Introduction & overview Cow's milk protein allergy Introduction & overview Dr Heidi Northover 2017

Programme Workshop A - diagnosis and recognition of CMPA via case studies Workshop B - ongoing management of CMPA - weaning, reintroduction of cm, role of specialist formulae for the infant > 6 months of age Q&A, quiz discussion

Contents The basics; allergy vs intolerance IgE and non IgE mediated reactions Lactose The myths and mix ups Extensively hydrolysed & AA formulae To test or not to test Useful resources

Top 9 allergens in UK; responsible for 90% allergic reactions Peanut Life long Tree nuts Life long Cow’s milk Transient Egg Transient Soya Transient Wheat Transient Shellfish Life long Fin fish Life long Sesame Life long

CMA can be a long and challenging process On average it takes 3.6 months from the first GP visit to diagnose CMA On average, an infant with CMA will visit the GP 18.2 times over the 12 months after their initial visit On average, 7.6 GP visits are needed before a referral to a specialist clinician for CMA   The average waiting time before seeing a specialist after referral is 3.7 months. Sladkevicius E et al. Resource Implications and Budget Impact of Managing Cows' Milk Allergy in the UK. J Med Econ. 2010;13(1):119-128

CMPA; a substantial burden on the NHS 8,350 infants will present to GPs each year with CMPA in the UK. Healthcare cost of patient management Cost of management over first 12 months following initial presentation: estimated @ £25.6 million ~ £1395 per infant (varies according to clinical symptoms)

Direct cost to the NHS of managing all allergic diseases: estimated at over £1 billion per annum in the UK. £900 million per annum spent by primary care on allergy Allergy accounts for about 11% of the total community drugs budget

Urticaria & other symptoms 1000 infants Sladkevicius E, Nagy E, Lack G, Guest JF, J Med Econ 2010;13:119-128 1000 patients Eczema & GI symptoms GI only Eczema only Urticaria & other symptoms Number 590 230 100 80 Mean number of GP visits over 12 months from initial presentation 19.4 18.1 13.4 15.6 Mean number of GP visits before starting clinical nutrition product 4.5 3.4 1.9 6.1 Mean number of GP visits before referral 7.6 7.8 8.2 % referred to a specialist 43% 45% 33% 34%

Taking an allergy focused history (NICE 2011) Ask about a personal & family history of: Atopic disease Food allergy Feeding history Breast or bottle (formula) fed Age at which formula was introduced; were symptoms associated with change? Age at weaning to solids; associated symptoms?

Symptoms suggestive of adverse reaction to cow’s milk Intolerance Lactose Allergy

Symptoms of adverse reaction to cow’s milk FPIES Colic Procto-colitis Eczema Reflux

Allergy involves the immune system; reaction to protein Allergy involves the immune system’s reaction to protein Intolerance is non immune mediated Lactose is a sugar, not a protein Therefore lactose does not cause allergy

World Allergy Organisation Food hypersensitivity Immune mediated (Allergy) IgE mediated Non IgE mediated Mixed reactions Non immune mediated (Intolerance)

Lactose intolerance Allergy involves the immune system’s Lactose is the natural sugar found in mammalian milk Disaccharide sugar; glucose + galactose Broken down by enzyme, lactase, in brush border of duodenum  Lactose intolerance is due to partial or total deficiency of enzyme lactase Lactase levels highest at birth, tend to naturally reduce thereafter

3 types of lactase deficiency Congenital; Inherited as autosomal recessive. Very rare especially in the UK (Finland & Russia) Primary; Primary lactase deficiency Develops during childhood, genetically determined Higher rates of lactose intolerance in Africans, Asians & South Americans Secondary; Acquired lactose intolerance; lactase deficiency after damage to bowel – typically following acute gastroenteritis in children, coeliac disease, surgery

Symptoms Undigested lactose reaches large bowel Creates abnormal osmotic load This causes; Bacterial fermentation of lactose to hydrogen gas Distension & pain Increased faecal water Increased gut transit time Explosive acid stools & Excoriated bottom reaction to protein

Making the diagnosis Difficult! History Elimination and re-challenge Stool pH & reducing substances (hot fresh sample, within the hour!) Normal stool pH ~6 < 5.3 is acidic and diagnostic of carbohydrate(sugar) malabsorption Breath hydrogen test rarely used in young children (often positive < 3 months) Rarely intestinal biopsy Allergy involves the immune system’s reaction to protein

