A further evaluation of the clinical use of specific IgE antibody testing in allergic diseases.

BACKGROUND: The evaluation and interpretation of the results from blood tests measuring specific immunoglobulin E (IgE) antibody concentration is currently made using the dichotomized result from the test despite a quantitative result is obtained. It has been shown that different levels of IgE antibodies, assessed by blood test and skin prick test, may have a relation to presence of symptoms, implying that there is more information in a quantitative result than in the dichotomous--positive or negative. OBJECTIVE: To investigate the clinical utility of quantification of IgE antibodies in the diagnosis of allergic patients and whether such procedure has any advantage to the presently dichotomously used sensitivity and specificity at a fixed cut-off. METHODS: Data from a previously published study (R. Paganelli, I.J. Ansoteugi, J. Sastre, C.-E. Lange, M.H.W.M. Roovers, H. de Groot, N.B. Lindholm, P.W. Ewan, Allergy, 1998; 53) analysing diagnosis of allergic patients in four different clinics were re-evaluated. In the original study consecutive patients with suspected IgE-mediated allergy had been examined and evaluated according to the clinical routine at each clinic, using case history, physical examination, skin tests and laboratory tests, except the test to be evaluated, and given a "doctors' allergen-specific diagnosis" as positive or negative. In the present study the relation between "doctors' allergen-specific diagnosis", expressed as pos/neg, and the quantitative levels of specific IgE antibody concentration was analysed using a logistic regression model. This presentation of results was also compared with the more common characteristics of sensitivity and specificity, and also with Receiver-operator characteristics (ROC) curves. RESULTS: The used logistic model described the relationship between allergen-specific diagnosis in each study and the levels of IgE antibodies. The shape of the curve illustrated the physicians' disposition for a positive diagnose in the study, in relation to the specific IgE antibody level. Differences in the shape of the curve was found both between allergens within clinics and between clinics for the same allergen. No association could be demonstrated between prevalence and shape of the curve. CONCLUSIONS: Conventional sensitivity/specificity figures or ROC concepts only use the qualitative statement of whether IgE is present or not. A risk assessment using the quantitative level of IgE antibody to an allergen increases the utility of the information in clinical context compared with a qualitative statement of whether IgE is present or not. The quantification demonstrated the link between specific IgE antibodies and allergic reactions. The use of objective, well performing quantitative tests should help improve diagnostic accuracy and might provide a way for the patient to understand and manage his or her daily situation and risk for reactions.

Specific IgE antibodies in the diagnosis of atopic disease. Clinical evaluation of a new in vitro test system, UniCAP, in six European allergy clinics.

A new immunoassay system utilizing new automatic instrumentation, new software for evaluation of data, and reagents updated for increased speed and accuracy was evaluated. Six clinical studies included 894 consecutive patients. Major symptoms were rhinoconjunctivitis, asthma, atopic dermatitis, and urticaria. The prevalence of inhalant allergy was 54-69%. Phadiatop, detecting atopic sensitization to common inhalant allergens, agreed with clinical diagnosis in 764/836 cases (91.4%). The clinical sensitivity and specificity were 93% and 89%, respectively. The clinical sensitivity and specificity of UniCAP specific IgE derived from 5170 comparisons with clinical diagnosis were 89% and 91%, respectively. Specific IgE measurements in UniCAP and in the Pharmacia CAP System agreed in 266/274 cases (97%). A comparison of the sensitivity and specificity of Pharmacia CAP System RAST in 1987 and with UniCAP specific IgE in 1995 showed equivalent performance without change of efficacy or degradation of IgE antibodies after 8 years. The systems were equivalent also in terms of measured values (r=0.96, slope=1.12), confirming the standardization of allergens and of assay calibration. UniCAP is an efficient laboratory system for routine diagnostic testing of allergy and a valuable tool for basic studies on allergens and antibodies.

Dose-ranging, placebo-controlled study of cetirizine nasal spray in adults with perennial allergic rhinitis.

A total of 360 patients with perennial allergic rhinitis were randomized in a placebo-controlled, dose-finding study comparing three concentrations (0.06%, 0.125%, and 0.25%) of a cetirizine nasal spray, administered three times a day for 2 weeks. The primary criterion of efficacy was the percentage of days with no or only mild symptoms of rhinitis (PDMax1), as evaluated by the patients. The median PDMax1 were 16.7%, 30.8%, 42.9%, and 26.7% for the placebo, 0.06%, 0.125%, and 0.25% groups, respectively. Although the global comparison among the four groups only approached statistical significance (P = 0.076), the difference (26.2%) between the placebo and 0.125% groups was clinically and statistically significant (P = 0.011). For the global evaluation by the investigator, the best results were seen in the 0.125% group (P = 0.03). The occurrence of adverse events did not differ among the four treatment groups and consisted mainly of nasal events, occurring in 22.5%, 17.1%, 12.9%, and 24.4% of the patients for the placebo, 0.06%, 0.125%, and 0.25% groups, respectively (P = 0.184). These results indicate that the 0.125% concentration is significantly better than placebo and offers the best therapeutic ratio.

[Anaphylaxis caused by chlorhexidine following cystoscopy or urethral catheterization]. / Anafylaxie door chloorhexidine na cystoscopie of urethrale catheterisatie.

Since 1983 the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 6 reports of anaphylaxis due to a chlorhexidine-containing lubricant used during cystoscopy or urinary catheterization. One case was described earlier. An accidental rechallenge in two patients was positive. In 5 cases, the causal relationship with chlorhexidine was confirmed by a positive reaction to intracutaneous testing. Although this adverse reaction is probably rare, medical practitioners should be aware of the possibility that a severe anaphylactic reaction may occur during use of these products.

[Exercise-dependent anaphylaxis]. / Inspanningsafhankelijke anafylaxie.

The clinical features of exercise-induced anaphylaxis in 5 patients are described, with an accurate history, skin tests, IgE determinations and exercise tests. In these 5 patients we were able to distinguish three different forms of exercise-induced disease: exercise-induced anaphylaxis based upon an IgE-mediated allergy to foods, exercise-induced anaphylaxis without food allergy and cholinergic urticaria.

Phazet skin prick tests versus conventional prick tests with allergens and histamine in children.

Forty children underwent two different skin prick tests with allergen-coated Phazet needles and conventional skin prick tests using Pharmalgen extracts (100,000 BU/mL). Good correlation between both skin test methods was found with house dust mites (Rs = 0.61; P less than .001), timothy pollen (Rs = 0.77; P less than .001), and cat epithelium (Rs = 0.74, P less than .001). The correlation coefficient in the case of histamine was lower (Rs = 0.50; P less than .01) than that obtained from the allergens. Larger wheals were generated with Phazet than with conventional prick tests (median: 54.5 mm2 and 24.5 mm2, respectively; Wilcoxon signed rank test, P less than .0001). Comparison of wheal areas and specific IgE did not reveal large differences between the two skin test methods. In conclusion, Phazet, a recently introduced simple, standardized, skin prick test method can replace the conventional skin prick test for the most important allergens such as house dust mites, timothy pollen, and cat epithelium.