How stress and anxiety can alter immediate and late phase skin test responses in allergic rhinitis

Abstract

Allergic rhinitis (AR) is the fifth most common chronic disease, and the association between allergic disorders and anxiety is well-documented. To investigate how anxiety and stressors modulate skin prick test (SPT) responses and associated inflammatory responses, 28 men and women with AR were selected by clinical history and skin test responses. The participants were admitted twice to a hospital research unit for 4h in a crossover trial. Changes in SPT wheals were assessed before and after a standardized laboratory speech stressor, as well as again the following morning; skin responses assessed twice during a lab session without a stressor and again the following morning served as the contrast condition. Anxiety heightened the magnitude of allergen-induced wheals following the stressor. As anxiety increased, SPT wheal diameters increased after the stressor, compared to a slight decrease following the control task. Anxiety also substantially enhanced the effects of stress on late phase responses: even skin tests performed the day after the stressor reflected the continuing impact of the speech stressor among the more anxious participants. Greater anxiety was associated with more IL-6 production by Con A-stimulated leukocytes following the stressor compared to the control visit. The data suggest that stress and anxiety can enhance and prolong AR symptoms.

Figures 1a,b,c

Unadjusted mean (± SEM) cortisol (1a), epinephrine (1b), and norepinephrine (1c) levels through the admission as a function of stressor (TSST) or control condition assignment for the day. Data are log₁₀-transformed. The shaded portion indicates the interval for the stressor or control tasks. The TSST significantly stimulated cortisol and epinephrine production, as seen in the significant visit by time interactions for both, while the interaction was not significant for norepinephrine.

Figures 2a-d

Mean wheal diameter for all positive allergens as a function of anxiety, plotted separately by stress and control condition for skin tests immediately after (2a,b) and the morning following (2c,d) the GCRC session; all SPT data are expressed as the difference between the allergen response and the concurrent saline control. Plotted points are unadjusted wheal diameter observations and lines are baseline-adjusted regressions of mean wheal on anxiety. Anxiety heightened the magnitude of SPT wheals following the stressor, and higher anxiety was associated with larger wheals on the day after both the stressor and control tasks.

Figures 2a-d

Mean wheal diameter for all positive allergens as a function of anxiety, plotted separately by stress and control condition for skin tests immediately after (2a,b) and the morning following (2c,d) the GCRC session; all SPT data are expressed as the difference between the allergen response and the concurrent saline control. Plotted points are unadjusted wheal diameter observations and lines are baseline-adjusted regressions of mean wheal on anxiety. Anxiety heightened the magnitude of SPT wheals following the stressor, and higher anxiety was associated with larger wheals on the day after both the stressor and control tasks.

Figures 3a-c

The probability of late phase responses following allergen skin tests as a function of anxiety and stress or control condition. Skin tests were performed (3a) before the stressor or control tasks, (3b) immediately after the stressor or control tasks, and (3c) the morning following the GCRC stressor or control session as a function of stress or control condition and anxiety. These responses develop 6-8 hours following challenge, and thus skin tests performed before the stressor could still be influenced by it. Anxiety enhanced the effects of stress on late phase responses at each of the three time points.

Figure 4a-d

Con A stimulated IL-6 production as a function of baseline anxiety, plotted separately by stress or control condition immediately following (4a,b) and 45 minutes after (4c,d) the stressor or control task. Plotted points are unadjusted IL-6 observations and lines are baseline-adjusted regressions of IL-6 on anxiety. Higher anxiety was associated with lower IL-6 production at the control visit compared to the stress visit after controlling for baseline.

Figure 4a-d

Con A stimulated IL-6 production as a function of baseline anxiety, plotted separately by stress or control condition immediately following (4a,b) and 45 minutes after (4c,d) the stressor or control task. Plotted points are unadjusted IL-6 observations and lines are baseline-adjusted regressions of IL-6 on anxiety. Higher anxiety was associated with lower IL-6 production at the control visit compared to the stress visit after controlling for baseline.