Who has recommended this? Allergy involves the immune system’s reaction to protein Colief is lactase drops

Allergy involves the immune system’s reaction to protein Allergy

World Allergy Organisation Food hypersensitivity Immune mediated (Allergy) IgE mediated Non IgE mediated Mixed reactions Non immune mediated (Intolerance)

Overviewilk 5-15% of infants show symptoms suggestive of adverse reaction to cow’s milk protein 2-8% allergic to cow’s milk protein Easily missed Wide variety of non specific clinical symptoms Causes infant & parental distress ++ +/- impaired growth <50% is type 1, immediate, IgE mediated >50% is type 4, delayed, non IgE (T cell) mediated tests not useful

Allergic reactions IgE mediated Non IgE mediated Milk protein Usually symptoms begin within minutes of ingestion Usually clear temporal link to food ingestion Often easier to diagnose Can be life threatening Non IgE mediated Milk protein (?+ other elements Slower onset Less easy to link to food ingestion Vague & variable symptoms Not acutely life threatening Often ‘dose responsive’ Type 4, T cell mediated

Taking an allergy focused history (NICE 2011) Ask about a personal & family history of: Atopic disease Food allergy Feeding history Breast or bottle (formula) fed Age at which formula was introduced; were symptoms associated with change? Age at weaning to solids; associated symptoms?

Event specific questions Were the symptoms typical of acute (IgE mediated) reaction? Was the reaction immediate? Within 2 hours? Were there any symptoms which suggest anaphylaxis? Has the child previously or subsequently tolerated the suspected allergen? What was the response to antihistamines?

Diverse spectrum of disease Diverse spectrum of protein allergy No one pathognomonic symptom Immediate Type 1 (IgE mediated) reactions; Lip and tongue swelling, difficulty breathing Many develop symptoms in at least 2 systems; GI 50-60% Skin 50-60% Respiratory tract 20-30% Typically, but not always, symptoms occur within few days of introduction of CMP, e.g. after period of breast feeding  Median onset of symptoms from exposure = 24 hours Mild, moderate or severe

Non IgE (type 4) mediated reactions Irritability, distress, colic, arching Regurgitation, vomiting, difficulty feeding Loose stools, bloody stools, constipation Worsening of atopic dermatitis Iron deficiency anaemia if severe Failure to thrive More common in atopic children Improve on elimination diet No validated tests ‘CMPA syndromes’ Food protein induced enterocolitis syndrome CMP induced proctocolitis CMP induced enteropathy Allergic dysmotility (GOR, constipation) CMP ‘sensitive’ eczema

Cows milk protein allergy- management

Bolton CCG Primary Care Pathway for the Management of Delayed Onset (Non IgE) Cows’ Milk Allergy (CMA) Bolton CCG Primary Care Management Pathway Acute Onset (suspected IgE) Cow’s Milk Allergy (CMA)

Any extensively hydrolysed protein formula will be suitable for 90% Extensively hydrolysed protein With added MCT (55%) Similac Alimentum Aptamil Pepti Aptamil Pepti Junior Nutramigen LGG Pregestimil Althera For the other 10%: Single amino acid (“elemental”) formula SMA Alfamino, Neocate LCP or Puramino CMPA persists in only a minority; most outgrow by teenage years (~80%) Only 1-2% adults have CMPA Those with positive IgE based tests, co existent asthma & rhinitis more likely to have persistent allergy

Hypoallergenicity Extensively hydrolyzed formula Single amino acid formula Standard infant formula ‘Comfort’ formula ‘Comfort’ formula Intact proteins Partially hydrolyzed peptide chains Extensively hydrolyzed peptide chains Single amino acids

Similac Alimentum Clinically lactose free Casein protein based

Formula fed babies with mild-moderate CMPA MAP guideline Diagnostic elimination diet (DED) ~90% will respond to an EHF (Extensively hydrolysed formula) Some casein based (Nutramigen, Pregestimil) Some whey based – taste better! (Aptamil Pepti) Allow at least 2 weeks, up to 4 weeks for some symptoms to resolve, but many improve in 48-72 hours ~10 % will not respond and will need single amino acid formula (Neocate LCP or Puramino)

What about breast fed babies? Continue to breast feed CMP elimination diet in mum, (may need to exclude egg too) Supplement with calcium & vitamin D MAP guidelines

Formula fed babies with severe CMPA Red flag indicators to use an AA formula Symptomatic on EHF Severe GI symptoms Faltering growth Multiple food allergies Severe eczema Symptomatic on breast milk Anaphylaxis

Soya Taste Lactose free Available over the counter Acceptable to vegans Is soya ever ok? Child over 6 months of age Absolutely refusing to drink EHF or AA formula; but dietitians can help!

