The difficult to manage allergy patient – an Allergy Research Foundation conference. November 2012


Chronic allergic gut disorders – Dr Neil Shah, paediatric gastroenterologist at Great Ormond Street Hospital

Acute food allergy and desensitisation – Dr Andrew Clark, Head of Paediatric Allergy services at Addenbrookes Hospital, Cambridge.

Difficult asthma – Professor David Price, Professor of Primary Care Respiratory Medicine, University of Aberdeen

Chronic urticaria and angioedema – Professor Marcus Maurer, Professor of Dermatological Allergology and Director of Research, Charité University Hospital, Berlin

Severe atopic eczema – Dr Susan Chan, clinical research fellow at Guy's and St Thomas' Hospital


Chronic allergic gut disorders – Dr Neil Shah, paediatric gastroenterologist at Great Ormond Street Hospital

By the time a patient reaches Dr Shah's clinic, he or she will on on their sixth or seventh referral beyond the GP – which gives some indication of how difficult chronic gut disorders are to diagnose. The problem could be:
• classic IgE mediated allergy
• non-IgE mediated allergy
• a mixture of an IgE mediate allergy and an eosinophilic disorder (for more on eosinophilic disorder see our report on the FABED eosinophilic study day)
• reflux or an obstructed oesophagus
• inflammatory bowel disease
• functional bowel disorder

Children with early food allergy have a three to four times greater risk of having functional abdominal pain when they are older. It may be that milk protein, for ex maple, disrupts the normal contraction of the gut so that he milk does not pass through properly, causing pain. The allergic reaction, involving the mast cells, may actually change the function and make up of the enteric nerve cells in the gut and this change may not reverse so that it will remain throughout the child's life. This change could affect bowel function so that you get straining but with normal stools; it could also be the cause of later abdominal pain.

Eczema from a very young age (first few weeks/months of life) is a key indicator of a food allergy in an older child but the GI symptoms of allergy are shared with so many other GI conditions that it is very hard to diagnose. Back arching and screaming in an infant is one of the few symptoms which is rarely shard with other conditions so is a good indicator of an allergy problem. Non-gastro symptoms are also very indicative of food allergy:
• mouth ulcers
• sleep disturbance
• fatigue
• bed wetting
• joint pain
The link would appear to be the autonomous nervous system.

Other points:

• Ten years ago only 20% of children had multiple organ problems/allergies; now it is nearly 40%.
• Although some children do 'outgrow' their allergies, many, especially those allergic to cow's milk, do not.
• The psyche of children with allergy can be badly affected.
• Growth charts irrelevant to the diagnosis of food allergy and 85% of allergic children will have normal growth rates. However, nearly 10% are likely to have weight problems.

Food aversion and elimination diets

If a child, at weaning, gets pain when it eats, it will, understandably, suffer from food aversion. More over, an allergic child may not make any grelin, the hormone which causes you to feel hungry.

The only reliable way to diagnose food allergy is via an elimination diet and the usual is to start with a six food (milk, egg, wheat, soya, nuts, gluten) elimination diet – but this si very hard to implement. Indeed, over 50% of treating dietitians say that they could not keep to it themselves.

Gut permeability

Dr Shah suggested that not enough attention was paid to gut permeability which is massive in many gut conditions.


So far the evidence of success in the use of probiotics in the treatment of paediatric gut conditions is not great but it may be that, so far, the probiotics have not been sufficiently specific.


Acute food allergy and desensitisation – Dr Andrew Clark, Head of Paediatric Allergy services at Addenbrookes Hospital, Cambridge.

(For a comprehensive introduction to desensitisation/immunotherapy see Linda Gamlin's article here.)

Desensitisation is appropriate for any allergy which has the potential to kill you – although there is a major disconnect between the actual risk of an allergy fatality and most parents' perception of it.

Possible routes for desensitisation:
• subcutaneous (under the skin)
• oral
• intranasal (through the nose)
• intralymphatic (directly into the lymphatic system)
• epicutaneous (shallow piercing of the skin which allows the substance to enter)

The goal is to achieve a degree of tolerance that will enable the patient to be intermittently exposed to the allergen without reacting.

