Figure 1.
Histamine data and severity scale.
Time profile of histamine release (A) for healthy controls and CUrt patients. Panel B shows the comparison of controls and CUrt patients at baseline and 10 minutes post-CHI for histamine. Panel C shows a comparison of normal control subjects and patients for histamine levels stratified by severity scale at 10 minutes post-CHI. Significance level, **p<0.01. No elevation in tryptase was detected in patients (D, p = 0.42, RM ANOVA) or controls (p = 0.48). In data not shown, no elevation in tryptase was detected through 120 minutes following CHI. Data shown as mean ± SEM. CHI challenge period is indicated with a horizontal bar in Panels A and D.
Figure 2.
Skin biopsy in CUrt patient stained for tryptase (red) at baseline at low (10×, upper panels) and high (60×, lower panels) magnification and at 15 minutes following cold stimulation time test (CSTT-see methods).
Figure 3.
Blood flow, temperature, and skin color images of a representative CUrt subject.
Images at baseline (A, C, E, and G) and at 10 minutes post-CHI (B, D, F, and H) for a CUrt subject (Table S1, Subject 6). Panel A and B, show blood flow images by LSCI; C and D, the temperature images by infrared (IR); E and F, the skin color images by polarized light colorimetry (PLC); and G and H, visible light photography. The blood flow image in A has been scaled up by a factor of 4 for visibility.
Figure 4.
Imaging time profiles for healthy controls and CUrt subjects.
Mean blow flow (A), temperature (B), and color index (C) are shown for healthy controls (gray) and patient with Curt (black). For summary data, mean baseline was subtracted from each individual time profile, and then the profiles were smoothed, down-sampled, and averaged based on subject groups. Significant differences between CUrt and control groups are seen for LSCI (A) and IR (B) imagers, but not PLC (C) as calculated by 2-way ANOVA. The dotted horizontal line in panel B represents baseline temperature.
Figure 5.
Maximum response marker: differences between healthy control and CUrt groups for blood flow, temperature, and skin color.
Maximum value above baseline (A, D, and G) and the time it was reached (B, E, and H) were calculated for LSCI (A, B, C), IR (D, E, F), and PLC (G, H, I). Recovery time marker: differences between control and CUrt groups for blood flow, temperature, and skin color. Time of recovery to reach half of maximum for LSCI (G), IR (H), and PLC (I).
Figure 6.
Comparison of the temperature recovery of a healthy control and CUrt subject.
Region of interest (ROI) of the fingers and hand of a healthy control (A) and a CUrt subject (B), and corresponding time profiles (C and D).
Figure 7.
Association of histamine and imaging derivatives.
Analysis of mean serum histamine levels for patients (A–C) and controls (D–F) plotted against the composite derivative (i.e. rate of change) of imaging time profiles for all subjects (see methods) for blood flow (A, D), temperature (B, E) and color index (C, F). For example, AU/min is a rate of change of AU with respect to time (dAU/dt). The data supports the association between histamine release as a surrogate marker for mast cell degranulation and vascular changes in those with CUrt, but not healthy subjects.
Figure 8.
Blood flow profile for CUrt subjects treated with antihistamine.
Three CUrt patients were re-imaged using LSCI during CHI while taking antihistamines (10 mg cetirizine). Blood flow time profiles for three patients (A, subject 1; B, subject 2; C, subject 4) before (black line) and after (gray line) treatment. The region of interest used for this plot included only the area between the base of the wrist and the knuckles.