Why not soya milk? Chief Medical Officer 2004 ‘Soya should not be used as first line management of CMPA or lactose intolerance Soya milks have high phyto-oestrogen content; long term risk to reproductive health of infants, male and female (COT 2003) Soy is a potential allergen, significant risk of cross reactivity of 10- 15% Scientific Advisory Committee on Nutrition 'there is no unique clinical condition which particularly requires the use of a soya based formula.’ SACN = COT = Committee onToxicity

What about rice or goat’s milk? Rice milk; high levels of arsenic 2006 DoH advice; Goat’s milk protein formulae not suitable for  infants under 12 months of age High chance of cross reaction, ~30%; close homology between protein allergens Low in folate Similar levels of lactose to cows’ milk (all animal milks contain lactose)

What about tests? GOLD standard is history + improvement on diagnostic elimination diet Other tests not usually necessary, unless history of  acute Type 1 reactions or anaphylaxis Problems with IgE based tests eg Serum specific IgE & Skin Prick Tests: Less than 50% of CMPA is IgE mediated 50% of healthy newborns have circulating IgE to cow’s milk IgE antibodies may appear & be present with no clinical history of CMPA Negative tests do NOT exclude allergy

CMPA and associations Significant overlap between CMPA and GORD (~40% of those with GORD have CMPA) Associated with other food allergies (eg soya up to 15%) Non IgE mediated CMA > IgE mediated CMA Associated with atopic dermatitis Associated with positive family history of food allergy and atopy

Resourcesrs Bolton CCG Primary Care Pathway for the Management of Delayed Onset (Non IgE) Cows’ Milk Allergy (CMA) NICE February 2011 Food allergy in children and young people Archives of Disease in Childhood Education and Practice edition October 2010 Volume 95 Issue 5 ‘Identifying and managing cow’s milk protein allergy.’ George du Toit et al Diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy - a UK primary care practical guide Ventner et al Clin Trans Allergy 2013; 3: 2 BSACI Executive Summary

Workshops

Case discussions

An allergy focused history What was eaten? How much? How long did it take for the symptoms to start? What were the symptoms? Was there anything to suggest anaphylaxis? Was an antihistamine given? If so what was the response? Has the food been tolerated before or since? Have reactions occurred more than once? Personal and family history of atopy?

Corey aged 3 months Bloody stools for 2 months Began when mum stopped breast feeding & changed to formula @ 4 weeks of age No vomiting, irritability or colic Mother has allergy to cats, dogs, peanuts, and has asthma  Dad’s sister had problems tolerating cow's milk as a baby Clinical diagnosis of CMPA; start EHF (Aptamil Pepti in this case)  No tests necessary Seen in clinic 4 weeks later, 4 months old Thriving & well  No blood in stools since 36 hours after EHF introduced Referral to dietitian for weaning advice

Corey

Case 2 - Olivia aged 2 months Admitted at 2 months of age with vomiting, loose stools & colic Formula fed (“hungry baby” formula as not settling with feeds) Taking Colief with little effect Mum allergic to cow's milk (diagnosed at 3 years of age) Clinical diagnosis of CMPA; changed to EHF Seen 3 weeks later: “much better” Diarrhoea stopped Less irritable, much happier, sleeping longer No longer on Colief Still some vomiting and regurgitation Started on anti reflux treatment

Case 3 Tom is a 5 month old boy Mother is a GP Mother is nut & fish allergic Baby breast fed for 5 months; well & no problems First weaning food @ 5 months– Aptamil baby rice made with formula milk Within 20 minutes – facial swelling, urticarial rash & vomiting Given antihistamines and steroids in ED with good effect Follow up with GP; what would you do?

