November 28, 2004
CLINICAL REVIEW: Allergy, Part 2
* Allergic rhinitis can severely reduce a sufferer's quality of life.
* In the UK, 1-2 per cent of children are now allergic to peanuts.
* Patients at risk of anaphylaxis should carry epinephhne injectors.
* Avoiding airborne allergens does not have much clinical impact.
1. Allergic rhinitis
Allergie rhinitis was considered a trivial disease 50 years ago, but has become a major health problem due to its high prevalence. It affects up to 40 per cent of the general population and individuals between 15-25 years are most affected.
The disease can cause a severe impairment in a patient's quality of life and is an important cause of school and work absenteeism, with socioeconomic implications. There are two forms of allergic rhinitis: intermittent (seasonal), caused mainly by pollens and fungal spores, and persistent (perennial), where house dust mites and pet allergens are the most common precipitants. Allergic conjunctivitis is often an accompanying feature in intermittent rhinitis.
An IgE-mediated disease
Allergic rhinitis, especially in its intermittent or seasonal form, is probably the most classical IgE-mediated disease. Most of the major nasal symptoms (sneezing, itching and rhinorrhoea) as well as eye symptoms (redness and itching) can be relieved by H^sub 1^- antihistamines.
Nasal obstruction, the other major feature of the allergic rhinitis, is caused by a more complex mechanism, with histamine only partly involved. The main component is the dilation of the venous capacitance vessels, which significantly increases tissue mass and responds poorly to antihistamine treatment. The other two components, excess secretions and tissue oedema, are histamine mediated and can be influenced by antihistaminic drugs, but they make only a minor contribution to nasal obstruction.
Two treatment options
There are two treatment options, guided by symptom seventy. In mild and some moderate forms, antihistamines control symptoms in most cases. In severe or prolonged forms, the presence of an eosinophil-dominated allergic inflammation aggravates the symptoms, particularly nasal blockage and nasal hyper-reactivity to non- allergic stimuli. As a result, more potent anti-inflammatory treatment such as nasal corticosteroids is necessary.
The treatment schedule and duration are important in allergic rhinitis. Studies comparing the 'daily' versus 'when needed' treatment show clearly that continuous therapy with either antihistamincs or corticosteroids offers better and more sustained improvement of symptoms.
Also, continuation of treatment for a few weeks after the symptoms have faded allows a better control of nasal allergic inflammation. Most apparent failures of nasal corticosteroids are due to poor nasal inhaler technique, so GPs should ensure patients know how to use them.
* Allergic rhinitis was a trivial disease 50 years ago but is now a major health issue.
* H^sub 1^-antihistamines relieve most symptoms.
* Nasal obstruction may require nasal steroids for adequate relief.
* GPs should review allergic rhinitis patients before the pollen season starts.
Urticaria is named after the Latin word 'urtica' meaning nettle. Urticaria or 'nettle rash' is common and affects up to 20 per cent of individuals at some time in their life. It is not a single condition but a syndrome, because there are many aetiological factors and mechanisms underlying the symptoms.
Some urticaria is allergic in origin. The allergens involved are mostly foods or drugs. Allergic urticaria is usually acute and, in most patients, the cause is easily identified. Exclusion of the food from the diet or slopping drugs (NSAIDs are commonly implicated) is followed, relatively quickly, by amelioration of symptoms.
The cause of chronic urticaria can be difficult to find. Allergy per se is not usually involved. In as many as 60 per cent of cases, auto-antibodies against IgE or the IgE receptor on the mast cells are the cause, but in other cases a correlation with a causative agent is never made. These cases are called chronic idiopathic urticaria.
Laboratory investigations are of little help in chronic urticaria, because abnormalities are rarely found. Inflammatory signs should raise the suspicion of a vasculitic urticaria. Usually the lesions in this form of urticaria last for more than 24 hours and after resolution can leave hyperpigmentation. Vasculitic urticaria in adults may be associated with lymphoma.
With physical urticarias, cold, heat, different types of skin pressure or sun exposure are precipitating factors. They can accompany chronic idiopathic urticaria or may exist as individual conditions. Avoidance of triggers is key, but in some cases first generation antihistamines or cyproheptadine (for cold urticaria) may be more effective than second generation antihistamines.
How children are affected
In children, most episodes of urticaria are due to viral infections. Antibiotics given for a possible bacterial infection are often blamed, and this leads to unnecessary worries about future use.
