Neutrophil and Eosinophil Disorders

Question 1

How long does it take for neutrophils to mature in bone marrow?

Answer 1

7-10 days

Question 2

What is the pathogenesis of leukocyte adhesion deficiency?

Answer 2

Defect in an integrin receptor that causes a defect in neutrophil adhesion, chemotaxis, and phagocytosis. Meaning neutrophils cannot leave the vasculature to migrate into tissue

Question 3

Clinical manifestations of leukocyte adhesion deficiency

Answer 3

High WBC, high neutrophil, recurrent skin infections (no abscesses), gingivitis. Many die before age 2

Question 4

Mutation seen in severe congenital neutropenia

Answer 4

ELANE

Question 5

What is Kostmann’s syndrome? What is the mutation?

Answer 5

Autosomal recessive severe congenital neutropenia. Mutation in HAX1

Question 6

What mutation is seen in almost 100% of cyclic neutropenia?

Answer 6

ELANE

Question 7

how long are the cycles of cyclic neutropenia?

Answer 7

15-35 days

Question 8

what does a bone marrow typically show in cyclic neutropenia?

Answer 8

Myelocyte arrest

Question 9

Clinical triad of Felty syndrome

Answer 9

Autoimmune neutropenia
Splenomegaly
RA

Question 10

What are the clinical manifestations of WHIM syndrome?

Answer 10

Warts (HPV)
Hypogammaglobulinemia
Immunodeficiency
Myelokathexis (retention and increased apoptosis of mature neutrophils in bone marrow causing peripheral neutropenia)

Question 11

What is the mutation and inheritance in WHIM syndrome?

Answer 11

AD mutation in CXCR4 gene, which prevents release of neutrophils and lymphocytes to the bloodstream

Question 12

Treatment for WHIM syndrome

Answer 12

Plerixafor to mobilize stem cells and reduce infection
Can try IVIG too

Question 13

Patient with a history of discoid lupus, recurrent infections as a kid, has chronic diarrhea and dyspnea from restrictive lung disease. What is the likely diagnosis? What test to order to make the diagnosis?

Answer 13

Chronic Granulomatous Disease
Nitroblue tetrazolium test or Dihidrorhodamine 123

Question 14

What treatment has been proven to reduce the rate of infection in chronic granulomatous disease?

Answer 14

Interferon gamma

Question 15

What is the defect in Chediak Higashi syndrome?

Answer 15

LYST gene defect causing generalized defect in granule morphogenesis

Question 16

Patient with oculocutaneous albinism, recurrent bacterial infections, peripheral neuropathy. Ultimately has an acute worsening and develops hepatosplenomegaly, pancytopenia, and potential signs of HLH. Diagnosis?

Answer 16

Chediak Higashi Syndrome

Question 17

What malignancy is more commonly associated with autoimmune neutropenia?

Answer 17

LGL

Question 18

In treating someone with RA-associated autoimmune neutropenia, what is a major consideration you need to have for treatment?

Answer 18

G-CSF can cause a flare of joint disease in RA

Question 19

What are three cytokines that regulate eosinophil production and function?

Answer 19

IL-5
IL-3
GM-CSF

Question 20

Diagnostic criteria for hypereosinophilic syndrome (6)

Answer 20

Persistent eosinophilia >1.5 and >10% eosinophils
Organ damage attributable to eos
No evidence of reactive, neoplastic, or autoimmune condition
Exclusion of LV-HES
Bone marrow generally normal with increased eos
No molecular genetic abnormality

Question 21

What is lymphocyte-variant hypereosinophilia?

Answer 21

rare abnormal T-cell population by flow cytometry and clonal T-cell receptor arrangement that causes skin changes, adenopathy, and rheymatologic problems.

Question 22

Patient with absolute eosinophil count above 1.5, 12% blasts in periphery, no fusion or other cytogenetic abnormalities. They have fever, fatigue, cough, pruritus. Diagnosis?

Answer 22

Chronic Eosinophilic Leukemia

Question 23

What is the mechanism of action of mepolizumab?

Answer 23

Anti IL-5 therapy

Question 24

What is the indication for mepolizumab?

Answer 24

Used for patients with >2 HES flares/year and AEC >1000

Question 25

What are risk factors for poor outcomes in patients with HES?

Answer 25

Age >60
Hemoglobin <10
Cardiac involvement
Hepatosplenomegaly
Presence of mutations