SCID: 50% X linked recessive, 50% AR.

WAS: X lnked.

DiG: Microdeletion on 22q11.

Question 9

What is the history and exam for innate PID?

Answer 9

NP: Life threatening, early presentation, bacterial infection.

CGD: Deep abscess formaiton, chronic granulomas, bowel granulomas.

CD: Meningococcal and neisserial infections.

Question 10

What is the history and exam for humoral PID?

Answer 10

SIGAD: Recurrent normal circualting infeciton (GI/URTI)

THI: as above.

CVID: Similar to SIGAD

Question 11

What is the history and exam for cell mediated PID?

Answer 11

SCID: Fail to thrive, diahrrea, lymphadenopathy, hepatosplenomegaly, recurrent bacterial viral fungal infections, PCP etc.

XLAG: Bacterial infections >6month due to maternal Ab decreasing.

WAS : Severe eczema, easy bruising, recurrent bacterial viral fungal infections.

DIG: Midline facial cleft, dysmorphic features, CHD. Hypocalcaemia, recurrent infections.

Question 12

What is the pathology for innate PID?

Answer 12

CGD: Imapried macrophage bacterial killing

CD: Deficiency in complement leading to lower encapsulated bacteria immunity.

SIGAD: Fail of maturation of IggA B cells, immature forms present.

Question 13

What is the pathology for humoral PID?

Answer 13

CVID: Defect in B cell class switch

THI: Delay in maturation of immune system.

Question 14

What is the pathology for cell mediated PID?

Answer 14

SCID: deficienct and defect in T and B cell function, impaired cell mediated immunity. Absence of lymph nodes, tonsils, adenoids.

XLA: Lack of mature B cells, no serum Ig. T cell funciton normal.

WAS: T cell dysfunciton, microthrombocytopenia and bleeding diatheses.

DIG: Absent thymus -> no T cell development.

Question 15

What investigations do you do for PID?

Answer 15

Baseline immunity screen: WCC and differential, Serum Ig, Ab response to vaccines.

Second line consider lymphocyte subset analysis, funcitonal complement analysis, NBT test for CGD. IgE levels.

CXR for absent thymus in DG or SCID.

Question 16

What management do you do for PID?

Answer 16

Imunisation if functional B and T cells present

If SCID, WAS< CGD, and DIG only cure is BM transplant.

Prophylactic Abx: azithromycin, cotrimoxazole PCP.

Antifungals: itraconazole/fluconazole in CGD/Tcell dysfuncitons.

G-CSF: for severe neutropenia.

Ig: IVIG or SCIG mat be required

Gene and enzyme therapy in some SCID forms,

Question 17

What are the complications and prognosis of PID?

Answer 17

Fail to thrive, days off school, bronchiectasis, opportunistic infections.

SIGAD normal life, THI usually resolve by itself, XLA good prognosis if receiving Ig before 5y of age, SCID requires a BMT ASAP.