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Pathology by week > W17 - Allergy > Flashcards

W17 - Allergy Flashcards

1
Q

Allergic disorder - immunological process that results in immediate and reproducible symptoms after exposure to an allergen - True or False?

A

True

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2
Q

Regarding allergic disorders, in clinical practice immunological process usually involves an ____ mediated _______ hypersensitivity reaction

A

Regarding allergic disorders, in clinical practice immunological process usually involves an IgE mediated type 1 hypersensitivity reaction

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3
Q

In terms of detection, how does immune detection of helminthes, worms, venoms, allergens, how does their recognition differ to detection of microbial PAMPs (bacteria viruses)?

A

Immune detection to microbial PAMPs is by recognition of conserved microbial structure and induces Th1 response

Immune detection of allergens involves proteases, phytochemicals, xenobiotics which cause loss of tissue function (disruption of epithelial function) and subseqeunt functional recognition; often by Th2 response

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4
Q

____ is the key cytokine in the development and expansion of eosinophils

A

IL-5 is the key cytokine in the development and expansion of eosinophils

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5
Q

IgE induces _____ and _______ degranulation associated with immediate hypersensitivity (allergic) reactions

A

IgE induces mast and basophil degranulation associated with immediate hypersensitivity (allergic) reactions

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6
Q

Mast cells degranulate in 2 ways - name them

A

Mast clel degranulation:

  1. IgE/IgG receptors which respond to ab-ag cross-linking
  2. GPCR which are ligands for soluble mediators such as complement and drugs
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7
Q

Cross-linking of bound IgE by antigen results in 3 things in mast cell/basophil degnraulation - name them

A
  1. Release of pre-formed inflammatory mediators (histamine)
  2. Release and synthesis of lipid mediators (leukotrienes, prostaglandings)
  3. Synthesis of pro-inflammatory cytokines
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8
Q

Mast cell degranulation also has 3 systemic effects - name them

A
  1. Recruitment of soluble proteins and inflammatory cells to site of infection
  2. Increase in rate of lymphatic flow back to regional LNs
  3. SM congraction in lungs and gut (expel pathogens) and activation of sensory neurons (itch/sneeze)
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9
Q

Eosinophils - how do they eliminate pathogens (3):

A
  1. Cytotoxic granules
  2. RNAse proteins
  3. Extracellular traps
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10
Q

Name 4 factors that influence IgE production in allergic reactions

A
  1. Antigen dose
  2. Length of exposure
  3. Route of exposure
  4. Physical properties of allergen:
    - source; carbs, resistance to heat/digestive enzymes
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11
Q

Defects in skin epithelial barrier is not a risk factor for development of IgE antibodies - True or False. Explain

A

False - defects in skin epithelial barrier IS a risk factor for development of IgE antibodies, such as in atopic dermatitis

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12
Q

When speaking about allergy, oral exposure promotes _____ ______ whereas skin and respiratory induces ____ __________

A

Oral exposure promotes immune tolerance whereas skin and respiratory induces IgE sensitisation

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13
Q

What is the one leading hypothesis explaining the rise in allergic disorders?

A

Hygiene hypothesis - nlack of childhood exposure to infectious agents increases susceptibility to allergic diseases by supressing natural development of immune system.

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14
Q

Age of onset of allergic diseases:

Atopic dermatitis

allergic rhinitis (HDM; grass; tree pollens)

food allergy (milk, egg, nuts)

Drug allergy

Bee allergy

Asthma (HDM; pets)

Oral allergy syndrome

Occupational allergy

A

Atopic dermatitis = infants

allergic rhinitis (HDM; grass; tree pollens) = childhood

food allergy (milk, egg, nuts) = infants

Drug allergy = adults

Bee allergy = adults

Asthma (HDM; pets) = childhood

Oral allergy syndrome = adults

Occupational allergy = adults

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15
Q

Name clinical features of IgE allergic responses under each system below:

