Term
True or False:
The homozygous HbS (SS) form of SCD is the most common cause of SCD in the Mediterranian |
|
Definition
| False: In the US this is true, but in the Mediterranian it is HbS/beta thallasemia SCD syndrome |
|
|
Term
| Explain the pathophysiological basis for chronic hemolytic anemia and vaso-occlusive cries (VOE) in SCD. |
|
Definition
Valine to Glutamic acid mutation in Beta-globin gene of hemoglobin causes abnormal "sickling" of RBC shape during hypoxemia, cellular dehydration (inadequate replacement of fluids), increased RBC concentration (altitude or infection) or increased blood viscosity (temperature).
1) Anemia is caused extravascular hemolysis by splenic macrophages and intravascular hemolysis due to microvascular adhesion.
2) VOE occurs because deformed HBS tends to polymerize and become insoluble, sicking cells and producing painful, end-organ vascular necrosis |
|
|
Term
Which of the following scenarios is unlikely to produce a VOE in a HBSS SCD patient?
1. Hiking up a mountain quickly
2. Strep pneumoniae sepsis
3. Hypersplenism
4. Surgical hemorrhage
5. Dehydration |
|
Definition
3- Hypersplenism is not known to cause VOE, since spleen is usually dysfunctional and atrophic in SCD. This only happens in a subset of SCd patients with HBSC and S/beta + thalassemia
1) low O2 tension
2) Sepsis stress
4) Surgical stress
5) Cellular dehydration |
|
|
Term
| What are the major hematological consequences of chronic SCD? |
|
Definition
1) Chronic intra and extra vascular hemolysis in patients with HBSS and S/beta 0 thalassemia (Hb 6-9) produces Normocytic anemia
2) Leukocytosis with Neutrophilia
3) Reticulocytosis
4-5 due to transfusion
4) Alloimmunization and reactive hemolysis to donor blood that can be missed on Indirect Coombs 2 months after exposure
5) Hemosiderosis of heart, liver and endocrine glands (elevated ferritin and transferrin saturation). |
|
|
Term
| What are 2 major complications of transfusion therapy for SCD? |
|
Definition
1) Alloimmunization and reactive hemolysis to donor blood that can be missed on Indirect Coombs 2 months after exposure
2) Hemosiderosis of heart, liver and endocrine glands (elevated ferritin and transferrin saturation). |
|
|
Term
| What are the major Neurological, Opthalmological and Nephrological complications of SCD? |
|
Definition
1) Neuro= Stroke
- Stroke (11% by age 20: highest in first decade)
- patients may develop anatomical abnormalities from stroke (Moyamoya) that may predispose to cerebral hemorrhage later in life
2) Opthalmology= Arteriolar occlusion and retinal hemorrhage (IV) and detachment (V)
3) Renal
- Hematuria, proteinuria and renal tubular acidosis
- Progress to renal failure in adult (20%)
- Hyperkalemia, Hyperphosphatemia, Hyperuricemia |
|
|
Term
| What are the major extremeties, GI, ID and Pulmonary complications of SCD? |
|
Definition
Leg Ulcers, Nausea/Vomiting/dyspepsia, Encapsulated organisms, ACS
1) Leg ulcers (10-20% of HbSS patients) because of chronic high hemolytic rate
- Osteomyelitis from Salmonella (splenic macrophages)
2) GI
- Nausea,vomiting, dyspepsia (gastric dysmotility from drugs narcotics and hydroxyurea)
- Liver sequestration crises
- Diarrhea (Deferasirox)
3) ID (Functional asplenia= encapsulated organisms)
- S. pneumoniae (most common cause of death), H. influenzae, N. meningitidis
- Pneumomax warranted at 2 years
4) Pulmonary
- Acute chest syndrome (ACS)- fever, pleuritic chest pain and O2 desaturation, with multilobar infiltrates
- Chronically, pulmonary fibrosis and htn can occur |
|
|
Term
| How is SCD generally diagnosed? |
|
Definition
Neonatal screening to prevent S. pneumoniae sepsis (30% fatality) and Acute splenic sequestration crisis.
