Allergy

Question 1

IgE mediated food allergy process:

Answer 1

1. Sensitisation: allergen -> dendritic cells -> allergen specific T cell -> Th2 -> IL4, 5, 13 -> B cell makes allergen-specific IgE free floating (measured in RAST) -> sit on mast cells
2. Allergy: re-exposure activates mast cells as antigen binding cross links mast cells -> histamine, leukotrienes, cytokine, prostaglandins, PAF (allergy median onset is 10 minutes post re-exposure) – this process is measured by skin prick testing

Question 2

Treatment of urticaria/angioedema + vomiting, diarrhoea or abdominal pain with insect sting?

Answer 2

Adrenaline

= Anaphylaxis

Question 3

Difference between anaphylaxis and anaphylactoid reactions?

Answer 3

Same symptoms
Different mechanism - direct mast cell activation in anaphylactoid (not IgE mediated, nil sensitisation required, skin prick tests/RAST tests unhelpful)
- anaphylactoid reactions commonly seen with medications: NSAIDs, opiates, contrast, vancomycin, blood products as can directly bind and activate mast cells

Question 4

Widespread rash

Welts when scratch skin

Answer 4

Cutaneous mastocytosis

So many mast cells

Question 5

Anaphylaxis biphasic reactions timecourse?

Answer 5

Initial symptom resolution with treatment
Rebound of symptoms within 4 hours (but can occur up to 72hours)

Risk of biphasic: more severe initial reaction

Question 6

Treatment for anaphylaxis?

Answer 6

0.01ml or mg per kg of 1:1000 (max 0.5mg or ml) IM adrenaline (alpha 1 agonist: vasoconstriction, reduce oedema; beta 2 agonist: bronchodilator, reduce mast cell activation)
Non-sedating anti-histamine

Question 7

If on beta blocker, what is the impact of adrenaline?

Answer 7

May be less effective

Give glucagon - will help with vasoconstriction, but won’t help with bronchoconstriction

Question 8

Most common cause of food related anaphylaxis?

Answer 8

Nuts (peanut > tree nuts)
Then cows milk
Then egg

Question 9

Most common food allergy in children?

Answer 9

Egg

Question 10

When and how to read skin prick test?

Answer 10

After 15 minutes, average height + width of wheal
Compare with saline and histamine control
Better than ssIgE for fruit/vegetables

3mm+ is positive

Question 11

How is ssIgE done?

Answer 11

ELISA for IgE against specific allergen- better standardisation

> 0.35 KuA/L is positive

Question 12

Skin prick test / ssIgE useful for what?

Answer 12

a) Confirm IgE mediated food allergy
b) Determine when safe to proceed to oral supervised food challenge, due to natural tolerance being developed
- - if minimal skin prick reaction as time has passed post last exposure
- - if ongoing strong positive test even after years post last exposure higher likelihood to have IgE reaction again

Question 13

Indication for skin prick test / ssIgE?

Answer 13

Suspected IgE reaction to food ie immediate reaction

Tells you the likelihood of reacting again (another IgE mediated reaction), but NOT the severity of future reactions

Question 14

Chronic idiopathic urticaria cause?

Answer 14

Likely post viral
Dysregulated mast cells
Not IgE

Question 15

When to prescribe adrenaline autoinjector?

Answer 15

• previous anaphylaxis to food/insect
• mild-mod reaction but at risk of fatal anaphylaxis: adolescent, asthmatic, nut/shellfish allergy, live far from medical service

Question 16

Severity of reaction is modulated by multiple co-factors. Thus next reaction may be worse or milder.
Co-factors?

Answer 16

Allergen
Amount of allergen
Raw vs baked - raw egg more allergenic 
Exercise can make reaction worse ie running post exposure 
Inter-current illness can make reaction worse 
Asthma and asthma control 
Alcohol can make worse
Menstruation can make worse

Question 17

If cow milk protein immediate reaction IgE but not anaphylaxis, avoid which other milk?

Can give which milk?

