allergy Flashcards

1
Q

definition of an allergic disorder

A

immunological process that results in immediate and reproducible symptoms after exposure to an allergen

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2
Q

what type of hypersensitivity reaction is allergy

A

IgE mediated type 1 hypersensitivity reaction

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3
Q

what is an allergen

A

harmless substance that can trigger an IgE mediated immune response and may result in clinical symptoms

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4
Q

definition of sensitisation

A

detection of specific IgE either by skin prick testing or in vitro blood tests: OCCURS MORE OFTEN THAN ALLERGIC DISEASE

Presence of IgE is necessary but not specific for dx of an allergic disease

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5
Q

differentiate the immune response to microbes vs worms, venoms and allergens (proteases, phytochemicals, xenobiotics and pollen

A

for microbes - the immune system recognises PAMPs
for worms, venoms and allergens (proteases, phytochemicals, xenobiotics and pollen the immune system recognises loss in tissue func ie disruption of epithelial barrier - type 2 immune response

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6
Q

summarise Th2 immune response

A

Key initial sensor are the epithelial cells
Loss of epithelial barrier func, or epi stress ellicted by allergens – induce number of cytokines
Lymphoid cells – innate lymphoid cells type 2 – charactised by response to initial cytokine and the secretion of effector cytokines inc IL4 key in type 2 response, il5 or 13 – lead on yo on effector cells – act on effector cells

Interaction between dendritic and Th2 cells – lead to secretion of IL4 or IL13 Induce B cell to secrete IgE Ab and IgG4

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7
Q

summarise Th2 immune memory response

A

Cross linking of high affinity IgE receptor by allergen -> degran mast cells -> release histamine etc – act on endothelium, smooth muscle cells

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8
Q

overview of Th2 immune response

A

Defects in skin epithelial barrier (atopic dermatitis) are a significant risk factor for development of IgE antibodies.

Stressed or damaged epithelial cells secrete IL-25, IL-33, GM-CSF and TSLP which act on tissue immune cells (DC, basophils, type 2 innate lymphoid cells) to induce Th2 cells immune responses (IL-4, IL-5, IL-9, IL-13) and sensory neurons (itch/sneeze)

IL-4 plays a crucial role in development of Th2 immune responses and is only induced following peptide-MHC presentation to naïve/memory Th2 cells

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9
Q

how is there a rapid sx onset in allergy

A

release of inflammatory mediators
following allergen cross linking of IgE on surface of mast cells and basophils

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10
Q

what causes the delayed sx in allergy

A

CD4Th2 cell cytokine secretion (IL-4, IL-5, IL-13) and eosinophilic related tissue damage

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11
Q

role of Th2 cytokines

A

secreted by tissue lymphocytes
act on effector cells (eosinophils, basophils, epithelial cells, B cells, sensory neurons endothelium and smooth muscle cells)
to eliminate and expel pathogens allergens, and repair tissue damage

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12
Q

what factors promote IgE production

A

ag exposure
length of exposure
physical properties of allergen:
* associated with carrier proteins
* proteolytic activity (HDM) - break down the cross linking between epithelial cells
* linked to chitin - (carb: epi damage
* resistant to heat, digestive enzymes

Route of exposure determine whether IgG or IgE: oral (IgG) v skin, RT (IgE)
-> The early introduction of food after weening – prevent development of severe food related sx

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13
Q

how do we have immuen tolerance to food

A

immune response to food is: anergic CD4 T cells - lack inflammatory capacity, but -> reg T cells in GIT -> suppress tissue damage

oral -> immune tolerance
skin and resp (esp if breach in epi layer) -> IgE

Early weaning 4-6 months reduced risk of peanut and egg allergy

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14
Q

why is there an increase in allergic disorders

A

hygeine hypothesis - lack of exposure in children -> increase susceptability to allergic disease - Default for mech for immune response th2 immunity – this is deviated by exposure to lots of pathogens onto th1 and th17 immunity

increae in epithelial damaging agenbts from industrialisation, urbanisation and modern lifestyle eg phytochemicals and xenobiotics

Loss of symbiotic relationship with bacteria with reduction in biodiversity and alteration in composition of composition of gut skin and respiratory bacteria -> secretion of IgE rather than IgA and IgG

diet
* change in food processing and prep - peanut
* delayed intro of peanut if have egg allergy/atopic dermatitis
* lack of vit D and dietary fatty food

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15
Q

summarise how the Amish provide evidence for the hygiene hypothesis

A

Amish more LPS (lipopolysaccharides ie part of gram –ve bacteria – if stimulate more proinflammatory cytokines) in dust samples than Hutterites

