Q:

2/19/2013
1) What is the rationale for skin testing to allergens after stopping antihistamines such as Zyrtec, Allegra for 5-7 days? Why not 3 days?
2) A colleague mentioned that if skin test is performed while the person is on antihistamine we will be better able to determine the allergens responsible for the persons current symptoms being, is there any truth in this?
3) Amongst grass allergens, there is cross reactivity amongst Kentucky Blue, Orchard, Timothy and we can use one of them in immunotherapy because of cross reactivity. Why then do we test for all? Why not test for just one? Thanks for your help.

A:

Thank you for your inquiry.

I will try and answer each question as they were posed:
1. What is the rationale for skin testing to allergens after stopping antihistamines such as Zyrtec, Allegra for 5-7 days? Why not 3 days?

As you can see from the abstracts copied below, it is unwise to be dogmatic about the duration of time an antihistamine must be discontinued prior to skin testing. The suppressive effect varies depending on the antihistamine being utilized. For example, with astemizole, which is no longer available, the suppression can extend beyond 7 days, whereas with other drugs, significant suppression only lasts 3 days. Not all allergists use a specific number of days, and in our practice, we oftentimes will test while the patient is taking an antihistamine if there is no suppression of the histamine positive control test. Nonetheless, I suppose that 7 days is a conservative number of days in that in most instances, the suppressive effect will be negligible after that amount of time.

2. A colleague mentioned that if skin test is performed while the person is on antihistamine we will be better able to determine the allergens responsible for the persons current symptoms being, is there any truth in this?

What I suppose your colleague is referring to is that if the patient reacts while on antihistamine, it can be assumed that their reactivity is “stronger” because it overcomes the suppressive effect of the antihistamine. I am unaware of any studies which have validated this theory, and could find none with a literature search.

3. Amongst grass allergens, there is cross reactivity amongst kentucky Blue, Orchard, Timothy and we can use one of them in immunotherapy because of cross reactivity. Why then do we test for all? why not test for just one?

There is no rule stating that you have to test to all three allergens mentioned. However, simply because there is strong cross-reactivity, it does not mean that every patient will react to each allergen. Even in view of the cross-reactivity, there may be epitopes which are clinically significant and which are not shared by all three allergens. There are still some opinions that it is more appropriate to treat with all three rather than one because of this theoretic possibility. Therefore, in the final analysis, it is left to the clinical judgment of the physician instituting testing and immunotherapy as to whether or not they choose to test to one or more of these allergens, and treat to one or more of these allergens. To my knowledge, there is no definitive evidence in the literature that would completely rule out either choice.

Thank you again for your inquiry and we hope this response is helpful to you.

Duration of effect of loratadine and terfenadine administered once a day for one week on cutaneous and inhaled reactivity to histamine
CHEST March 1993, Vol 103, No. 3
Abstract
Study Objective: The duration of action of several new non-sedative antihistamine preparations as assessed by skin and bronchial reactivity to histamine has still not been well established. The aim of the study was to evaluate the duration of effect of loratadine (10 mg) and terfenadine (120 mg) administered once a day for one week on cutaneous and inhaled reactivity to histamine by comparison with a placebo.
Subjects: Twenty-four adult asthmatic subjects were included in a parallel group study that compared the duration of effect of two antihistamines and a placebo on cutaneous and inhaled reactivity to histamine.
Study Design: Baseline cutaneous and inhaled reactivity (concentration causing a fall of 20 percent in FEV1 [PC20]) to histamine was obtained on three consecutive days. Loratadine (10 mg), terfenadine (120 mg) and a placebo loratadine were administered daily for 1 week to 3 groups of subjects. The PC20 was measured at the end of the medication period, 3 days later, and weekly until PC20 returned to baseline value (upper limit of 2 SD from the mean baseline value).
Results: The mean blocking duration on cutaneous reactivity for loratadine was 6.9 days and for terfenadine, 7.2 days. The mean duration of the blocking effect on PC20 histamine was 8.5 days for loratadine and 7.2 days for terfenadine. These figures were significantly longer than for the placebo.
Conclusion: These data suggest that terfenadine and loratadine have a comparable blocking effect on reactivity to cutaneous and inhaled histamine. A daily dose taken for one week will result in a mean blocking effect of one week

Journal of Allergy and Clinical Immunology
Volume 82, Issue 5, Part 1, November 1988, Pages 752–757
Abstract
The antihistaminic properties of the tricyclic antidepressants have been recognized since these compounds were first developed. Antidepressants, which are equally effective for treating depression or used in the treatment of chronic urticaria, have varying in vitro antihistaminic properties. We compared the duration of H1-receptor blockade by two tricyclic antidepressants, doxepin (the most potent antihistamine) and desipramine (the least potent antihistamine), in a single dose, double-blind, noncrossover study. After baseline prick test with histamine phosphate 1:1000 by Multitest (Lincoln Diagnostics, Decatur, Ill.), the suppression of cutaneous histamine-induced wheal-and-flare responses were measured daily for 7 days in 33 healthy volunteers who were randomly administered a single 25 mg dose of oral desipramine or doxepin. Significant differences in the suppression of the wheal-and-flare responses to histamine between the two drugs were noted (p < 0.05) during the first 3 days. Desipramine suppressed the wheal for 2 days and flare for 1 day. Doxepin suppressed the wheal for 4 days and flare for 6 days. Our results suggest doxepin should be withheld for at least 7 days before allergy skin testing.

Journal of Allergy and Clinical Immunology
Volume 51, Issue 2, February 1973, Pages 71–77
Abstract
The ability of antihistamines to suppress the wheal response of an intradermal skin test is well recognized, but the degree and duration of this suppression have not previously been adequately studied. This double blind study employed five commonly used antihistamines in recommended therapeutic doses. Wheal suppression was recorded immediately after completing a 3 day course of the respective drug and was followed for up to 7 days or until the wheal regained control levels. Mean suppression ranged from 30.7 per cent to 62.7 per cent and required from 1.89 to 4.31 days to re-establish control levels. Incidence and degree of side effects from each antihistamine are also discussed.

Rev Alerg Mex. 1999 Mar-Apr;46(2):58-60.
[Inhibitory effect of astemizol in skin tests with histamine].
[Article in Spanish]
Rodríguez Medina R, Lozada Andrade S, Gasca Bauza MR.
Source
Clínica de Asma y Alergia, Hospital General de Zona 30, Iztacalco, México, DF.
Abstract
Objective: To determine the effect of the astemizol to inhibit the cutaneous response to the histamine.
Material and Methods: We made a clinical assay in healthy adult subjects realizing skin tests with histamine for prick (1 mg/ml) and intradermal (0.01 mg/ml) daily during the taking of astemizol 10 mg during 7 days and during 7 days after suspending it, as well as the day 14, 21 and 28. It was determined the inhibition and the reappearance of the cutaneous response.
Results: They were 12 subjects with mean age of 36 years old +/- 11.2 SD. The complete inhibition was presented starting from the fourth day and most (79%) until the seventh day. The normal reaction, recovered in more than seven days but less than fourteen in 100%.
Conclusions: According to these results, the astemizol inhibits the skin reaction to the histamine from the first day in 50% of the subjects and its principal action is to the seventh day, while when suspend it the normal response it recovers in more than seven days.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology