White cell disorders Flashcards by Soumitra Tole

Name 5 drugs associated with neutropenia

Penicillins
Cephalosporins
Phenothiazine
Dilantin
Phenytoin (most anti-epileptics)
Sulfonamides

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Name syndrome and gene:

Hepatic enlargement, growth retardation, neutrophil dysfunction

GSD Type 1

G6PT1 (AR)

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Name syndrome and gene:

Episodic neutropenia, cardiomyopathy, methylglutaconic aciduria, pancytopenia

Barth Syndrome

TAZ1 (XL)

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Name syndrome and gene:

Vacoulated erythroid and myeloid precursors, ringed sideroblasts, pancytopenia

Pearson Syndrome

mitochondrial

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Name syndrome and gene:

Oculocutaneous albinism, giant granules in myeloid cells, platelet defect, neurodegeneration, HLH

Chediak-Higashi

LYST (AR)

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Name syndrome and gene:

Partial albinism (silver hair), HLH

Griscelli Syndrome II
Rab 27alpha (AR)

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WHIM syndrome

Warts
Hypogam
Infections
Myelokathexis (neutrophils stuck in marrow)

CXCR4 (AD)

Rx: Pelrixafor

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Name syndrome and gene:

Lymphopenia/neutropenia, dwarfism, fine sparse hair

Cartilage hair hypoplasia

RMRP (AR)

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Leukocyte adhesion defect

clinical manifestations
infectious organisms

Delayed separation of umbilical cord
Neutrophilia w/o pus
Skin and periodontal infections
rectal abscess
sepsis
pneumonia

S. aureus, Pseudomonas, Proteus, E. coli, Klebsiella, Candida, Aspergillus

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Leukocyte adhesion defect

genetics
treatment

LAD1 - CD18
LAD2 - CD 15s (Sialyl Lewis)
LAD3 - FERMT3 (switches on Integrins)

Rx: Oral care, prophylactic cotrimoxazole,
HSCT for severe cases
G-CSF does NOT work

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Specific granule deficiency

gene
diagnosis

Defect in CEBPalpha (AR)

No specific granules, mild neutropenia with bi-lobed neutrophils

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CGD

genetics
diagnosis

gp91phox - XL
gp22phox, p47phox, p67 phox all AR

Diagnosis: DHR (flow-based), sequencing

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CGD

clinical
treatment

Recurrent infections
liver abscess and osteo
S. aureus and Aspergillus
Chronic granulomas

Rx:
Prophy with sulfa and itraconazole
Prophy IFN gamma (enhance nonoxidative phagocytosis)
HSCT

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Child with Candida albicans sepsis and diabetes

MPO deficiency (AR)

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List causes of leukocytosis

Physiologic (newborn, exercise)
Acute infection
Metabolic (DKA, burns, seizures)
Drugs (steroids, epi)
Poisoning (lead)
Acute hemorrhage
Neoplastic
Connective tissue disease (RA, IBD)
Hematologic disease (leukemia, splenectomy, transfusion, hemolytic anemia, etc)

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Eczematous skin lesions, sinopulmonary infections, high igE and eosinophilia,
Coarse facies and retain primary dentition

Hyper IgE syndrome (Job’s)

STAT3, TYK2, DOCK8

Supportive care, prophylaxis and HSCT

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1 year old with regression of milestones, hepatosplenomegaly and cytopenias. BM shows crumpled paper appearance

Gaucher’s disease

Mutation in glucoceribrosidase (AR)

Type 1 does not involve CNS

Diagnosis: BM phenotype and low GB activity, genetics

Rx: enzyme replacement

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Metabolic syndromes associated with neutropenia

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GSD Type 1
Barth Syndrome
Isovalearic acidemia, MMA, Propionic acidemia

Severe congenital neutropenia with neurologic abnormalities

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Kostman (AR) - HAX1 mutaition

Organs affected by eosinophilia

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skin
lung
GI tract
heart
CNS is late stage

Idiopathic Hypereosinophilic syndrome definition

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persistent (>6m) HE > 1.5
evidence of eosinophilic tissue damage
no alternate explanation

Fungal infection by

1) Profound neutropenia
2) Defective cellular immunity

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1) Candida, aspergillus

2) Crytococcus, Histoplasma, Coccidiodes

SCID with normal T-cell number?

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Maternal engraftment

SCID definition and w/u

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Lack of functional autologous T-cells (B cells can be present or absent but don’t work because T don’t work)

ALC + subsets
Lymphocyte proliferation
Total immunglobulins +/- specific Ab if vaccinated

Which immunodef can you support with enzyme supplementation

ADA deficiency

Boy with enteroviral meningoencephalitis and no lymph nodes

X-Linked Agam Dx: absent CD19 t-cells - low/absent IgG (unless maternal present)

Boy with low IgG, IgA, and high IgM - Diagnosis and genetics

HyperIgM, CD40L mutation | can't class switch from IgM

Malignancies associated with HIV

Kaposi sarcoma NHL Leiomyosarcoma ALL be

What is the differential for neutropenia?

1) Decreased production or intrinsic defects - ethnic - SCN - cyclic - familial benign chronic neutropenia - metabolic: GSD type Ib, barth syndrome, - bone marrow failure syndrome: FA, DKC 2) Increased destruction or extrinsic defects a) congenital: XLA, CVID, hyperIgM, WHIM, IgA def b) acquired: - drugs - infection - bone marrow infiltration-neoplastic or not - Immune: drugs, alloimmune, maternofetal, autoimmune, secondary to SLE, lymphoma, RA, HIV - ALPS - hypersplenism

What is the definition of left shift?

>5% increase in the percentage of immature precursors (usually bands)

For neonatal alloimmune neutropenia what target are the antibodies commonly formed against?

HNA-1a, HNA-1b and HNA-1c (inherited from the father and not present in the mother)

what conditions are associated with secondary autoimmune neutropenia?

``` Evans syndrome AIHA thyroiditis CVID SLE RA autoimmune thrombocytopenia ```

Define chronic idiopathic neutropenia

decreased or ineffective production or excessive apoptosis of neutrophils due to unknown causes. Happens in late childhood or early adulthood, with female predominance

What is the definition of hypereosinophilia?

eosinophil count >1500 on 2 occasions minimum 4 wks apart

``` Give a disease name for each of leukocyte dysfunctions: Adhesion Chemotaxis Opsonization Degranulation Oxidative metabolism ```

``` Adhesion-LAD Chemotaxis-Hyper IgE Opsonization-complement deficiency Degranulation-Chediak Higashi Oxidative metabolism-CGD, G6PD ```

What test is done to investigate LAD type 1

flow cytometry to assess expression of CD11b or CD18 on neutrophil surface

What mutation causes hyper IgE syndrome (Job syndrome)?

inherited or sporadic AD mutation in STAT3 (JAK activation transcription factor)

What clinical findings are associated with Job syndrome?

chronic eczema, delay in shedding primary teeth, broad nose, hyperextendible joints, scoliosis, coarse facies get recurrent staph abscesses

what mutation causes chediak higashi?

AR defect in LYST1 gene-a lysosomal trafficking protein leading to abnormal granule formation

for chediak higashi patients what is the accelerated phase?

occurs in 85% patients, have lymphoproliferative infiltration of CNS, nerves, liver, spleen by histiocytes and lymphocytes-HLH

What infections are commonly associated with CGD?

staph, serratia, salmonella, burkholderia, aspergillus

what genetic mutation is most commonly associated with CGD?

x-linked mutation in CYBB gene (65% cases) affects gp91^phox (one of the components of the NADPH oxidase complex) the other are AR inherited

ALPS criteria

chronic non-malignant LN elevated DNT cells Supportive: - elevated B12 - family history - pathogenic mutation in Fas/FasL/Casp10 - lymphocyte apoptosis assay

What are patients with ALPS at risk for?

lymphoma

White cell disorders Flashcards

(44 cards)