Allergies Flashcards
1
Q
FOOD ALLERGY
A
2
Q
Examples of IgE immunologic mediated responses.
A
IgE-Mediated
- Oral allergy syndrome
- Anaphylaxis
- Urticaria
3
Q
Examples of Non-IgE immunologic mediated responses to food?
A
Examples of Non-IgE mediated:
- Protein-induced enterocolitis/enteropathy
- Eosinophilic proctitis
- Dermatitis herpetiformis
4
Q
Examples of foods that cause a toxic, non-immunologic, response?
A
Toxic non-immunologic:
- Scromboid fish poisoning
- Bacterial food poisoning
- Caffiene
- Alcohol
- Histamine
5
Q
Examples of nontoxic (intolerance) non-immunologic reactions to food?
A
Non-toxic, non-immunlogic, reactions:
- Lactose intolerance
- Galactosemia
- Pancreastic insufficiency
- GB/Liver disease
- Hiatal hernia
- Anorexia
6
Q
Top 3 Foods children are allergic to? Overal prevalence?
A
Children:
- Milk (2.5%)
- Egg (1.3%)
- Peanuts (0.8%)
Overal - 6%
7
Q
What food is most likely to cause allergy in adults?
Overall Allergy in Adults?
A
Adults
- Shellfish (2%)
- Peanuts (0.6%)
Overall: 3.7%
8
Q
What is largest antigenic load the body processes?
A
Food
9
Q
Antigen Absorption:
- What decreases absorption?
- What increases absorption?
A
Antigen Absorption?
- Decreases: presence of other food and increase stomach acidity
- Increases: presence of alcohol and decrease in stomach acidity
10
Q
Type I IgE reactions vs. Type II vs. Type IV?
A
- Type I IgE
- Sensitization in mast cells of gut
- Degranulation (mucous secretion, smooth muscle contraction, mucosal edema, and increased absorption of foreign antigens)
- Type II reactions
- Ab-dependent thrombocytopenia secondary to milk
- Type IV
- Supports role in atopic dermatitis, EGID
11
Q
Clinical manifestations of IgE?
A
- Skin
- 84% of pts: urticaria, angioedema, atopic dermatitis
- GI
- 52%: edema, pruritis of lips/palate/pharynx, N/V
- Respiratory
- 32%: rhinitis, dyspnea, wheezing, cought
12
Q
When should anaphylaxis be considered?
Most common reason cited for fatal reaction?
A
Anaphylaxis: 2+ organ systems involved
Fatal reaction: delay in administration of epinepherine
13
Q
What are the highest risk foods resulting in anaphylaxis?
A
Anaphylaxis foods:
- Peanuts
- Tree nuts
- Seafood
14
Q
Fatal food anaphylaxis risks?
Often lack what symptoms?
A
Risks:
- underlying asthma
- symptom denial
- previous severe reaction
- delayed use of epinepherine
Often lack cutaneous symptoms
15
Q
Oral allergy syndrome:
- Usually due to?
- What occurs?
- Cause?
A
Oral allergy syndrome:
- Fresh fruits and veggies
- Oral pruritis, rapid onset, IgE-mediated
- Cause - cross reactive proteins with pollen/food
16
Q
Interpretation of Lab Tests?
A
Lab tests:
- Positive prick/RAST
- Presence of IgE ab NOT clinical reactivity (50% FP)
- Negative prick/RAST
- Excludes IgE ab (>95%)
- ID skin test with food
- Risk of systemic reaction and not predictive
- Unproven (useless)
- Neutralization, cytotoxic tests, applied kinesiology, hair analysis, IgG4
17
Q
Absolute diagnosis?
A
Absolute diagnosis:
- Elimination diets
- Specific IgE ab negative - reintroduce food
- Specific IgE ab positive - eliminate
18
Q
Substitutes for infant formulas?
A
Formula substitution:
- Soy
- <15% soy allergy among IgE-cows milk allergy
- Cow’s milk protein hydrolysates
- >90% tolerance in IgE-CMA
- Partial hydrolysates
- Not hypoallergenic
- Elemental amino acid-based formulas
- DOESNT CAUSE ALLERGY
19
Q
Food allergy prevention is aimed at?