Increased secretion of innate immune cytokine (TNF and IL1) by PBMC exposed to LPS in Amish than Hutterites

Dust samples from Amish suppress allergic inflammation in a murine asthma model

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16
Q

reasons for change in asthma prevalence

A

HDM, cat, cockroach, fungi are linked with exposure and sensoitisation
links for HDM with increase exposure to indoor allergen - children play more indoors than outside, exercise less and put on weight
childhood vaccines
increased exposure to broad spectrum abx

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17
Q

summarise hx of food allergy

A

1990 onwards: Significant increase in peanut allergy

Early oral exposure will protect against peanut allergy

Sensitisation to peanut and wheat can occur through the skin

Differences in preparation of peanuts (roast promotes IgE whereas boiled IgG)

Epidemic of delayed food allergy to red meat observed in SE USA for last 10 years: increasing case in France, Germany, Australia but not in UK to date)

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18
Q

what is involved in dx allergy

A

hx
ex
allergen specific IgE test - (sensitisation) - skin prick nad intradermal, or IgE blood tests

functional allergen tests :
in vitro
* Basophil activation
* Serial mast cell tryptase

ex vitro: open/blinded allegen challenge

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19
Q

hx for infants looking for allergy

A

Atopic dermatitis
Food allergy (milk, egg, nuts)

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20
Q

hx for children looking for allergy

A

Asthma (HDM, pets)
Allergic rhinitis (HDM, grass, tree pollens)

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21
Q

hx for adults looking for allergy

A

Drug allergy
Bee allergy
Oral allergy syndrome
Occupational allergy

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22
Q

clinical features of IgE allergic response

A

within mins - up to 3-4hrs after exposure
at least 2 organ systems
reproducible - after every exposuyre
sx can be triggered by cofactors eg exercise, alcohol, NSAIDs, viral infection

  • Skin: angioedema (swelling of lips, tongues, eyelids) , urticaria ( wheals or ‘hives’), flushing and itch
  • Respiratory tract: cough, SOB wheeze, sneezing, nasal congestion and clear discharge, red itch watery eyes
  • Gastrointestinal tract: nausea, vomiting and diarrhoea
  • Blood vessels and Brain: symptoms of hypotension (faint, dizzy, blackout) and a sense of impending doom
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23
Q

how do NSAIDs -> allergy

A

disruption of lining of GIT

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24
Q

why is hx important for allergy

A

used to select what allergens should be tested by skin prick and/or blood tests

Note: Link between exposure and onset symptoms may not be obvious
House Dust mite, Fungal and Staph skin colonisation, Red meat ingestion

