Is it an Allergy ?.

alaisdair.stewart@medway.nhs.uk

Ulterior motive

• Allergy is common

• Allergy is misunderstood

• Allergy is mis-used

• Allergy is under resourced

• There is a great public demand

• Many charlatans and alternative practitioners

Today I will talk:

• Allergy or not

• Simple clues to making a diagnosis

• Common theme: – good history, a bit in the examination backed

by simple tests and then appropriate treatment

Allergy is simple

• If you can’t easily identify the allergen

• It probably ain’t due to an allergy

• But life is not always that simple……..

The numbers:

• 50% of the population are Atopic

• What does that mean ?

The numbers:

• 50% of the population are Atopic

• Half the population have the genetic make-up that allows production of specific IgE

• Kent 900,000

The numbers:

• 50% of the population are Atopic

• 30% will have an allergic disease

• What does that mean ?

The numbers:

• 50% of the population are Atopic

• 30% will have an allergic disease

• Have a disease (tissue damage) caused by specific IgE and allergic inflammation

• Kent 540,000 people,

“Hay fever” affects 13% population

• Kent that means 230,000 sufferers

• Assume 1% severe:– Kent 2,300 who meet criteria for desensitisation

Who is going to do all this work ?

Allergy Services in the UK

• Never developed, Never funded• Despite many reports on its importance…..

• No targets, few bed days, few A&E waits, no QOFF• Mostly ignored, tendency for OTC

• Few clinics, mostly in academic units• Quasi NHS clinics • Medway Allergy Service covers Kent…

• Due to lack…………….public opt for alternatives

Due to lack of Allergy services patients frequently seek private/ alternative tests

• This has led to patients presenting the results of alternative diagnostic tests to their doctors, e.g.:– electrodermal testing1,3,4

– kinesiology2-4

– reflexology3

– hair analysis4

– iridology4

• Such tests are not proven and are not recommended• Reduce the size of your wallet not your polyps

Is it an allergy26 year old woman

• Runny nose

• Mainly in the summer for the past 5 years

• Antihistamines have not helped

• What’s the diagnosis ?

• What do you do ?

How to diagnose allergic diseases

• Good history, examination

• Challenge– Skin prick tests– challenge

• RAST (or CAP),

• not total IgE

Sneeze, itch block and run plus eyes, wheeze or cough

Adapted from ARIA http://www.whiar.org/docs/ARIA_WR_wm.pdf

Intermittent symptomsIntermittent symptoms

<4 days per week

Or <4 weeks

MildMild

Normal sleep

Normal daily activities, sport, leisure

Normal work and school

No troublesome symptoms

Persistent symptomsPersistent symptoms

>4 days per week

And >4 weeks

Moderate/SevereModerate/Severe

One or more itemsOne or more itemsAbnormal sleep Impairment of daily activities,

sport, leisureProblems caused at work

or schoolTroublesome symptoms

Grass: The Most Important Allergen

Adapted from Allergy: the unmet need. A blueprint for better patient care. Royal College of Physicians. June 2003: 35.

Pol

len

seas

on

Jan Feb Mar Apr May Jun Jul Aug SeptHazel

Willow

Birch

Oak

Grass

Nettle

Lime

About 95% of allergic rhinitis sufferers in the UK are allergic to grass pollen

Copyright © March 2005 ALK-Abelló

What do

you see?

Allergy - investigation.

SPT are safe, cheap, easy, support (+ or -), seen

RAST are less useful

Total IgE is rarely helpful

Pros and cons of skin prick tests

Advantages Disadvantages

• Easy to perform

• Non-invasive

• Immediate results• Safe cheap, Cost

effective• Negative test is highly

predictive of absence of allergy

• Must stop antihistamines 48 h before testing

• Severe eczema, urticaria or dermatographism may prevent use

Specific IgE results (RAST/CAP)

Results are categorised as 0-6:

0 negative result < 0.35 KUA/L

1 borderline 0.35–0.7

2 weak positive 0.7–3.50

3 positive 3.50–17.5

4 positive 17.5–50

5 positive 50–100

6 strong +ve >100

Total IgE is non-diagnostic and has limited use

Pros and cons of RAST/CAP tests

Advantages Disadvantages• No need to stop

antihistamines

• Appropriate when standardised skin prick testing not available

• Useful for patients with severe eczema

• Expensive

• Invasive

• Delay in obtaining results

• Extra patient visit required for results

• Few understand the results

• Does not re-inforce the cause

Unlikely allergic rhinitis

• No eye symptoms

• Lack of block and sneeze

• Variable, affected by smells, physical factors

• History of IBS, cough, urticaria, fibromyalgia.

