Skin Prick Testing And SIT: Allergen Selection; Methods

Skin prick testing and SIT: allergen selection; methods, monitoring
response, success rates
Graham O Solley MBBS FACP FAAAAI
Consultant physician in clinical immunology and allergy, Royal Brisbane Hospital and in private practice, Watkins
Medical Centre, Qld
Respiratory allergic diseases, (allergic rhinitis and asthma) cause severe debility in large numbers in Australia. Most have to
take medication every day that is expensive. SIT gives the patient a chance of reducing the dependence on medication. In a
significant number it can even cure the sufferer.
The major allergens are house dust mites, pollens from grasses, trees and weeds, animal emanations and mould spores.
a. House dust mites
The major species is Dermataphagoides pterronyssinus with D. farinae to a lesser degree. In tropical and subtropical areas,
Blomia sp. may be a significant allergen as well.
b. Pollens
Grasses are the most important of these. Because Australia is a vast country with varying climate zones, there are regional
differences in the major players. Most grasses cross-react allergenically, but in the northern areas, couch grass, Paspalum
and Johnson grass are major allergens while in southern regions ryegrass allergy is particularly severe. Very few trees,
especially those native to Australia including wattle, cause significant allergic disease. Callitris sp, known in various parts
of the country as ‘Bribie Island Pine’, ‘Cypress pine’ etc are a major exception. Imported varieties, e.g. olive and Birch trees
are causing disease in certain areas. The pollen types which need more research here are the weeds. Plantago (English
plantain) and Echium (‘Patterson’s Curse’ or ‘Salvation Jane’) are well documented as important allergens, but many people
in rural areas suspect other weeds responsible for their hay fever. Parthenium, not a native weed, is spreading like wildfire
through central Queensland and probably into New South Wales. It has already responsible for severe allergic contact
dermatitis and is likely to cause allergic respiratory disease. Ragweed [Ambrosia sp] is a major allergen in the USA and has
invaded Australia but is mainly restricted to the Northern Rivers district of NSW.
c. Animals
People are more allergic to cats than to any other animal. Horse allergy would rank second with dog allergy relatively
uncommon. Increasingly guinea pig allergy is being recorded, while a number of laboratory workers react to rats, mice and
rabbits. A few in the dairy industry develop allergy to their cattle. Bird allergy is very rare. A common misconception in the
community is that the major allergic component of cats and dogs is hair and as a consequence, many claim that some breeds
which don’t shed hair are well tolerated, e.g. Devon Rex cats and poodles. Significant respiratory allergens are microscopic
and readily airborne. Thus salivary proteins are considered to be the primary allergens.
d. Moulds
There remains a large gap in our knowledge of mould allergy. Some are well documented, e.g. Alternaria, Aspergillus
(various species), Cladosporium and Penicillium. Many other species are probably important but have not been adequately
investigated. The other difficulty is that mould spores are ubiquitous. Most houses carry numerous mould species even
though there are no obvious sources of mould evident. Definite exposures include grain dust, horse feed, mulch and
compost.
Clinical features
a. House dust mites
Dust mites are microscopic. They populate houses in their millions. They are present because their major food source is
human skin cells which accumulate especially in beds, soft furnishings, carpets, woollen fabrics and stored clothing.
Allergic symptoms are thus present most days but are especially prominent first thing in the morning often with a relapse at
night. House dust exposure will induce typical hay fever. Dust mites flourish in warm, humid climates and thus are in very
high concentrations in coastal areas of Australia especially in northern regions. Measures to reduce indoor levels are
extremely limited.
b. Pollens