Diagnose CMPA & prescribe EHF; a clinical diagnosis & therapeutic trial approach Diagnose CMPA and recommend soya milk OTC; soya is cheap and suitable alternative Refer to secondary care for further investigation and management; will need blood or skin prick tests to confirm diagnosis Advise mum to re-expose in 2 weeks; cannot diagnose allergy on first exposure

Diagnose CMPA & prescribe EHF; a clinical diagnosis & therapeutic trial approach Diagnose CMPA and recommend soya milk OTC; soya is cheap and suitable alternative Refer to secondary care for further investigation and management; will need blood or skin prick tests to confirm diagnosis Advise mum to re-expose in 2 weeks; cannot diagnose allergy on first exposure

Diagnose CMPA & prescribe EHF; a clinical diagnosis & therapeutic trial approach Diagnose CMPA and recommend soya milk OTC; soya is cheap and suitable alternative Refer to secondary care for further investigation and management; will need blood or skin prick tests to confirm diagnosis Advise mum to re-expose in 2 weeks; cannot diagnose allergy on first exposure

Mum unhappy with recommendation Sought advice elsewhere

Case 4 Oscar is an 11 month old baby boy Mum is peanut allergic, asthmatic and had CMPA as a child Baby exclusively breast fed for 7 months Always screamed, was irritable, vomited; mum questioned CMPA; told “not possible” as baby breast fed. What would you do? Take an allergy focussed history.

Take an allergy focused history At 4 months; Colic and GOR; prescribed Infacol, Infant Gaviscon & Domperidone; no change At 7 months – Aptamil Comfort* introduced; no better * partially hydrolysed milk At 8 months – Wysoy; much worse; urticarial rash, facial swelling, eye swelling, constant runny nose At 10 months – Nutramigen LGG; no better * Partially hydrolysed whey, 40% less lactose, GOS/FOS oligosaccharides, thickened formulation

At 4 months; Colic and GOR; prescribed Infacol, Infant Gaviscon & Domperidone; no change At 7 months – Aptamil Comfort introduced; no better At 8 months – Wysoy; much worse; urticarial rash, facial swelling, eye swelling, constant runny nose At 10 months – Nutramigen LGG; no better So what next?

So what next? Refer for ‘allergy tests’ Review the symptoms & diagnosis Trial of amino acid formula eg Neocate LCP Reintroduce trial of cow’s milk Exclude egg, wheat and rice from diet

So what next? Refer for ‘allergy tests’ Review the symptoms & diagnosis Trial of amino acid formula eg Neocate LCP Reintroduce trial of cow’s milk Exclude egg, wheat and rice from diet

Summary; Themes and messages Cow’s protein milk allergy is common Lactose intolerance is uncommon Most CMPA is non IgE mediated, vague & variable symptoms, poor temporal relationship to food Parents are invariably exhausted and desperate by diagnosis Clinical diagnosis; tests often unhelpful An allergy focussed history is vital 90% babies with CMPA will respond to an EHF, usually very quickly (72 hours) GORD, eczema, soy allergy commonly co-exist

Deaths due to food allergy Risk to all food allergic people: Risk is 1.81 micromorts 100+ times more likely to die in RTC than from food anaphylaxis Those < 19 years of age; higher risk group Risk is 3.25 micromorts Still more likely to be murdered! Higher risk individuals; asthma, teenagers, previous history of anaphylaxis

Emergency treatment plans Action plan and antihistamine for all Cetirizine or desloratidine; non sedating, long acting Piriton; sedating, short acting Adrenaline auto injector pens (Epipen ®) JEXT®

Adrenaline auto-injectors (AAI)) New BSACI guidance October 2016 AAP update on use of adrenaline in anaphylaxis

BSACI Joint statement; key recommendations As soon as possible after a suspected anaphylactic reaction, an adrenaline auto injector is prescribed (as recommended by NICE), by A&E or the GP. Prescriber to give training on how and when to use an auto-injector; aim to start treatment early (improves outcome) & before help arrives; delays may lead to more severe and treatment resistant anaphylaxis. BSACI has not made a blanket recommendation on the number of auto-injectors anyone should carry as this should be based on a risk assessment. Refer to an allergy specialist for comprehensive risk assessment & personal action plan, discussion of practical steps on how to minimise potential risks as part of everyday life. Sample action plans available on BSACI website

Make an allergy referral for; Accurate diagnosis of the aetiology & allergen(s) Assessment of severity and future risk, including consideration of the amount of allergen involved in previous reactions (trace amounts?) Does the patient still need the AAI? How easy is it to avoid the trigger? Assess other risk factors: Certain co-factors increase the risk of anaphylaxis, asthma in the case of food allergy, raised baseline serum tryptase and the age of the patient (teenagers) Every patient should have a personally tailored management plan, which should determine whether one, two (or no) auto-injectors should be prescribed.

