Primary Immunodeficiency

Question 1

What are primary immunodeficiency diseases?

Answer 1

Conditions characterized by intrinsic deficits within the immune system and are caused by inherited or de novo genetic defects

Question 2

What are three general symptoms of immunodeficiency?

Answer 2

Frequent, severe, unusual infections

Autoimmune disease

Immune dysregulation

Question 3

When do phagocytic usually present?

Answer 3

Early in infancy, childhood

Question 4

What is the infection pattern associated with phagocytic defects?

Answer 4

Catalase + bacteria (S. aureus)

Klebsiella, enteric flora

Mycobacteria including BCG

Fungi: Candida, Aspergillus, Paecilomyces

Question 5

What is the workup for suspected neutrophil defects?

Answer 5

CBC with diff. (absolute neutrophil count)

Test ability of polymorphonuclear cells to generate an oxidative burst: Dihydrohodamine test (DHR), Nitroblue tetrazolium (NBT)

Question 6

What are the clinical features of Chronic Granulomatous Disease?

Answer 6

Recurrent infections

Granulomas of skin, liver, lungs, viscera

GI/GU obstruction

X-linked or autosomal recessive

Question 7

What is the diagnosis and treatment for chronic granulomatous disease?

Answer 7

Neutrophil oxidative burst assay by flow cytometry using DHR

Prophylactic antibiotics, Gamma interferon, Bone marrow transplantation

Question 8

What are the clinical features of leukocyte adhesion deficiency type 1?

Answer 8

Infections affecting skin, respiratory tract, bowel and perirectal areas

Delayed wound healing, absence of pus

Severe periodontitis

Delayed separation of the umbilical cord

Question 9

What is the diagnosis and treatment of LAD type 1?

Answer 9

Leukosytosis,

Absence of CH18 and CD11

Prophylactic antibiotics, bone marrow transplant

Question 10

How are NK cell deficiencies characterized?

Answer 10

Severe, recurrent, or atypical infections with herpes virus

Can occur due to quantitative or functional NK cell deficiency

Question 11

What is the infection pattern for complement deficiency?

Answer 11

Encapsulated organisms: Neisseria, pyogenic infection

Frequent autoimmune disease

Question 12

What is the test for complement defects?

Answer 12

CH50

Generally 0 in complement deficiencies

Question 13

What are the clinical features of complement component deficiency?

Answer 13

Recurrent pyogenic infection and CT disease

Late component deficiency - Neisseria infection

Deficiency of regulatory protein C1 esterase inhibitor is associated with angioedema

Question 14

What is the infection pattern of antibody deficiency?

Answer 14

S. pneumonia, H. influenza, S. aureus, N. meningitidis etc.

Common respiratory and enteroviruses, rotavirus

Giardia, Cryptosporidium

Question 15

What is the workup for antibody deficiencies?

Answer 15

Quantitative Igs

Vaccine titers - qualitative measure of antibodies

Lymphocyte subsets

Question 16

What are the clinical features of X-linked Agammaglobulinemia?

Answer 16

Infancy/childhood with recurrent sinopulmonary pygoenic infections, 25% with neutropenia

Question 17

What are the diagnostic criteria for XLA?

Answer 17

Absent B cells

~50% positive family history

Low IgG

B cells <2% of lymphocytes

Question 18

What are the clinical features of common variable immunodeficiency?

Answer 18

Recurrent sinopulmonary infections

Autoimmune dieases

Possible malignancy

Question 19

What are the diagnostic criteria and treatment for CVID?

Answer 19

Reduced IgG

Low IgA and low/normal IgM

Poor response to immunization

Treat: Replacement IG

Question 20

What are the clinical features of Hyper IgM?

Answer 20

Recurrent sinopulmonary infections

Susceptible to opportunistic infections as well as liver disease due to CMV

Question 21

What is the cause of Hyper IgM?

Answer 21

Mutations of CD40L - X-Linked

Question 22

What are the diagnostic criteria for Hyper IgM?

Answer 22

Reduced total serum concentrations of IgG, IgA, and IgE

Norma/elevated IgM

Lack of antibody repsonse to protein

Normal total B cells, reduced memory B cells

Question 23

What is the treatment for Hyper IgM?

Answer 23

Replacement IG

Prophylaxis for opportunistic infections

Hematopoietic cell transplantation (HCT)

Question 24

What are the clinical features of selective IgA Deficiency?

Answer 24

Recurrent sinopulmonary

AI disease

Increased risk for GI disease

Allergic disease

Question 25

What are the diagnostic criteria for selective IgA deficiency?

Answer 25

Reduced IgA

Normal IgM and IgG

Patient over 4

Normal antibody response

Question 26

What is the workup for suspected T-cell/combined defects?

Answer 26

CBC with diff - low absolute lymphocyte count

Lymphocyte subset enumeration

Quantitative immunogloculins

T-cell proliferation

Question 27

What are the clinical features of SCID?

Answer 27

Failure to thrive, chronic diarrhea, erythroderma or other skin eruption

Question 28

What is the diagnostic criteria for SCID?

Answer 28

Lymphopenia in most

Diminished or absent T cells

Poor/absent in virto mitogen-induced T cell proliferation

Question 29

What is DiGeorge Syndrome and the clinical features?

Answer 29

Underdevelopment of the thymus

Conotruncal cardiac anomalies, hypoplastic thymus, hypocalcemia

Question 30

What is Wiskott-Aldrich Syndrome?

Answer 30

X-linked disease characterized by thrombocytopenia with small platelets, excema, cellular and humoral immunodeficiency

Caused by mutations in WASP protein

Question 31

What is Ataxia-Telangiectasia?

Answer 31

Autosomal recessive chromosomal breakage syndrome characterized by progressive cerebellar neurodegeneration, ID, radiosensitivity, and increased cancer susceptibility