Give pneumovax prophylaxis |
|
|
Term
| What are the major available treatment options for SCD? |
|
Definition
1) Allogeneic HSCT is only curative option
- Given with h/x of stroke, recurrent ACS or frequent pain crises
- Novel sources (umbilical blood) is focus of current research
2) Hydroxyurea for acute complications such as pain crises and ACS (does not prevent organ damage). |
|
|
Term
| What are the different manifestations of pediatric alpha thalassemia? |
|
Definition
Variable alpha deletions from chromosome 16
1) Silent carrier or trait with microcytosis without anemia
2) Hemoglobin H (4 beta) disease with moderately severe HA
3) Hb Barts (4 gamma)
- Hydrops fetalis with intrauterine anemia and cardiac failure
4) Hb Constant Spring
- Nondeletional one bp susbstitution in chain termination codon producing unstable mRNA |
|
|
Term
| Why does Hydrops fetalis tend to occur in children of Southeastern descent? |
|
Definition
Deletion mutations of alpha globin genes occurring in-cis alpha-1 trait/same chromosome) appear more commonly in this community, so it is more likely for all 4 alpha alleles to get deleted.
Deletions in trans (alpha-2 trait) are more common in the Mediterranean (greeks and italians) and Africa, so you rarely see Hydrops fetalis in this community |
|
|
Term
| What are the major maternal complications associated with Hydrops fetalis? |
|
Definition
Newborn hypoxia by 6 weeks gestation, with severe intrauterine anemia and cardiac failure, as well as neurological sequele down the line.
1) Pre-eclamptic toxemia 61%
2) Polyhydramnios 59%
3) Antepartum Hemorrhage 11%
4) Malpresentation 37%
5) Mean duration of gestation 31 weeks
6) PPH, DIC, abruptio placentae, retained placenta, renal failure, pleural effusion |
|
|
Term
| Describe the pathophysiological basis of beta thalassemia in the pediatric population. |
|
Definition
B0= absent mRNA and B+= decreased
Excess alpha chains are toxic to RBC membrane and Erythropoiesis is ineffective.
- Heterozygous B thalassemia mutation produces mild microcytic, hypochromic anemia (minor)
- Homozygous mutations produce severe transfusion dependent HA (major)
- HgbEE is mild, but Hgb E/B0 double heterozygote is severe |
|
|
Term
| What are the recent advancements that have been made in terms of thalassemia treatment? |
|
Definition
1) Safety of PRBC transfusion (problems with iron overload)
- Splenectomy may reduce need after age 5
2) Iron chelators
3) MRI imaging for monitoring iron overload
4) Bone marrow transplant for cure
- Most successful in younger patients, and those without hepatic complications (based on Pisaro risk stratification)
**gene therapy in the future** |
|
|
Term
| What are the major endocrine complciations of severe Thalassemia? |
|
Definition
1) Cardiac
- LVH
- Arrhythmia
- Refractory and chronic HF
2) Hepatic
- Fibrosis
- Cirrhosis
- Chronic hepatitis and failure
3) Endocrine
- Diabetes
- Hypothyroidism
- Hypoparathyroidism
- Osteoporosis
- Growth hormone deficiency |
|
|
Term
| What are the major causes of inherited hemolytic anemias? |
|
Definition
MAD
1) Membrane disorders
- DAF deficiency- PNH
- Hereditary spherocytosis
- Pyropoikilocytosis
2) Abnormal Hgb
- Sickle Cell
- Thalassemia
3) Deficient enzymes
- G6PD (X-linked)- decreased NADPH and glutathione
- Pyruvate kinase deficiency |
|
|
Term
| What is the pathophysiological basis for inherited hemolytic anemias due to G6PDH deficiency? |
|
Definition
Tend to be caused by drugs like primaquine (malaria) and dapsone (leprosy)
1) Decreased NADPH leads to decreased Glutathione
2) Oxidative stress is not resisted and RBCs hemolyze
**Assay for enzyme AFTER resolution of acute episode** |
|
|
Term
| What is the pathophysiological basis for inherited hemolytic anemias due to Pyruvate kinase deficiency? |
|
Definition
1) Increased ATP production leads to increased 2,3 DPG
2) Increased 2,3 DPG facilitates O2 release from hemoglobin to the tissues and partially compensates for anemia |
|
|
Term
| What are the major Extrinsic and Acquired Causes of Hemolytic Anemia in children? |
|
Definition
1) Immune mediated hemolysis
2) Mechanical Destruction
- Microangiopathic Hemolytic Anemia (MAHA)
- Drug Induced Hemolysis
- Thermal Burns
- Toxins
- Hypersplenism
3) Complement Mediated Destruction
- Paroxysmal Nocturnal Hemoglobinuria (decreased DAF) |
|
|
Term
| What is the pathophysiological basis of Neonatal Alloimmune Hemolytic Anemia (Erythroblastosis fetalis)? |
