Allergy & Immunology Flashcards
What is an important organism to vaccinate against in children with Nephrotic syndrome?
Strep pneumo (pneumococcal polysaccharide 23-valent vaccine is recommended)
What is the risk associated with the oral polio vaccine?
Vaccine viruses are excreted in the stool of the vaccinated person for up to 6 weeks after a dose.
Maximum viral shedding occurs in the first 1–2 weeks after vaccination, particularly after the first dose.
Vaccine viruses may spread from the recipient to contacts. Persons coming in contact with fecal material of a vaccinated person may be exposed and infected with vaccine virus.
What are the CPS recommendations for post-splenectomy antibiotic prophylaxis?
Antibiotic prophylaxis for a minimum of two years postsplenectomy and for all children <5 years of age. Lifelong prophylaxis in all cases is ideal!
What is the percent cross-reactivity between penicillins and cephalosporins?
2% (risk of allergic reaction to cephalosporins in patients with positive skin test responses to penicillin)
What are key features of Wiskott-Aldrich syndrome?
Eczema, thrombocytopenia, recurrent infections, low IgM, high IgE and IgA
Diagnostic criteria for anaphylaxis
Any one of the following three criteria:
- Acute onset of an illness with involvement of the skin and/or mucosal tissue AND at least one of respiratory compromise or hypotension
- Two or more systems involved (skin/mucosa, resp, CV, GI) after exposure to likely allergen
- Reduced BP following exposure to known allergen (>30% drop)
Child with abscesses, lymphadenopathy, serratia infection
Chronic granulomatous disease
Unilateral facial weakness, vesicles in ear canal
Ramsay-Hunt Syndrome (herpes zoster oticus) - treated with acyclovir and steroids
Treatment of type III hypersensitivity reaction (ie serum sickness)
anti-histamine and NSAIDs
How do you diagnose CGD?
nitroblue tetrazolium test for neutrophil oxidative ability
Influenza vaccine and egg allergy - contraindicated?
Administration of inactivated trivalent or quadrivalent influenza vaccines is safe for individuals with egg allergy. Unless children have experienced an anaphylactic reaction to a previous dose of influenza vaccine, they can and should be immunized with a full dose of trivalent or quadrivalent inactivated vaccine. Don’t give the live attenuated vaccine (not tested).
Low IgA, normal IgM and IgG
IgA deficiency Can’t be diagnosed until 4 years of age (when IgA reaches adult levels). Occurs in 1/500, most asymptomatic. Associated with recurrent sinopulmonary infections, IgG2 subclass deficiency, food allergy, autoimmune disease and celiac.
What is important to test in a patient with neisseria meningitis?
Terminal complement (C5-9) - the membrane attack complex
What patients respond to allergen immunotherapy?
seasonal/perennial allergic rhinoconjunctivitis, asthma triggered by allergen exposures, and insect venom sensitivity
(no evidence for food allergy, atopic dermatitis, latex allergy, and acute/chronic urticaria)
What can result in false positive RAST testing?
High IgE
Infections, absent thymus?
SCID
Hypocalcemia, congenital heart disease, absent thymus?
DiGeorge (22q11)
SCID genetic defect
x-linked, gamma chain defect of the IL-2 receptor
Hallmark of leukocyte adhesion deficiency
delayed separation of umbilical cord
Classic presentation of SCID
thrush, recurrent sepsis, pneumonia, otitis media, diarrhea, FTT, absent lymphoid tissue
Work up of suspected humoral immunity deficiency
- CBC, diff
- immunoglobulins
- vaccine titres
- RBC isohemagglutinin (IgM)
- CXR (to evaluate for thymus, bronchiectasis)
What is a hallmark sign of CVID?
Recurrent sino-pulmonary infections
IVIG replacement therapy dose
400-600 mg/kg Q3-4 weeks
In what condition could you have anaphylaxis to IVIG?
