6. Allergy Flashcards
(96 cards)
1
Q
Define allergic disorder
A
Immunological process that results in immediate and reproducible symptoms after exposure to an allergen. Usually involves an IgE-mediated type 1 hypersensitivity reaction
2
Q
Define allergen
A
Usually a harmless substance that can trigger an IgE-mediated immune response and may result in clinical symptoms
3
Q
Define sensitisation
A
Detection of specific IgE either by skin prick testing or in vivo blood tests. NOTE: This shows risk of allergic disorder but does not define allergic disease
4
Q
Summarise the immune response to pathogens, multicellular organisms and allergens:
A
- Pathogens have conserved structures (microbial PAMP) that can be recognised by cells of the immune system (Th1 and Th17)
- Multicellular organisms (helminthes, venoms) and allergens don’t necessarily have conserved structures that are recognised by immune cells, instead they release mediators (e.g. proteases) that disturb epithelial barriers which is a functional change that is recognised by the immune system and gives rise to Th2-mediated responses
5
Q
There are two main Th2 immune responses to worms, allergens and pathogens. Summarise the Th2 immune response where the stressed or damaged epitheliun releases signalling cytokines:
A
- Stressed or damaged epithelium will release signalling cytokines (e.g. TSLP)
- These cytokines will act on Th2 cells, Th9 cells and ILC2 cells and promote the section of IL4, IL5 and IL13
- These then act on eosinophils and basophils which plays a role in the expulsion of parasites and allergens but can also contribute to tissue injury
- The TSLP and other cytokines released by the damaged epithelium can also activate follicular Th2 cells which then releases IL4
- IL4 stimulates B cells to produce IgE and IgG4
6
Q
There are two main Th2 immune responses to worms, allergens and pathogens. Summarise the Th2 immune response where the sensor is the mast cell:
A
- In another form of allergic response, the sensor is the mast cell
- The allergen will cause cross-linking of IgE giving rise to the release of histamine, prostaglandins and leukotrienes
- These mediates act on the endothelium causing increased permeability, the smooth muscle (contract) and neurones (to cause an itch)
- This response will expel the parasite/allergen or it will be responsible for the symptoms of asthma, eczema and hayfever
7
Q
What causes the induction of Th2 immune responses? What is the take home message?
A
- Not well understood.
- Primary defect thought to be in epithelial barrier. E.g. skin defect is a significant risk factor for the development of IgE antibodies (atopic dermatitis)
- Skin dendritic cells (Langerhans and dermal dendritic cells) promote secretion of Th2 cytokines much more efficiently than other dendritic cell subtypes
- This suggests that different dendritic cell subsets will prime the Th2 immune responses in humans to different levels
- IL4 secretion is only induced by peptide-MHC presentation to TCR or naive/memory Th2 cells
TAKE HOME MESSAGE: oral exposure promotes immune tolerance whereas skin and respiratory exposure induces IgE sensitisation
8
Q
Why does oral exposure promotes immune tolerance whereas skin and respiratory exposure induces IgE sensitisation?
A
When an allergen is ingested through the oral route, Tregs derived from the GI mucosa will inhibit IgE synthesis to keep the immune system in balance.
9
Q
What allergic diseases typically onset in infancy?
A
Atopic dermatitis, food allergy (milk, egg, nuts)
10
Q
What allergic diseases typically onset in childhood?
A
Asthma (house dustmite, pets), allergic rhinitis
11
Q
What allergic diseases typically onset in adulthood?
A
Drug allergy, bee allergy, oral allergy syndrome, occupational allergy
12
Q
Which one of the following proteins/cytokines is NOT a drug target for current drugs and/or biologics used to treat allergic disorders? A. IL-13, B. Histamine, C. IL-33, D. IgE, E. IL-5
A
Answer: C
NOTE: allergic rhinitis is the most common allergic disorder in adults (food allergy is the least common). Allergic disorders seem to have increased in prevalence
13
Q
What are theories behind the increasing prevalence of allergic disorders?