Unlikely to be hay fever............

• Vasomotor rhinitis

• NARES

• Unlikely atrophic rhinitis• Infective

• Drug-related esp aspirin,

• Cystic fibrosis, Immunoglobulin deficiency,

• Gastroesophageal reflux disease,

• Autonomic, (diabetes), hormonal, menopause, old mans drip

• granulomatous, sarcoid, wegeners

Can we avoid pollenor other allergens ?

mildintermittent

mildpersistentmoderate

severeintermittent

moderatesevere

persistent

Treatment of allergic rhinitis AGS version of ARIA

allergen and irritant avoidance – always give someImmunotherapy- the future

intra-nasal decongestant (<6 days) or oral decongestant

intra-nasal steroid eg nasonex or avamys

Oral eg desloratidine or local non-sedative H1-blocker

LTRA eg montelukast

http://www.whiar.com/

Persistent effect of Alutard® SQ– 7 year study

Data from Durham et al 1999

Bef

ore

tre

atm

ent

100%

80%

60%

40%

20%

0

-91% -66% -86% -91%

Con

trol

– n

o S

IT

Eyesymptoms

Nosesymptoms

Chestsymptoms

Medication

Grazax improved symptoms one year after discontinuation

GRAZAX®

GT-08Study

First season2005

Second season2006

Third season2007

First follow-up year2008

Median Median Median Median

Symptom score reduced:Entire season

34%* 44%** 37%# 31%##

Medication score reduced:Entire season

53%* 73%** 60%# 52%##

AlutardAlutard®® SQ significantly reduces the risk SQ significantly reduces the risk of developing asthmaof developing asthma

50 %

25

0

0 3 5 years

-54%

OR=2.52

OR=2.68

Num

ber

of

child

ren

in %

who

hav

e de

velo

ped

asth

ma

afte

r 5

yea

rs

Alutard® SQ

Placebo

Data from Möller et al 2002Jacobsen et al 2003

Anaphylaxis and Allergy - food

Terms frequently muddled

• Atopy, Allergy

• Anaphylaxis

• Intolerance– Nickel– Biogenic amines include Histamine, tyramine– Salicylic acid– Enzyme lack

• Other imune mediated diseases

• Anaphylactoid reactions

What is Anaphylaxis

is an increased sensitivity to a poison

needs prior challenge

incubation period

IgE mediated mast and basophil degranulation

Are these anaphylaxis ?

MILD pruritis, (itch), erythema, urticaria

MOD mild asthma, abdo pains/diarrhoea

minor throat constriction

SEVERE bad asthma, laryngeal oedema

tachycardia, hypotension, LOC

“impending doom”

Most food allergy is simple...

• Prior exposure without reaction

• Symptoms start lips, mouth, throat within minutes then generalised reaction develops

• 20-60 minutes after tend to be milder

• Reactions > two hours after probably not

• Settles over hours, can be biphasic

• Bowels symptoms alone probably not

• Consistent

Food allergy

• Consistent

• Usually timely

• Exceptions– Wheat exercise anaphylaxis– Alpha gal allergy with pork– Am sure will find a few more…….

Is it an allergy 2?

• 29 year referred to AMU – with mouth itch and throat swelling, – rhino-conjunctivitis – and severe difficulty in breathing

• What else might you find in the history ?

• Do you dispense/prescribe adrenaline?

Better history

• ABC

• six events over the past couple of years.