IgA deficiency
T-cell problem work-up
- CBC & diff
- intradermal candida skin testing
- T & B cell markers (flow cytometry)
- Day 3 proliferation (mitogen - stimulate proliferation)
- Day 6 proliferation (antigen)
- thymic biopsy
Most common cardiac issue in DiGeorge?
interrupted aortic arch, type B
Can SCID babies be breastfed?
NO. Unless the milk is irradiated.
Features of Omenn’s syndrome
Erythroderma
Lymphadenopathy
Hepatosplenomegaly
Short limbs
Ataxia telangiectasia
Abnormal DNA repair
15% develop malignancy
up to 80% have IgA deficiency
Wiskott-Aldrich Syndrome - immunoglobulin pattern
normal IgG, low IgM and elevated IgA and E
Wiskott-Aldrich syndrome clinical symptoms
x-linked, eczema, thrombocytopenia and recurrent pyogenic infections
What prophylaxis should a patient with CGD be on?
septra, itraconazole
What component of penicillin are people anaphylactic to?
Minor component
What component of penicillin are people allergic to?
Major component
How often do IgE-mediated systemic reactions occur to penicillin?
approximately 2% of the time
Cross-reactivity of penicillins and cephalosporins?
<2%
most common food allergy in kids?
cows milk
what percent of children will outgrow peanut allergy?
20%
When should you evaluate for an immunodeficiency?
- unusual bugs (PJP, aspergillus, etc)
- unusual site (CNS, liver)
- 2 or more serious resp/bacterial infections within 1 yr (pneumonia, cellulitis, etc)
- 1 or more systemic bacterial infection (sepsis)
- usual bugs, but very severe
Hypocalcemia
Unusual facies/ears
Cardiac disease
DiGeorge (22q11)
Delayed separation of the umbilical cord
Leukocytosis
Recurrent infections
Leukocyte adhesion defect
Persistent thrush, diarrhea
FTT
Pneumonias
SCID
Bloody stools
draining ears
atopic eczema
thrombocytopenia
Wiskott-Aldrich syndrome
CBC findings in SCID
lymphopenia (t-cells = 70% of lymphocytes)
Suspected B-cell defect. What tests would you order to work-up?
CBC, diff, ESR
IgA, IgM, IgG
Vaccine antibody titres
Isohemagglutinins
Suspected T-cell defect. What tests could you do to evaluate?
CBC (lymphopenia)
Candida albicans intradermal skin test
Screen for phagocytic cell defects
Absolute neutrophil count
Respiratory burst assay
Screen for complement deficiency
CH50
Most common B-cell defect
IgA deficiency
Three conditions where isohemagglutinins would be low/absent
B cell defect
First 2 yrs of life
Blood type AB
If you wanted to test antibody response to a polysaccharide vaccine, which could you use?
PPV23 (pneumococcal polysaccharide vaccine)
If you wanted to test antibody response to a protein antigen, which vaccine could you use?
DTaP
What should you do if IgM/IgG are low in serum, but the patient has normal antibody responses to vaccines?
Check for protein loss in gut (enteropathy) or urinary tract (nephrotic syndrome)
If a child lacks IgG2, what will they not be able to do?
make antibodies in response to polysaccharide antigens
If you detect agammaglobulinemia, what should you test next?
flow cytometry for b-cells
absent in x-linked agammaglobulinemia, present in CVID
B cell specific CD antigens
CD 19
CD 20
Negative candida skin test, what does this mean?
negative = < 10mm at 48 hrs
Normal T-cell function!
T cell specific CD antigens
CD2, CD3, CD4, CD8
Child with lymphopenia. What type of cell defect should you suspect?
T-cell! Usually 70% of lymphocytes are T-cells
You suspect a T-cell deficiency, but the T-cell numbers are normal on flow cytometry. What do you do next?
Mitogen stimulation testing
functional testing of T-cell
Recurrent staph abscesses + infections with gram-negative bugs. What type of defect?
Phagocytic cells
How do you assess for a phagocytic cell defect?