A
- Hygiene hypothesis, 2. lack of vitamin D in infancy (leading to food allergy), 3. dietary factors (reduced omega and linoleic fatty acids), 4. high concentration of dietary advanced glycation end-products and pro-glycating sugars which the immune system mistakenly recognises as causing tissue damage (e.g. fast food and soda)
14
Q
What is the hygiene hypothesis?
A
Lack of childhood exposure to infectious agents increases susceptibility to allergic diseases by suppressing natural development of the immune system
15
Q
What are clinical features of an IgE mediated response?
A
- Occurs minutes to 3 hours after exposure.
- Symptoms include: angioedema (swelling of lips, tongue, eyelids), urticaria, flushing, itching, cough, SOB, nasal congestion, wheeze, red watery eyes, nausea, diarrhoea and vomiting, hypotension (dizziness, faints), sense of impending doom.
- Usually at least 2 organ systems are involved
- The symptoms are reproducible (occurs after every exposure)
- Allergic symptoms can be triggered by co-factors (e.g. exercise, alcohol)
- The clinical history is used to select what allergens should be tested by skin-prick testing and/or blood tests
16
Q
What investigations can be done in allergic diseases, elective investigations and during acute episode?
A
Elective investigations include: skin prick and intradermal tests, laboratory measurement of allergen-specific IgE, component-resolved diagnostics, basophil activation test, challenge test.
During acute episode: evidence of mast cell degranulation can be determined through serial mast cell tryptase, and blood and/or urine histamine
17
Q
What are specific IgE sensitisation tests?
A
Skin prick and blood tests are used to detect the presence/absence of IgE antibody against external proteins
18
Q
A positive IgE test demonstrates sensitisation AND clinical allergy, true or false?
A
False. A positive IgE test only demonstrates sensitisation NOT clinical allergy
19
Q
How to interpret the risk profile of serum IgE for prediction of allergic symptoms:
A
- Concentration - higher levels = more symptoms
- Affinity to target - higher affinity = increased risk
- Capacity of IgE antibody to induce mast cell degranulation
20
Q
Detection of IgE is necessary but not sufficient to make a diagnosis of allergic disease. What does diagnosis require?
A
Diagnosis requires history, examination, blood tests, skin prick tests etc. to be combined
21
Q
Skin prick testing is more sensitive and specific than blood tests to diagnose allergy. Describe how the procedure is done and a positive test:
A
- Expose the patient to a standardised solution of allergen extract through a skin prick on the forearm.
- Uses a standard skin test solutions with a positive control (histamine) and negative control (diluent).
- Measure local wheal and flare response to controls and allergens.
- A positive test is indicated by a wheal > 3 mm greater than the negative control
- Antihistamines should be discontinued for at least 48 hours before the test
22
Q
What are the advantages of a skin prick test?
A
- 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
23
Q
What are the disadvantages of a skin prick test?
A
- Requires experience to interpret
- Risk of anaphylaxis: 1 in 3000
- Poor positive predictive value: high false positive rate
- Limited value in patients with dermatographism or extensive eczema
- False negative results with labile commercial food extracts
24
Q
How does serum specific IgE blood tests work?
A
Allergen is bound to a sponge and the specific IgE (if present) will bind to the allergens. This is washed over with anti-IgE antibody which is tagged with a fluorescent label. May help in the diagnosis of an allergic disorder in someone with an appropriate clinical history. Higher values are more likely to be associated with allergic disorders
25
What is the downside of serum specific IgE blood test?
Reliable but expensive
26
How reliable is serum specific IgE blood test?
Reliable. Lot of false positives but it has good negative predictive value.
27
What can the concentration of IgE in serum specific IgE blood test tell us?
Concentration of IgE can be used to predict whether a child will outgrow allergy
28
What can serum specific IgE blood test be used to monitor?
Anti-IgE therapy
29
What are indications for serum specific IgE blood tests?
1. Patients who can't stop antihistamines
2. Patients with dermatographism - development of localised hive-like reaction when the skin is scratched
3. Patients with extensive eczema
4. History of anaphylaxis
5. Borderline/equivocal skin prick test results
30
What is component resolves diagnostics (CRD)?