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25
sx not associated with IgE allergic reactions
Fatigue Migraine (food can cause it – but it is because of high tyramine – not an allergy!!) Recurrent abdominal pain, diarrhoea, constipation, bloating Hyperactivity Depression Symptoms which vary over time, with antigen dose and source
26
summarise use of sensitisation tests
Presence of IgE - necessary not sufficient for allergic disease sensitisation is more common than allergic disease hx determine what tested for on blood test if right hx - large skin wheals and high blood IgE - more likely associated with allergy results of skin prick, or serum IgE dont predict reaction severity
27
summarise skin prick test method/theory
standard soln of allergen extract through skin prick to the forearm positive control - histamine -ve control - diluent measure wheal Antihistamines and some anti-depressants should be discontinued for at least 48 hours beforehand IgE cross linking on mast cells -> degranulation and release of histamine and inflammatory mediators
28
interpreting skin prick test
wheal ≥ 3mm greater than the negative control has high +ve and -ve predictive value for aeroallergens
29
advantages of skin prick test
Rapid (read after 15-20 minutes) Cheap and easy to do Excellent negative predictive value usually more than > 95% Increasing size of wheals correlates with higher probability for allergy Patient can see the response
30
disadvantages of skin prick test
Requires experience to interpret Risk of anaphylaxis: 1 in 3000 Poor positive predictive value: high false positive rate Limited value in patients with dermato-graphism or extensive eczema False negative results with labile commercial food extracts
31
intradermal sensitisation tests
positive, negative controls and allergens into the skin more sensitive, less specific than SPT best used to follow up negative venom and drug allergy test - better than blood tests use if -ve SPT but convincing hx labour intensivce more anaphylaxis risk
32
sensitisation IgE blood tests
Detection of IgE to whole allergen extract or to individual protein (component) with in an allergen extract automated assays
33
limitation of sensitisation blood tests
* Detection of IgE antibody with little clinical relevance * Allergen in low abundance may lead to reduced sensitivity * Clinical utility and cost of multiplex assay remain to be determined * Limited understanding of their role in diagnosis of allergic disorder outside of allergist/immunology specialists
34
Component Resolved Diagnostics for allergy
Abundance and stability of individual protein within allergen extract can contribute to risk of allergic disease CRD: Test for IgE sensitisation against individual protein within whole allergen extract Diagnostic use * Food allergy (nuts, egg, milk) * Insect allergy (wasp and bees) * Guide to immunotherapy (grass and HDM)
35
Food components allergen tests for nuts
Storage proteins (2s albumins) - severe reactions pathogenesis related proteins - (PR10 bet v1 homologue) which are also found in tree pollens, fruits and vegetables (ie cross-react with these things): mild reaction Non specific lipid transfer proteins, also found in in fruit (peach) , tree pollen (plane), vegetables and legumes ( can be mild or severe)
36
Food components allergen tests wheat
Omega-5-gliadin better marker of specific wheat allergy than total wheat IgE
37
Food components allergen tests egg and milk
Heat stable proteins ovomucoid (egg) and caseins ( estimate who outgrows allergy)
38
Food components allergen tests fish and shellfish
Parvalbumin in fish, Tropomyosin in crustaceans (cross reactive)
39
indications for blood sensitisation tets
No access to SPT and/or IDT - ie GP can’t stop anti-histamines history of dermatographism, extensive eczema history of anaphylaxis – because wouldn’t want to do skin prick Decision on who needs food challenge Prediction for resolution of egg, milk, wheat allergy monitor response to anti-IgE therapy
40
summarise the risk profile of serum IgE for prediction of allergic sx
concentration - higher more likely = sx molecular target (within whole extract or even individual epitope) can be linked to sx affinity to target - higher associated with risk - dont measure affinity Capacity of IgE antibody to induce mast/basophil degranulation
41
summarise use of mast cell tryptase
it is a **biomarker for anaphylaxis** tryptase is a pre-formed protein **found in mast cell granules** **systemic degranulation of mast cells -> increase in tryptase** peak at 30min - 2hrs return to baseline by 6-12hrs - need serial measures Failure to return to baseline after anaphylaxis may be indicative of systemic mastocytosis and hereditary alpha tryptasaemia useful if anaphylaxis dx not clear reduced sensitivity for food induced anaphylaxis because mucosal immune response (rather than drug/venum that effect endothelial cells)
42
summarise basophil activation test for allergy
**measure basophil response to IgE cross linking** **Activated basophils increase the expression of CD63, CD203, CD300 protein on cell surface** used in dx of food and drug allergy - surrogate marker for challenge test Efforts to standardise test to use by diagnostic laboratories to reduce need for challenge tests problem is some of the population have basophils that are refractory to responding to ag
43
summarise challenge tests for food and drug allergy
gold standard ingest increasing volumes of the allergen either double blind placebo/open challenge close medical supervision - very expensive in terms of clinician time difficult to interpret mild sx risk of severe rn
44
define anaphylaxis