Check neutrophil respiratory burst
Best test = flow cytometric assessment of the respiratory burst using rhodamine dye
(replaced nitroblue tetrazolium dye test)
Inheritance of CGD
1 type is x-linked (65%)
3 types are AR (35%)
Most common cause of an abnormal CH50
Delay or improper transfer of the specimen to the lab
Newborns are deficient in IgM. Why is this? What does this make them susceptible to?
Only IgG crosses the placenta
They have increased susceptibility to gram-negative organisms
When does the thymus begin to involute?
after puberty
No tonsils/lymph nodes, flow cytometry shows no circulating B-cells, very low (almost absent) IgG/M/A/E
normal thymus and increased number of T-cells
X-linked agammaglobulinemia
Due to mutation in Bruton tyrosine kinase gene
What kind of infections do boys with X-linked agammaglobulinemia get?
Recurrent sinopulmonary infections with respiratory pathogens (strep, h.flue, staph, pseudomonas, mycoplasma)
ALSO
hepatitis, enterovirus
What other cell line can be affected in XLA?
they can have neutropenia
BTK also important for myeloid cell differentiation
Treatment of XLA?
Replace absent immunoglobulins! (IVIG)
What would flow cytometry and mitogen stimulation tests (of B-cells) show in CVID?
Normal numbers of circulating peripheral B-cells, no antibody response to mitogens (or T-cells)
Patient with CVID, increased risk of what cancer?
Lymphoma! (438x increased risk)
Encapsulated bacteria
SHiNE SKiS Strep pneumo Haemophilus influenza typeB Neisseria meningitidis E.coli
Salmonella
Klebsiella
Group B Strep
Medications that may be related to CVID or IgA deficiency
Phenytoin
Gold
Sulfasalazine
Penicillamine
What GI infection do with IgA deficiency get?
Giardia
If someone had anaphylaxis after IVIG or blood products, what would you suspect?
IgA deficiency
44% of IgA deficient people have antibodies to IgA - if these are IgE antibodies, can cause anaphylaxis!
Is hyper IgM syndrome of T-cell or B-cell defects?
T-cell defect! B-cells function normally, but t-cells can’t undergo gene rearrangement to direct B-cells to make other types of immunoglobulins
Features of hyper IgM syndrome
Profound neutropenia PJP pneumonia Recurrent infections with encapsulated organisms (can't make IgG) Warts Crytosporidium enteritis Liver disease Increased risk of malignancy
Baby with DiGeorge syndrome. What condition did mom have during pregnancy?
15% of babies with DiGeorge are born to diabetic mothers
Which antibody deficiency is at increased risk of PJP pneumonia?
Hyper IgM Syndrome - is actually T-cell defect, unable to “switch” to stimulate B-cells to make other types of immunoglobulins
What conditions would prompt you to look for DiGeorge (and for T-cell deficiency)
primary hypoparathyroidism, CHARGE syndrome, truncus arteriosus, and interrupted aortic arch type B
Chronic mucocutaneous candidiasis + hypoparathyroidism (hypocalcemia). What should you check for?
test for addison’s disease
could be autoimmune polyendocrinopathy type I, or APECED
Profound lymphopenia, no T cells, absent antibody response, rachitic rosary.
ADA-deficient SCID
(presence of rib cage abnormalities similar to a rachitic rosary and numerous skeletal abnormalities of chondro-osseous dysplasia)
Omenn syndrome
AR, fatal
Erythroderma, profound diarrhea / FTT, lymphadenopathy, HSM, eosinophilia
Absence of BOTH B+T cells
Immunoglobulin pattern in Wiskott-Aldrich
Low IgM
High IgE/IgA
Clinical features of Wiskott-Aldrich
Thrombocytopenia (microplatelets)
Eczema
Recurrent infections (encapsulated organisms, herpes viruses, PJP)
Major causes of death (name 3) in Wiskott-Aldrich syndrome
hemorrhage
Recurrent infection
EBV-associated malignancy
Management of Wiskott-Aldrich
Platelet transfusions prn
IVIG
BMT
What should you avoid in a patient with Ataxia-Telangectasia Syndrome?
