Effects of pharmacotherapy on allergy testing

Test related documents

Lars Yman, Pharmacia Diagnostics AB, Uppsala, Sweden

Effects on tissues and cells
It is obvious that drugs given to relieve allergic symptoms should be expected to influence in vivo testing, i.e. change the result of allergen challenge of skin, nose, bronchi, etc. Depending on the drug, discontinuation of treatment is recommended for 48 hours up to several weeks prior to in vivo testing (1-4).
Also release of mediators in vitro from mast cells and basophils have been shown to be supressed by modern antiallergic drugs. For example, the antihistamine azatadine inhibited histamine and leucotriene release from human mastcells in vitro and in vivo (5). Cetirizine treatment reduced the sulfidoleucotriene release from blood leucocytes by mite allergen as measured by CAST (6).  Both mediator release and secretion of cytokines from basophils were inhibited by corticosteroids (7,8).
 
Effects on serum IgE and IgE antibodies
IgE antibody production is dependent on the degree and frequency of exposure, i.e. the allergen dose. The link between allergen exposure, IgE antibody concentration and severity of disease is an obvious result.  Pollen-allergic patients show lower sensitivity prior  to the season than by  the end of  it and lower average concentration of IgE antibodies before season than after. However, the magnitude of the change is often moderate and varies considerably between individuals, between allergens, and between years. The most important cause of  the variability is likely  to be variation in allergen dose. A study on the IgE antibody response to ragweed pollen season showed an average increase of 18%. A considerably greater and longlasting increase was observed as a result of allergen challenge (9).
 

Drugs are known to influence these fluctuations to various degrees.

Antihistamines have no effect on baseline specific IgE antibody levels of allergic patients and do not supress the rise caused by allergen exposure (10).

Corticosteroids influence the immune system. However, even large doses of steroid have little or no effect on serum IgE (11-12).

Also allergen-specific IgE antibody shows little or no change as a result of corticosteroid therapy. Available data (examples reviewed below) on the effects of some commonly used drugs suggest an unaffected IgE antibody 'baseline' but under some conditions a reduction of the seasonal rise discussed above.

-Beclomethasone (or in one case methylprednisolon) for 21 days to control symptoms during birch pollen season did not significantly change IgE antibody. The seasonal increase may be blunted (13).

-Beclomethasone 336 mg daily or triamcinolone acetonide 220 mg daily reduced the expected seasonal rise in ragweed-specific IgE (14).

-Beclomethasone 336 mg daily did not significantly change the secondary IgE antibody response to nasal ragweed challenge (9).

-Beclomethasone 200 mg daily for five weeks influenced the seasonal rise in birch specific IgE antibody (15).

-Fluticasone 200 mg daily for one week did not change ragweed specific IgE antibody level (16).

-Treatment of patients with perennial allergic rhinitis for 5 years with antihistamine and topical steroid had no effect on house dust mite specific IgE antibody (17).

References:

    1. Pipkorn U. Pharmacological influence of antiallergic medication on in vivo allergen testing. Allergy 1988; 43: 81-86
    2. Niemeijer NR, et al. Optimization of skin testing. I. Choosing allergen concentrations and cutoff values by factorial design. Allergy 1993; 48: 491-497
    3. Pipkorn U, et al. Prolonged treatment with topical corticosteroids results in an inhibition of the allergen-induced wheal and flare response and a reduction in skin mast cell numbers and histamine content. Clin Exp Allergy 1989; 19: 19-25
    4. Grant JA, et al. A double blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: supression of histamine-induced wheal and flare response for 24 h in healthy male subjects. Allergy 1999; 54: 700-707
    5. Togias AG, et al. Demonstration of inhibition of mediator release from human mast cells by azatadine base. In vivo and in vitro evaluation. JAMA 1986; 255: 225-229
    6. Kalayci Ö. et al. The effect of cetirizine on sulfidoleukotriene production by blood leukocytes in children with allergic rhinitis. Allergy 1995; 50: 964-969
    7. Schroeder JT, et al. Regulation of Ige-dependent IL-4 generation by human basophils treated with glucocorticoids. J Immunology 1997; 158: 5448-5454
    8. Crocker IC, et al. Glucocorticosteroids inhibit leukotriene production. Ann Allergy Asthma Immunol 1997; 78: 497-505
    9. Naclerio RM, et al. Nasal provocation with allergen induces a secondary serum IgE antibody response. J Allergy Clin Immunol 1997; 100: 505-510
    10. Masamoto T, et al. Specific immunoglobulin E, interleukin-4, and soluble vascular cell adhesion molecule-1 in sera in patients with seasonal allergic rhinitis. Ann Otol Rhinol Laryngol 1999; 108: 169-176
    11. Schleimer RP. Glucocorticosteroids. Their mechanisms of action and use in allergic diseases. In: Allergy. Principles and Practice. Fourth Edition (Ed: Middleton E, et al) Mosby - Year Book, Inc, St Louis Mi, 1999
    12. Klebl FH, et al. In vitro and in vivo effect of glucocorticosteroids on IgE and IgG subclass secretion. Clin Exp Allergy 1994; 24: 1022-1029
    13. Crimi E, et al. Effect of seasonal exposure to pollen on specific bronchial sensitivity in allergic patients. J Allergy Clin Immunol 1990, 85: 1014-1019
    14. Naclerio RM, et al. Intranasal steroids inhibit seasonal increases in ragweed-specific immunoglobulin E antibodies. J Allergy Clin Immunol 1993; 92: 717-721
    15. Pullerits T, et al. An intranasal glucocorticoid inhibits the increase of specific IgE initiated during birch pollen season. J Allergy Clin Immunol 1997; 100: 601-605
    16. Diaz-Sanchez D, et al. Effect of topical fluticasone propionate on the mucosal allergic response induced by ragweed allergen and diesel exhaust particle challenge. Clin Immunol 1999; 90: 313-322
    17. Ohashi Y, et al. A comparative study of the clinical efficacy of immunotherapy and conventional pharmacological treatment for patients with perennial allergic rhinitis. Acta Otolaryngol 1998; Suppl 538: 102-112