A blood test to detect IgE to single protein components - abundance and stability of protein contributes to risk of allergic disease
31
What is component resolves diagnostics useful for?
CRD is useful for peanut and hazelnut allergy (may reduce need for food challenges)
32
What causes minor symptoms and severe reactions in CRD, when IgE is sensitised?
IgE sensitisation to:
1. Heat labile and proteolytic susceptible birch pollen homologue in peanuts and hazelnuts = MINOR symptoms.
2. Heat and proteolytic stable seed storage peanut and hazelnut allergen = SEVERE reactions
33
What are indications for allergen component testing?
1. Detect primary sensitisation
2. Confirm cross-reactivity
3. Define risk of serious reaction for stable allergens
4. Improve diagnostic sensitivity on addition of components which are poorly represented in whole food extracts
5. Improve diagnostic sensitivity for unstable molecules in whole food extracts
34
What is mast cell tryptase used for?
A biomarker for anaphylaxis
35
What happens to the levels of serum tryptase in an anaphylaxis reaction?
- Systemic degranulation of mast cells during anaphylaxis results in increased serum tryptase
36
What is tryptase?
a pre-formed protein found in mast cell granules
37
What does failure of return of mast cell tryptase to baseline after anaphylaxis mean?
This may be indicative of systemic mastocytosis
38
When does mast cell tryptase reach peak concentration and when does it reach baseline?
Peak concentration = 1-2 hours; baseline = 6-12 hours
39
When may mast cell tryptase levels be useful as a biomarker for anaphylaxis?
Useful if the diagnosis of anaphylaxis is uncertain e.g. hypotension and rash during anaesthesis
40
Is mast cell trypase a good marker to diagnose anaphylaxis which is food-induced?
No, it has a reduced sensitivity for food-induced anaphylaxis
41
What is the gold standard for food and drug allergy diagnosis and how does it work
Chellenge tests.
1. Increasing volumes of the offending food/drug are ingested
2. Double-blind placebo or open challenge
3. Take place under close medical supervision
4. Difficult to interpret mild symptoms
5. Risk of SEVERE reaction
42
What is the basophil activation test?
1. Measurement of basophil response to allergen IgE cross-linking
2. Activated basophils increase the expression of CD63, CD203 and CD300 protein on their cell surface
3. Increasingly used in the diagnosis of food and drug allergy
43
What is the sensitivity and specificity of inhalants when tested by serum IgE assay, puncture skin test and intradermal skin test?
Serum IgE assay sensitivity = +++, specificity = ++. Puncture skin test sensitivity = +++, specificity = ++. Intradermal skin test sensitivity = ++++, specificity = +.
44
What is the sensitivity and specificity of foods when tested by serum IgE assay, puncture skin test and intradermal skin test?
Serum IgE assay sensitivity = +++, specificity = +. Puncture skin test sensitivity = +++, specificity = +. Intradermal skin test sensitivity = ++++, specificity = +.
45
What is the sensitivity and specificity of venoms when tested by serum IgE assay, puncture skin test and intradermal skin test?
Serum IgE assay sensitivity = ++, specificity = +++. Puncture skin test sensitivity = ++, specificity = +. Intradermal skin test sensitivity = ++++, specificity = ++.
46
What is the sensitivity and specificity of drugs when tested by serum IgE assay, puncture skin test and intradermal skin test?
Serum IgE assay sensitivity = ++, specificity = +++. Puncture skin test sensitivity = ++, specificity = +++. Intradermal skin test sensitivity = ++++, specificity = +++.
47
A 15 y/o boy with a history of asthma and hayfever who notices an urticarial and angioedema skin rash shortly after eating peanuts. What is the most appropriate initial diagnostic test?
Skin prick test (it is rapid)
48
A 60 year old female with hypotension and skin rash under general anaesthesia. What is the most appropriate test to diagnose anaphylaxis?
Serial mast cell tryptase
49
What is the definition of anaphylaxis?
a severe potentially systemic hypersensitivity reaction. Rapid onset, life-threatening airway, breathing and circulatory problems which is usually but not always associated with skin and mucosal changes.
50
What is the incidence of anaphylaxis?
