Allergy/Immunology Flashcards
What is the most common form of SCID?
X-linked, about 50% are of this variety
What is the mutation in X linked SCID
mutation in the cytokine receptor subunit gamma chain which is a component of several cytokine receptors including those or interleukins.
T cells do not develop.
Maternal T cells engraft but they do not work well,
B cells are present but do not work well
What is the resulting flow cytometry of X linked SCID
B+ T cell - and NK cell -
What medical intervention should not be given to a child with SCID?
Live virus vaccines
What kind of blood does a child with SCID need and why?
Irradiated
because non-irradiated blood has T lymphocytes which can cause graft vs hose disease
What clinical and laboratory findings do children with SCID have?
lymphopenia
absence of a thymus shadow on chest XR
present with overwhelming sepsis, eczematous like skin lesions, chronic lung infections, diarrhea and failure to thrive. PCP pneumonia, candidiasis, CMV pneumonia
What purine salvage pathways disorders manifest as SCID?
adenosine deaminase deficiency
purine nucleoside deficiency
How does ADA cause immunodeficiency?
accumulation of deoxyadenosine and deoxyadenosine trisphospate accumulate in lymphocytes which kills the lymphocytes. so no b cells, t cells or NK cells.
What skeletal abnormalities are seen with adenosine deaminase deficiency
cupping and flaring of the costochondral junction and pelvic dysplasia
what autoimmune disease is common in those with purine nucleoside phosphorylase deficiency
Rare, less severe than ADA
autoimmune hemolytic anemia and thrombocytopenia
What is RAG deficiency?
autosomal recessive
most severe form of SCID and accounts for 25-30%
mutation/deletion in RAG 1 and 2 genes that makes the cell unable to rearrange the genes for immunoglobulin and for T cell antigen receptors.
B and T cells do not work. NK cells are ok
What is reticular dysgenesis
Form of SCID where myeloid and lymphoid cell lines do not develop.
What is Omenn Syndrome
variant of RAG deficiency, with partial as oppose to complete deletion
present with erythroderma, diarrhea, hepatosplenomegaly and failure to thrive.
hypogammaglobulinemia, elevated IgE and marked eosinophilia.
What is bare lymphocyte syndrome
Failure to express MCH class 2 molecules have guarded prognosis even after bone marrow transplant
What is Waiskott-Aldrich Syndrome?
x-linked EXIT: eczema x linked immune deficiency thrombocytopenia
What symptoms and signs are suggestive of Waiskott-Aldrich Syndrome?
abnormal bleeding bloody diarrhea eosinophilia and increases IgE recurrent sino pulmonary infections, chronic otitis media, severe viral infections small platelets are diagnostic
What immunoglobulins are made or not made in Waiskott-Aldrich Syndrome and what is the treatment?
Makes IgA and IgE and IgG
Does not make IgM
since the respond poorly to vaccines, IVIG is recommended
What are the main characteristics of Ataxia-Telangiectasia?
cerebellar ataxia
oculocutaneous telangiectasia
immunodeficiency
high incidence of cancer with increased sensitivity to radiation
How does ataxia-telangiectasia present? How is it diagnosed?
Around the age of 5 starts to have ataxia, telangiectasias also start to appear at age 5, but sometimes later
sinopulmonary disease with bronchiectasis
Diagnosis is ataxia plus telangiectasias plus positive alpha fetoprotein
immune problems are usually less than the ataxia
What are children with ataxia-telangiectasia most at risk for?
lymphocytic leukemias or lymphoma
What are the signs of Bloom syndrome?
deficiency in DNA ligase 1
small stature, telangiectasia, CNA abnormalities and immunodeficiency
at risk for leukemia
What are the signs of Nijmegen Breakage syndrome
“bird like” face and microcephaly with normal IQ
cellular and humoral deficiency
high incidence of lymphoid cancers
What chromosomal deletion causes DiGeorge Syndrome?
Catch 22
22q11
What are the clinical signs of DiGeorge?
cardiac abnormalities ( tetralogy, transposition of great vessels, VSD, double outlet RV)
hypoparathyoirism
thymus abnormalities
micrognathia, hypertelorism, low set ears, small philthrum
What is the immune deficiency like in DiGeorge?
immunodeficiency with severity depending on extent of syndrome, can be SCID like, some will get better with time
IVIG used if antibody production is poor
What is Nezelof Syndrome
autosomal recessive form of thymic hypoplasia
leads to varying degrees of T-cell dysfunction
How does X-linked (Burton’s) agammaglobulinemia present?