All types of urticaria have a common initial pathogenetic event - the release of large amounts of mast cell-derived histamine.
Histamine, acting at H^sub 1^-receptors, causes localised oedema (the weal) and activates sensory nerves. The latter effect is responsible for the widespread neurogenic erythema (the flare) and pruritus (itch), usually the most troublesome symptom. In chronic urticaria, pruritus is exacerbated by the deposition of eosinophil- derived proteins that cause hyper-responsiveness.
Because histamine is so important in the pathogcncsis of urticaria, H^sub 1^-antihistamincs arc the drug of choice, but relatively large doses of the most potent drugs are often required.
This is because the physical structure of the dermis severely restricts diffusion of histamine to less than lmm. This allows high concentrations to build up locally, in contrast to mucosal surfaces, where diffusion of histamine occurs freely. Because steroids do not inhibit mast cell degranulation, they should not generally be used to treat urticaria.
* Most urticaria is not allergic in origin.
* Urticaria that results in bruising or pigmentation should be referred to rule out urticarial vasculitis and associated conditions.
* Higherthan usual doses of antihistamines may be needed to control symptoms.
3. Peanut allergy
The peanut, a member of the legume family, has become an important and potentially lethal source of allergy. In the UK, 1-2 per cent of children are now allergic to peanuts, and these figures appear to be rising.
Prevalence is higher in families of peanut allergy sufferers than in the general population. This rise parallels the general increase in atopic diseases, as well as increased exposure of young infants to peanut allergens. Due to its potential severity, suspected cases of peanut allergy should be referred to a specialist.
Oral exposure to peanuts or other foods containing peanuts, such as crude peanut oil, is probably the commonest route for sensitisation. Another possibility, particularly in children with infantile eczema, is trancutaneous absorption from skin creams and oils using peanut oil as a base, even though peanut oils were withdrawn from cosmetics and creams in the mid-1990s.
Up to 80 per cent of patients develop symptoms on their first known exposure, meaning that occult exposure is common and can cause sensitisation. Exposure in utero or through a mother's milk may explain why allergic reactions occur in infants who have no known previous exposure to peanuts.
Over 90 per cent of people allergic to peanuts also have other allergic diseases. Possible risk factors are a history of eczema in childhood and use of soy milk formulas during infancy. Soy milk use may be merely a surrogate of atopy in general, because soya was frequently used for children with suspected cow's milk allergy.
Peanut allergy is usually life-long, but 20 per cent outgrow this sensitivity. If specific IgE becomes undetectable, the patient is probably no longer sensitive, but an oral challenge test should be performed in hospital for confirmation.
Cross-reactivity to other nuts in peanut allergy is a cause for concern. Tree nuts are not in the same botanical family, but up to 50 per cent of those allergic to peanuts eventually become sensitised to tree nuts, so peanut allergic patients should avoid them. Cross reactivity with other members of the legume family such as soy, peas and beans is unusual. Peanut allergic patients do not need to avoid other legumes unless they are known to react to that individual legume.
The two main goals in managing peanut allergy are educating patients to avoid contact and identifying high-risk individuals, who should be given an emergency kit and a clear emergency treatment plan for accidental exposure.
Patients and relatives should be educated, verbally and in writing. People who work with children, such as teachers and Brownie Pack leaders, also need this education. Patients should be told about the Anaphylaxis Campaign, MedicAlert Foundation and Allergy UK. They can help sufferers to understand their disease.\Key points
* Prevalence of peanut allergy is higher in families of peanut allergy sufferers than in the general population.
* Oral exposure is probably the commonest route for sensitisation.
* Cross-reactivity to other nuts in peanutallergy is a cause for concern.
* Anyone involved with the care of peanut allergic individuals should be educated about emergency treatment.
Anaphylaxis can result in severe impairment of quality of life and often death. At-risk patients should have an emergency care plan, involving the self-administration of epinephrine.
Patients and GPs are concerned about epinephrine, mainly because of possible side-effects from overdosing. However, the risks of not using epinephrine must be considered. In almost all reported fatalities from anaphylaxis, epinephrine was either administered too late or not at all.
Epinephrine: benefits vs risks
Using epinephrine in time will prevent death in most cases. The risk of overdosing is very low with self-administered preloaded syringes. Preloaded syringes or autoinjectors containing a single dose of 0.15mg epinephrine (Epipen Junior, Anapen Junior) or 0.30mg (Epipen, Anapen) are available in the UK.
