Abstract:
Dear Editor,
Cold urticaria manifests with a wide range of reaction severity, from localized wheals and cutaneous angioedema to cardiovascular, respiratory and gastrointestinal symptoms.1,2
Interestingly, not all individuals react to the ingestion of cold
food or drinks.3,4 This clinical variability remains poorly
understood, highlighting the need for better phenotyping in
ColdU.
Typical ColdU (ColdUT
) is diagnosed by whealing within
10min on skin exposed to a melting ice cube or the TempTest?
device (either version 4.0 [TT4] with a 4-44?C gradient, or
the older version 3.0 [TT3] with 12 fixed 4-26?C probes). The
critical stimulation time threshold (CSTT) and critical temperature threshold (CTT) indicate the shortest exposure time
and highest temperature needed to elicit a wheal.5
These parameters vary substantially among patients,5,6 and their associations are not yet fully understood. Magerl et al. reported a
correlation between CTTs obtained via TT4 and TT3.7
This analysis expands on our previous COLD-CE study
report,5
which identified oropharyngeal and laryngeal
symptoms as risk factors for systemic reactions. In the
present analysis, we define these symptoms as mucosal angioedema involving the oropharynx (MAO), characterized
by a sensation of swelling of the tongue, pharynx or larynx
and examine this phenotype in depth. A total of 535 patients
with ColdUT
were recruited from 2019 to 2025, including
123 additional patients enrolled after the first phase of the
study. All underwent cold stimulation testing (CST) with an
ice cube and/or TempTest?. Patients receiving omalizumab
(n=55) at enrolment were included based on CST results
obtained prior to treatment, and only their clinical histories
were analyzed.
Statistical analyses were performed using IBM SPSS
V25.0, with a significance level set at p(0.05. Numerical
variables were non-normally distributed and expressed as
medians and interquartile ranges (IQR), while categorical
variables were presented as counts and percentages. The
Mann-Whitney and Fisher's exact tests were used for continuous and categorical variables, respectively. Correlations
were assessed with Spearman's rho (r), interpreted as weak
(0.10-0.29), moderate (0.30-0.50) or strong ()0.50).8
MAO triggered by ingestion of cold food or drinks was reported by 32.1% of patients and was significantly associated
with generalized wheals (p(0.001), cutaneous angioedema
(p(0.001) and systemic symptoms (cardiovascular: p(0.001;
respiratory: p(0.001; gastrointestinal: p=0.001). MAO was
also linked to a higher number of relevant cold triggers
(p(0.001), including weaker stimuli like localized contact
with cold liquids or surfaces (both p(0.001). Moreover, MAO
patients had shorter CSTTs and higher CTTs measured with
TT4 (both p(0.001), and reported greater quality-of-life impairment per the Dermatology Life Quality Index (DLQI)9
(Table 1).
To our knowledge, this is the first demonstration that
shorter CSTTs correlate with higher CTTs and