Recurrent bacterial infections particularly pneumonia, ear infections, sinusitis.
Often testing is prompted after boy over 1 year of age has been treated over and over again with antibiotics.
What is X-linked agammaglobulinemia?
mutation in gene BTX burton’s tyrosine kinase at Xq22
this is necessary for b cell development so there are only pre-b cells in circulation, no mature b cells
How is x-linked agammaglobulinemia diagnosed and treated?
severe deficiency of all immunoglobulins
need at least monthly IVIG
small tonsils and lymph nodes
What are the symptoms and lab values of Common Variable Immunodeficiency
recurrent sinopulmonary infections with encapsulated bacteria
deficiency in at least two classes of immunoglobulins (IgG, IgM or IgA) and poor immunoglobulin function as demonstrated by low vaccine titers to Dtap and pneumococcus
IgG < 300
IgA and IgM < 50
What other findings are associated with CVID?
sarcoid like disease with noncaseating gramulomas of spleen, liver, lungs, and skin
may have hepatosplenomegaly
autoimmune conditions: (ITP, pernicious anemia, hemolytic anemia, malabsorption, pancytopenia)
sprue like illness: diarrhea, malabsorption, protein losing enteropathy, steatorrhea
increase incidence of lymphoma
giardia
chronic enteroviral meningitis
How is CVID treated?
IVIG and specific therapy for infectious complications
What is the deficiency in Hyper-IgM syndrome?
deficiency in IgG and IgA with normal or high IgM
What is the genetics and cause of Hyper-IgM syndrome
can be either x-linked or AR X linked is due to deficiencies in coding CD40 ligand on T cells so, b cells can not class switch to more specific antibodies
How does hyper IgM syndrome present?
recurrent sino pulmonary infections particularly with encapsulated organisms, giardiasis and meningitis
X-linked also susceptible to PCP
How is Hyper-IgM syndrome treated?
IVIG and prophylaxis for those at risk for PCP
bone marrow transplant is considered for those with x-linked variety
How does X linked lymphoproliferative disease (Duncan disease) present?
severe or fatal EBV infection causing:
fulminate hepatitis, b-cell lymphoma, agranulocytosis, aplastic anemia, or acquired hypogammaglobulinemia
polyclonal expansion of B and t cells resulting in hepatic necrosis and bone marrow failure due to NK and cytotoxic t-cells
prior to EBV no immune problems
How is x linked lymphoproliferative disease (Duncan disease) treated?
steroids, immunosuppressants, cytotoxic agents
What is transient hypogammaglobulinemia of infancy
either a normal variant or abnormal prolongation of accentuation of the physiological hypogammaglobulinemia that occurs between 4-6 months
diagnosis of exclusion
Do children with transient hypogammaglobulinemia require treatment?
Most have normal levels by age 3-4 and do not need treatment.
However IVIG can be considered for those with recurrent infections or markedly low IgG levels
What are the three forms of chronic neutropenia and how are they treated?
Kostmann syndrome: AR
Severe chronic neutropenia: AD
Cyclic neutropenia: AD, levels of neutrophils increase and decrease over time
all are treated with G-CSF
What symptoms are suggestive of Leukocyte adhesion defect type 1?
Delayed umbilical cord separation
patients have a baseline leukocytosis because they lack CD-18 and circulating cells can not get into tissue.
recurrent necrotizing infections in areas where body interfaces with environment (skin, lungs, gut, mucosa) leaves “cigarette paper” scarring
What are the symptoms of Job syndrome or hyper IgE syndrome
eczema, scoliosis, hyperextensibility, delayed dental exfoliation, fractures and recurrent infections
cold abscesses (staph aureus, H. flu, strep pneumoniae)
post infection pneumatoceles
IgE levels normalized as they get older
What are the symptoms of chediak-higashi syndrome
recurrent cutaneous and sino-pulmonary infections
partial oculocutaneous albinism
mild intellectual disabilities
peripheral neuropathy
how s chediak-higashi syndrome diagnosed?
peripheral smear which shows large neutrophil granules caused by fusion of primary and secondary granules
How dose chronic granulomatous disease present
chronic recurrent organ and skin abscesses (staph. aureus, serratia, burkholderia, aspergillus)
How is chronic granulomatous disease diagnosed
nitroblue tetrazolium
yellow dye should turn blue on cell activation, but in those affected, it does not
X-linked
treated with BMT
How do you evaluate a possible complement deficiency?