|
Definition
1) Transplacental passage of maternal alloantibody directed against fetal antigens, leading to hemolysis of fetal RBCs with resulting anemia, hyperbilirubinemia, hydrops fetalis, kernicterus
2) May be due to Rh incompatibility, ABO incompatibility, or other blood groups (Kell, Duffy, Lewis and others)
3) Fetomaternal hemorrhage leads to maternal immune response |
|
|
Term
| What are the major differences between warm reactive and cold reactive autoimmune hemolytic anemias of childhood? |
|
Definition
1) Warm-reactive
- IgG with positive DAT (C3b and IgG)
- Extravascular clearance primarily via the reticuloendothelial system (spleen)
- Treatment: Steroids, splenectomy, other immunosuppressive drugs, + IVIG, transfusion with least incompatible blood
2) Cold-reactive
- IgM-RBC immune complex forms at 4 degrees
- Activates complement when warmed centrally
- DAT + for C3, thus Intravascular lysis
- Treatment: Keep patient warm, supportive therapy, plasmapheresis for severe disease |
|
|
Term
True or False
In children, Hemolytic uremic syndrome is more common than Thrombotic thromobytopenic purpura |
|
Definition
True!
Both cause MAHA, but HUS will not have CNS and fever. |
|
|
Term
| What is the major cause of iron deficiency in infancy vs. adulthood? |
|
Definition
1) Infants get it because rapidly growing infant outstrips iron stores acquired from mother
2) Adults is blood loss (GI bleed due to cow milk ingestion, parasite, esophageal varices or anatomical lesions, H. pylori).
**Major cause of failure in iron therapy is improper administration (with milk or formula!) |
|
|
Term
| What are the most common causes of iron malabsorption in infants? |
|
Definition
Less common than other causes: Diagnosed by iron absorption test
1) Celiac disease
2) Medications (proton pump inhibitors, H2 – receptor antagonists)
3) Chronic giardiasis
4) Isolated defect |
|
|
Term
| What characteristic hematological abnormality might you see in a blood smear taken from a child with elevated free protoporphyrin levels in the peripheral blood and a h/x of pica? |
|
Definition
Lead Poisoning
- Basophilic stippling in erythrocytes |
|
|
Term
| How does one clinically manage a case of iron deficiency in a child? |
|
Definition
1) Treat with ferrous sulfate ( 3-6mg/kg elemental iron/day)
2) Monitoring after initiation of therapy:
- 1-2 weeks: In moderate or severe cases only; document rise in reticulocyte count and hemoglobin (» 1-2 gm/dl)
- 4-6 weeks: In all patients; document nearly complete correction of anemia
3) Duration:
- 3-4 months (at least 2 months after correction of anemia)
4) Side Effects:
GI intolerance
Dark stools
Stained teeth |
|
|
Term
| What are the most common causes of Macrocytosis in infancy? |
|
Definition
B12/Folate, Drugs (Megaloblastic)
Hypothyroidism
Liver Failure |
|
|
Term
2 year old who recently suffered from a common cold (otherwise healthy) presents with sudden onset, generalized non-blanching red lesions all over his body, with bleeding from his gums and nasopharynx.
You order some blood work and discover his platelets are very low (10 X 10^8). There is no hepatosplenomegaly on lymphadenopathy on PE.
What is the likely prognosis of this patient? |
|
Definition
Idiopathic Thrombocytopenic Purpura- 70% have complete resolution in 1 month. Treat with IVIG (induces a rapid rise in platelet count, but $$$), Prednisone, or IV Anti- D Therapy (RBC-antibody complexes bind to macrophage Fc receptors and interfere with platelet destruction)
Young child with sudden onset, generalized petechiae/purpura and bleeding from mucosa and gums , along with severe TP, following viral infection
Absence of hepatosplenomegaly and lymphadenopathy is important to rule out other conditions |
|
|
Term
| When should Pseudothrombocytopenia be suspected? |
|
Definition
In vitro clumping of platelets, resulting in artificially low platelet count. Most often due to EDTA-dependent antibodies against platelets ( most IgG, some IgM, IgA )
1) Suspect when thrombocytopenia is reported in non-bleeding patient
2) Platelet clumps on blood film from EDTA specimen
Accurate platelet counts may be obtained by:
3) Examination of EDTA blood at 37°C
4) Manual platelet count performed on blood collected by finger/heel stick into citrate anticoagulant |
|
|
Term
An otherwise healthy infant presents with isolated thrombocytopenia. Its mother has a normal platelet count, and no h/x of ITP or SLE.