Answer 17

Avoid:

• partial hydrolysed formula
• sheep/goat milk

Give:

a) soy / novalac rice
b) extensively hydrolysed formula
c) amino acid formula
- - less palatability but lowest risk of reaction

Question 18

If cow milk protein anaphylaxis, which milk recommended?

Answer 18

Amino acid formula or Novalac rice
– lowest risk

Under medical observation: trial extensively hydrolysed formula or soy challenge

Question 19

If IgE immediate reaction (non anaphylaxis) to egg/cows milk, can they have it baked?

Answer 19

70% of children with egg/cow milk allergy tolerate it baked

- but unable to predict, so can challenge under medical observation

Question 20

If severe eczema and/or food allergy:
The longer the delay to peanut introduction, the higher the risk of?
Recommendation?

Answer 20

Transforming to immediate reaction
Introduce from 4-6 months at home and regular exposure to reduce further risk of allergy
No fatal reactions in those under 12 months

Question 21

MMR incubated in?

Answer 21

Chicken fibroblasts not eggs

Safe in egg allergy/anaphylaxis

Question 22

Influenza vaccine with egg allergy?

Answer 22

Safe in egg allergy/anaphylaxis
Can be given as single dose 
15 minute observation time 
Can be given in community 
The amount of egg allergen in the vaccine is so small, vast majority of cases no reaction

Question 23

Most children with egg, cow milk and wheat allergy will outgrow the allergy by what percentage at 3, 5 and 12 years of age?

Answer 23

30% by 3 years
50% by 5 years
80% by 12 years

Question 24

What proportion of those with peanut/tree nut/shellfish allergy will be tolerant/outgrown by age 5?

Answer 24

10% - 20%

Question 25

Difference in symptoms between non-IgE food allergies and IgE?

Answer 25

Time from ingestion to reaction: hours to days GIT inflammation +/- eczema flare No urticaria/angioedema/respiratory difficulties ssEge/SPT usually negative/low positive No fatalities Combined cow's milk + soy trigger is common (up to 50%) - soy uncommon in IgE mediated reactions Nuts/seeds are a rare trigger

Question 26

Can FPIES change from non IgE to IgE reaction?

Answer 26

Yes

Question 27

Coeliac's is mediated by which cells?

Answer 27

T cells

Question 28

``` Healthy, non febrile baby 2-8 weeks of age BF or just started cows milk/soy formula Gradual onset, blood specks/clots + mucous in stools Diarrhoea uncommon ```

Answer 28

``` Allergic proctocolitis Clinical diagnosis (after ruling out other causes of bloody stool) Cows milk most common trigger Soy also common Can have cows milk + soy cross reaction ``` Mx: Generally exclude dairy first Then egg/corn exclusion Then extensively hydrolysed formula Generally resolves with food elimination Re-introduce food trigger after 12 months of age Most outgrow it Even without exclusion diet, may still tolerate regular diet by 12 months of age

Question 29

6 month old girl Chronic diarrhoea, FTT, abdo distention Onset coincided with introduction of cow's milk formula Anaemia and low albumin

Answer 29

Food protein enteropathy Chronic non-bloody diarrhoea within weeks of introduction of a food (common trigger: cow's milk, soy, egg, wheat) Villous atrophy on endoscopy Avoid allergen, amino acid formula, resolves by 2-3 ages = different to coeliac's disease