Best way to prevent?
A
Prevention is aimed at “high risk” newborn with FMHx:
Delay introduction of solid foods >6 months:
- Milk/dairy: 6-12 months
- Egg: 12-24 months
- Peanut/tree nut/ seafood: >24-48 months
20
Q
What is Eosinophilic GI Disorders (EGID)?
A
Primary eosinophilic GI disorders taht affect the GIT with eosinophil rich inflammation in the absence of known causes for eosinophilia (eg. drug reactions, parasites, malignancy)
21
Q
Different types of EGID?
A
EGID: Eosionophilic….
- Esophagitis
- Gastritis
- Gastroenteritis
- Enteritis
- Colitis
22
Q
EGID signs and symptoms?
A
EGID S/S:
- Failure to thrive
- Ab pain
- Irritability
- Gastric dysmotility
- N/V/D
- Dysphagia
- Reflux
23
Q
EGID:
- How can severity be reversed?
- Most common foods?
- What is found in tissues?
A
EGID:
- Reverse severity with allergen free diet
- Most common foods: milk, egg, wheat, soy, nuts, and seafood
- Mast cell degranulation found in tissue specimens
24
Q
EGID is a cross of what mediated disorders?
What is histologically characteristic?
A
EGID is a cross of Type I IgE and CMI disorders
Histologically characteristic: >24 eiosinophils/high power field
25
ALLERGIC RHINITIS
26
What is allergic rhinitis?
Risk factors?
IgE mediated inflammation of nasal mucous membranes
Risk factors:
* +Family history
* Ethnicity other than white
* Birth in a pollen season
* + inhalant skin tests
* Early introduction of foods/formula
* Sedentary lifestyle
27
3 most common complications/comorbidities of Allergic rhinitis?
Complications/Comorbidities of AR:
* Chronic sinusitis (40-80%)
* Asthma (38%)
* Serous otitis media (21% in kids)
28
Signs and symptoms of AR?
Most common symptom of chronic allergic rhinitis
AR S/S:
* nasal pruritis and sneezing
* clear rhinorrhea with post nasal drip
* Watery, itchy eyes
* Fatigue, irritability, HA
* Disrupted sleep and declines in cognitive processing
Chronic allergic rhinitis: Nasal obstruction
29
Pathophysiology:
How does sensitization occur?
Sensitization:
* Macrophages present Ag to T/B cells
* B cells mature into a plasma cell that produces an Ag specific strain of IgE
* Plasma cells secrete this IgE and it binds to mast cell Fc receptors --\> NOW SENSITIZED
30
What is the acute (early) phase response?
Acute phase response:
* Re-exposure to Ag results in cross bridging to two IgE molecules and trigger degranulation
* Vascular leakage, mucous secretion, and vasodilation
* LTs/Acute Phase Proteins: function as chemotactic factors for immune cells
31
What is the Late Phase Response (LPR)?
LPR:
* Activation of leukocytes 2-12 hrs after acute phase
* _Hallmark_ is the activated eosinophil
32
Review:
1. APCs present by what class to T cell receptor?
2. What type of T cells are activated?
Review:
1. APCs present by _MHC II_
2. Activation of _specific CD4+ helper T cells of Th2 phenotype and secretion of cytokines_
33
Diagnoses:
What establishes a pattern?
Examples of seasonal allergies?
Diagnosis:
History establishes a pattern
Seasonal allergens:
* Ragweed (August and Sept)
* Tree (March-May)
* Grass (May and June)
* Molds (Spring-Fall)
34
Perennial allergens (long lasting) examples?
Perennial allergens:
* Dust mites
* Insects
* Animal dander
* Indoor molds
35
Phyical diagnosis of allergic rhinitis?
Physical diagnosis:
* Pale/boggy/enlarged turbinades
* Clear secretions
* Dark puffy lower eyelids
* Allergic shiners
* Mouth breathing
* Allergic Gape
36
Allergy testing?
