Allergy Flashcards
IgE mediated food allergy process:
- 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
- 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
Treatment of urticaria/angioedema + vomiting, diarrhoea or abdominal pain with insect sting?
Adrenaline
= Anaphylaxis
Difference between anaphylaxis and anaphylactoid reactions?
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
Widespread rash
Welts when scratch skin
Cutaneous mastocytosis
So many mast cells
Anaphylaxis biphasic reactions timecourse?
Initial symptom resolution with treatment
Rebound of symptoms within 4 hours (but can occur up to 72hours)
Risk of biphasic: more severe initial reaction
Treatment for anaphylaxis?
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
If on beta blocker, what is the impact of adrenaline?
May be less effective
Give glucagon - will help with vasoconstriction, but won’t help with bronchoconstriction
Most common cause of food related anaphylaxis?
Nuts (peanut > tree nuts)
Then cows milk
Then egg
Most common food allergy in children?
Egg
When and how to read skin prick test?
After 15 minutes, average height + width of wheal
Compare with saline and histamine control
Better than ssIgE for fruit/vegetables
3mm+ is positive
How is ssIgE done?
ELISA for IgE against specific allergen- better standardisation
> 0.35 KuA/L is positive
Skin prick test / ssIgE useful for what?
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
Indication for skin prick test / ssIgE?
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
Chronic idiopathic urticaria cause?
Likely post viral
Dysregulated mast cells
Not IgE
When to prescribe adrenaline autoinjector?
- previous anaphylaxis to food/insect
- mild-mod reaction but at risk of fatal anaphylaxis: adolescent, asthmatic, nut/shellfish allergy, live far from medical service
Severity of reaction is modulated by multiple co-factors. Thus next reaction may be worse or milder.
Co-factors?
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
If cow milk protein immediate reaction IgE but not anaphylaxis, avoid which other milk?
Can give which milk?
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
If cow milk protein anaphylaxis, which milk recommended?
Amino acid formula or Novalac rice
– lowest risk
Under medical observation: trial extensively hydrolysed formula or soy challenge
If IgE immediate reaction (non anaphylaxis) to egg/cows milk, can they have it baked?
70% of children with egg/cow milk allergy tolerate it baked
- but unable to predict, so can challenge under medical observation
If severe eczema and/or food allergy:
The longer the delay to peanut introduction, the higher the risk of?
Recommendation?
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
MMR incubated in?
Chicken fibroblasts not eggs
Safe in egg allergy/anaphylaxis
Influenza vaccine with egg allergy?
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
Most children with egg, cow milk and wheat allergy will outgrow the allergy by what percentage at 3, 5 and 12 years of age?
30% by 3 years
50% by 5 years
80% by 12 years
What proportion of those with peanut/tree nut/shellfish allergy will be tolerant/outgrown by age 5?
10% - 20%
Difference in symptoms between non-IgE food allergies and IgE?
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
Can FPIES change from non IgE to IgE reaction?
Yes
Coeliac’s is mediated by which cells?
T cells
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
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
6 month old girl
Chronic diarrhoea, FTT, abdo distention
Onset coincided with introduction of cow’s milk formula
Anaemia and low albumin
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
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
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
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
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
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
Multiple food protein intolerance
– issue after starting solids esp cow’s milk / soy
Mx: amino acid formula
Outgrow it by age 3
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
?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
What drives urticaria?
Mast cell + histamine driven
Late phase: eosinophils, basophils, macrophages, neutrophils, T cells
Acute urticaria: less than 6 weeks, 25% lifetime prevalence, most common cause?
Mx?
Infections, usually viral URTI
Other causes: amoxicillin, NSAID, food
Usually self limiting
Mx: anti-histamine
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
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
Histamines binds and stabilises the active form of Histamine1-receptor. What do H1 antihistamines do?
Bind and stabilise inactive form of Histamine1-receptor
= inverse agonist
Urticaria pigmentose
Cutaneous mastocytosis - aggregates of mast cells
- activate and itchy with contact
- lesions last years
Inducible causes of urticaria?
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)
Most common cause of angioedema?
Allergy
Other causes of angioedema?
Idiopathic: histamine or bradykinin induced
ACE inhibitor induced
Hereditary angioedema (C1 esterase inhibitor deficiency)
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
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
What is the most common type of hereditary angioedema?
Type 1:
Low production of functionally active C1 inhibitor
What is atopic march?
Eczema -> food allergy -> asthma -> rhinitis
IL4 + IL13
B cell -> Mast cells
IL5
Eosinophils
What does immunotherapy do in allergic rhinitis?
Reduces symptoms and medication requirement
Reduces progression to asthma
Reduces risk of new allergen sensitisations
NOT a cure
Is allergic rhinitis a risk factor for asthma?
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
How frequently is asthma present in fatal food anaphylaxis?
In 75% of cases
Type of bugs responsible for most serious sting related reactions?
Hymenoptera = bees (most commonly honey bee), vespids, stinging ants
Frequency of systemic allergic reactions in children?
1%
Cutaneous most commonly
Gastrointestinal signs with sting indicate SYSTEMIC reaction
Risk of anaphylaxis with future stings after anaphylaxis?
50%
Risk of reaction to cephalosporins after + skin prick test to penicillin?
2%
Higher risk with first generation
Penicillin skin prick test useful because of what value?
Good negative predictive value
First line ix for severe bee/wasp bite reaction?
Serum IgE
