Teaching Clinic: Three cases of allergies

Question 1

What are the most common causes of allergy?

Answer 1

Drug allergy
Food allergy
Anaphylaxis

Question 2

Case 1: Drug allergy
* M 40
* Coarctation of aorta
* Admitted for bacteraemia associated with aortic graft infection
* List of antibiotics given during admission:
* Vancomycin, gentamicin, rifampicin, benzylpenicillin
* Five weeks later…. developed fever, maculopapular rash with eosinophilia (1.5 x 109) + deranged LFTs (ALT
644 IU/L)
What questions would you like to ask?

Answer 2

• Onset
• Rash
• Other extracutaneous symptoms (bronchospasm, lymphadenopathy, fever)
• Any deranged liver function test
• Allergy is IgE or T-cell mediated immune reactions (adaptive) = must be exposed to the drug before allergic reaction is mounted [having an absence of reaction of to a drug in the past does not rule out allergy to the drug]
• Any other medications taken?

You can differentiate two main groups of allergies asking about onset of allergy
- Type I (immediate): Allergic reaction developed one hour within taking drug / urticarial / bronchospasm
- Type IV (delayed): Maculopapular rash, inflammatory, fever,

Question 3

What are the SCAR syndromes?

Answer 3

Severe cutaneous adverse reaction (SCAR) is life-threatening
- Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Acute generalized exanthematous pustulosis (AGEP)

Question 4

How to approach allergy?

Answer 4

Is it really allergy? Infection?
How severe was it? Is it worth re-testing?
Was it immediate or delayed? Which test must we order?
(For delay we must rule out scar)

Question 5

How do we ask the likelihood of it being an allergy?

Answer 5

History: 3 important questions
1. Really an immune-mediated reaction (actually allergy)?
* i.e. what is the likelihood of it being an allergy:
* Allergen (Likely cause? Clinically plausible?)
* Better explanation? (Non-immune mediated reaction? Urticaria?)
– [Every 100 people in HK have chronic urticaria, sometimes when they are ill, the rash could come out (could the rash be caused by underlying immune reaction? low platelet = petechiae? anti-coagulants = bruising?), tummy upset above antibiotics (not an allergy)]
* Clinical features (Typical presentation? Immune-mediated symptoms?)
* Duration since index reaction (childhood history vs recent history) – [Allergies can resolve. Even if you penicillin allergy, patient may one day outgrow the allergy and not become allergic anymore]
* Extra information (serum tryptase levels, test results - beware validity)

Question 6

How do we assess the severity of an allergic reaction? Is it worth re-testing?

Answer 6

Severity:
- Immediate [airway/cardiovascular compromise/anaphylactic shock]
- Delayed [SCAR: severe cutaneous adverse reaction]

Question 7

What is anaphylaxis?

Answer 7

Acute + life-threatening + multi-system

Question 8

What are the severe cutaneous adverse reactions? What time duration must we ask?

Answer 8

SCAR takes WEEKS to occur

Never miss a delayed drug reaction = ASK ABOUT PRECEDING 2 MONTHS, IF THERE HAS BEEN ANY NEW MEDICATIONS STARTED

Deranged LFT, eosinophilia, fever = delayed (takes 2 months to occur, the most severe take the longest)

Toxic epidermal necrolysis: Toxic, sick looking, classically, patient’s skin will fall off in sheets (Nikolsky’s sign)

Must ask if there is:
- Mucosal involvement = conjunctiva and eyes (red flag)

Less than 10% is SJS
in between is SJS/TEN syndrome
More than 30% is TEN

DRESS is not epidermal necrolysis, usually a generalised, morbiliform, small haemorrhage = skin does not peel off, mucosa is not involved, there will be fever and lymphadenopathy, 1 in 10 will die

AGEP is quicker, take the drug in the morning, it will happen at night. Very red, exanthematous rash, pin-point pustules, no bacteria (NSAIDs and antibiotics are most common causative agents)

Question 9

Which HLA must we test?

Answer 9

• HLA-B*58:01(allopurinol)
• HLA-B*15:02 (carbamazepine)

Question 10

What is REGISCAR criteria?

Answer 10

Prediction of likelihood of scar reaction

Question 11

If likely allergy + worth testing, was it immediate or delayed?

Answer 11

Worth-restesing is an individual decision
based on allergen, drug, patient
i.e. peanut allergy is very commnon

Question 12

Why is the timing of the allergy important?

Answer 12

Immediate (IgE): Urticaria, angioedema
- Generation of drug-specific IgE
- Develops early (<1 hour) if there has been previous exposure to the casual drug (~7-14 days if first treatment course)

Non-immediate / delayed (non-IgE)
- Maculopapular rashes
- Contact dermatitis
- Fixed drug eruption
- Erythema multiforme
- Severe cutaneous adverse reactions (SCAR)
Activation and expansion of T-cells
Lesions last days and develop >1 hour (usually ~2-4 days) after commencing the causative drug

Question 13

THIS IS EXAMINED EVERY YEAR IN FINAL MB

What allergy tests do we order?

Answer 13

Immediate: Generation of drug-specific IgE

Delayed: Activation and expansion of T-cells

Immediate: Generation of drug-specific IgE / Delayed: Activation and expansion of T-cells

Question 14

Do we do allergy tests in SCARs?

Answer 14

NO!!! Allergy tests usually contraindicated in SCARs

JUST REFER TO IMMUNOLOGY & ALLERGY

Question 15

What is this test?