• Event: Always in March/Spring

• Apple for lunch 20 minutes before

• Cycling pick up child from school

• Does similar in rest of year no problems

• Mild rhinoconjunctivitis in Spring

Tests

• Don’t measure total IgE

• SPT better than RAST (Immunocap)

• SPT with food better than commercial extract

• Component resolved diagnostics

• Positive to early flowering trees, apples, hazlenut

Is this anaphylaxis ?

• Depends on what is happening…..

– Is it all local contact symptoms– Any features of generalised systemic symptoms

Or is it OAS/FFS ?

How did mange her ?

• Challenged her….

• Good tree pollen RC treatment

• Avoid the combinations

• Access to adrenaline………..

• but why not salbutamol 4-20 puffs…….

Oral Allergy Syndrome

• OAS produces symptoms when an affected person eats – certain fruits, – vegetables and – nuts.

• Some individuals may only show allergy to only one particular food, and others may show an allergic response to many foods.

Oral Allergy Syndrome

• Local contact allergy

• Background of pollen allergy

• Cooked food safe

• Nuisance, rather than life threatening

• Good history

• Avoidance

• Beware food RAST tests...do SPT!

OAS – heat labile allergen

• The IgE antibody may react to the – linear (amino acid) sequence of the protein

– or to a conformational epitope.

• If the response is to the conformational epitope, then the person with OAS may be able to eat the food when it is cooked, but not when it is raw.

• If the response is to the linear sequence (common in celery/peanut allergies), then cooking the food has no

effect on its ability to trigger an allergic reaction.

SPT with food rather than RAST

• Patient education better

• RAST > 20% false positive and false negative rate

• In Grass pollen allergics common to see false positive peanut and wheat RAST– Take the history again

Contact Food Allergy

• Not all peanut allergy is anaphylactic• Most food allergy produces less severe events,

• Fresh fruit syndrome (oral allergy syndrome)– Northern – tree pollen, tree nuts, apples etc – Southern – grass pollen, peanut, apricot etc

Cooked fruit OKPotatoes, raw carrotsSometimes seasonal, sometimes only the skin….

Unfortunately Food Anaphylaxis is not always so simple

• Prior sensitisation not always clear, – ? In utero, breast milk, creams/ointments

• Cross reacting antigens

• Several factors may be additive– role of temperature– Role of exercise– Concomitant illness– Additional non-IgE mechanisms

Component-resolved diagnosis

• Allergens are made up of many allergic epitopes on several peptides found within the food

• Component-resolved diagnostics (CRD) characterises – each patient’s IgE antibody (sensitisation) profile

– to individual allergen components,

– thereby discriminating between genuine sensitisation (allergy and risk of severity) to certain specific allergen sources and simple cross-reactivity where reactions are mild

Peanut (Arachis Hypogaea)

Components:• Ara h1–storage protein (7S globulin);

• Ara h2-storage protein (2S albumin);

• Ara h3-storage protein (11S globulin);

• Ara h8-Bet v 1 (birch) homologue;

• Ara h9-lipid transfer protein (LTP)

• IgE against Ara h2 and 1or 3 95% have symptoms

• IgE against Ara h2 87% symptoms tend to be severe.

• IgE against Ara h8 18% have symptoms, mild

Hazelnut (Corylus avellana)

• Components: – Cor a1-Bet v 1 (birch) homologue - mild disease

– Cor a8 -lipid transfer protein (LTP) - severe

So when investigating hazlenut positive RAST always assess birch sensitivity as the positive test could be merely reflecting birch allergy

Egg (Gallus Domesticus)

• Egg white is the most important allergen source in hens’ eggs.

.

• High concentrations of Gal d1 IgE are associated with persistent allergy to eggs.

• The lower the Gal d 1 concentration, the higher the probability of tolerance to cooked egg

• ? If Gal d 1 IgE levels are low gives guidance on whether or not oral provocation should be performed

26 year old university lecturer

• Exercising in the Gym 3 hour post lunch

• Hands itch, body red, urticaria, lips swell

• Throat lump, difficulty breathing

• Feels faint collapse.............

• What would you do?

• What happened, can you prevent it ?

Diagnosis: Anaphylaxis

What is the cause ?

