Immunodeficiencies

Question 1

• Recurrent viral, fungal, and protozoal infections
• hypocalcemia and tetany
• congenital heart defects

Answer 1

Thymic aplasia (DiGeorge) 
-due to 22q11 deletion most commonly

Question 2

DiGeorge syndrome

Answer 2

• 3rd and 4th pharyngeal pouches fail to develop
• leads to no mature T cells and no parathyroids
• results in recurrent viral/fungal/protozoal infections + hypocalcemia/tetany

Question 3

T cell dysfunction resulting in recurrent candida infections

Answer 3

Chronic mucocutaneous candidiasis

Question 4

Prophylaxis for chronic mucocutaneous candidiasis

Answer 4

ketoconazole

Question 5

Mycobacterial and fungal infections

Answer 5

IL-12 receptor deficiency

Question 6

X-linked B-cell deficiency that leads to recurrent bacterial infections after 3-6 mo. of age

Answer 6

Bruton agammaglobulinemia

• defective tyrosine kinase gene –> low levels of ALL immunoglobulins
• seen in boys

Question 7

Sinus and lung infections, associated with atopy and asthma

Answer 7

Selective IgA deficiency

-concern for anaphylaxis with blood products

Question 8

Severe recurrent infections (chronic mucocutaneous candidiasis, fatal or recurrent HSV/VZV/RSV/measles/flu/paraflu, PCP)
Chronic diarrhea
Failure to thrive
no thymic shadow on CXR

Answer 8

Severe combined immunodeficiency (SCID)

Question 9

Major defect leading to SCID

Answer 9

adenosine deaminase deficiency - leads to defect in early stem cell differentiation

Question 10

sinus and lung infections, cerebellar ataxia, poor smooth pursuit of moving targets with eyes, telangiectasia of face after age 5, elevated AFP

Answer 10

Ataxia-telangiectasia

Question 11

Components of ataxia-telangiectasia

Answer 11

ATAXIA - ataxia, telangiectasia/trafficking difficulty, lymphoma/leukemia risk, X-ray sensitive (avoid X-ray), IgA deficiency, increased AFP

• increased AFP after 8 months
• avg. age of death is 25 yrs
• IgA and T cell deficiency –> lung and sinus infections

Question 12

Wiskott-Aldrich Syndrome components

Answer 12

WAITER - Wiskott-Aldrich, immunodeficiency, thrombocytopenia and purpura, eczema, recurrent pyogenic infections

• X-linked
• no IgM –> no defense against encapsulated bugs
• low IgM, high IgA

Question 13

Hyper-IgM syndrome

Answer 13

• increased IgM, other isotypes decreased
• Autosomal recessive is due to no CD40 on B cells
• X-linked is due to no CD40 ligand on helper T cells

Question 14

Defect in Chronic Granulomatous disease

Answer 14

lack of NADPH oxidase –> phagocytes are not effective against catalase + organisms

Question 15

Features of Chronic granulomatous disease

Answer 15

• X-linked

- staph aureus and aspergillus infections

Question 16

Which bugs are pts with Chronic granulomatous disease esp. susceptible to?

Answer 16

Staph aureus, Aspergillus

Question 17

Diagnosis of Chronic granulomatous disease

Answer 17

negative nitroblue tetrazolium (NBT) test

- no yellow to blue-black oxidation

Question 18

Treatment of Chronic granulomatous disease

Answer 18

Prophylactic TMP-SMX and itraconazole; IFN-gamma as well

Question 19

Defect in Chediak-Higashi syndrome

Answer 19

defective LYST gene –> defect in lysosomal transport in phagosomes –> giant cytoplasmic granules in PMNs are diagnostic

Question 20

Classic triad of Chediak-Higashi syndrome

Answer 20

partial albinism
recurrent respiratory tract and skin infections
neurologic disorders

Question 21

Classic presentation of Leukocyte adhesion deficiency syndrome

Answer 21

delayed separation of umbilical cord

Question 22

Defect in Leukocyte adhesion deficiency syndrome

Answer 22

abnormal integrins –> inability of phagocytes to exit circulation

Question 23

Classic presentation of Hyper-IgE syndrome

Answer 23

eczema, recurrent cold S. aureus abscesses, coarse facial features (frontal bossing, broad nose, prominent forehead, deep-set eyes, doughy skin)

• also can have retained primary teeth –> two rows of teeth
• high IgE and eosinophils

Question 24

Defect in Hyper-IgE syndrome

Answer 24

mutation in gene for STAT3 signaling protein –> impaired differentiation of Th17 cells and impaired recruitment of neutrophils