Answer 15

Patch test: Positive to penicillin & amoxicillin

We are testing for cross-reactivity, which is why we are testing for penicillin and other antibiotics too! (see if other doctors can use other drugs)

Question 16

What is the % of incidence of penicillin allergy in Hong Kong?

Answer 16

2% of people are allergic to penicillin in Hong Kong

86% of labels are incorrect and inaccurate = we must ask a proper history!

Question 17

Case 2: Food allergy
* F/20
* History of severe atopic dermatitis
* Suspected ‘allergies to egg’ since birth

When to suspect food allergy?

Answer 17

20 year old girl
‘Have you eaten egg before? Have you ever eaten egg? Have you ever eaten mayonnaise? Fried rice?’ [patient may have self-challenged, i.e. tried to eat some of the food themselves]

MMR and influenza vaccine have egg protein BUT IT DOES NOT CAUSE ALLERGY (PH Li said!)

Food is always type I!! Never delayed!!

Question 18

When to suspect (type I) food allergies?

Answer 18

History must meet ALL of the following:
1. Correct context
* Have they ever eaten the food before?
* Was there actually food involved? (not colourings [except for red velvet colouring, its made from crushing a red beetle = proteins], MSG, additives, antibiotics)
* Sequence of ingestion and symptoms (not just exacerbating existing conditions) [if skin rash was already there when you’re eating, it is definitely not food allergy]
* Likelihood of suspected food allergen (the “big eight”)
* Co-factors involved? (alcohol, NSAID, exercise, intercurrent illness…)
* Alternative diagnosis (e.g. scombroid poisoning = fish/degrading fish contains a lot of histadin = if you eat a lot of histadin at once, you will get histamine-like reactions = angioedema, hives, vomiting, diarrhoea [presents very similarly to food allergy, but it is a type of food poisoning], your mast cells did not produce the histamine, rather you ate the histadin from the fish)
2. Correct timing
* Immediate reaction (usually within one hour after ingestion)
There are exceptions….!
* If tolerated culprit(s) on re-challenge (i.e. after index reaction) = not allergic [just because you tolerated something in the past, it doesn’t mean you don’t have an allergy] = it is impossible to get an allergy and become allergic every now and then, but not every single time (it is consistent)
* Consistent and stereotypical reactions
3. Correct manifestations [food allergy is ALWAYS due to IgE]

Big 8
- Peanuts (peanut is a not a nut, it is a legume, grows on roots) and treenuts (macadamia, almonds, cashews, pistachio, hazelnut)
- Shellfish (crustacean) and fish (with fins)
- Soy and wheat
- Milk and egg

Crustaceans include molluscs, snails, octopus (shellfish)

Question 19

How do we search for IgE (i.e. sensitization)?

Answer 19

1. Skin prick test
2. Specific IgE (and components)
3. Oral food challenge

Look at IgE on mast cells, look at patient’s blood for serum specific IgE, perform challenge tests

Question 20

Patient is allergic to hen’s egg and milk.
However, when both foods are cooked, the patient is allergic.

Answer 20

Linear epitope vs conformational epitope
Protein structure changes, IgE will no longer recognise the allergen since you have denatured the allergen

Don’t cook peanuts tho, the allergens will be even more concentrated

Question 21

Skin prick test for food?

Answer 21

NEVER intradermal for food

Question 22

Oral immunotherapy: Induction of tolerance

Answer 22

If you give an antigen to a patient for a prolonged time, bit by bit with diet, patient’s may one day be able to eat it.

Reintroduce egg to allergic child

Question 23

What % of adults are allergic to some food?

Answer 23

10%

half of them will develop food allergy in adulthood! it’s not always children. The same allergy in the big 8

Question 24

If patient has anaphylaxis, what should we do?

Answer 24

GIVE THEM SUBCUTANEOUS OR INTRAMUSCULAR ADRENALINE

Epi-pen, adrenaline auto-injector

Save serum for acute tryptase (released by mast cells = evidence for mast cell degranulation) = usually blood levels is very stable, when all mast cells degranulate, tryptase will go up = marker of anaphylaxis

First 4-6 hours (test tryptase before 4 hours = confirm allergy)

20%+2 rule (everyone has different baseline tryptase, must test baseline first) = need to know baseline for that individual before we determine whether tryptase is high or not

Give epi-pen for future event if patient has anaphylaxis

TRYPTASE WILL HELP YOU DIAGNOSE ALLERGY

Question 25

Idiopathic anaphylaxis?

Answer 25

Idiopathic is a diagnosis of exclusion
Keep on looking for trigger(s)/explanation

Hidden allergies vs anaphylaxis mimics: acute urticaria/angioedema, asthmatic attacks, vasovagal syncope, panic attacks, shock and other causes of sudden collapse/respiratory distress

Question 26

What is WDEIA?

Answer 26

Other co-factors other than excerise can be alcohol, NSAIDs

Subtype of FDEIA and EIA

Question 27

What advice should we give to a WDEIA patient?

Answer 27

• Strict and complete avoidance of culprit foods
• Strict adherence to a gluten-free diet is a safe and easy alternative
• Further testing to other grains to assess potential cross-reactivity.
• Failing that, any culprit foods should at least be avoided for four to six hours before exercise or other cofactors
• Other potential cofactors include NSAIDs, alcohol, extremes of temperature and pollen exposure (in sensitized patients)
• Adrenaline auto-injector and individualized emergency treatment plan (i.e. take an anti-histamine and get epi-pen ready)
• Documentation in medical record and a medical alert bracelet/jewelry

Question 28

HKU/QMH Anaphylaxis Pathway

Answer 28

Give patient epi-pen if you don’t know what patient is allergic to