Airborne concentrations vary widely. Plants pollinate at different times of year. Trees generally pollinate in early spring,
grasses throughout spring and summer and weeds in the hotter months as well as in autumn. Ragweed pollinates only in
autumn. Symptoms occur outdoors but because many houses are built in hot/warm climates with open windows and doors
symptoms can occur indoors as well, but often improve in an air-conditioned environment. They tend to improve also on
wet days, during drought and at the coast [the prevailing winds across water carry very low pollen levels]. They increase on
windy days and after periods of rain. Lawn mowing can, but not always cause significant symptoms.
c. Animals
Because salivary proteins are the major source of cat allergy for example, symptoms mainly occur indoors. Getting rid of
the cat will not result in allaying the allergy problem because these particles will remain in carpets, soft furnishings, etc, for
months and perhaps years. Furthermore many cat-allergic people have only to enter a house with an indoor cat and
experience hay fever immediately on entry as the allergens are in the air.
d. Moulds
As indicated above, significant exposure to mould spores may be unknown. People involved in agricultural activities are
those most prone to develop mould allergy.
Medications such as antihistamines, nasal decongestants, bronchial dilators, and topical nasal or bronchial steroids provide
adequate relief for the majority of people suffering from respiratory allergic disease. Many however have debilitating
symptoms. For these SIT offers a chance to control and for some to eliminate the problem.
Specific immunotherapy
SIT is one of the longest standing medical therapies still in use, having been first employed in 1911. It of course has been
modified, especially in the past two decades, to improve its efficacy and safety.
a. Principles of treatment
The specific allergens are administered to the patient, most commonly by subcutaneous injection and occasionally
sublingually. Because the patient is challenged with a reagent he/she is allergic to, the treatment must be done in a very
carefully controlled manner. The initial dose is so low that an allergic response is unlikely to develop. With tolerance of this
challenge, subsequent doses rise gradually in a systematic manner. The aim of the exercise is to achieve tolerance of a dose
higher than the level of allergen to which the person is naturally exposed. Suppression however following this induction
series will only give brief relief. To gain long term control a maintenance regimen must follow. The patient then receives
the top dose reached in the induction course for an indefinite period; e.g. 3 to 5 years.
b. Reagents
The most common include the house dust mite, D pterronyssinus, and grass pollens. In regard to the latter, the specific
allergens vary in accordance with the region. Plantago SIT often is used. SIT is particularly effective in suppressing animal
allergies, cat especially. [Indeed many veterinary science students have successfully had their cat, horse and dog allergies
eliminated!]. Mould allergy remains the difficult one, but some patients do respond very well.
c. Response to treatment
Numerous studies, including double-blind, placebo-controlled, randomised, clinical trials demonstrate beneficial effect of
SIT in allergic rhinitis, asthma and conjunctivitis, both in adults and children. My own review of 1210 patients with the
above conditions in 2002 indicated that 21% achieved complete resolution of their illness, 54% were much better with only
the occasional need for additional medication, 19% improved but required frequent medication. In only 6% SIT was
ineffective.
d. Immunologic observations
Immunological changes during SIT are complex. [1] Successful SIT is associated with a change towards a Th1 CD4+
cytokine profile. [2] SIT is associated with immunological tolerance defined as a relative decrease in allergenic-specific
responsiveness and by the generation of CD4+CD25+ regulatory T lymphocytes. [3] Efficacy of SIT is not dependent on
reduction of specific IgE antibody levels. In most patients with successful outcomes there is an initial rise in specific IgE
levels which then decline as the treatment progresses. [4] Allergen-specific IgG antibodies generally increase but are not
predictive of the duration and degree of efficacy of SIT.

e. Safety
Large local swellings at injection sites are very common, ranging from 25 to 80% in patients in various studies. In most
cases, these are of little consequence. Although there is a low risk of severe systemic reactions with appropriately
administered SIT, life-threatening and fatal reactions have occurred. The most common reactions are urticaria with/without
asthma. Systemic reactions develop in about 5% of recipients of SIT. In a retrospective analysis of the incidence and
features of non-fatal systemic reactions in Italy during 1981 to 2000, there were 115 systemic reactions [5.2%] in 4000]
patients in the first decade and 1.1% in the second. Systemic reactions may result from [1] incorrect dosage, [2] long
intervals between injections, [3] the presence of respiratory infections or of asthma, [4] exercise soon after and occasionally
before SIT, and [5] possible concomitant treatment with ß-adrenergic drugs. Typically if a systemic event occurs, the patient
can continue the course usually free of further adverse systemic responses. Modification of the schedule is essential, e.g.
reduction in dosage.
Summary
SIT gives the sufferer of significant allergic respiratory disease a real chance of a cure. It almost invariably provides
adequate relief, it reduces dependence on medication and is usually well tolerated.
Reference
Cox L, Li JT, Nelson H, Lockey R Eds, Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol.2007;120: S25-85.