  • skin:
  • respiratory:
  • GI
  • Blood vessels and brain:
A
  • skin: angiooedema (swelling of lips/tongue/eyelids), urticaria (wheals/hives), flushing, itch
  • respiratory: cough, SOB, wheezing, sneezing, nasal congestion, clear discharge, red watery eyes
  • GI: N&V, diarrhoea
  • Blood vessels and brain: symptoms of hypotension = faint, dizzy, blackout, sense of impending doom
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16
Q

Timeframe for development of clinical features of IgE allergic responses

A

occurs within minures or up to 3-4 hours post-exposure to allergen

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17
Q

Clinical features of IgE mediated allergic responses must be reproducible after every exposure

A

True

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18
Q

Clinical features of IgE mediated allergic responses may be triggered by cofactors - name 3 cofactors in all and 1 specific to children

A
  1. exercise
  2. alcohol
  3. NSAIDs
  4. Viral infections (children)
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19
Q

Symptoms (4) NOT associated with IgE allergic reactions

A
  1. Fatigue
  2. Migraine
  3. Recurrent episodes of abdo pain/diarrhoea/constipation/bloating
  4. Hyperactivity or depression
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20
Q

Name 2 IgE sensitisation tests

A
  1. Skin prick and intradermal test
  2. IgE blood tests
21
Q

A positive IgE test demonstrates clinical allergy - true or false?

A

FALSE - a positive IgE test is necessary to demonstrate sensitisation (risk of allergic disease) but not sufficient for diagnosis!

22
Q

Results of skin prick test or serum specific IgE predict the severity of allergic reaction - true or false?

A

False

23
Q

Skin prick testing - what does it involve? What is the + and - control?

A

Expose patient to solution of allergen extract to a skin prick to the forearm => measure local wheal and flare response

+ control => histamine

  • control => diluent
24
Q

What is the pathophysiology of a (+) response to skin prick test?

A

allergen stimulates IgE production => IgE crosslinking on skin mast cells => degranulation and release of histamine and other inflammatory mediators

25
Q

What is a positive wheal size in skin prick testing?

A

>= 3 mm

26
Q

Increasing size of wheals correlates with higeher probability of allergy in skin prick testing - True or False?

A

True!

27
Q

Name some advantages (4) and disadvantages (4) of skin prick tests

A

Advantages of SPT:

  1. Rapid (read in 15-20 mins)
  2. Cheap and easy to do
  3. Excellent negative predictive value (>95%)
  4. Patient can see results

Disadvantages of SPT:

  1. Experience to interpret correctly
  2. Risk of anaphylaxis (1/3000)
  3. Poor positive predictive value (high false positive rate)
  4. limited value in patients with dermatographism/extensive eczema
28
Q

Intradermal tests - what is the main difference when compared to SPT?

A

more sensitive

less specific

greater risk of anaphylaxis

can be used if SPT is negative but clinical history is convincing!

29
Q

Sensitisation (IgE antibody) blood tests for allergen:

  • what does the assay involve?
A

Allergen bound to solid phase => add patient serum => specific IgE binds to allergen => labelled anti-IgE added => fluorescent light signal measured

30
Q

Sensitisation (IgE antibody) blood test - if positive, does patient have allergic disease?

A

Detection of IgE is necessary but not sufficient to make a diagnosis of allergic disease

31
Q

Name 5 indications for sensitisation (IgE antibody) blood test for allergy?

A
  1. no access to SPT and/or IDT
  2. Patient cant stop anti-histamine
  3. Patient with history of severe eczema/dermatographism
  4. patient with hisotry of anaphylaxis
  5. monitor resopnse to anti-IgE therapy
32
Q

Component resolves/molecular allergen testing - what is it? what is it mostly used for?

A

2nd line investigation method that can check for IgE sensitisation against individual protein within a whole allergen extract

  • food allergy (esp nuts, egg, milk)
  • insect allergy (wasp, bees)
33
Q

mast cell tryptase - what is this test for? When is it used?

A

mast cell tryptase is a biomarker anaphylaxis

systemic degranulation of mast cells during anaphylaxis => increase in serum tryptase

  • test is used for when diagnosis of anaphylaxis is unclear (i.e. hypotension + rash during anaesthesia)
34
Q

Basophil activation test - what is it? When is it used?