CH50 measures the total complement hemolytic pathway, normal test means all factors are present
if abnormal: check for individual complement factors
When should complement disorders be suspected
if child has invasive pneumococcal or meningococcal infection
What causes hereditary angioedema
autosomal dominant
defect in the C1 inhibitor enzyme (C1-INH) which turns off the complement cascade.
consumes C2 and C4
What are the types of hereditary angioedema?
Type 1- decreased amount of the C1 inhibitor enzyme
Type 2- non-functioning C1 inhibitor enzyme
How does hereditary angioedema present
recurrent episodes of localized swelling / angioedema of distensible tissues such as lips, gastrointestinal tract, genitalia, and upper airway
sudden onset abdominal pain and extremity swelling
laryngeal edema can lead to respiratory arrest and death
How is hereditary angioedema diagnosed
Check C4 levels. If low ->
C1-INH functional assay-> if low
check C1-INH level if low -> type 1, if normal Type-2
what is the treatment for hereditary angioedema
purified C1-INH enzyme
or FFP if unavailable
attenuated androgens like danazol can be used
What happens in a Type 1 hypersensitivity reaction?
acute phase occurs with in 1 hour after exposure
mast cell degranulation after IgE binds with accompanying antigen
as more IgE binds, mast cell releases histamine and other cytokines, leukotriene
What is the late phase response in a Type 1 hypersensitivity reaction?
3-12 hours later,
lasts hours to days
usually infiltrate of IgE with erythema burning and itching
What is a Type 2 hypersensitivity reaction?
Cytotoxic
igG or IgM bind to a fixed tissue antigen or cell receptor resulting in cell destruction via complement or phagocytosis
examples: autoimmune hemolytic anemia, myasthenia gravis, good pasture’s
What is a type 3 hypersensitivity reaction
IgG complexes with an antigen and precipitates in blood vessels, activates complement leading to vasculitis
seen on the skin or on pathology as a leukocytoclastic vasculitis
What are the two animal models for Type 3 hypersensitivity reaction
serum sickness- necrotic vasculitis
Arthus Reaction: animal is hyperimmunized prior to antigen exposure, painful lesion appears at the injection site and becomes an abscess
These types of reactions are normally self limited
What is Type 4 hypersensitivity reaction
previously sensitized T cells interact with an antigen
reaction peaks 24-72 hours later
examples: tuberculin sensitivity, contact dermatitis
What is a type 5 hypersensitivity reaction
Auto IgG antibody has a stimulatory effect
examples: grave’s disease
What foods are the most common to cause allergy?
Wheat Eggs Milk (soy) Peanut Seafood
What kind of reaction is anaphylaxis
Type 1 hypersensitivity reaction
What are the symptoms or anaphylaxis?
histamine release causes increase in heart rate and vascular permeability, vasodilation, smooth muscle contraction
hypotension, vasodilation, loss of intravascular volume, urticaria, angioedema, flushing, respiratory tract edema with stridor / difficulty breathing
How do you treat anaphylaxis?
If stridor or severe angioedema, airway must be secured with intubation
For those with hypotension, give IV fluid bolus and epinephrine 0.01 mg/kg can repeat IM doses every 15-20 min or give IV
antihistamine like diphenhydramine are given
albuterol can be sued for bronchospasm
Steroids are given to prevent late phase reaction
What can be given to reverse beta blockers?
glucagon
vasopressin
patient’s at risk for anaphylaxis should avoid beta blockers as it blunts effect of epi
What is the difference between chronic and acute urticaria?
Chronic urticaria has been present for longer than 6 weeks
both consist of superficial blanching transient pruritic lesions
What is often the cause of chronic urticaria and do any laboratory studies need to be done?
the majority were thought to be idiopathic however, many of these patients have an autoimmune cause and develop an autoimmune disease later
No standard laboratory studies need to be sent
What are some other types of urticaria?
Acquired cold urticaria: IgE mediated or cryoglobulin, caused by exposure to cold
Familial cold urticaria: AD urticaria, myalgias fever and joint pain after cold exposure
Cholinergic urticaria: precipitated by heat
Immediate pressure urticaria: severe dermatographism
delayed pressure urticaria: swelling and burning of palms and soles after walking a long distance or carrying a heavy object
Urticarial vasculitis: like chronic urticaria except hives last more than 24 hours in the same location, eccymosis and hyperpigmentation: need skin biopsy
What criteria must a patient with asthma meet to be well controlled?