What do you suspect is going on and how might you confirm your diagnose and treat? |
|
Definition
Sounds like Alloimmune TP, where mother mounts an antibody response to child's platelets that cross the placenta.
1) Diagnose
- Confirmation of anti-platelet alloantibodies in mother
- Documentation of fetomaternal incompatibility for a platelet-specific antigen (most often HPA-1a ( PlA1) in a Caucasian population)
2) Treatment (in case of hemorrhagic complications)
- washed maternal platelets
- while awaiting compatible platelets consider trial of random donor platelets + IVIG |
|
|
Term
Infant presents with sudden, severe, episode of mucocutaneous bleeding.
Blood work comes back and shows normal RBC and Platelet counts, with normal morphology. Ristocetin-induced platelet agglutination test is also normal.
What is most likely going on and how do you manage it? |
|
Definition
Age and presentation fits congenital disease of primary hemostasis, consistent with Glanzmann's Thrombasthenia (AR disorder with deficient/abnormal GPIIb/IIIa).
In GT, Platelets do not AGGREGATE in response to ADP, Epi or Collagen, but do agglutinate in response to Ristocetin.
Treatment
1) Local measures
2) DDAVP (induce vWF release from Weibel pallade)
3) Fibrinolytic inhibitors, platelet transfusion, FVIIa |
|
|
Term
| How can Glanzmann's Thrombasthenia be distinguished from Bernard Soulier Syndrome clinically? |
|
Definition
Both may present with acute episodes of mucocuntaeous bleeding during infancy, with high rate of co-sanguitity (AR conditions).
1) GT will have normal platelet count/morphology and normal Ristocetin agglutination, but ABNORMAL aggregation in response to Epi, ADP and collagen (GPIIb/IIIa)
**Similar to effect of Abcixumab**
2) BSS will have prolonged bleeding time, normal platelet aggregation in response to ADP, epinephrine, and collagen
Abnormal or absent AGGLUTINATION in response to ristocetin (GP1b-a, GP1b-b, GPIX) |
|
|
Term
Which congenital platelet function disorder (and it pathophysiology) is described by each of the following.
1) Mild, mucocutaneous bleeding with prolonged bleeding time due to large, agranular, gray, platelets that are deficient in alpha storage granules
2) Acute mucocutaneous bleeding episodes in infant with normal platelet count/morphology, Ristocetin agglutation test and abnormal aggregation in presence of ADP, Epi and collagen
3) Acute mucocutaneous bleeding episodes in infant with normal aggregation of platelets in response to ADP, Epi and collagen, but abnormal agglutination in response to Ristocetin and prolonged bleeding time |
|
Definition
All are qualitative platelet disorders of infancy.
1) Gray Platelet Syndrome (AR, NBEAL2 mutation)
- Alpha granules contain IGF1, PDGF, PF4, TGFB
2) Glanzmann's Thrombasthenia (AR, GPIIb/IIIa deficiency)
3) Bernard Soulier Syndrome (AR, GP1b-a/GP1b-b/GP1X) |
|
|
Term
| How are Qualitative Platelet disorders of infancy treated? |
|
Definition
Include Gray Platelet Syndrome, Glanzmann's and Bernard Soulier.
1) Remove or discontinue offending agent (e.g. drug)
2) Treat underlying disease ( e.g. dialysis )
3) Local measures (pressure, Gelfoam, desiccated collagen, etc.)
4) Tranexamic acid
5) Desmopressin (DDAVP)
6) RBC transfusion if patient anemic
7) Recombinant Factor VIIa
8) Platelet transfusion |
|
|
Term
| How can ITP of infancy be treated? |
|
Definition
1. Intravenous immunoglobulin (IVIG).
- IVIG therapy is both expensive and time-consuming to administer.