Intramuscular administration of these doses will not cause severe side-effects, even from a second dose after 20 minutes, which is recommended if symptoms do not resolve. IV epinephrine should not be given in primary care.
Epinephrine autoinjectors should be carried by patients with food allergy having concomitant asthma, even if well controlled, due to the potential development of severe bronchospasm, and to those who are severely allergic to hymenoptera (bee and wasp) venom. An autoinjector is not usually required for localised reactions.
Education about signs and symptoms of impending anaphylaxis helps to alleviate panic and ensures the emergency care plan is followed.
Death occurs in children mainly through asphyxia due to a laryngeal oedema and severe bronchospasm, leading to respiratory arrest. Adults can also die from respiratory arrest, but cardiovascular shock is more common.
Oral pruritus, oedema of the lips and tongue, dysphagia, hoarseness, a 'lump in the throat', stridor and breathing difficulties can all be early signs of a laryngeal oedema. Breathing difficulties with chest tightness and wheezing suggest bronchospasm. Palpitations, rapid pulse, light-headedness or faintness can be early signs of a cardiovascular collapse.
If these symptoms develop, patients must be told to use epinephrine promptly. Patients should be nursed supine to help venous return and be aware that anaphylactic reactions can be biphasic. Complete resolution can be followed after a few hours by a late-phase reaction. This can be more severe and less responsive to treatment. This is why all patients experiencing an anaphylactic reaction should receive antihistamines and systemic steroids and remain under medical surveillance for several hours.
Patients at risk from anaphylaxis should be under regular specialist follow-up so that the acute management plan is remembered, autoinjectors are in date and of appropriate strength, and any asthma is optimally treated.
* The risks of not giving epinephrine are much greater than giving it.
* IV epinephrine should not be given in primary care.
* Death in children is mainly through asphyxia due to laryngeal oedema. In adults, it is more often from cardiovascular shock.
5. The prevention of allergy
Exposure to aeroallergens correlates with sensitisation and development of allergic diseases, so reducing allergen exposure should reduce allergy. In the past, patients were advised to undertake all sorts of draconian measures to reduce allergen levels including removing carpets, using acaricides and buying expensive specialist vacuum cleaners. More recent studies show most of these strategies do not reduce airborne allergens or have much clinical impact.
Avoiding food allergens
Food allergy avoidance has been more successful than with airborne allergens. Avoiding specific foods by pregnant and breastfeeding mothers and delaying the introduction of solid foods for infants have not been shown to prevent sensitisation. But once sensitisation is evident, avoiding allergens becomes the cornerstone of management. Avoidance not only prevents the clinical symptoms, but if done for a year or two can result in the sensitisation disappearing in 80 per cent of sufferers of milk and egg allergy.
Sensitisation to peanuts tends to be life-long, and avoidance does not influence the degree of sensitisation. Allergen avoidance is essential.
Careful reading of labels of all food products is vital. Patients should also be told about potential hidden sources of allergen. Eating out may cause problems, especially in fast food and oriental restaurants where there is a risk of accidental contamination with nuts. Contamination with peanut products can also occur in bakeries, delicatessens and with packed products.
Allergen-specific immunotherapy by subcutaneous injection is only used in the UK in specialist units, for treatment of cat, hymenoptera and grass pollen allergies. Oral immunotherapy remains a tantalising hope.
An 'immune modulator', already marketed in Australia and US and soon to come to the UK, is anti-IgE. This seems effective in severe allergic disease and asthma by preventing the initiation of an allergic response. Drawbacks are cost (several thousand pounds per annum) and delivery, by intramuscular injection every few weeks.
* Avoiding food allergens is the cornerstone of the management of food allergy.
* Allergen avoidance for peanut allergy sufferers is essential.
* Anti-IgE may soon be available in the UK.
Allergy (second edition) by S T Holgate, M K Church and L M Lichtenstein, published by Gower Medical Publishing
See Medicine on the Web, page 50
Previously in Clinical Review
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* Allergy, part one (29 October)
* Palliative care in motor neurone disease (22 October)
* Inflammatory bowel disease (15 October)
NEXT WEEK: Knee problems, part one, by Steven Cutts and Alison Edwards
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By Dr Diana S Arion, visiting fellow, Dr Martin K Church, professor of immunopharmacology, and Dr Jonathan O'B Hourihane, consultant in paediatric allergy, School of Medicine, University of Southampton
Copyright Haymarket Business Publications Ltd. Nov 5, 2004