BSACI guideline: Ewan et al Clinical and Experimental Allergy; Volume 46, Issue 10 October 2016  American Academy of Pediatrics guidance (2017) Adrenaline/epinephrine is the first-line treatment for anaphylaxis; does not reduce death but does reduce cardiorespiratory symptoms. Use in patients with significant airway involvement or hypotension, occurring as part of an anaphylactic reaction. All other medications, including antihistamines and bronchodilators such as salbutamol, provide adjunctive treatment but do not replace epinephrine. Do not hesitate to use epinephrine for possible anaphylaxis, even in the absence of proof that patients' symptoms are the result of an allergic reaction. No absolute contraindications to use in anaphylaxis. Epinephrine in appropriate doses is safe.

Adrenaline auto-injectors; who should have one? Those patients who should be considered for adrenaline auto-injectors include; Severe systemic reactions where the allergen cannot be easily avoided Allergic to high-risk allergens, for example nuts with other risk factors (such as asthma), even if the reaction was relatively mild Who had a reaction in response to trace amounts of allergen/trigger Who cannot easily avoid the allergen With continuing risk of anaphylaxis (e.g. food-dependent exercise-induced) With idiopathic anaphylaxis Strongly positive skin prick tests With significant co-factors e.g. asthma requiring brown inhalers Teenagers (Parents insist) (Peanut allergy) Some patients have never experienced anaphylaxis but still considered to be at risk; ask for specialist guidance.

Also; Train patients, parents or carers in both when and how to use the auto-injector device at the time of prescribing. Reinforce training when the device is dispensed by the pharmacist and during allergy clinic appointments. Pharmacists should be encouraged to undertake device training at every opportunity. Prescribing an adrenaline auto-injector is only one step in managing anaphylaxis risk. Regular re-training in the use of the auto-injector. For children, education of parents/carers and school staff is required.

How much should be used? In a healthcare setting; up to 500 ug in a teenager/adult Adrenaline should be given in the muscle of the mid-outer thigh because that helps achieve peak efficacy and is safer than injecting a bolus intravenously. An action plan should be provided for all regardless of whether they have an AAI JEXT/Epipen Junior = 150 ug (15-30 kg) JEXT/Epipen = 300 ug (>30 kg)

Adrenaline auto-injectors The prescriber must take responsibility for training

NICE recommendations on testing Do not carry out allergy testing without first taking an allergy focused clinical history. Interpret the results of tests in the context of information from the allergy-focused clinical history.

Taking an allergy focused history (NICE 2011) Ask about a personal & family history of: Atopic disease Food allergy Feeding history Breast or bottle (formula) fed Age at which formula was introduced; were symptoms associated with change? Age at weaning to solids; associated symptoms?

Event specific questions Were the symptoms typical of acute (IgE mediated) reaction? Was the reaction immediate? Within 2 hours? Were there any symptoms which suggest anaphylaxis? Has the child previously or subsequently tolerated the suspected allergen? What was the response to antihistamines?

Lily aged 2 years History – what was unusual? Mother made home made brownies containing hazelnuts and Nutella (hazelnut spread) Eaten Ferrero Rocher chocolates before without problems Ate a brownie for breakfast, went to school Came home and felt ‘hot’ – mum took her uniform off – covered in red itchy blotchy rash No complaints from school Gave her Piriton – little effect Repeated Piriton – little effect Went to bed- rash improved overnight Ate another brownie the next morning – rash returned Referred ? Hazelnut allergy History – what was unusual?

History – what was unusual? Had eaten hazelnuts before without problems Rash appeared over hours – not typical of type 1 reactions Piriton didn’t seem to help So what next? SPT to hazelnut Negative control 0 mm, positive control 8 mm Hazelnut 0 mm Serum specific IgE – total = 780 Hazelnut, brazil, cashew, walnut, pistachio < 0.4

Allergy testing Recommendations Based on the results of the allergy-focused clinical history, if IgE mediated allergy is suspected: Offer a skin prick test and/or blood tests for specific IgE antibodies to the suspected foods and likely co-allergens Do not use atopy patch testing or oral food challenges to diagnose IgE-mediated food allergy in primary care or community settings