2. Prednisone.
3. IV Anti- D Therapy
- RBC-antibody complexes bind to macrophage Fc receptors and interfere with platelet destruction. |
|
|
Term
| What are the primary disorders that cause Neutropenia due to decreased bone marrow reserve in childhood? |
|
Definition
If reserve is normal, think immune of non-immune (hypersplenism, infection, excessive margination)
1) Kostmann syndrome
- EL2-A mutations cause apoptosis of myeloid precursors
- aggressively treat infections and consider BMT
2) Shwachman-DIamond syndrome
- AR, FAS associated apoptosis of marrow precursors, ↓ CD34+ cells, marrow stromal defect (Often have SBDS gene defect and produce pancreatic exocrine insufficiency)
3) Cyclic Neutropenia
- ELA2 mutations and apoptosis in precursors and cyclic hematopoiesis |
|
|
Term
| What are the major immune Neutropenias of childhood? |
|
Definition
Low PMN count with normal/high marrow reserve and normal/low granule pool
1) Neonatal alloimmune neutropenia
- Maternal anti-PMN antibodies again neonate-specific antigens
2) Chronic benign neutropenia of childhood autoimmune neutropenia
- Anti-PMN antibody that can lead to infection
3) Drug-induced |
|
|
Term
What is the most common cause of neutropenia in a newborn.
1. Autoimmune
2. Infection
3. Congenital
4. Drug-induced |
|
Definition
|
|
Term
| What are the most common mechanisms/causes of Neutropenia secondary to drugs/toxins? |
|
Definition
Withdraw unnecessary drugs, Eliminate toxins, G-CSF may be helpful with severe infections
1) Immune (acute symptoms in days with positive antibody test)
- PCN (and other antibiotics)
2) Toxic (insidious with direct cellular toxicity)
- Phenothiazine
3) Hypersensitivity (insidious onset with rash, fever, lymphadenopathy due to direct cellular toxicity)
- Dilantin
- Phenobarbitol |
|
|
Term
What conditions are described by each of the following?
1) AR condition with impaired DNA repair, predisposing to AML
2) AR mutation in RPS19 on chromosome 19 (20-25% of time) producing macrocytic anemia and bone marrow failure. |
|
Definition
Congenital Marrow Failure Syndromes with short stature and other physical abnormalities
1) Fanconi anemia- Treat with HSCT
- Have to use alternative, low-dose chemotherapy
- Skeletal abnormalities (heterogeneous)
2) Diamond Blackfan anemia- Treat with HSCT
- Normal platelets and WBCs, with decreased RBC precursors
- Corticosteroids and red blood cell transfusions are the mainstays of therapy (curative with BMT) |
|
|
Term
True or False:
Aplastic anemia in children can be associated with prior episode of EBV infection |
|
Definition
True! As well as Hepatitis
Need Expedient HSCT from sibling donor, otherwise use cyclosporine A and ATG (may eventually develop myelodysplastic syndrome)
EBV affects B cells (CD21) and is targeted by T cells |
|
|
Term
| Name 4 common causes of secondary neutropenia in childhood. |
|
Definition
1) Chemotherapy
2) Aplastic anemia
3) B12/folate deficiency
4) Hypersplenism |
|
|
Term
| What abnormalities do you expect to see in a peripheral blood smear from a patient with Kostman's syndrome. |
|
Definition
Severe congenital neutropenia due to bone marrow reserve failure.
1) Marked increase in myeloid precursors without evidence of maturation (EL2-A mutation)
2) Promyelocytic or myelocytic arrest
3) Eosinphils are increased.
4) Increase in small to intermediate sized lymphocytes |
|
|
Term
What is the pathophysiology/treatment of the childhood disease characterized by
- hypopigmentation of the skin, eyes, and hair;
- prolonged bleeding times; easy bruisability;
- recurrent infections |
|
Definition
Chediak Higashi
1) AR, immunodeficiency characterized by defective intracellular protein transport
- Mutation in the LYST or CHS1 gene localized to bands 1q42-43
2) Treat with aggressive antibiotics for infection and BMT |
|
|
Term
| Why is SCID usually fatal by age 2? What is the treatment? |
|
Definition
Severe immune depletion of T cells and B cells (may be present, but do not function) leading to overwhelming infection.
Can be due to IL-2 receptor defect (most common), Adenosine deaminase deficiency, or failure to synthesize MHC II antigens
Immediate referral for curative HSCT (previously irradiated) |
|
|
Term
1 year old child presents with failure to thrive. They have a h/x of chronic diarrhea and recurrent infections, including a oral thrush and PCP.
