Results
Characteristics of the study subjects and index HSRs
We assessed the results of 482 skin test panels performed on 431
patients with a history of LOCM-related immediate HSR (including 186
patients with severe index HSR) (Table 1). In 17.6% of the patients,
the initial HSR occurred on their first exposure to LOCM. The mean age
of these patients was 57.0 ±13.2 years, and 269 (62.4%) patients were
female.
According to the severity of the index HSR, there were 216 moderate
cases (44.8%), 186 severe cases (38.6%), and 80 mild cases (16.6%).
The most common culprit LOCM was iopromide (23.1%), followed by iohexol
(22.8%), iobtridol (18.7%), iopamidol (16.5%), iomeprol (8.2%),
ioversol (8.0%), and iodixanol (3.8%).
The outcome of skin test with LOCM and time interval
Skin test positivity to any LOCM was only 3.1% (15/482) in the skin
prick test but increased to 51.8% (250/482) when the IDT was performed.
The mean number of reactive LOCMs per test was 2.29 ± 1.34 in cases
showing positivity in skin tests. Of the LOCMs,
iohexol
showed the highest positive rate (70.0%), while iopamidol showed the
lowest positive rate (44.1%, Figure 1A). Positive rate was not
different between monomers and dimer (56.6% vs. 58.3%, respectively).
The occurrence of previous severe HSRs was associated with a higher
likelihood of a positive skin test (Figure 1B). Among the mild HSR
group, 38.7% (31/80) of patients had positive results. Furthermore,
45.8% (99/216) of patients with previous moderate HSR demonstrated
positivity, while 64.0% of those with severe HSR (119/186) showed
positive results (P = 0.002 among three groups, Figure 1B). Skin
test positivity was dependent upon the time interval between the index
HSR and the skin test; 67.2% (39/58) < 4 weeks, 60.7%
(34/56) in 4-8 weeks and 46.0% (160/348) > 8 weeks,
respectively. (P = 0.007, Figure 1C).
Cross-reactivity classified by common N-(2,3-dihydroxypropyl)
carbamoyl side chain
To evaluate cross-reactivity among LOCMs, we calculated the
co-positivity between different LOCM pairs. Among the 250 patients with
skin test positivity, 157 cases (62.8%) showed co-positivity to at
least two different LOCMs (Supplement B). The most common co-positivity
was observed in the iohexol-iomeprol pair (36.3%). The co-positivity
proportion in the LOCM pairs sharing common side chain was 21.5%, which
was significantly higher than the 13.3% that was observed in the LOCM
pairs without common side chain (P = 0.008) (Figure 2). This significant
difference was observed in the severe index HSR group (20.7% vs 11.5%,
P = 0.003), but not in the non-severe cases.
Outcomes of re-exposure to LOCM
Of 431 patients of LOCM skin tests, 355 cases were subsequently
re-exposed to LOCM and the consequences of LOCM re-exposure were
assessed based on the skin test results. The overall BTR rate was 12.3%
in the 244 cases in which the LOCM was changed, which is significantly
lower than the 46.6% BTR rate observed upon re-exposure to the culprit
LOCM (Figure 3-A, P-value = 0.004). The subgroup analyses by severity
showed that patients who had a severe index HSR exhibited a
significantly lower rate of recurrent HSR when changing the LOCM
compared to those who had re-exposure to the same culprit LOCM (11.3%
vs. 100%, P-value < 0.001). However, reduction of recurrence
due to the changing of the contrast media was not significant in
patients who had non-severe HSR to LOCM.
The recurrence of HSR was evaluated based on the presence of the
N-(2,3-dihydroxypropyl) carbamoyl side chain. Among cases that used an
alternative LOCM on re-exposure, the reaction rate was 15.1% when the
alternative LOCM had an identical side chain to the culprit LOCM. This
was slightly higher than the 11.8% rate observed when the alternative
LOCM had a different side chain than the culprit LOCM (Figure 3-B).
However, this did not reach statistical significance (P -value =
0.428). When cases were divided into two groups according to the
severity of their index HSR, analysis revealed that, in patients that
had severe index HSRs, the use of an alternative LOCM with a different
side chain significantly reduced the BTR rate from 24.0% to 7.8%
(P = 0.049). However, this difference was not observed in those
who had a non-severe HSR to LOCM. In addition, changing between a
monomer and dimer did not demonstrate an advantage in reducing the risk
of HSR (Data not shown).