Oral immunotherapy

The studies done so far have been positive. In one milk study from 2008, 23% of 60 participants were able to resume an unrestricted diet, 54% achieved partial tolerance and only 10% achieved no tolerance at all.
In a 2011 study of 22 subjects with serious peanut allergy, 20% had mild reactions during the treatment but 86% reached a maintenance dose of 5 peanuts a day although they had to keep eating the peanuts to retain their tolerance. However, it appears that the longer you continue the treatment the more successful it will be in the long term but there is no certainty that if it is stopped the patient's allergy will not reappear. Even in patients who appeared to have achieved tolerance, IgE levels had not dropped which may suggest that they will never achieve total tolerance.

In terms of safety, some patients had predictable, but not dramatic and mainly gastrointestinal, reactions when the dose was doubled every two weeks. Unpredictable reactions only occurred if there was an outside factor involved – such as exercise, excessive tiredness, illness etc.

There are some minor side effects to the treatment – itching, stomach ache etc – but they were quite tolerable bearing in mind the good overall outcome.

Dosing weekly rather than daily is much better for patient compliance and did not appear to make much difference in terms of outcome.

Sublingual delivery

This appears to be less efficacious than oral delivery but is better tolerated.


This appears to be a possible route for desensitisation as it also appears to be a common route for the original sensitisation through, for example, eczema creams which include peanut oil. It may offer the opportunity for using very low doses to gradually build up tolerance.

The role of IgE in oral immunotherapy

15% of patients in most trials appear to fail and it is not understood why. However, combining OIT with anti IgE therapy did appear to work – again it is not understood why. So there may be a role for using IgE therapy to allow for a more rapid escalation of doses which would allow for fewer attendances, reduced cost and therefore greater availability.


As yet, OIT is not available as a treatment on the NHS. The need is to convince e NICE of its benefits in terms of both patient quality of life and reduced cost in treating them, unsuccessfully, for allergy.


Difficult asthma – Professor David Price, Professor of Primary Care Respiratory Medicine, University of Aberdeen

Ideal asthma control means that the patient has:
• no night time waking
• no limitations on their activity
• symptoms no more than three times per week

Severe, uncontrolled asthma is difficult for both the patient and for the doctor. The patient has frequent exacerbations of his/her condition, which can even result in death. It is normally:
• non eosinophilic
• steroid resistant
• the patient is steroid non-responsive

The average GP only actually fully controls asthma in from 20% to an absolute maximum of 60% of their asthmatic patients with around 15–80% being almost totally uncontrolled.
Control depends largely on the patient's doctor and, within primary care, very few high risk patients are getting specialist care.
Quite a part from the discomfort and danger suffered by the patient, poorly controlled asthma is very expensive.
• A controlled/low risk patient costs £187 per annum
• a partially controlled patient £254 per annum
• an uncontrolled patient @348 per annum
• a high risk, uncontrolled patient £700+ per annum

Why is control so poor?

• Patients, especially low risk patients, tend not to take their medication either because they do not really understand the therapy and are fearful of side effects of because they do not think that they asthma is bad enough to need it. In fact, taking the appropriate medication correctly has minimal side effects and will prevent their asthma escalating.
Compliance may be as little as 50%.

• Regime too complex. Once a day dosage gets far better compliance than twice a day.

• Combination of long and short acting medication and a degree of self management (the patient can increase the dosage as needed) seems to work more efficiently.

• Poor inhaler technique. Very few doctors or nurses use the correct technique (for more on correct technique see the Dr Sophie Faroque's presentation here) so it not surprising that most patients do not either. As result most of the drug is wasted.
It is also important to keep patients on the same sort of inhaler as techniques differ with different inhalers.

• Smoking is very bad for asthma control as smokers tend to be steroid resistant and therefore suffer from increased inflammation.

• Co-occurring rhinitis, obesity and GERD (gastrointestinal reflux).
Rhinitis in particular causes upper airway inflammation which then spreads tot he lower airways. Asthma patients who also suffer from rhinitis have four times worse asthma control, including hospitalisations.