1.5-8/100,000
51
What is the most frequent organ involved in anaphylaxis?
Skin (84%)
52
What cardiovascular symptoms may anaphylaxis cause?
Collapse, syncope, drop in BP
53
What respiratory symptoms may anaphylaxis cause?
Respiratory compromise (SOB, wheeze, stridor). NOTE: respiratory symptoms are more common in children
54
How quick is the onset of symptoms in anaphylaxis?
Acute onset
55
Who is anaphylaxis more common in?
Children
56
What are the types of mechanisms of anaphylaxis are there?
IgE, IgG, complement, pharmacological
57
Which cells are associated with each type (IgE, IgG, complement, pharmacological) of anaphylaxis?
IgE - mast cells and basophils; IgG - macrophages and neutrophils; complement - mast cells and macrophages; pharmacological - mast cells
58
What are the different mediators associated with each type of anaphylaxis (IgE, IgG, complement, pharmacological)?
IgE - histamine and PAF; IgG - histamine and PAF; complement - PAF and histamine; pharmacological - leukotrienes and histamines.
59
What are examples/aetiology of each type of anaphylaxis?
IgE - food, insect venom, ticks, penicillin; IgG - biologicals, blood and IgG transfusions; complement - lipid excipients, liposomes, dialysis membranes and PEG; pharmacological - NSAID including aspirin, opiates, neuromuscular and quinolones drug.
60
What reactions in the skin can mimic anaphylaxis?
Chronic urticaria and angioedema (ACEi)
61
What throat swelling reactions can mimic anaphylaxis?
C1 inhibitor deficiency
62
What cardiovascular reactions can mimic anaphylaxis?
Myocardial infarction and PE
63
What respiratory reactions can mimic anaphylaxis?
Very severe asthma, vocal cord dysfunction, inhaled FB
64
What neuropsychiatric reactions can mimic anaphylaxis?
Anxiety or panic disorder
65
What endocrine reactions can mimic anaphylaxis?
Carcinoid and phaeochromocytoma
66
What toxic reactions can mimic anaphylaxis?
Scromboid toxicity (histamine poisoning)
67
What immune reactions can mimic anaphylaxis?
Systemic mastocytosis
68
What is the management of anaphylaxis? Include supportive treatments and further management.
1. IM adrenaline
2. Supportive treatments include adjust body position, 100% oxygen, fluid replacement, inhaled bronchodilators, hydrocortisone 100mg IV (prevent late phase response), chlorpheniramine 10 mg IV.
3. Further management: referral to allergy/immunology clinic; investigate cause; written info on recognition of symptoms and triggers, avoidance of triggers and indications of self treatment with epipen; prescription of emergency kit to manage anaphylaxis; copy of management plan and training for patient, carers, school staff and GP; venom immunotherapy and drug desensitisation as appropriate; refer patients with food-induced anaphylaxis to a dietician; advise patients to get a medic alert bracelet; review patient's understanding; and utilise patient support groups e.g. anaphylaxis campaign
69
Which receptors does IM adrenaline act on?
Alpha 1, beta 1 and beta 2
70
IM adrenaline acts on alpha 1, what does this do?
Causes peripheral vasoconstriction, reverses low BP and mucosal oedema
71
IM adrenaline acts on beta 1, what does this do?
Increases HR, contractility and BP
72
IM adrenaline acts on beta 2, what does this do?
Relaxes bronchial smooth muscle and reduces the release of inflammatory mediators
73
What is further management of anaphylaxis?
Further management: referral to allergy/immunology clinic; investigate cause; written info on recognition of symptoms and triggers, avoidance of triggers and indications of self treatment with epipen; prescription of emergency kit to manage anaphylaxis; copy of management plan and training for patient, carers, school staff and GP; venom immunotherapy and drug desensitisation as appropriate; refer patients with food-induced anaphylaxis to a dietician; advise patients to get a medic alert bracelet; review patient's understanding; and utilise patient support groups e.g. anaphylaxis campaign
74
```
A 55 year old man who attends A&E with angioedema involving lips and tongue which has developed over previous hours. He has a history of hypertension and is taking an ACEi and calcium channel blocker. Clinical examination show a pulse of 75bpm, blood pressure 150/90, respiratory rate of 18/min and oxygen saturation 78% on air. What is the most likely diagnosis?