• Food allergy

• Stung by a wasp ?

• Latex allergy ?

• Something else in the air

• Idiopathic Anaphylaxis

Diagnosis

• Food allergy

• Stung by a wasp ?

• Latex allergy ?

• Something else in the air

• Idiopathic Anaphylaxis/Mastocytosis

• Wheat exercise induced Anaphylaxis

Wheat (Triticum aestivum)

There is a significant cross-reactivity between wheat and grass pollen which leads to over-diagnosis of wheat allergy

• IgE antibodies to omega-5 gliadin are associated with genuine wheat allergy .

• Omega-5 gliadin can be positive when wheat is negative

•

• Wheat isolates, manufacturer altered wheat protiens to improve texture……..makes molecule more allergenic

What about the 26 year old with Wheat exercise induced anaphylaxis

• Grass pollen and wheat isolate SPT +ve• Negative to wheat• Normal serum mast cell tryptase at rest

• Avoid all wheat for at least 6 hours before exercise• Prophylactic anti histamines ? No• Have access to adrenaline

Generally food allergy is simple..

• But always take a good history/keep a diary

• Challenge assumptions

• Consider alternatives

• None allergic factors can interact with allergy tendency to worsen the outcome

Other reactions

• Food intolerance…… rarely thru allergic mechanisms• Aspirin …….. Salicylates in most foods• Colourings, preservatives, flavour enhancers• Nickel dermatitis and food• Tyramine content… age of food• Histamine …in strawberries• Histamine releasing factors in Kiwi• Acidity eg orange juice• Tomato/ketchup in young children• Osmotic load eg marmite, honey

All are idiosyncratic

6 year old child referred as peanut allergic, has epi-pen

• Awoke swollen lip

• Peanut butter snack night before

• Used epi pen twice for similar reactions

• Is it allergic ?

Food Allergy-Diagnostic tests

• SPT are safe, ………with caution– Negative SPT excludes IgE allergy– Positive test alters probability but beware false

positives

• RAST are very safe but many false positives• Challenge…..

– Rub on the lip– Dose incremental challenge– Double blind placebo controlled challenge,

• are more helpful in excluding a diagnosis.

Some scenarios-what would you do

• Please test Johnny (age 3) his uncle died from peanut allergy ?

• Cheese makes me go red and itchy ?

• 2 year old blotchy with tomato ketchup ?

• What allergy is making Jonnies eczema worse?

• Wheat causes abdomenal pain and bloating ?

• Milk causes diarrhoea ?

Case 1. JR age 27C/o “wasp anaphylaxis• Wasp sting August 2005• Immediate pain, red mild swelling• Further sting September 2005• Pain very large swelling develop over 2 day• “next will be your last” given adrenaline Epipen

PMH nil of note,

Case 2. AS age 37

C/o “collapse”

• Insect sting ankle, insect unknown

• Stinger left behind.

• Within minutes felt hot, nose itch, itchy red all over, tried to run into house,

• Aware of itch in throat, wheeze, felt faint

• Called ambulance

Conclusions

• Allergy is common, yet over and under diagnosed• Its all in the history so take a good one• If it ain’t obvious it probably isn’t an allergy• Confirm with SPT or RAST or challenge• Avoidance main treatment, educate/advice• Make sure treatment is appropriate for severity…• If you use adrenaline give out two…and warn• Reassure, death is rare

Who to refer to the allergy clinic?

• Anyone if the funding comes with the patient!!

• Bee and Wasp anaphylaxis

• Uncontrolled hay fever, despite proper treatment

• Cat allergy if affects occupation….

• Food allergies in children

• Food reactions within 2 hours of eating

• Difficult asthma, rhinitis

• Important drug/anaesthetic reactions

Who not to refer..

• ME, chronic fatigue syndrome

• Hyperactivity in children, ADHD

• Diarrhoea and bowel symptoms

• Dental amalgam

• Migraine, psychiatric diseases

• Chronic urticaria and angioedema!!!!!!!!!

©GSK Presentation • Department • Author

Now you’re all experts so no-one needs to be referredNow you’re all experts so no-one needs to be referred