Allergy in a ‘nutshell’

GP guide to survival Dr Gillian Vance

Allergy care Starts with early diagnosis

Session Better understanding of the basic immunological mechanisms underlying food allergic disease Apply mechanisms to clinical evaluation & appropriate therapy

Objectives Recognise typical features of allergic disease Appreciate areas of complexity Explain what, how & why we evaluate at the allergy clinic

‘Allergy’ 1 st coined in 1906 by Austrian paediatrician, Clemens von Pirquet ‘altered reactivity’ to any antigenic stimulation, whether Immunity – protection Hypersensitivity –

adverse clinical response

‘Allergy’ ‘ An exaggerated sensitivity to a substance (allergen) that is inhaled, swallowed or injected, or that comes into contact with the skin or eyes’

Allergic disease spectrum Food allergy Eczema Asthma Allergic rhinitis Drug allergy

Allergy – a public health problem Prevalence of asthma & hayfever have increased over the last 20 years (3 - 8.2% and 5.8 - 20% respectively) Upton, BMJ 2000 12 million people per year may seek treatment for allergy Children: 20.4% asthma; 18.2% hayfever; 47% 1 or more current symptoms (ISAAC study, 1999)

Epidemiology of Food Allergy Peanut allergy (3 yr olds) – Sensitisation: threefold increase 1989-1994-6 from 1.1 3.3.% – Doubling of reactivity from 0.5-1% JACI 2001;107:S231 Admission rates Anaphylaxis risen 7-fold; 5/million 1990/1- 36 2003/4 Food allergy risen 7-fold; 16 - 107/million Urticaria doubled; 20 – 44/million – especially children

Allergy – a primary care problem 6% of GP consultations Primary Care Prescribing – 1991-2004: community prescriptions increased – Nasal allergy - by 60% (to 4.5 million) – Anaphylaxis – 12 fold (to 124,000) – Ocular allergy – by 50% (to 1.4 million) Costs NHS £900 million pa – Excludes costs of A&E attendances, outpatient consultations, hospital treatment BSACI, London, commissioned study, 2002

Why should children with suspected allergy be tested?

May be lifelong – Specific treatment – Early treatment may influence severity May be life threatening Associated with poor quality of life May herald other allergic diseases – ‘Allergic March’

Eczema Asthma

Adverse Reactions to Food Adverse Reaction to Food Aversion Toxic Non toxic Food poisoning Immune mediated Non-immune mediated Allergy Enzymatic Pharmacological IgE Non IgE Undefined

Non-immune ARF ‘Undefined’ – Mechanism unknown – Food additives, preservatives, colourings – ‘Generally Recognised as Safe products [GRAS] – Sulphites, nitrites, nitrates, MSG – Urticaria, rhinitis, asthma, migraine

Food Allergy - Definition An immune-mediated adverse reaction to food that occurs in genetically predisposed individuals – IgE urticaria; oral allergy; anaphylaxis – Non IgE Cell-mediated; mixed – Consistent – Reproducible

How

does the immune system malfunction in food allergies? Step 1: Sensitisation B cell Th cell Allergen Exposure Processing Presentation Th2-biased cytokine production IgE production

Step 2: Activation - Effector Phase Vasodilatation Pain Cell recruitment Immune Modulation IgE induction Smooth muscle contraction Peristalsis Mucosal oedema Tissue remodelling

Clinical Manifestations: Immediate Erythema Pruritus (generalised) Urticaria Angioedema Rhinitis Laryngeal oedema Asthma GI upset

Symptoms Immediate Delayed type / Chronic – Inflammation – Abdominal pain – Altered gut function – Poor asthma control

Clinical Manifestations: non IgE mediated reactions Delayed type SKIN: eczema flares GUT: – Mucousy / bloody stools in an infant – Chronic diarrhoea, vomiting – Failure to thrive – Malabsorption – Dysphagia, abdominal pain Proctitis / dietary protein enteropathy / eosinophilic gastroenteropathies

What foods?

Cow’s milk, Egg white, Soybean, Wheat, Peanut, Tree nuts, Fish & Shellfish account for >90% reactions

Red flag features of allergy

Clear temporal relationship with trigger Consistency of reaction Trigger – likely allergen Timing – within 2 hours of ingestion ‘Typical’ clinical symptoms Other features of atopy Family history of atopy

Example 1 3½ year old girl Eczema since 1 year age Ate 1 salted peanut 18 months ago Developed – lip swelling & wheeze – No rash, GI upset or respiratory distress Mum – asthma & hayfever

Example 2 11 year old girl No other atopic disease Xmas - ate raisin from bowl of mixed nuts Developed lip swelling & local urticaria 5 – 10 minutes later Settled with oral piriton Father – eczema & occasional ‘wheeze ’

What’s the diagnosis?