Acute onset of symptoms and/or signs (minutes to 4-6 hours) Severe/life threatening ABC problems Skin and mucosal symptoms and signs (can be absent 10-20% of cases)
45
clinical features of anaphylaxis
Skin (hives, itch, swollen lips, tongue, uvula) (84%), Cardiovascular compromise (collapse, syncope, incontinence symptoms, drop in BP) (72%) Respiratory compromise (SOB, wheeze, stridor, fall in PEF, hypoxemia in 68%. resp more in children adults - CVS
46
epidemiology of anaphylaxis
Incidence: 1.5-8/100,000 persons years incidence is increasing prevalence 0.3-5.1% more common aged 0-4yrs children - food adult - drug and venum idiopathic in 20-30% of cases - shrimp, wheat, red meat
47
mechanisms of anaphylaxis
Distinction doesn’t matter for treatment but might change Ix IgE and complement - more associated with monoclonal ab infusion related reactions
48
reactions that can mimic anaphylaxis
SKIN: Chronic urticaria and angioedema (ACE inhibitors) THROAT SWELLING: C1 inhibitor deficiency CARDIOVASCULAR: Myocardial infarction and PE RESPIRATORY: Very severe asthma, vocal cord dysfunction, inhaled FB NEUROPSYCHIATRIC: Anxiety or panic disorder ENDOCRINE: carcinoid and phaechromocytoma TOXIC: Scromboid toxicity (Histamine poisoning ) IMMUNE: Systemic mastocytosis
49
lab dx of anaphylaxis
**serial tryptase mx - 30min-2hr, then at 24hr ** Concentration greater then (1.2 x baseline tryptase) + 2ug/L support a diagnosis of anaphylaxis. it is retrospective dx -ve doesnt rule out anaphylaxis - esp if food and have mucosal sx
50
why is adrenaline used in the rx of anaphylaxis
α1 receptors: causes peripheral vasoconstriction, reverses low BP and mucosal oedema β1 receptor: increases heart rate and contractility and BP β2 receptor: relaxation of bronchial smooth muscle and reduces release of inflammatory mediators from mast cells/basophils
51
emergency mx of anaphylaxis
supine raise legs IM adrenaline - if no response -> repeat and administer IV crystalloid fluids *anti-histamine after ABC corrected*
52
what is the refractory anaphylaxis protocol
if no improvement in ABC (no improvement after 2 IM adrenaline) :
53
follow up mx of anaphylaxis
refer - allergy clinic ix cause give info on - sx recognition, avoidance of triggers, epipen prescription of emeergency anaphylaxis kit Copy of management plan and training for patient, carers, school staff and GP venum immunotherapy and drug desensitisation as appropriate if food - refer to dietician medic alert bracelet utilise support groups
54
definition of food allergy
adverse health effect arising from specific immune response that occurs reproducibly on exposure to a given food
55
definition of food intolerance
non immune reactions which include metabolic, pharmacological and unknown mechanisms eg * Food poisoning (bacterial, scromboid toxin) * Enzyme deficiencies (lactase) * Pharmacological (caffeine, tyramine )
56
types of food aversion
fads eating disorders
57
types of food allergy
IgE mediated reactions (anaphylaxis, OAS) Mixed IgE and cell mediated (atopic dermatitis) Non IgE mediated (coeliac disease – type 4 hypersensitivity) Cell mediated (contact dermatitis)
58
do children outgrow food allergy
milk and egg yes rarely peanut and treenut
59
how does atopic dermatitis alter food allergy ix
an important risk factor for food allergy (indication for allergy testing even in absence of clinical history)
60
important to determine in hx of food allergy
what does pt mean by allergy Is it IgE or not determine dose of allergen, how prepared, co-factors - all alter sx hx of atopy previous ix elimination of food make a difference ddx - intolerance, eating disorder, coeliac disease
61
important to determine in hx of food allergy
what does pt mean by allergy Is it IgE or not determine dose of allergen, how prepared, co-factors - all alter sx hx of atopy previous ix elimination of food make a difference ddx - intolerance, eating disorder, coeliac disease
62
ix for food allergy
hx SPT/IgE blood test - if -ve basically excludes IgE mediated allergy monitor results over time - for persistance or resolution Fruit and vegetable skin prick test solutions are labile and it often better to useful use actual fruit or vegetable. Testing for individual allergen protein component can distinguish between IgE sensitisation and IgE mediated allergy gold standard is double blind oral food challenge
63
mx of food allergy
avoidance * education - labels, restaurants, school * nutritional input * mental health support emergency * anaphylaxis mx * ensure allergic asthma is well controlled
64
prevention of food allergy
breast feeding early introduction of peanut
65
what are the IgE mediated food allergy syndromes
**anaphylaxis** - Peanut, tree nut, shellfish, fish, milk and eggs are most common **food associated exercise induced anaphylaxis** - food -> anaphylaxis if exercise within 4-6hr of ingestion - wheat, shellfish, celery **Delayed food-induced anaphylaxis to beef, pork, lamb** **oral allergy syndrome**
66
summarise Delayed food-induced anaphylaxis to beef, pork, lamb
sx 3-6hr after red meat and gelatin IgE antibody to oligosaccharide alpha-gal (α1, 3-galactose) found in gut bacteria Induced by tick bites: * Human make ab to alpha-gal * Human eat meatr with alpha-gal – Ig E
67
summarise oral allergy syndrome
Limited to oral cavity, swelling and itch: only 1-2% cases progresses to anaphylaxis Sensitisation to inhalant pollen protein -> cross reactive IgE to food Onset after pollen allergy established: affect adults > young children Respiratory exposure to pollen (birch) -> IgE directed to homologous proteins in stone fruits (apple, pear) vegetables (carrot) and nuts (peanut, hazelnut) Cooked fruits, vegetables and nut cause no symptoms: heat labile allergens detected by component allergen tests