X-rays!
DNA repair defect, increased risk of malignancy
Recurrent staph infections, candida, retained primary teeth, coarse facial features. What syndrome?
Hyper IgE
Treatment of hyper IgE syndrome
anti-staph antibiotics
IVIG replacement
Causes of neutropenia
Infectious Post-infectious Medication induced Starvation/anorexia Ineffective myelopoesis Syndrome-associated
Severe congenital neutropenia - other blood counts?
Monocytosis, eosinophilia
Often anemia of chronic disease
Risk of what cancer with severe congenital neutropenia?
AML
MDS
Pancreatic insufficiency, neutropenia
Shwachman-Diamond
Schwachman-Diamond
Inheritance?
Major features?
AR mutation in SBDS gene
Neutropenia
Pancreatic insufficiency
FTT
Delayed separation of the umbilical cord - think of what condition?
Leukocyte adhesion defects
Neutrophil count in leukocyte adhesion defects?
Often > 30! very high peripheral blood neutrophilia, neutrophils cannot extravasate and migrate
Diagnosis of leukocyte adhesion defect (type 1)
flow cytometry - absence of CD11b/CD18 on neutrophils
Diagnosis of Chediak-Higashi syndrome
Large lysosomal inclusions in all nucleated cells - may not be evident on peripheral blood (large cells can’t get out of bone marrow) - check BMA if suspect CHS!
Treatment of chediak-higashi syndrome?
High dose Vit C
BMT
Inheritance of CGD
1 type x-linked
3 types AR
Most common organism causing infection in CGD
Staph aureus
Non-immune signs of CGD
anemia of chronic disease FTT HSM lymphadenopathy dermatitis ginigivitis hydronephrosis pyloric outlet narrowing?
Supportive care in CGD
septra prophy
itraconazole prophy
interferon gamma 3x/wk (mechanism unknown)
What order do classical complement proteins fix to the immune complex?
1-4-2-3
Terminal complement deficiency (C5-8) predisposes you to what types of infections?
- meningococcal meningitis
- extragenital gonococcal infection
Suppurative lymphadenopathy is a feature of what condition?
CGD
Which condition is associated with a lack of purulent discharge?
LAD
Which condition is prone to getting serratia?
CGD
Sinopulmonary infections + enterovirus
XLA
most common cause of out-of-hospital anaphylaxis
food allergy (most commonly, peanut)
Common causes of anaphylaxis in children
Food (peanuts, milk, eggs, fish) Drugs (Penicillins) Insect venom (bee) Latex Vaccines
Dose and administration of epinephrine for anaphylaxis
0.01 mg/kg IM (up to 0.3)
If prescribing EpiPen:
- 15mg (for 8-25 kg)
- 3mg (for >25 kg)
Other medications used in anaphylaxis (other than epi)
Corticosteroids (Methylpred IV)
H1 blockers (Cetirizine/Diphenhydramine)
H2 blockers (Ranitidine/Cimetidine)
O2
IV fluids
Salbutamol (beta-agonist)
Kid treated with amoxicillin and develops a non-pruritic rash over body. What infection did they likely have?
EBV
Two antibiotic classes with cross-reactivity to penicillins
Cephalosporins
Carbapenems
Most common hematologic abnormality in allergic patients
Eosinophilia
Name two diseases that have significantly elevated IgE
Hyper IgE
Allergic bronchopulmonary aspergillosis
What is Red Man syndrome and how do you manage it?
Non-specific histamine release due to Vancomycin.
Can be prevented by slowing infusion rate and administering H1 blocker (benadryl)
What autoimmune antibody is associated with chronic urticaria?
anti-thyroid antibodies
patient with chronic urticaria. what might you see on skin testing?
positive autologous skin test (ASST) result (their own serum injected intradermally)
How do you treat chronic urticaria?
H1 antihistamine
if not responding - increase dose
if still not responding, add H2 blocker (NOT H2 alone)
consider short course of steroids
What is elevated in the blood in anaphylaxis?
plasma b-tryptase
