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Diagnosis and management of allergic diseases

Samantha Walker
RGN PhD
Head of Allergy and Research
National Asthma and Respiratory Training Centre
Warwick

The prevalence of atopy (the predisposition to develop allergic disease), which is defined clinically by positive skin-prick tests to two or more  common aeroallergens, is increasing worldwide.(1,2) Increases have been attributed to Western diet, smaller family size, high economic status, and increased allergen exposure caused by insulated housing conditions.(3,4) Pollution has been shown to be unrelated to the development of atopy, although it may be an important influence in the development of asthma and other wheezing illnesses.(5) Factors thought to be protective against atopy include breastfeeding up to 4 months of age,(6) living in a rural farming community,(7) and exposure to infection in childhood.(8,9)

Atopy and allergic diseases
Increases in atopy are reflected by significant increases in atopic dermatitis, hayfever and peanut allergy, the latter now affecting approximately 1% of British preschool children.(10) A twofold increase in anaphy­laxis was observed in the UK between 1991 and 1995.(11) Ten percent of the population in the 15-25 age group are reported to suffer from perennial allergic rhinitis, while over 80% of children and 70% of adults (under 55 years) with asthma are sensitive to one or more aeroallergens on skin-prick testing/radioallergo­sorbent test (RAST).(12)
Peanut allergy is increasing, although there are differences between the perceived prevalence of food allergy and "true" food allergy - that is, symptoms temporally related to exposure and confirmed by identification of relevant IgE. Approximately 20% of the UK population report some form of food intolerance,(13) although symptoms can be confirmed only by double-blind placebo-controlled food challenge in 1.4% of adults and 5-7% of children. IgE-mediated food allergy is more common among patients with other atopic diseases.
Atopy is a risk factor for occupational asthma caused by low-molecular-weight allergens such as laboratory animals and biological enzymes, although not for those caused by high-molecular-weight compounds (such as isocyanates and colophony). Approximately 80% of those with laboratory animal allergy are atopic (as defined by a positive skin-prick test to grass pollen, house-dust mite or cat). Atopic individuals also have an increased risk of developing latex allergy.(14) Confirming atopy, by performing skin-prick tests/RASTs to common aeroallergens, may be a useful guide if an IgE-mediated trigger is suspected.
Allergic diseases are often associated with significant morbidity, although they are often trivialised by health professionals. For example, the underdiagnosis and undertreatment of hayfever (currently affecting approximately 15% of adults and a staggering 35% of 12-14- year-olds in the UK) leads to documented learning disability in children,(15) and significant impairment of quality of life (with related reductions in working ability and attendant costs) in adults. An American study reported the cost of allergic rhinitis in 1994 to be $1.2 billion. However, differences in healthcare systems between the UK and the USA make direct translation of cost impossible.
Deaths from food-induced anaphylaxis remain rare despite the increased prevalence in food allergy, although fatalities have been associated with the delayed administration of epinephrine (adrenaline).(16)
Common allergy problems in primary care include allergic asthma, rhinitis and eczema. Diagnosis may be difficult, particularly in patients with perceived food-related symptoms. Specialist allergy clinics are rare, meaning that the majority of responsibility falls on those working in primary care. Encouraging patients to attend their surgery instead of seeking help from alternative practitioners is helpful only if staff in general practice have been trained in diagnosis and management of common allergic conditions. Information on training is available at www.nartc.org.uk

Allergy diagnosis

Taking a history
Making an accurate diagnosis of allergy is of primary importance and should be made by interpreting the results of objective tests (skin-prick tests/RAST tests) in the context of the clinical history. History-taking requires time and effort but is vital in establishing the cause of any allergic disease. It is important to question patients closely as they are often unaware of all allergy-related symptoms. Important areas to focus on include:

  • Patients' account of symptoms.
  • History of presenting complaint, such as the ­duration and nature of the symptoms and trigger factors (allergic and non-allergic).
  • Impact on lifestyle: for example, sleep, work or school and leisure activities.
  • Past history, including family history.
  • Environmental history, such as exposure to furry animals or house-dust mites.
  • Occupation or hobbies.
  • Previous treatments, compliance, efficacy, side-effects.
  • Past medical history and physical examination.

It is worth remembering that patients may trivialise their symptoms and that parents may not present an accurate picture of their child's complaint. For example, it has been reported that the parents of young children (6-12 years) with allergic rhinitis appear to be more bothered by their children's nasal symptoms but tend to be less aware of less overt problems such as sleeping difficulties.
Seasonal allergic rhinoconjunctivitis (hayfever) is relatively simple to diagnose from a history of symptoms in relation to seasonal triggers alone. Perennial allergic rhinitis is more difficult to diagnose, given the existence of similar differential diagnoses such as infection, structural problems and hormonal, drug-induced or atrophic rhinitis. Identification of allergic triggers is vital when giving time-consuming, often expensive allergen avoidance advice; it is clearly inappropriate to advise avoidance in someone who does not get symptoms on exposure to mites (and, conversely, not to advise avoidance in someone who does).