• non responsive disease

• diagnostic confusion – many of those diagnosed with asthma in fact have COPD (chronic obstructive pulmonary disease) or a combination of asthma and COPD

• anxiety and dysfunctional breathing also often misdiagnosed as asthma

Other points raised:

• Immunotherapy may work with children but is rarely tried

• Exercise induced asthma. Steroids do not work although Anti-Leukotrienes Antagonists (a drug which blocks the chemical reactions which can lead to inflammation of the airways) appear to do so.

• Virus-induced asthma is also unresponsive to steroid although they may work in high doses.


Chronic urticaria and angioedema – Professor Marcus Maurer, Professor of Dermatological Allergology and Director of Research, Charité University Hospital, Berlin

Urticaria is one of the most difficult conditions in allergy to manage. It can dramatically affect the patient's quality of life yet most patients think that there is no treatment.
Nearly all urticaria will resolve naturally, eventually, but this can take up to seven years and the need is to keep the patient symptom free during that period.

Symptoms and diagnosis

The symptoms of urticaria are 'wheal and flare' (raised, extremely itchy bumps) plus angioedema (swelling), normally together although they can appear separately. Both symptoms can also be symptoms of other conditions although these are very rare.

The condition nearly always appears in later life, not in childhood.

Urticaria is hard to treat as the cause is rarely unknown – although it is never caused by an allergy so skin prick testing is not helpful. However, induced (as opposed to spontaneous) urticaria can be triggered (but not caused) by:
• cold
• sun
• heat
• delayed pressure
• contact with specific substances
• water

Spontaneous urticaria appears to be caused by:

• auto reactivity – approximately 20% of cases – when something in the body reacts to something else in the body, often to something circulating in the blood
• bacterial infection – approximately 25% of cases.
Around 50% of us carry bacterial infections but they do not trigger urticaria. If infections are eliminated, around 50% of spontaneous urticaria sufferers will benefit.
• intolerance – approximately 29% of cases
This intolerance is never to food but may be to additives or preservatives. There are no tests so elimination of the most likely substances (all drugs that can induce urticaria, pseudo allergens and histamine) for at least 14 days followed by a challenge is the only way to identify an intolerance. Again, around 50% of spontaneous urticaria sufferers will benefit.

Therapeutic strategies.

• find and eliminate the cause/triggers if possible

• if this is not possible, treat with non-sedating anti-histamines.

Antihistamines are nearly always under dosed in urticaria. If they do not work at the original dose, that that dose should be upped four times. However, it is important to up dose with the same antihistamine, not to give four doses of different antihistamines as each one works in a slightly different way and the effect will be dissipated.

• anti IgE drugs

Although urticaria is never cause by an allergy, anti-IgE drugs appear to work with some urticaria patients for whom antihistamines do not work – even though they do not have raised IgE. However they only work as long as the patient continue to take the drug.


Severe atopic eczema – Dr Susan Chan, clinical research fellow at Guy's and St Thomas' Hospital

One in five children now suffer from eczema in infancy, 60% of them before the age of one but most are in remission by the age of 15. Adult onset of eczema is rare.
The earlier the onset of the condition the more persistent it seems to be.
Risk factors appear to be a family history of atopy and the mutation in the filagrin gene which occurs in approximately 10% of Western populations.

Most children improve over the age of seven but around 45% will develop asthma or allergic rhinitis instead.

Pollen would appear to exacerbate eczema in approximately 50% of cases of eczema in childhood but not to be relevant in adult eczema.

Relationship with food allergy

Skin prick testing suggests that there is only a connection in 15% of cases but this does not take account of delayed reactions and so may be very inaccurate. The only way really to establish a connection is through elm in at ion and challenge tests.

Studies of infants using cow's milk formula, partially hydrolised and totally hydrolised cow's milk formula show some reduction in eczema for the children on the hydrolised formula but not sufficient to be decisive.

Immunotherapy and Ige medication

There are positive case studies of the use of immunotherapy in eczema but no DBPCTs.
In a pilot study, anti IgE medication appeared to help eczema but no one knows why this should be.




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