A. C1 inhibitor deficiency
B. Acute anxiety attack
C. Systemic mastocytosis
D. Idiopathic anaphylaxis
E. ACE inhibitor induced angioedema
```
Answer: E (significant upper airway angioedema is associated with ACE inhibitor use and can happen at any point during treatment)
75
What is the definition of food allergy?
adverse health effect arising from specific immune response that occurs reproducibly on exposure to a given food
76
What is the definition of food intolerance?
Non-immune reactions which include metabolic, pharmacological and unknown mechanisms
77
What percentage of adults and children does food allergy affect?
5% of adults and 8% of children
78
What may cause food intolerance?
Food poisoning (bacterial, scromboid toxin); enzyme deficiencies (lactase); pharmacological (caffeine, tyramine)
79
What may cause food aversion?
Fads, eating disorders
80
What may cause food allergies?
IgE mediated reactions (anaphylaxis, OAS), mixed IgE and cell mediated (atopic dermatitis), non-IgE mediated (coeliac disease), cell-mediated (contact dermatitis). NOTE: children tend to outgrow milk and egg allergies
81
What type of allergies are anaphylaxis and OAS?
IgE mediated reactions
82
What type of allergy is atopic dermatitis?
Mixed IgE and cell mediated
83
What type of allergy is coeliac disease?
non-IgE mediated
84
What type of allergy is contact dermatitis?
Cell mediated
85
What things to consider in a clinical history in food allergy?
Patient's definition of allergy; distinguish between IgE and non IgE mediated symptoms; dose and how food is prepared; any history of atopic disease; previous Ix; if elimination of foods made a difference; consider other differential diagnoses
86
What Ix in food allergies?
Clinical history, positive skin-prick test or specific IgE blood test is useful to confirm, testing for individual allergen protein component can distinguish between IgE sensitisation and IgE mediated allergy
87
Management of food allergy
Avoidance, anaphylaxis for emergencies
88
What are IgE mediated food allergy syndromes?
Anaphylaxis; food associated exercise induced anaphylaxis; delayed food-induced anaphylaxis to beef, pork, lamb; oral allergy syndrome
89
What are triggers for anaphylaxis?
Peanut, tree nut shellfish, fish, milk and eggs are most common. Natural history dependent on food.
90
What triggers food associated exercise induced anaphylaxis?
Food induces anaphylaxis if individual exercises within 4-6 hours of ingestion. Common triggers are wheat, shellfish, celery.
91
What triggers delayed food-induced anaphylaxis to beef, pork, lamb?
Symptoms occur 3-6 hours after eating red meat and gelatin. IgE antibody to oligosaccharide alpha-gal (alpha 1, 3-galactose) found in gut bacteria. Induced by tick bites which should be avoided.
92
How severe is oral allergy syndrome?
Limited to oral cavity, swelling and itch: only 1-2% cases progresses to anaphylaxis.
93
What causes oral allergy syndrome to occur?
Sensitisation to inhalant pollen protein lead to cross reactive IgE to food. Respiratory exposure to pollen (birch) results in IgE directed to homologous proteins in stone fruits (apple, pear), vegetables (carrots) and nuts (peanut, hazelnut). Cooked fruits, vegetables and nuts cause no symptoms: heat labile allergens detected by component allergen tests.
94
What is the onset for oral allergy syndrome?
Onset after pollen allergy established: affect adults > young children
95
A 35 year old man with tree pollen hayfever and immediate lip tingling and swelling immediately after eating apples. What is the most likely explanation for IgE hypersensitivity? A. IgG4 subclass deficiency, B. cross reactive IgE sensitisation between hay fever and apple allergens, C. apple-hay fever immune complex disease, D. increased Th17 immune response to apple allergen, E. food aversion disorder
B
96
A positive skin test or food specific IgE blood test indicates sensitisation (allergy risk) but not necessarily allergy disease which can only be diagnosed by doctor in clinic. True or false?
True