Question 30

``` 12 year old boy IgE to milk, egg Eczema Asthma Vomiting Fussy eaters Slow eater, hard to swallow esp textured foods, need to drink a lot of water, cut foods up finely Food bolus obstruction ```

Answer 30

Eosinophilic eosophagitis Commonly triggered by cow milk, soy, wheat, egg Eosophageal stenosis with time M>F Can have fhx+, higher risk in siblings Diagnose with endoscope: linear furrows, white dots = eosinophils accumulating, rings seen in oesophagus appear like trachea Determine food trigger by elimination and then re-introduce with repeat scope biopsy to measure eosinophilia + to assess symptom response PPI (25% respond) Amino acid formula if young

Question 31

6 month old girl First time eating rice 4 hours later, ++ profuse vomiting pale floppy lethargic Presented to ED Recovered well within 12 hours Ate rice x2 times, and same reaction: 4 hours later, ++ vomiting pale floppy hypothermic

Answer 31

FPIES Infants, clinical diagnosis +/- oral food challenge if unsure of diagnosis Innate immune system activated Rice is commonest trigger; milk, egg, chicken can also trigger 75% react to only one food Rare to be triggered by food proteins through breastmilk but can occur with dairy/soy Within 2-4 hours after eating newly introduced food: profuse vomiting, floppy/pale, hypothermic/hypotensive, neutrophilia/thrombocytosis. NOT febrile; quickly self-recover to normal within 12 hours; CRP/ESR not elevated; no fatalities. DDx: sepsis/gastroenteritis Can transform to IgE mediated reaction esp with egg / milk FPIES Challenge 12 months after last exposure under medical observation / skin prick test if unsure if now IgE Vast majority of children will outgrow it

Question 32

``` 6 month old girl BF Irritable, mucous stools, poor sleep Worse loose stools, screaming, irritable and poor sleep after introducing new foods - after each new food Otherwise growing well Symptoms settle on amino acid formula ```

Answer 32

Multiple food protein intolerance -- issue after starting solids esp cow's milk / soy Mx: amino acid formula Outgrow it by age 3

Question 33

3 year old boy URTI + amoxicillin -> Rash for 2 weeks Widespread lesions, itchy wheals, appear to migrate 'Hives' intensify by mid-morning Parents subsequently eliminated cow's milk from breakfast Phx: eczema, no food allergies Examines well

Answer 33

?infection related urticaria Urticaria = wheals/hives +/or angioedema Wheals = superficial swellings of upper/mid dermis, surrounding erythema, itch/sometimes burn sensation, fleeting with skin returning to normal within 30mins-24 hours Angioedema = deep swelling, pain or itch, may take several days to resolve

Question 34

What drives urticaria?

Answer 34

Mast cell + histamine driven Late phase: eosinophils, basophils, macrophages, neutrophils, T cells

Question 35

Acute urticaria: less than 6 weeks, 25% lifetime prevalence, most common cause? Mx?

Answer 35

Infections, usually viral URTI Other causes: amoxicillin, NSAID, food Usually self limiting Mx: anti-histamine

