White cell disorders Flashcards
Name 5 drugs associated with neutropenia
Penicillins Cephalosporins Phenothiazine Dilantin Phenytoin (most anti-epileptics) Sulfonamides
Name syndrome and gene:
Hepatic enlargement, growth retardation, neutrophil dysfunction
GSD Type 1
G6PT1 (AR)
Name syndrome and gene:
Episodic neutropenia, cardiomyopathy, methylglutaconic aciduria, pancytopenia
Barth Syndrome
TAZ1 (XL)
Name syndrome and gene:
Vacoulated erythroid and myeloid precursors, ringed sideroblasts, pancytopenia
Pearson Syndrome
mitochondrial
Name syndrome and gene:
Oculocutaneous albinism, giant granules in myeloid cells, platelet defect, neurodegeneration, HLH
Chediak-Higashi
LYST (AR)
Name syndrome and gene:
Partial albinism (silver hair), HLH
Griscelli Syndrome II Rab 27alpha (AR)
WHIM syndrome
Warts
Hypogam
Infections
Myelokathexis (neutrophils stuck in marrow)
CXCR4 (AD)
Rx: Pelrixafor
Name syndrome and gene:
Lymphopenia/neutropenia, dwarfism, fine sparse hair
Cartilage hair hypoplasia
RMRP (AR)
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
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
Specific granule deficiency
- gene
- diagnosis
Defect in CEBPalpha (AR)
No specific granules, mild neutropenia with bi-lobed neutrophils
CGD
- genetics
- diagnosis
gp91phox - XL
gp22phox, p47phox, p67 phox all AR
Diagnosis: DHR (flow-based), sequencing
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
Child with Candida albicans sepsis and diabetes
MPO deficiency (AR)
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)
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
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
Metabolic syndromes associated with neutropenia
GSD Type 1
Barth Syndrome
Isovalearic acidemia, MMA, Propionic acidemia
Severe congenital neutropenia with neurologic abnormalities
Kostman (AR) - HAX1 mutaition
Organs affected by eosinophilia
- skin
- lung
- GI tract
- heart
- CNS is late stage
Idiopathic Hypereosinophilic syndrome definition
- persistent (>6m) HE > 1.5
- evidence of eosinophilic tissue damage
- no alternate explanation
Fungal infection by
1) Profound neutropenia
2) Defective cellular immunity
1) Candida, aspergillus
2) Crytococcus, Histoplasma, Coccidiodes
SCID with normal T-cell number?
Maternal engraftment
SCID definition and w/u
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