Objective tests for atopy

Skin-prick tests
Skin-prick testing is regarded as a routine diagnostic procedure in hospital allergy clinics, but it is underused in general practice. Concern persists about its usefulness and safety, although the procedure is reported to be well tolerated by patients and by nurses performing the tests. Anaphylaxis following skin-prick testing to common aeroallergens has not been reported.(17) Skin-prick testing identifies atopy (IgE-mediated reactions) but not the clinical relevance of individual allergens.
Skin tests involve the application of drops of allergen extracts to the volar aspect of the forearm which are then pricked with individual sterile lancets. Drops are blotted with a tissue and the tests are read at 15 minutes. Tests for "quality control" are also included ­- allergen diluent (negative control) and histamine (positive control). The application of the negative control solution (allergen diluent) identifies patients who have dermatographism. This condition exists as a traumatically induced urticaria in response to the prick of the lancet. It is important to identify dermatographism, which makes the results of the allergen skin-prick tests difficult to interpret. A positive control test is performed using histamine dihydrochloride, which produces a reaction similar to that seen in a positive response to allergen and should be evident in all patients. If the histamine test is negative, the test should be repeated. Reasons for false-negative results include the patient having taken antihistamine tablets in the previous 48 hours and the deterioration of allergens on storage.
False-positives may result from dermatographism. Allergen extracts derived from foods are often poorly defined and unstandardised and are therefore less reliable than those for aeroallergens. This may result in higher rates of both false-positive and false-negative tests. Skin-prick tests should always be interpreted in the light of the clinical history.
Antihistamines should be stopped at least 48 hours before the test being performed, although there is no need to discontinue systemic steroids as they have no effect on early IgE-mediated skin responses. The response to histamine is maximal at 12-20 minutes, and that to allergen at 15-30 minutes, so arbitrarily the responses are measures at 15 minutes.
Skin-prick testing is relatively painless and well tolerated, even by small children. Positive reactions usually subside within 1 hour, although occasionally large responses may persist for 24 hours. Skin-prick testing is a sensitive but not very specific test, meaning that not everyone who has a positive reaction has symptoms related to exposure to that allergen. If the reaction is negative, one can be reasonably sure that allergen is not implicated in the patient's disease. However, a positive reaction to an allergen that is not related to clinical symptoms may be an indication that problems with that allergen may develop later in life. Alternatively, some patients with a past history of hayfever now resolved may maintain positive skin tests to grass pollen - that is, "clinical tolerance" may occur in the presence of positive skin tests.
As mentioned previously, skin-prick testing is extremely safe, with no systemic reactions to testing with common aeroallergens reported. However, in view of the hypothetical risk associated with giving allergens to which the patient is sensitive, by whatever route, it is logical to have epinephrine (adrenaline) available for immediate use. Occasional systemic reactions have been seen to skin-prick tests to some foods and venoms in those patients who have previously had an anaphylactic reaction, and so caution is recommended when performing skin-prick tests with allergens other than inhaled aeroallergens. Advantages of skin-prick testing include low cost, ability to obtain results immediately and educational value for the patient. A RAST test to measure allergen-specific IgE may be performed instead, although, in general, skin-prick tests are more sensitive.

Serum-specific IgE
Measurement of allergen-specific IgE antibodies present in the serum is an alternative and comparably reliable way of diagnosing atopy when skin-prick tests are not available. Briefly, allergen is adsorbed onto a filter paper disk and the patient's serum (containing IgE) is added. Subsequent washing leaves any allergen-specific IgE bound to allergen on the disc. Radiolabelled anti-IgE is then added. After further washing, the amount of remaining radiolabelled anti-IgE is detected by a b-counter. This is proportional to the amount of the patient's antigen-specific IgE. More modern methods (ELISA: enzyme-linked immunosorbent assay) have the same principle, although they involve a detection system involving anti-IgE linked to an enzyme to which substrate is added, resulting in a coloured product which is measured photometrically. These tests are generally used when a skin-prick test is not appropriate - for example, to diagnose food or venom allergy when the patient has previously experienced a severe reaction. Levels of specific IgE to many allergens can be measured, which may be more cost-effective, particularly for less common allergens. Other advantages are that tests measuring blood IgE levels are not affected by concurrent drugs or skin disease and are completely safe. Again, the interpretation of these tests should be considered with the clinical history.