What measures of immunological function should you collect and what do you think you will find. |
|
Definition
Recurrent infections with opportunistic instances in infant with FTT and diarrhea screams SCID.
Order CBC and genetic testing to determine "flavor" of SCID (T- B+ vs. T- B-, types of molecular defects and AR vs. X-linked)
1) CD Markers for cell numbers
- CD3 T cells (CD4 Helper and CD8 Killer)
- CD19 B cells
- CD16/56 NK cells.
2) Cell function (mitogens for T cells and IG for B cells) |
|
|
Term
| What is the pathophysiological basis/treatment of the condition of infancy that presents with immunodeficiency, eczema and thrombocytopenia (small platelets) |
|
Definition
Wiskott Aldrich Syndrome (WAS)
1) Pathophysiology
- X-linked mutation in WASP gene, which encodes a protein that activates actin polymerization by binding to the Arp2/3 complex, leading to important cytoskeletal rearrangements at the immunological synapse.
- Produces combined B and T defect
- variable T cell functional defect, normal to low T cell numbers
- normal B cell numbers/declining IgG and specific antibody production over time
2) Treatment
- Curative with early, well-matched HSCT |
|
|
Term
What congenital immunodeficiency is described by each of the following and what is the correct treatment?
1) X-linked mutation in WASP gene, producing combined B/T cell defect, presenting as eczema, thrombocytopenia and recurrent infections
2) X-linked deficiency in CD40L on T cells, impairing B cell class-switching with primary manifestation of hypogammaglobulinemia, low IgG, low IgA and normal or high IgM. Severe pyogenic infections early in life
3) X-linked mutations in the SAP gene (normally associates with SLAP receptors on T/B/NK cells) with normal T and B cell numbers, but defective B cell memory
4) X-linked disorder of B cell development due to mutation of the BTK (Bruton’s tyrosine kinase) gene producing boys that are prone to chronic enteroviral meningoencephalitis |
|
Definition
1) Wiskott-Aldrich Syndrome- HSCT early
2) Hyper-IgM syndrome- HSCT
3) X-linked lymphoproliferative disease (XLP)- often associated with fulminant EBV infection and treated with HSCT
4) X-linked (Bruton's) agammaglobulinemia- IgG replacement |
|
|
Term
| How does CVID differ from SCID? How do the treatments differ? |
|
Definition
1) SCID is severe, early T cell depletion with B-cell functional defects (Can be T-B+ or T-B-, AR or X-linked, with different molecular bases)
- Treated with HSCT
2) CVID is heterogenous group of immunodeficiencies that are characterized by late-onset humoral immunodeficiency, low IgA and/or IgG, poor specific antibody responses
- Treated mostly with IgG replacement and supportive treatment of infectious and autoimmune complications |
|
|
Term
Which congenital B cell disorder pathophysiology is characterized by each of the following clinical/laboratory profiles?
1) Normal pro-B cells with decreased maturation and number of mature B cells. Low IG of all classes
2) High IgM, Low IgG, IgA and IgE, with severe pyogenic infections in childhood
3) IgA deficiency with sinus and lung infections, milk allergies and diarrhea
4) Normal B cell number, but decreased plasma cells and IG with increased risk of autoimmune disease, lymphoma and sinopulmonary infection. |
|
Definition
1) Bruton's agammaglobulinemia
- X-linked defect in BTK (tyrosine kinase), blocking pro-B cells from forming pre-B cells
- Recurrent bacteria infections after 6 months with absent thymic shadow.
2) Hyper-IgM syndrome
- Defective CD40L on CD4+ T cells- inability to class switch
3) Selective IgA deficiency
- Defect in isotype switching
- Anaphylaxis when exposed to blood products with IgA
4) CVID
- Defect in B cell maturation; heterogenous causes
- Acquired in 20s-20s with increased risk of autoimmune disease, lymphoma and sinopulmonary infection. |
|
|
Term
Which congenital T cell disorder pathophysiology is characterized by each of the following laboratory profiles?