Question 36

``` 14 year old girl, urticaria present >12 months Hives daily Lip angioedema several times per week Impacting function, always tired No fever/msk symptoms ``` Hx: hypothyroidism, improvement of hives during first 6 months of thyroxine treatment Previous treatment: antihistamine, montelukast, azathioprine Current treatment: cetirizine, prednisolone

Answer 36

Chronic urticaria (same pattern as acute ie hives transient <24 hours with skin returning to normal, itch - NOT painful) 6 weeks or longer with continuous disease activity Less common than acute No systemic inflammation Cause: Spontaneous or Inducible -- in this case spontaneous! - -> autoantibodies to mast cells - -> can also have autoantibodies against thyroid **RASH LASTING SEVERAL DAYS IS ALMOST NEVER ALLERGIC IN ORIGIN** Monitor: urticaria activity score over 7 days (UAS7) - number of wheals + itch Mx - chronic spontaneous urticaria: Non pharma - reassurance (usually resolves), no role of diet, minimise triggers Pharma - daily antihistamine (H1 antagonists, second generation: cetirizine, loratadine = less sedation, less anticholinergic side effects): reduces pruritis. Can use x4 manufacturer's dose. Controls it in most cases. Second line (in addition to H1 antagonist): H2 antagonists (ranitidine) - mainly GIT effect Leukotriene antagonists Doxepin (weak tricyclic antidepressant, good histamine blocker) Third line: Omalizumab (recombinant humanised monoclonal antibody IgG which binds to IgE, and inhibits it from binding to mast cells and basophils)- reduces IgE levels and down regulates expression of FceRI IgE receptors (use higher doses if higher pre-treatment IgE) Used is asthma age >6, chronic spontaneous/idiopathic urticaria age >12 --> important to note that IgE levels remain elevated for up to a year post treatment See response in ~12 weeks

Question 37

Histamines binds and stabilises the active form of Histamine1-receptor. What do H1 antihistamines do?

Answer 37

Bind and stabilise inactive form of Histamine1-receptor | = inverse agonist

Question 38

Urticaria pigmentose

Answer 38

Cutaneous mastocytosis - aggregates of mast cells - activate and itchy with contact - lesions last years

Question 39

Inducible causes of urticaria?

Answer 39

Dermographism: at sites of friction / stroking Pressure Vibratory (ADGRE2 mutation) Contact Solar (triggered by light/UV) Heat Cold (phospholipase Cgamma2 associated antibody deficiency: PLAID) Cholinergic (after heating of body core ie exercise / hot bath --> pinpoint wheals + intense itch) Aquagenic (induced by water)

Question 40

Most common cause of angioedema?

Answer 40

Allergy

Question 41

Other causes of angioedema?

Answer 41

Idiopathic: histamine or bradykinin induced ACE inhibitor induced Hereditary angioedema (C1 esterase inhibitor deficiency)

Question 42

Recurrent oedema anywhere on the body NO URTICARIA, not itchy, not pitting Swelling can take hours to peak, and takes 2-3 days to resolve Swelling of GIT can lead to abdo pain/vomiting/ hypotension Laryngeal swelling can lead to fatal asphyxiation Attacks may be preceded by tingling or erythema marginatum (non-itchy rash) Stress and infection are common precipitants Increased risk of autoimmune conditions Ix: C4 low

Answer 42

Hereditary angioedema (C1 esterase inhibitor deficiency) ``` 1:50,000 Often family history SERPING1 gene C1 esterase inhibitor is a protease inhibitor; inhibits C1 and inhibits other circulating enzymes including kallikrein which leads to increased and unchecked BRADYKININ production Median age of onset: age 10 ``` Test C1 inhibitor level and function Treatment of attack: - Replace C1 inhibitor - Bradykinin antagonist Prevention: - Minimise triggers - Androgen (Danazol) & Antifibrinolytic (Tranexamic acid) -- but NOT super helpful Adrenaline, antihistamines, steroids of NO use

Question 43

What is the most common type of hereditary angioedema?

Answer 43

Type 1: | Low production of functionally active C1 inhibitor

Question 44

What is atopic march?

Answer 44

Eczema -> food allergy -> asthma -> rhinitis

Question 45

IL4 + IL13

Answer 45

B cell -> Mast cells

Question 46

IL5

Answer 46

Eosinophils

Question 47

What does immunotherapy do in allergic rhinitis?

Answer 47

Reduces symptoms and medication requirement Reduces progression to asthma Reduces risk of new allergen sensitisations NOT a cure

Question 48

Is allergic rhinitis a risk factor for asthma?

Answer 48

Yes Is upper airway version of asthma 80% of patients with asthma have allergic rhinitis Treatment of allergic rhinitis can also improve asthma, as it can sometimes be an asthma trigger

Question 49

How frequently is asthma present in fatal food anaphylaxis?

Answer 49

In 75% of cases

Question 50

Type of bugs responsible for most serious sting related reactions?

Answer 50

Hymenoptera = bees (most commonly honey bee), vespids, stinging ants

Question 51

Frequency of systemic allergic reactions in children?

Answer 51

1% Cutaneous most commonly Gastrointestinal signs with sting indicate SYSTEMIC reaction

Question 52

Risk of anaphylaxis with future stings after anaphylaxis?

Answer 52

50%

Question 53

Risk of reaction to cephalosporins after + skin prick test to penicillin?

Answer 53

2% | Higher risk with first generation

Question 54

Penicillin skin prick test useful because of what value?

Answer 54

Good negative predictive value

Question 55

First line ix for severe bee/wasp bite reaction?

Answer 55

Serum IgE