Focusing on urticaria and/or angioedema and maculopapular
eruptions in a point-by-point comparison, the data show no significant
association between these reactions and the patients'
background (demographic data, atopic diathesis, underlying
diseases, history of any previous drug allergy, a smoking habit,
alcohol consumption, concurrent medication, or previous type
of drug eruption). Onsets of the eruptions following administration
of PPIs were 2.5 ± 1.8 days for maculopapular rash with
prior PPI administration, and 10.8 ± 15 days for maculopapular
rash without prior PPI administration. For urticaria and/or
angioedema, the onset was 1.4 ± 1.4 days for secondary sensitization
and 8.3 ± 16.4 days for primary sensitization. The
mean recovery time after stopping the culprit drug was 2.6 ±
1.8 (range 1-6) days for maculopapular eruptions and 2.0 ± 1.3
(range 0-4) days for urticaria and/or angioedema.
Severe reactions such as Stevens-Johnson Syndrome (SJS)
or toxic epidermal necrolysis (TEN) were reported in four patients
(6.3%), of whom three had a reaction to omeprazole and
one to pantoprazole. Among SJS or TEN patients who had a
reaction to omeprazole, none had been exposed to any PPIs
before the events. The reactions occurred between four and
nine days after the drug was taken. Two out of four patients
were hospitalized, and the mean improvement duration of all
cases was 4.0 ± 1.4 (range 3-5) days. No anaphylactic reaction
to PPIs was reported.
In our study, none of the 64 cases with a reaction to PPIs experienced
a fatal outcome. All cases, even one with a minor drug
eruption, discontinued the medications after the eruption occurred.
Most cases recovered after discontinuation of the drug,
together with symptomatic and supportive treatment. Forty-six
patients (73%) were treated with antihistamines, while 10 subjects
(21.7%) were given short-course systemic corticosteroids.
Adrenaline was given to one patient who presented with angioedema
and urticaria.
DISCUSSION
Even though skin prick testing and patch testing are useful for
the etiological diagnosis of cutaneous drug reactions, the positivity
rates are low, varying between 17% and 35%, and their
specificity and relevance are still to be determined.16,17 A reliable
clinical approach and examination of drug administration
remains the mainstay for diagnosing a drug allergy.18 Therefore,
we used the WHO Uppsala Monitoring Centre guidelines
for the diagnosis of drug imputability.
In our study, the proportion of cutaneous reactions among all
adverse reactions to PPIs was 64 out of 105 (61%). Most of the cutaneous
reactions (50 [78.1%]) were caused by omeprazole. The
proportion of cutaneous reactions to omeprazole in our study
was higher than that reported in a previous publication.19 It was
previously reported that among 521 patients reported to have reactions
to omeprazole, skin reactions accounted for 104 reactions
(20%). However, the detail of all reactions was not mentioned.
Among available PPIs in our hospital, omeprazole was the most frequently prescribed drug. Despite the high number of
prescriptions, omeprazole had a lower prevalence of cutaneous
drug reaction than lansoprazole and pantoprazole. Esomeprazole
was demonstrated to have the lowest prevalence of
cutaneous drug eruption.
There are a number of reports on cross-reactivity between PPIs,20-22 but our study did not find any cross-reaction. However,
one case was suspected of developing a maculopapular
rash in response to omeprazole, lansoprazole, or both. As both
drugs were administered on a consecutive day before the reaction,
both could be responsible for the eruption. However, the
patient declined to undergo a skin test or oral provocation test
to clarify this. In addition, cross-reactivity between omeprazole
and lansoprazole have been described previously in several
reports.23 Maculopapular rash was the most common reaction
found in our study, followed by angioedema and/or urticaria.
Our data showed no significant association between previous
types of drug eruption and current reactions. A previous
publication similar to our own study also described that an
immunoglobulin E–mediated reaction might be followed by a
T-cell mediated reaction.24