Peanut allergy Tree-nut allergy ‘Other’

Diagnostic Adjuncts Skin Prick Testing – Cheap – Painless – Fast – Sensitive & specific Specific IgE measurement – Blood test – Hx of anaphylaxis – Recent antihistamine use – Widespread eczematous skin

Skin prick test

Results - cases Case 1: – SPT peanut 6 mm – SPT tree nut panel negative – Specific IgE peanut 5.6 kU/L Case 2: – SPT peanut 6 mm – SPT brazil nut 4 mm; remainder negative – Specific IgE peanut 90 kU/L; brazil 2.4 kU/L

Interpretation Case 1: peanut allergic Case 2: peanut & tree-nut allergic SPT weal size or Specific IgE level – No relation with severity of reaction

Red flag features of management

A wareness A voidance A sthma control A nti-histamine A drenaline autoinjector

Management AWARENESS – Parents – Wider family – School – Physician GETTING THE DIAGNOSIS RIGHT

Management AVOIDANCE OF ALLERGENS

Management AVOIDANCE

Management ASTHMA CONTROL

Management ANTI-HISTAMINE

Management ADRENALINE (EPINEPHRINE)

Who should get an epipen?

Lethal anaphylaxis Uncommon 0.65-2% of severe anaphylaxis ‘KISS OF DEATH FOR NUT ALLERGY GIRL’ A teenage girl with an extreme allergy has died after kissing her boyfriend who had eaten a peanut-butter sandwich hours earlier.

Christina Desforges, 15, from Saguenay, Canada, went into anaphylactic shock. She was given an adrenalin shot and taken to hospital but died four days later from acute respiratory failure.

Doctors said that a nut allergy brought on by the kiss was the cause of death. The boy, who has not been named, had minute traces of peanut on his lips.

Nov ‘05

Lethal anaphylaxis: ‘predictable’ risk factors Peanut / treenuts Asthma Adolescents / young adults

Lethal anaphylaxis: ‘unpredictable’ risk factors Severity history of previous food reaction Pumphrey • 22% of fatal cases had had previous severe reaction

Severity History Current Not severe Severe Near fatal Fatal Previous None 77 15 1 0 Mild / moderate 74 22 3 2 Severe 11 8 1 1 Macdougall et al, 2002, Arch Dis Child

Red flag features of epipen prescription Indicated: – History of severe reaction – Reactions becoming more severe – Asthma (requiring inhaled steroid use) Consider: – If low dose (trace) exposure – At a distance from nearest medical facility – If having difficulty avoiding – If parents anxious +

Prognosis

IgE mediated reactions Resolve: Cow’s milk, Egg, Soya, Wheat – By 5 years age, tolerance in 85% of CMA children 66% of egg allergic children Persist: Peanut, Tree nut, Fish & Shellfish – However, around 20% of PA will resolve Youngest patients Low specific IgE Mild reaction at presentation

Frequently Asked Questions

Is a food allergy causing my child’s hyperactivity?

Number of ways in which food could affect cognition & behaviour in children Mechanism not ‘allergy’ Some benefit in ‘extreme’ subgroups – Complex behavioural problems +/- neurological deficits Possibility that food additives may have a pervasive effect across the population

‘Food Allergy’ & behaviour • Bateman study – 277 children – Hyperactivity / atopy – Randomised, placebo-control, Double blind, cross-over: food colouring & Na benzoate – Assessed weekly by psychologists; parents daily – Parental ratings associated with dietary additives – No association with atopy

‘Food Allergy’ & behaviour Confirmed in follow on study 3-year old children (n=153) 8/9 year old children (n=144) Within subject crossover – 2 active mixes; 1 placebo (3 year olds x2 56g sweets; 8 yr olds 2-4 bags sweets / day Global Hyperactivity Aggregate increased in both age groups with active mix

My child has egg allergy – should he have the MMR?

YES Unless – Immunocompromised – Had an anaphylactic reaction to previous MMR – Had an anaphylactic reaction to gelatin / neomycin Close observation if – Previous acute severe reaction to egg – Current active, chronic asthma

(Other) Indications for referral GI symptoms: – vomiting, diarrhoea, colic, FTT Atopic dermatitis: – severe, persistent, young child, allergen-related Chronic urticaria: – duration > 6 weeks Wheezers / asthmatics Rhinitis / conjunctivitis – Severe, persistent, treatment-resistant, allergen-related Insect allergy (not local reaction – even if large)

What have we learned?

 Allergy has a wide range of manifestations  Diagnosis relies on careful history taking, & appropriate interpretation of IgE testing.

 Management represents a ‘package’ of education, specific allergen avoidance measures, relevant pharmacotherapy & possibly desensitisation (inhalants)  ‘Early’ evaluation can make a difference to both the child & family life

Thank you for listening Feel free to discuss / refer your patients to the allergy team.