Using allergy tests with a clinical history Likelihood of clinical allergy from specific IgE Likelihood of clinical allergy from history Low (<0.35 Ku/L) Intermediate (0.35-15 Ku/L) High (>15 Ku/L) High, eg urticaria & wheeze on more than one exposure Possible allergy Probable allergy ALLERGY Intermediate eg urticaria on one exposure Low eg non IgE symptoms No allergy

Using and interpreting allergy tests Allergy tests provide supportive evidence Should only be used if there is evidence from the history to suggest the responsible allergen They should not be used as a screening test Used incorrectly there is a significant risk of misinterpretation of the results/misdiagnosis SPT and SSIgE give a prediction of likelihood of reaction not severity

Allergy tests; which are valid in the diagnosis of food allergy? Skin prick tests Oral food challenge Hair analysis Patch testing VEGA testing Serum specific IgE IgG4 York test

Allergy tests Skin prick tests Oral food challenge Hair analysis Patch testing VEGA testing Serum specific IgE (RAST) IgG4 York test

Evidence based allergy tests Oral food challenge; gold standard but labour intensive and slow Avoid antihistamines for 5 days before Pin-head size amount Pea size amount Double every 15 min until normal portion tolerated Observe for 2 h after food has been eaten Skin prick tests; cheap, instant results, almost any food can be tested (prick- prick) – 8 allergens = £47.27 Serum specific IgE; “RAST” or Immunocap; one blood test, risk free, more expensive, delayed results 8 allergens = £126.97 Patch testing; only useful for contact dermatitis

Molecular allergy or component resolved diagnosis (MA or CRD) Maps the allergen sensitization of a patient at a molecular level; increased accuracy in allergy diagnosis & prognosis Currently more than 130 allergenic molecules commercially available for in vitro  testing. Enables three key aspects of allergy diagnosis: Resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens Assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing Identifying patients and triggering allergens for specific immunotherapy (SIT). All sIgE tests including MA & CRD should be evaluated within the framework of a patient’s clinical history, since allergen sensitization does not necessarily imply clinical responsiveness.

Peanut FC & IgE tests RAST – specific peanut IgE or Skin prick test Positive IgE to team The team is dangerous The team is a threat 13 players or components to the threat Is one more dangerous & significant than the others?

Molecular allergy, component resolved diagnosis 13 players or components to the threat Is one more dangerous & significant than the others? Component resolved diagnosis tells us that …. Only 4 players are a real threat The others may look like a threat (perhaps one is the twin brother of a star player in another team?) or be insignificant/harmless

CRD for peanut allergy Component resolved specific IgE testing for peanut allergy more accurately identifies patients with peanut allergy than the routine use of peanut extract–specific IgE serology or skin prick testing. Among the peanut component proteins, IgE antibodies to Ara h2, and to a much lesser extent Ara h1, Ara h3, Ara h6, and Ara h9, have been identified as the major driver of clinically relevant allergy. Sensitization to Ara h2 is found in 40% to 90% of patients with clinical peanut allergy.

Use of Ara h1, 2 & 3 in peanut allergy The peanut seed storage proteins Ara h1, Ara h2, and Ara h3 are all major allergens and seem to be associated with primary sensitization to peanut in susceptible individuals. (ie not cross reactions) Among these seed storage proteins, Ara h2 in particular, is considered a risk marker for severe allergic reactions. In individuals sensitized to peanut and with a cut off point of 0.35 kU/L, Ara h2 correctly classified 97.5% of the patients. Importantly, all children with peanut allergy were given correct classification, using Ara h2.

Typical example of how allergen components can meet clinical needs On investigation, a child with a suspected peanut allergy gives a positive skin prick test or in vitro (RAST) allergy test for peanut extract. The prognosis can be very different depending on whether the sensitization is linked to a Bet v 1-like protein (major allergen component of white birch pollen), a seed storage protein (Ara h2), or an lipid-transfer protein (LTP). In the first case, there is almost no risk of the child’s experiencing serious anaphylactic shock (Positive RAST reflects cross reactivity to Bet v 1 like protein) In the second and third cases, true allergy to peanut is likely and the child is advised to carry injectable adrenaline (e.g., Epipen or Jext). the major allergen component of birch pollen (Betula verrucosa).

Ara H2 cut off points Various IgE anti-Ara h2 cut points have been proposed to predict clinically relevant peanut allergy & improve diagnostic characteristics Nicolaou and Custovic similarly proposed 0.35 kU/L as a threshold. In their study, this threshold exhibited a 100% diagnostic sensitivity. ? Could these thresholds be used to suggest home introduction of peanuts to patients (if they fall below the threshold) or to replace an oral food challenge (if they rise above the threshold).