Testing:
* Immunoassays - RAST/ELISA
* Detects presence of Ag-specific IgE
* Useful in those that cant be skin tested
* Non-specific tests
* Nasal smear for eosinophils
* Serum total IgE
* Peripheral blood eosinophils
37
HYMENOPTERA ALLERGY
38
3 classes of Hymenoptera and insects included?
* Apids
* Honey/Bumble/Sweat Bee
* Vespids
* Yellow Jacket, hornets, wasps
* Formicids
* Fire ants and hervester ants
39
What do most venoms contain?
Venoms:
* Vasoactive amines
* Histamine, dopamine, and NE
* ACh
* Kinins
* Hyaluronidase
40
Major allergen in the honeybee?
Major allergen in vespids?
_Honeybee_: phospholipase A
_Vespids_: Antigen - 5
41
3 types of common venom induced reactions and symptoms?
* Normal
* Local pain/erythema/mild swelling
* Large local
* Extended swelling/erythema
* Anaphylaxis: onset 15-20 min
* _Cutaneous_: urticaria/flushing/angioedema
* _Respiratory_: dyspnea
* _CV_: hypotension/dizziness/loss of consciousness
42
Large local reaction:
1. Most represent what phase? Devolpment time?
2. How long to subside?
Large local reaction:
1. _LATE phase IgE_; Develops over 12-24 hrs
2. 5-10 days to subside
43
What type of reactions can occur to a large number of stings?
What specific reaction may happen with a large amount of fire ant stings?
Many stings:
* Acute RF
* Rhabdomyolysis
* Hemolysis
* ARDS
* DIC
_Fire ants_: seizures
44
Name some reactions of unknown mechanisms?
Reactions of unkown mechanisms:
* Serum sickness
* Encephalitis
* Peripheral/cranial neuropathy
* Glomerulonephritis
* Myocarditis
* Guillan-Barre syndrome
45
Primary evidence of allergic reactivity?
History is the primary evidence of allergic reactivity
46
Skin testing for hymenoptera:
1. When?
2. Cross reactivity?
Skin testing:
1. Performed 4-6 weeks after a sting
2. Very high cross reactivity among vespids
47
Skin testing:
1. Reactivity correlation with severity of sting reaction?
2. Largest reactions in what patients?
Skin testing:
1. Degree of skin test reactivity does not correlate with severity of the sting reaction
2. Largest reactions are often in patients with large local reactions
48
What can large local reactions be mistaken for?
Large local reactions can be mistaken for _cellulitis_ (unlikely if reaction appears 24-48 hrs after a sting)
49
ANAPHYLAXIS
50
Anaphylaxis definition?
A life-threatening, multiorgan, IgE mediated disorder characterized by signs and symptoms of histamine release and other mediators released from mast cells and basophils
51
Risk factors for anaphylaxis?
Risk factors:
* Atopy
* Gender/Age
* Route/constancy of administration
* Time since last reactions
* Economic status
52
What things are NOT risk factors?
NOT risk factors:
* Race
* Geography
* Chronobiology
* Occupation
53
Gender differences?
Females\>Males for:
* Latex
* Muscle relaxants
* Aspirin (ASA)
* Idiopathic and OVERALL
54
Risk factors in the role of Atopy in anaphylaxis?
Atopic Risk Factors:
* Latex
* Oral administration
* Exercise
* Radiocontrast media (RCM)
55
Non-Risk factors in the role of Atopy in anaphylaxis?
Non-risk factors of Atopy:
* Parenteral administration
* Penicillin/Insulin
* Hymenoptera
* Muscle relaxants
56
4 Mechanisms of anaphylaxis?
* Immunologic
* IgE-dependent
* Non-IgE immunologic
* C3a, C5a, and bradykinin
* Nonimmunologic
* Degranulation from physical factors (cold/exercise)
* Degranulation from certain medications
* Idiopathic
57
IgE- Mediated Haptens?
(hapten is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein)
IgE Mediated Haptens:
* ABX
* Penicillin/Cephalosporins/Sulfa
* Other theraputic agents
* Folic acid
* General anesthetics
58
IgE Mediated complete antigens?