Relationship between skin-prick tests and RASTs
In general, skin-prick tests tend to be more sensitive, whereas allergen-specific IgE measurements may be more specific. Skin-prick tests or RASTs demonstrate sensitisation to a particular allergen, although they cannot predict their relevance to exposure. However, a recent study suggests that skin test responses of greater than 6mm diameter, and specific IgE levels of approximately 11kU/l (to seasonal and perennial allergens) are associated with clinical symptoms on exposure to the relevant allergen.(18) This may not, however, be relevant in individual patients. Skin sensitivity to allergen has been shown to predict bronchial sensitivity. In food allergy, there is a greater ­concordance between skin-prick tests with fresh foods and a positive food challenge than that observed between commercial extracts and a positive food challenge.(19) Given the relatively good correlation between skin-prick tests and RASTs, the choice of test is likely to be based on the nature of the symptoms, safety, availability of extracts, cost and operator expertise in interpretation. Patients in whom there is a discrepancy between the clinical history and results of an objective test should be referred to an allergist or organ-based specialist with an interest in allergy.

Summary
Allergic diseases are increasing, and are debilitating and occasionally life-threatening conditions. Good allergy practice depends on correct diagnosis, appropriate treatment, patient education and regular follow-up. The role of the GP or practice nurse in implementing guidelines for the management of allergic diseases has great scope for development but relies on allergy training and support by individual GP practices for the development of allergy services in primary care. Greater attention needs to be given to diagnosing and managing allergic diseases appropriately.

References

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  3. Strannegard O, Strannegard I-L. The causes of the increasing ­prevalence of allergy: is atopy a ­microbial deprivation disorder? Allergy 2001;56:91-102.
  4. Von Mutius E, Weiland SK, Fritzsch C, et al. Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany. Lancet 1998;351(9106):862-6.
  5. Nicolai T, von Mutius E. Pollution and the development of allergy: the East and West Germany story. Arch Toxicol 1997;19:201-6.
  6. Oddy WH, Holt PG, Sly PD, et al. Association between breast feeding and asthma in six-year-old children: findings of a prospective birth cohort study. BMJ 1999; 319: 815-19.
  7. Riedler J, Eder W, Oberfeld G, Schreuer M. Austrian children living on a farm have less hay fever, asthma and allergic sensitisation. Clin Exp Allergy 2000;30:194-200.
  8. Shaheen SO, Aaby P, Hall AJ. Measles and atopy in Guinea-Bissau. Lancet 1996;347:1792-6.
  9. Shirakawa T, Enomoto T, Shimazu S. The inverse association between tuberculin responses and atopic ­disorder. Science 1997;275:77-9.
  10. Tariq SM, Stevens M, Matthews S, et al. Cohort study of peanut and tree nut sensitisation by age of four years. Br J Hosp Med 1996;313:514-17.
  11. Sheikh A, Alves B. Hospital ­admissions for acute anaphylaxis: time-trend study. BMJ 2000;320:1441.
  12. Burrows B, Martinez FD, Halonen M, et al. Association of asthma with serum IgE levels and skin-test ­reactivity to allergens. N Engl J Med 1989;320:271-7.
  13. Young E, Patel S, Stoneham MD, et al. A population study of food ­intolerance. Lancet 1987;343:1127-30.
  14. Kelly KJ, Kurup VP, Reijula KE. The diagnosis of natural rubber latex allergy. J Allergy Clin Immunol 1994;93:813-16.
  15. Vuurman EPF, van Veggel LMA, Uiterwijk MMC, et al. Seasonal ­allergic rhinitis and anti-histamine effects on children's learning. Ann Allergy 1993;71:121-6.
  16. Stewart AG, Ewan PW. The ­incidence, aetiology and management of anaphylaxis presenting to an ­accident and emergency department. QJM 1996;89:859-64.
  17. Reid MJ, Lockey RF, Turkeltaub PC, et al. Fatalities from ­immunotherapy and skin testing. J Allergy Clin Immunol 1990;85:180.
  18. Pastorello EA, Incorvaia C, Ortolani C, et al. Studies on the ­relationship between the level of specific IgE antibodies and the clinical expression of allergy. I. Definition of levels distinguishing patients with symptomatic from patients with asymptomatic allergy to common aeroallergens. J Allergy Clin Immunol 1995;96:580-7.
  19. Rance F, Juchet A, Bremont F, et al. Correlations between skin prick tests using commercial extracts and fresh foods, specific IgE, and food challenges. Allergy 1997;52:1031-5.

Resources
National Asthma and Respiratory Training Centre
The Athenaeum
10 Church Street
Warwick
CV34 4AB
T:01926 493313
F:01926 493224
W:www.nartc.org.uk

The British Allergy Foundation
Deepdene House
30 Bellgrove Road
Welling
Kent
T:020 8303 8583
W:www.allergyfoundation.com

British Society of Allergy and Clinical Immunology
66 Weston Park
Thames Ditton
Surrey
KT7 0HL
T:020 8398 9240
F:020 8398 2766

National Asthma Campaign
Providence House
Providence Place
London N1 0NT
T:0845 701 0203
W:www.asthma.org.uk

GPIAG (General Practice Airways Group)
2nd Floor
9 Windsor Court
Clarence Drive
Harrogate
West Yorkshire
HG1 2PE
T:01461 600 639
W:www.gpiag-asthma.org