Demographic data and clinical data for patients with and without
maculopapular rash or urticaria and/or angioedema were
compared, using the Pearson chi-square test for qualitative
data and the Mann-Whitney U test for quantitative data. All statistical
data analyses were performed using SPSS for Windows
(version 17.0; SPSS Inc, Chicago, IL).
RESULTS
We conducted a retrospective review of all patients aged 18 years
and older who received PPI therapy at Siriraj Hospital in Bangkok,
Thailand, between January 2005 and May 2010 (n=462,969)
and identified 105 patients who experienced an adverse drug reaction
following PPI therapy. Of these, 41 subjects who did not
have cutaneous adverse reactions were excluded, leaving 64
subjects in the final case group analysis. Patients with a consecutive
hospital number from a member of the case group who had
received PPIs during the study period without experiencing an
adverse reaction were enrolled in the control group (n=65). The
prescription data of each PPI were obtained from the database at
the Information Technology Center at Siriraj Hospital.
The prevalence of adverse reactions was 22.6 (per 100,000 treated population) and of cutaneous adverse reactions was
13.8 (per 100,000 treated population). The prevalence of cutaneous
reactions to each PPI (per 100,000 treated population) was
20 for lansoprazole, 16 for pantoprazole, 15 for omeprazole, 10
for rabeprazole, and 3 for esomeprazole, as shown in Table 1.
Table 2 shows the demographic and clinical data of the participants. Sixty-four patients with a history of cutaneous reaction
to PPIs were identified as cases, and there were 65 controls
without a history of reaction to PPIs. Among all participants, 49
(38%) were males, and 80 (62%) were females. The mean age of
cases was 58.4 years (range 18-94 years). The mean age of controls was 53.2 years (range 20-86 years). However, there was no statistically significant difference in demographic data and
type of PPIs used between the groups. Twenty subjects (15.5%)
had a history of atopic diathesis, of whom 11 were cases and 9
were controls. The causes of PPI usage were dyspepsia (44.2%),
NSAID-induced ulcer prevention (21.7%), stress ulcer prevention
(14.7%), prednisolone-induced ulcer prevention (10.1%),
gastroesophageal reflux disease (7%), and upper–gastrointestinal
tract hemorrhage (2.3%).
Among the cases, 11 patients (8.5%) had received only one medication before the adverse events occurred, a probable
diagnosis was made in 8 patients (12.5%), and a possible diagnosis
was made in 56 patients (87.5%).
Patients with a history of drug reaction of any type before PPI therapy had a significantly higher frequency of cutaneous reaction
to PPIs than the controls. In addition, cutaneous reaction
to PPIs was significantly associated with a smaller number of
concurrent medications.
Most cutaneous reactions were attributed to omeprazole (n=50; 78.1%), and the most frequently observed adverse cutaneous
reaction was maculopapular rash (43.8%). Other types of adverse
cutaneous eruptions and responsible agents are shown
in Table 3. None of the cases experienced cross-reaction between
individual PPIs.