IgE Mediated complete antigens:
* Animal/Human proteins
* Egg vaccines/stinging insects/animal dander
* Hormones
* Insulin/progesterone
* Enzymes
* Foods
* Latex
* Allergenic extracts
* Skin testing/immunotherapy
59
Non-IgE Immunologic
Due to activation of?
Examples?
Non-IgE Immunologic:
Due to activation of _compliment_ anaphylatoxins and _bradykinin_ from the contact system
Examples:
* RCM
* Dextran
* Oversulfated chondroitin sulfate
60
Examples of nonimmunologic agents that can cause anaphylaxis?
Non-immunologic Anaphylaxis
* Drugs
* Aspirin and NSAIDs
* Opiates and Ethanol
* Physical
* Exercise
* Cold/Hot (air/water)
* UV radiation
61
Key to all forms of anaphylaxis/anaphylactoid reactions?
What is the rule of 2's?
_Mast cell/basophil degranulation_ is the key
_Rule of 2's_: signs and symptoms occur within 2 minutes to 2 hours after exposure
62
Degranulation preformed mediators?
Degranulation newly generated mediators?
Preformed
* Histamine
* Tryptase and carboxypeptidase A
* Proteoglycans (heparin)
Newly generated
* PGD2 and LTD4
* PAF
* Kinins
63
Pathophysiology:
Mediators result in an abrupt increase in?
Increase in
* Vascular permeability
* Vasodilation
* Bronchoconstriction
* Mucous secretion
64
Most common organs involved?
Cutaneous (\>90%)
Respiratory (55-60%)
Cardiovascular (30-35%)
Shock (30%)
65
Anaphylaxis gross pathology?
Gross pathology:
* Pulmonary hyperinflation
* Laryngeal edema
* RT edema
66
Anaphylaxis histology?
Histology:
* Increased bronchial secretions
* Eosinophilic infiltration
* Of RT, spleen, and liver sinusoids
67
Anaphylaxis serologic indications?
Serology:
* Elevated:
* Histamine (rises in 5 min; only lasts up to 1 hr)
* Tryptase (Lasts up to 5 hrs)
* Carboxypeptidase A3
* May be the better marker
* Urinary histamine metabolites may remain elevated for up to 24 hours
68
Anaphylaxis evaluation:
\_\_\_\_\_ is the key.
What supports the diagnosis?
Anaphylaxis eval:
_History_ is the ky
_Physical exam_ supports the diagnosis
69
I know it says we dont need to know treatment buttt....
What position should a patient be in for the treatment of anaphylaxis and why?
Patient should lie flat bc those sitting up may be subject to an "empty heart" and sudden death
70
ASTHMA
71
Asthma definition?
Inflammation is associated with?
Asthma - is a _chronic inflammatory disorder of the airways_ (doesnt matter what severity)
Inflammation is associated with hyperresponsiveness and airflow limitations
72
What is the strongest predisposing factor for the development of asthma?
Atopy, the genetic predisposition for IgE mediated responses, is the strongest predisposing factor
73
Asthma complications/comorbidities?
Asthma complications/comorbidities:
* 80% of allergic asthmatics also have AR
* 40% of all patients with AR experience asthma at some point
74
Exercise induced bronchospasm:
General population versus patients with AR?
Asthmatics?
Exercise induced bronchospasm:
* 10% of general population
* 40% of individuals with AR
* ALL Asthmatics
* For some, this will be the only asthmatic manifestation
75
Cluster 1 phenotype?
Cluseter 1 (15%)
* Younger with child hood onset
* Mostly female
* Minimal meds
* Atopic with normal lung function
76
Cluster 2 phenotype?
Cluster 2 (44%)
* Occurs in 30's with childhood onset/atopic
* 2/3 female
* 2/3 have normal lung function
* 30% use \>3 meds
77
Cluster 3 phenotype?
Cluster 3 (8%)
* Obese older females
* Late onset
* _NON_ atopic asthma
* Moderate reduction in lung function
* Frequent OCS for exacerbations
(OCS = oral corticosteroids)
78
Cluster 4/5 phenotypes?