1) Decreased T cells, parathyroid hormone and Ca2+ levels, with absent thymic shadow on CXR
2) Decreased IFN-y
3) High IgE only
4) Normal T cell levels with opportunistic Candida infections
2) High IgM, Low IgG, IgA and IgE
3) IgA deficiency
4) Normal B cell number, but decreased plasma cells and IG |
|
Definition
1) Thymic aplasia (Digeorge)
- 22q11 deletion with failure to develop 3rd and 4th pharyngeal pouches
- Presents with tetany (calcium), viral/fungal infections (T-cell deficiency), and congenital heart/great vessel defects
2) IL-12 receptor deficiency
- Decreased Th1 response
- Disseminated mycobacterial infections
3) Hyper-IgE syndrome (Job's)
- Th cells fail to produce IFN-y, causing instability of PMNs to respond to chemotactic stimuli
- FATED (coarse Facies, cold staph Abscesses, retained primary Teeth, increased igE, Dermatology problems)
4) Chronic mucocutaneous candidiasis
- T cell dysfunction |
|
|
Term
Which congenital combined T/B cell disorder pathophysiology is characterized by each of the following laboratory profiles?
1. Low IL-2R and/or increased Adenine
2. IgA deficiency
3. Increased IgE and IgA, with decreased IgM
1) Normal pro-B cells with decreased maturation and number of mature B cells. Low IG of all classes
2) High IgM, Low IgG, IgA and IgE
3) IgA deficiency
4) Normal B cell number, but decreased plasma cells and IG |
|
Definition
1) SCID
- Defective IL-2R (T cell activation defect) or Adenine deaminase deficiency (toxic to B and T cells)
- Need HSCT
2) Ataxia-Telangiectasia
- Defect in ATM gene which codes for DNA repair enzymes
- Cerebellar defects (ataxia), spider angiomas (telangiectasia), IgA deficiency
3) WAS
- X-linked recessive defect in WASP gene
- TIE (TP, Infections, Eczema) |
|
|
Term
Which congenital disorder of phagocyte function is characterized by each of the following clinical/laboratory profiles?
1) Neutrophilia with recurrent bacterial infections without pus formation
2) Recurrent pyogenic infections by staph and strep; partial albinism and peripheral neuropathy
3) Negative Nitro blue tetrazolium dye reduction test with increased susceptibility to catalase-positive organisms (S. aureus, E. coli, Aspergillus) |
|
Definition
1) LAD-1
- Defect in LFA-1 integrin (CD18) on phagocytes
2) Chediak-Higashi
- AR defect in lysosomal traffickign gene (LYST)
- microtubule dysfunction in phagosome/lysosome fusion
3) CGD
- Lack of NADPH oxidase- decreased ROS and absent respiratory burst from PMNs |
|
|
Term
True or False:
Congenital immunodeficiency syndromes often predispose kids to blood cancers like NHL |
|
Definition
True
WAS, CVID, AT, XLP, CHS, ect |
|
|
Term
| What are Autoimmune Lymphoproliferative Syndromes (Alps) and what is their general pathophysiological basis? |
|
Definition
Present with adenopathy, hepatosplenomegaly and are associated with increased risk of lymphoma.
Abnormalities of programmed cell death (apoptosis) due to mutations in the Fas, Fas ligand or caspase 8 / 10 genes that can be treated with mycophenylate mofetil ( MMF ) |
|
|
Term
| What are the characteristic laboratory findings associated with the congenital diseases associated with hepatosplenomegaly, lymphadenopathy and increased risk of lymphoma? |
|
Definition
Autoimmune Lymphoproliferative syndromes (ALPS)
1) immune cytopenias ( ITP, neutropenia, hemolytic anemia )
2) hyperglobulinemia
3) increased double negative ( CD4 / CD8 ) T cells
4) Increased IL – 10 |
|
|
Term
What group of congenital hematological disorders are characterized by uncontrolled activation of cellular immune system and defective triggering of apoptosis, presenting with fever, hepatosplenomegaly, neurological symptoms (seizures), enlarged LN, skin rash and jaundice?
What is the treatment protocol? |
|
Definition
1) Hemophagocytic Lymphohistiocytosis
2) Treated with induction therapy (8 weeks) with Decadron, CSA and VP16
Familial and refractory cases proceed to HSCT. |
|
|
Term
| What are the 3 major classes of histiocyte disorders? |
|
Definition
1) Class I
- Langerhans cell histiocytosis (Localized disease-skin, bone, lymph nodes, minimal treatment required)
2) Class II
- Non-Langerhans cell histiocytosis
- Hemophagocytic Lymphohistiocytosis (HLH)
3) Class III
- Malignant Histiocytic Disorder |
|
|
