DISCUSION
The use of ICM in radiological examinations can be challenging when a
patient has a history of HSR. Recommending an alternative ICM is
difficult due to high CR among them32. Additionally,
the efficacy of premedication has been debated, and there is increasing
support for conducting an allergy study to identify a safe ICM for
allergic patients 21,23. Additionally, the
efficacy of premedication remains controversial, and there is growing
support for considering a more effective approach, such as recommending
the switch to an ICM, especially with a targeted selection based on an
allergy work-up to identify a safe ICM for allergic
patients21,23.
In this study, we employed a protocol to evaluate both the safety and
efficacy of rapid DPT for identifying a safe alternative ICM for 130
patients with a previous HSR to ICM. This population exhibited diverse
characteristics and varying severity of symptoms, enhancing the
robustness of the results. Notably, there was a significant proportion
of patients with anaphylaxis (13%), which supports the safety of rapid
DPT even in high-risk populations. Furthermore, a higher percentage of
patients with delayed HSR was included compared to previous
studies2,13,23,27,43,44. Enrolling such patients is
challenging because their symptoms often manifest outside of healthcare
settings and are frequently unrecognized19,45–47.
In our population, the occurrence of HSR upon first contact with ICM was
53.8%, higher than previously
reported19,26,30,48–51, which reported percentages
around 30%. This phenomenon has been classically attributed to the
nonspecific release of mast cell mediators. However, the fact that 33%
of patients demonstrated positive ST upon first contact with ICM
suggests the possibility of sensitization mechanisms. These may include
sensitization to the carbamoyl side chain of ICM, potentially induced by
prior contact with other molecules sharing this chain, such as the
antibiotic cefuroxime, or that sensitization may have occurred through
inadvertent exposure to ICM via drinking water52,53.
The results regarding the ICM involved in HSR can vary depending on the
availability of ICM at each center, making direct comparisons among
studies challenging. For example, some publications have reported a
higher incidence of HSR, particularly immediate reactions, with
iopromide and iomeprol compared to iohexol, ioversol, and
iopamidol54–56. Conversely, other studies have
identified iohexol57 or iodixanol58as the most frequently implicated ICM, and a meta-analysis found no
significant differences between various hypoosmolar
ICM59. In our population, the most used ICMs were
iohexol and iodixanol. Then, it is not surprising that they were also
responsible for the majority of HSR that occurred.
A significant association was observed both with the type of HSR
(immediate or delayed) (p<0.001) and with the symptoms presented
(p<0.05) in our population. Iodixanol was more closely
associated with delayed cutaneous symptoms and was not related to any
episodes of anaphylaxis, which is consistent with previously reported
results60–63. In contrast, iohexol was associated
with mild symptoms, with no significant difference between immediate and
delayed reactions. Unknown ICM was significantly associated with more
severe symptoms, which may be related to the fact that, with such a
prolonged delay, the involved ICM was of the hyperosmolar type. The ICM
was unknown for a large proportion of subjects (40.7%), similar to
findings in previous studies (49, 64), with a significantly longer delay
in initiating the study (median of 168 months). This delay may
contribute to recall bias due to the difficulty in remembering the
specific ICM involved
Both the percentage of ST and the NPV in our study were comparable to
those reported in previous research26,36,47,64,
underscoring the necessity of completing the allergy study with DPT. The
main objective of the current study was to evaluate the safety and
usefulness of rapid DPT in a large population, including patients with
severe symptoms. The safety of the protocol was well-established as all
positive DPT results were mild, even among patients with a history of
anaphylaxis. In terms of usefulness, we were able to successfully
recommend an alternative ICM to 94% of patients by the end of the
study. Additionally, 50 of these patients required a new radiological
examination, which could be performed using the recommended ICM without
premedication, with good tolerance observed in all cases.
A previous retrospective study has reported clinical phenotyping of
patients with HSR to ICM (65), based on patient characteristics,
clinical history, and ST results. This study identified different risks
for developing an ICM allergy, but it did not report on the risk
associated with the administration of new ICM. In contrast, our study
conducted a statistical analysis phenotyping patients with HSR to ICM
into three distinct clusters, each associated with different risks for
developing a DPT when administering an alternative ICM. According to our
results, by grouping our patients into three clusters, the safety of DPT
could be enhanced. An expected limitation of our approach could be that
the proposed clusters may only be implemented in similar populations and
where the ICM used for the allergy study overlaps with ours.
Consequently, it may be complex to apply our results to populations with
different attributes.
Higher risk of a positive ST has been associated with immediate HSR,
anaphylactic shock, and a shorter delay in initiating the allergy
evaluation10,64. However, the only identified risk
factor for a positive ST was the involvement of iopromide. History of
oncological pathology was found to increase the risk of developing a
positive DPT.
In the mathematical model designed to predict the positivity of ST and
DPT, the ROC curves showed an acceptable AUC, although the predictive
statistical power was limited due to a low goodness-of-fit. This suggest
that the model lacked the ability to generalize to other populations. We
think that the regression analysis was limited by the number of patients
included, and more specifically, by an insufficient number of patients
with positive ST or DPT results. This limitation may be attributed to
the selected variables lacking sufficient discriminatory power.
In any case, we consider that predictive mathematical models represent a
valuable tool for improving the safety of high-risk tests, such as DPT.
Further research with larger sample sizes, potentially through
multicentre studies, is needed to achieve more statistically significant
results.
Another limitation of our study was that the median age of the patients
was higher compared to previous studies, which could influence the type
of comorbidities, the radiological examinations performed, and the ICM
used. Therefore, our results should be cautiously extrapolated to
younger populations.
Additionally, the high percentage with unknown ICM involvement increased
the likelihood that the implicated ICM was not included in the panel
used for the allergy study. As a result, we could not be certain whether
the DPT were performed with an alternative or the implicated ICM.
However, this situation reflects daily practice in Allergy Units, where
DPT are often conducted without knowing the specific suspected drug.
In conclusion, we successfully evaluated the tolerability of a protocol
using rapid DPT in a prospective allergy study to identify alternative
ICM for patients with immediate or delayed HSR to ICM, with varying
degrees of severity, ranging from mild episodes to anaphylaxis. We also
characterized our population into three clusters with different risk
profiles for DPT outcomes. Finally, we have developed a predictive model
for allergic test results. Larger studies are needed to confirm our
findings and improve the predictive accuracy of the proposed regression
model.
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