Clusters 4/5 phenotypes (33%)
* Severe airflow obstruction
* Variability in age of onset
* Atopic status
* Use of OCS
79
Aspirin Sensitive Asthma:
Percent? Atopy?
Classic cases presentation?
Aspirin Sensitive Asthma:
* 5-10% of asthmatics will worsen with Aspirin/NSAIDs
* 2/3 of these are NOT atopic
* Classic presentation
* Nasal polyps with chronic sinusitis
* Asthma with peripheral eiosinophilia
* ASA/NSAID sensitivity
(often have high levels of LTs)
80
Diagnosis:
50% of asthmatics will have?
Diagnosis
50% of asthmatics will have _NORMAL PFT (pulmonary functions?) at rest_
81
IMMUNODEFICIENCY
82
Main categories of primary immunodeficiency?
* Complement deficiency
* Immunoglobulin (B cell) deficiency
* Lymphocyte defects (T cell)
* Phagocyte Defects
83
Acquired immunodeficiencies?
Acquired ID:
* Malnutrition
* AIDS
* Chemotherapy
* Organ transplant
84
What does Compliment normally regulate?
Complement regulates:
* Mast cell degranulation
* Smooth muscle contraction
* Chemotaxis of leukocytes
* Phagocytosis
85
Compliment deficiencies result:
Classic pathway?
C3 deficiency?
Late components?
Classic Pathway (C1/2/4)
* Recurrent GP infections and high autoimmune incidence
C3 deficiency
* Recurrent pyogenic infections with GP and GN
Late Components (C5-9)
* Recurrent neisserial infections
86
Complement Deficiency - Hereditary Angioedema:
Signs and Symptoms?
Hereditary Angioedema S/S:
* Nonpitting edema of skin, GI, and respiratory tract
* Skin = asymmetric; _no_ pruritis or hives
* Bowel wall edema = cramping and diarrhea
* Laryngeal edema = most common cause of death
87
Hereditary angioedema:
Deficiency?
Genetics?
Mediator responsible for the angioedema?
Hereditary Angioedema:
* Deficiency of _C1 esterase inhibitor_
* Genetics: _AD inheritance_
* Mediator: _Bradykinin_ (degradation slowed in absence of the enzyme)
88
Hereditary angioedema:
Levels of C4?
Levels of C2?
Levels of C1 INH?
Hereditary angioedema:
* C4: low or absent all the time
* C2: drops during attacks only
* C1 INH: low/absent OR nonfunctional
89
Symptoms of Antibody deficiency?
Ab Deficiency S/S:
* Recurrent OM/Sinusitis/pneumonia
* Cellulitis
* osteomyelitis
* meningitis
* Enteric infections
90
X Linked Agammaglobulinemia:
Also known as?
What is abnormal? Linked to what part of X?
X Linked Agammaglobulinemia:
* AKA Bruton's
* Abnormal Tyrosine kinase
* Linked to q22
91
X Linked Agammaglobulinemia:
What kind of infections?
Due to what bugs?
X Linked Agammaglobulinemia:
Recurrent Sinopulmonary pyogenic infections due to:
* H. influenzae
* Staph
* Strep
* Pneumococci
* Meningococci
92
X Linked Agammaglobulinemia:
Other infections? What do they lead to?
X Linked Agammaglobulinemia:
* Sinusitis, pneumonia, abscesses, meningitis, septiciemia
Infections lead to:
* bronchiectasis
* Pulmonary insufficiency
93
X Linked Agammaglobulinemia:
Resistance to fungi/viruses/GN -- intact or no? Why?
X Linked Agammaglobulinemia:
Resistance to fungi/viruses/GN:
* Intact
* Normal T cell number and function
94
X Linked Agammaglobulinemia:
Diagnosis:
Levels of Immunoglobulins and B lymphocytes?
X Linked Agammaglobulinemia:
Diagnosis:
Low to absent levels of all Ig, B lymphocytes, and circulating plasma cells
95
Common variable immunodeficiency:
Suceptible to same infections as? But also?