Sibling testing

San Antonio – testing the siblings of food allergic children False-positive results could lead to food avoidance, which can increase the risk of developing an allergy down the road. "Many children are sensitized to a food, so they will have a positive test result, but that does not mean they have a true food allergy" 1:10 children are positive for peanut IgE (ie sensitised) 1:100 are clinically allergic to peanut The presence of sIgE reflects allergic sensitization and not necessarily clinical allergy.

Chicago Family Cohort food allergy study 478 children with confirmed food allergy, and 642 of their siblings. Caregivers completed detailed screening histories for both the allergic child and the siblings. Skin prick testing (SPT) and serum specific IgE (sIgE) was performed on the siblings for cow’s milk, egg white, soybean, wheat, peanut, walnut, sesame seed, a fish mix, and a shellfish mix.

Sensitisation vs clinical allergy Sensitization was defined as a positive skin prick test or positive sIgE with no clinical symptoms. Food allergy was defined as a positive skin prick test (mean wheal diameter, >3 mm) or positive sIgE (>0.35 kUA/L) plus clinical symptoms. 34% of the siblings had no sensitization to foods and no clinical symptoms 53% had sensitization to food (potential for false positive in > 50%) 13% had an actual food allergy

LEAP study- Gideon Lack et al Introduction of peanut-containing foods into the diets of high-risk infants aged between 4 and 11 months. High risk infants are those with early-onset atopic disease, such as severe eczema or egg allergy. Delaying introduction can be associated with an increased risk for peanut allergy.

LEAP - findings Early, sustained consumption of peanut products was associated with a substantial & significant decrease in the development of peanut allergy in high-risk infants. Conversely, peanut avoidance was associated with a greater frequency of clinical peanut allergy than was peanut consumption.

Cost of allergy tests per person (8 allergens) Skin prick test* Blood test** Test cost £1.70 £96.00 Staff cost £44.49 £30.97 Consumables £1.08 Total cost £47.27 *The average cost of a vial is estimated at £17 with 80 drops per vial. Average of eight allergies tested per person, this equates to a maximum number of ten people tested without wastage. Add on 30 minutes of nurses’ time @ £0.483 per minute & 10 minutes of doctors’ time @ £3 per minute; estimated staff cost of £44.49 per test. One lancet is required for each test, (packs of 200 costing £12 each) £12 buys two controls with 80 drops in each vial. **The cost per allergy tested was estimated to be £12. Average of eight allergies tested per person Add on 2 minutes of nurses’ time @ £0.483 per minute & 10 minutes of doctors’ time @ £3 per minute; estimated staff cost of £30.97 per test. (Personal Social Services Research Unit 2009)

New allergies emerging; Asian Indian children in the US n = 114 Top 9 allergens seen, also some more unusual fruit and vegetable allergens. Tree nut, the most common allergy, was seen in 59% of the children (very common in cooking?) Other more unusual allergens: Chick pea flour, capsicum, Indian lentils,bulgur wheat, coconut, corn, aubergine, food dye, garlic, ginger, green peas, jalapeno peppers, melon, rice, and tomato.

Prices for Aptamil Pepti & Nutramigen LGG (January 2017)

Medscape Medical News Updated Guidelines for Prevention of Peanut Allergy Nicola M. Parry, DVM January 05, 2017

Prices for Aptamil Pepti & Nutramigen LGG (January 2017)

Mead Johnson Nutramigen Danone/Nutricia Standard infant formula Cow and Gate 1 & 2 Aptamil products SMA products Cost Taste Allergen-icity Extensively hydrolysed formula Aptamil Pepti Whey formula Contains LCPs (omega 3&6) 80-85% short peptide chains 15-20% single amino acids 63% protein chains < 1000 daltons Calcium & iron enriched, residual lactose Mead Johnson Nutramigen Casein formula Lactose free 95% protein chains < 1000 daltons Low High Good Poor EHF + MCT Pepti Junior (+50% MCT) Appropriate for malabsorption disorders Pregestimil (+55% MCT) Single amino acid formulae Neocate LCP 100% amino acid formula Calcium enriched Produced in a milk free environment Per 400g tin £38.00 Puramino* (blend of Omega 3 (DHA and Omega 6 ARA fatty acids present in breast milk) Per 400 g tin £35.05