A

Basophil activation test - measurement of basophil response to allergen IgE crosslinking

  • not commonly used now; increasing use in diagnosis of food and drug allergy; efforts to standardise this test
35
Q

Challenge tests are the gold standard for ______ & _____ allergy

A

food & drug allergy

36
Q

How is a challenge test for allergy conducted? What are its 3 caveats?

A

Give patient increasing volumes of offending food/drug => takes place under medical supervision and can be double blind placebo or open challenge

caveats:

  • risk of severe reaction
  • expensive + time consuming
  • difficult to interpret mild symptoms
37
Q

Food allergy vs food intolerance - describe the difference

A

Food allergy: adverse health effect arising from specific immune response that occurs reproducibly on exposure to a given food

Food intolerance: non immune reactions which include metabolic, pharmacological and unknown mechanisms. i.e. excess tyramine in cheese or wine causing headaches

38
Q

Food allergy - what 4 types of allergic reactions could it be?

A
  1. IgE mediated reactions (anaphylaxis, OAS)
  2. Mixed IgE and cell mediated (atopic dermatitis)
  3. Non IgE mediated (coeliac disease)
  4. Cell mediated (contact dermatitis)
39
Q

Prevalence of food allergy differs in young children vs adults - what is common in each group? What is outgrown and what isn’t?

A

Young children - milk and egg => usually outgrown

adults => mostly fish and nut allergy

*children dont usually outgrow peanut and treee nut allergy

40
Q

Moderate/severe atopic dermatitis is an important risk factor for food allergy - true or false?

A

True - (indication for allergy testing even in absence of clinical history)

41
Q

What is the goldstandard test for food allergy?

A

double blind oral food challenge

42
Q

What investigations (4) are done for food allergy?

A
  1. Good clinical history
  2. SPT
    - positive => indicates sensitisation but no necessarily allergy
    - negative => 95% negative predictive value so probs doesnt have IgE mediated
  3. Individual allergen protein component
  4. GOLD STANDARD - ORAL FOOD CHALLENGE!
43
Q

Describe the management of food allergy

A

1. Avoidance

  • Education about food labelling, interaction with restaurants, school
  • Nutritional input for dietary balance, growth in children
  • Acknowledge anxiety, potential bullying: mental health support if needed

2. Emergency management

  • Anaphylaxis guidelines
  • Ensure allergic asthma is well controlled

3. Prevention

•LEAP study: early rather than delayed introduction of peanut in high risk children (moderate/severe AD and egg allergy) significantly reduces development of peanut IgE sensitisation and allergy

44
Q

Which foods commonly cause aanphylaxis reactions and which cause delayed food-induced anaphylaxis (3-6 hr after eating)

A

Anaphylaxis => peanut, tree nut, shellfish, fish, milk, eggs

Delayed food-induced anaphylaxis => beef, pork, lamb

45
Q

Describe how red meat can cause delayed food-induced anaphylaxis?

A

implication of tick bites

IgE ab to oligosacccharide alpha-gal

(tick feeds on mammal; tick bites human; human makes IgE antibody to alpha-gal; human eats red meat with alpha-gal carb; 3-6 hours later reacts!)

46
Q

Which 3 foods are associated with exercise induced anaphylaxis?

A
  1. wheat
  2. Shellfish
  3. Celery

if exercise within 4-6 hours of ingestion

47
Q

What is the oral allergy syndrome? Why is it caused?

A

limited to oral cavity, causing swelling and itch

  • rarely progresses to anaphylaxis

typically due to sensitisation to inhalant pollen protein leading to IgE cross-reactivity to food

48
Q

What is the oral allergy syndrome - which food are commonly implicated? Are they heat labile?

A

•Respiratory exposure to pollen (birch) results in IgE directed to homologous proteins in stone fruits (apple, pear) vegetables (carrot) and nuts (peanut, hazelnut)

they are HEAT LABILE - will no longer cause problem if you heat them!

49
Q

60 year old with hypotension and rash, what test is ordered to diagnose anaphylaxis?

  1. Skin prick
  2. Drug challenge
  3. Blood histamine
  4. Serial mast cell tryptase
  5. Urine prostaglandin D2
A

Serial mast cell tryptase

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