Increased incidence of what cancer?
Common variable immunodeficiency:
Suceptible to same infections as Brutons and also Giardia
Increased incidence of lymphomas
96
Common variable immunodeficiency:
Signs/Symptoms?
Common variable immunodeficiency S/S:
* Lymphadenopathy
* Splenomegaly
* Lymphoid hyperplasia of the gut
97
Common variable immunodeficiency:
B cell and T cell levels and functions?
Common variable immunodeficiency:
* B cell
* Present but abnormal function
* T cell
* Levels usually normal
* Function may not be normal
98
Most common primary immunodeficiency?
IgA deficiency
99
IgA deficiency:
What types of recurrent infections?
May have anti-IgA abs that can cause what?
IgA:
* Recurrent sinopulmonary infections
* Anti-IgA antibodies
* Anaphylaxis when given blood products
100
T cell ID:
Often occur when? And how does it present?
What can occur with live viral vaccines?
T cell ID:
Often occur in infancy
Present as failure to thrive with diarrhea
Live viral vaccines can result in severe illness
101
T Cell ID:
What is Hyper-IgM syndrome linked to?
What occurs in DiGeorge?
T Cell ID:
* Hyper IgM syndrome
* CD40 ligand
* DiGeorge
* Thymic dysplasia/aplasia
* Facial clefts, hypocalcemia, cardiac defect
102
T cell ID
What is reticular dysgenesis?
What is Ommen syndrome?
T Cell ID:
* Reticular dysgenesis
* Early defect in hematopoesis
* Ommen syndrome
* Hypereosinophila
* High IgE
* Hymphocytosis
* Hepatomegaly
* Rashes from birth
103
T Cell ID:
What occurs in Wiskott Aldrich syndrome?
Wiskott Aldrich Syndrome:
* Small platelets
* Petechiae
* Eczema
* Early sinopulmonary infections
* Atopy
104
T Cell ID:
What is Ataxia Telangectasia?
What serum levels are increased?
T Cell ID:
* Ataxia Telangectasia:
* Loss of motor milestones in early childhood
* Telangectasias appear later
* Increased alpha fetal protein in serum
105
Phagocyte Defects:
Average number of neutrophils?
What is neutropenia?
Phagocyte Defects:
* Neutrophils: 5000/mcl
* Neutropenia: \<1000/mcl
106
Phagocyte Defects:
Chronic granulomatous disease:
Presents?
Infections with what bugs?
Chronic Granulomatous disease:
Presents with lymphadenopathy
Infections with:
* Staph aureus
* Aspergillus
* Nocardia
107
Phagocyte Defects:
Chronic granulomatous disease:
Defect is in?
Bacteria/fungi and what enzyme cause recurrent life threatening infections?
Chronic Granulomatous Disease:
Defect: _Oxidative killing of ingested microorganisms_
Bacteria/Fungi + _catalase_ = life threatening
108
Phagocyte Defects:
Chronic granulomatous disease:
Organs affected?
Chronic granulomatous disease:
Organs:
* Lungs
* Liver
* Lymph nodes
* Skin
* Bone
109
Phagocyte Defects:
Leukocyte adhesion deficiency:
What is this?
How is it clinically characterized?
Mutation in?
Leukocyte adhesion deficiency:
* Neutrophils fail to mobilize and migrate
* Characterized by:
* Delayed separation of umbilical cord
* Gingivitis
* Severe scarring skin infections
* Mutation in CD18
110
Phagocyte Defects:
Chediak-Higashi syndrome:
Inheritance?
Infections?
Signs/symptoms?
Chediak-Higashi syndrome:
* Autosomal Recessive
* Recurrent cutaneous and sinopulmonary pyogenic inf.
* Dont respond well to abx
* Signs:
* Partial oculo-cutaneous albinism
* mental retardation
* neuropathy (late)
* Weird hair sheen
111
In the lab what does the presence of isohemagglutinins indicate?
Isohemagglutinins:
Presence indicates IgM antibodies to blood groups