< or equal to 2 episodes per week during the day, and < or equal to 2 episodes per month at night and less than 2 ED visits or hospitalizations in the last year
What criteria must a patient with asthma meet to be well controlled if they are under the age of 12?
< 2 episodes per week during the day, and < 2 episodes per month at night and less than 2 ED visits or hospitalizations in the last year
What are the criteria used to determine the risk of asthma for children who are less than 3 and have wheezing?
1 Major or 2 minor = high risk Major: one parents has asthma child has eczema Minor: child has physician diagnosed allergic rhinitis wheezing when there is no URI eosinophilia
Signs and symptoms of allergic rhinitis
nasal congestion and itchy nose, throat and ears. sneezing with clear coryza. No fever
Nasal polyps can happen in teenagers but not children
allergic shiners
nasal salute
Dennie-Morgan lines:
During what times of the year are certain pollens more common?
Tree-spring
Grass-early summer
weeds- fall
mold-year round
What are the treatments for allergic rhinitis
Avoidance of the allergen Antihistamines (2nd generation, cetirizine, fexofenadine, loratadine, desloratadine) Leukotriene receptor antagonists intranasal corticosteroids If the above do not work: immunotherapy
For what condition are intranasal steroids the treatment of choice?
non-allergic rhinitis with eosinophilia syndrome
NARES
What are the treatment options for Atopic dermatitis
1st: moisturize
2. topical corticosteroids or topical calcineurin inhibitors
3. antihistamines
4. wet wraps (wet PJs under the dry PJs)
5. Oral steroids (5 day burst of prednisone to get control)
6. antibiotics: at risk for super infection, particularly staph aureus
What are the four general immune response / hypersensitivities with drugs.
Type 1: IgE hypersensitiy reactions
Type 2: antibody mediated hemolysis with the drug binding to RBCs
Type 3: Antibody: antigen precipitation (serum sickness)
Type 4: delayed type hypersensitivity mediated by t cells
When does someone need to be desensitized to a medication?
drug is the only known effective therapy
desensitization works best if reaction is IgE mediated
patient will need to be desensitized each time prior to being given the medication
Those with anaphylaxis to penicillin should be desensitized prior to getting cephalosporins.
What should be done if someone has an allergic reaction to insect sting?
If it is a local reaction there is no risk they will have anaphylaxis, no further work up
If they have anaphylaxis, patient needs skin testing and allergy shots
In whom is latex allergy most common?
health care workers and children who need multiple surgeries at an early age such as those with spina bifida, or those with congenital urologic problems
What fruits and vegetables have cross reactivity with latex?
Peekaboo PACT
Papaya, kiwi, banana
potato, avocado, chestnut and tomato
What medication must be discontinued prior to skin testing?
antihistamines
What causes serum sickness?
IgG complexes with an antigen. Do not need prior exposure so sometimes can take 6-12 days for the reaction to occur
occurs most frequently with penicillin and cefaclor
antithymocyte globulin, Hymenoptera stings, antilymphocyte globulin
What are the symptoms of serum sickness
fever, skin rashes, (itching redness, urticaria and angioedema) joint pain, muscle aches, lymph node swelling and proteinuria. GI complaints, nausea and vomiting
what is the treatment for serum sickness
stop offending agent
NSAIDS for pain
diphenhydramine for urticaria
if no improvement can give steroids
What is mastocytosis
rare disorder
abnormal mast cell proliferation and accumulation in various organs
What are the three levels of possible involvement for mastocytosis
cutaneous mastocytosis: increased mast cells in dermis, urticaria pigmentosa (wheal is formed with gentle pressure on the macule)
Systemic mastocytosis:
increased mast cells in tissue, abdominal symptoms, flushing, fatigue and urticaria pigmentosa
malignant mastocytosis: severe systemic symptoms though often on skin findings, hepatomegaly and lymphadenopathy
How is mastocytosis diagnosed?
elevated tryptase level.
skin biopsy for cutaneous
bone marrow biopsy if there are systemic symptoms
What is the treatment for mastocytosis?
avoid cold, heat, ETOH and ASA and opiates
oral cromolyn helps GI symptoms
sometimes chemotherapy is used but it does not work well.
What are some nutritional guidelines about prevention of atopic disease?
Delaying introduction of food, soy formula and avoidance by mom of food during pregnancy does not help
breast feeding till 4 months prevents or delays atopic dermatitis, milk allergy and wheezing
if an infant is at high risk of atopy and not breast fed, atopy can be delayed or prevented by use of hydrolyzed formulas
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