Immune diseases and clinical pearls - Hunter

Question 1

Describe congenital asplenia.

Answer 1

This is a condition where an individual is born without a spleen. Most cases follow an autosomal dominant pattern of inheritance.

Question 2

Asplenia can lead to what?

Answer 2

Increased susceptibility to encapsulated bacteria like H. Flu. Uncleared bacteremia can lead to meningitis and pneumonia. Scintillation scanning following injection of radioactive colloidal gold can reveal the absence of a spleen.

Question 3

What is IRAK4 deficiency?

Answer 3

IRAK4 is part of the intracellular signaling pathway triggered by the binding of PAMPS to Toll-like receptors on APC’s. This pathway lead s to the activation of a transcription factor called NF-kB which up regulates the expression of inflammatory genes (more than 100). This disease is a rare autosomal recessive defect.

Question 4

How is IRAK4 deficiency diagnosed?

Answer 4

By clinical suspicion and demonstration of responses of monocytes to TLR agonists.

Question 5

IRAK4 is important for what?

Answer 5

It is critical for the functioning of the inflammatory response which is a host defense against pyogenic bacterial infections.

Question 6

Describe chronic granulomatous disease.

Answer 6

It results from a failure to assemble the NADPH oxidase in phagolysosomes. This is needed for neutrophils to kill the pathogens it phagocytoses. This leads to granulomatous lesions in the skin and various internal organs caused by pyogenic bacteria and fungi.

Question 7

What is the treatment for CGD?

Answer 7

Long term prophylaxis with antibacterial and antifungal agents.

Question 8

How can you test for CGD?

Answer 8

By using the dihydrorhodamine test. Dihydrorhodamine is produced if the NADPH is working properly and is making reactive oxygen species. On flow cytometry if this disease is present you will see a defective respiratory burst.

Question 9

CGD may present with what?

Answer 9

Abcesses, leukocytosis, lymphadenopathy, and hepatosplenomegaly.

Question 10

What is Chediak-Higashi syndrome?

Answer 10

An autosomal recessive disease with a defect in microtubule polymerization that decrease phagolysosome formation and impairs killing of phagocytosed bacteria.

Question 11

How might chediak-Higashi syndrome present?

Answer 11

It may present in early childhood with recurrent pyogenic infections such as with staph and strep - particularly gingival infections. Children have partial albinism.

Question 12

How is Chediak-Higashi syndrome treated?

Answer 12

Prophylactic antibiotics mainly and sometimes via bone marrow transplant.

Question 13

How is chediak-Higashi syndrome diagnosed?

Answer 13

Diagnosed by seeing large, lysosomal vesicles in neutrophils and eosinophils on a peripheral blood smear.

Question 14

What is neutropenia?

Answer 14

Decreased absolute neutrophil count. Low normal is 1500-2000 cells /mm cubed and infections increase below 1500.

Question 15

Describe drug-induced neutropenia.

Answer 15

This decreased absolute neutrophil count due to cytotoxic anti-cancer drugs or other drug therapies. It can lead to neutropenic sepsis due to infection with a variety of pyogenic bacteria and fungi.

Question 16

How is drug induced neutropenia diagnosed and treated?

Answer 16

It is diagnosed by using a CBC with differential and clinical presentation. It is treated with initial antibiotics and then human recombinant granulocyte colony stimulating factor.

Question 17

Describe severe congenital neutropenia or Kostmann disease?

Answer 17

This disease is phenotypically heterogeneous but patients often present with recurrent infections of skin, soft tissues, lungs and deep organs. Sepsis is also common.

Question 18

How is Kostmann disease diagnosed and treated?

Answer 18

It is diagnosed by a CBC with differential showing an absolute neutrophil count below 200 ul. Also can get an aspirate of bone marrow where you will see a block in neutrophil maturation at the promyelocyte stage. Treatment includes giving human granulocyte colony stimulating factor and sometime by bone marrow transplants.

Question 19

Describe Leukocyte Adhesion Deficiency Type 1.

Answer 19

This is a rare autosomal recessive disorder that presents with recurrent bacterial infections due to defects in neutrophil adhesion. Which results in poor chemotaxis, phagocytosis as well as neutrophilia.The molecular defect is a deficiency of the adhesion molecule CD18 or CD11. It presents in infants as omphalitis, pneumonia, gingivits and peritonitis.

Question 20

How is LAD diagnosed and treated?

Answer 20

It is diagnosed by finding low CD18 on neutrophils by flow cytometry. Treatment involves bone marrow transplant.

Question 21

Describe Mannose-binding lectin deficiency.

Answer 21

MBL is a component in the MBL pathway of complement and is one of the most common complement deficiencies. It presents with increase pyogenic bacterial infections in children (adults can compensate) and is also common in lupus patients.

Question 22

What is the second most common complement deficiency?

Answer 22

A deficiency in C2. This usually characterized by recurrent but mild infections in children over the age of 1. C2 deficiency prevents the formation of C3 convertase.

Question 23

Describe a C8 deficiency.

Answer 23

A deficiency in C8 would lead to a lack of the formation of the immune attack complex and so it would present with recurrent neisserial infection - as would a lack of anything from C5-C9, Factor P or Factor D. Diagnose by ordering a CH50 and AH50 and more specific tests if needed and treat by giving the tetravalent meningococcal vaccine.

Question 24

Describe Hereditary Angioedema.

Answer 24

It is caused by a deficiency in the complement regulatory protein C1INH. This protein is a serine protease inhibitor that also inhibits a serine protease that generates the vasoctive mediator bradykinin. Bradykinin causes recurrent swelling of the skin, intestine, and airways.

Question 25

How is hereditary angioedema diagnosed and treated?

Answer 25

Diagnosis is made by finding of very low C1INH and C4 levels with normal C3 levels. Treatment involves administration of human recombinant C1INH -epinephrine does not work.

Question 26

Describe atopic dermatitis.

Answer 26

This is a Type 1 Hypersensitivity disease. I t is the most common chronic skin disease of young children. It is characterized by intermittent, pruritic rashes. The rashes are itchy and scratching can cause lesions that can be colonized by staph and strep. Look for elevated serum IgE, eosinophilia and elevated TH2 cytokines in the serum. Treat with topical anti-inflammatory agents and avoid irritants.