Discussion
Recently, the voices in the allergy community have been growing louder
favouring a turn away from the classical allergological approach
including in vitro plus skin tests putting DPT at the end as the
final method and instead heading to a direct DPT without prior testing.
This has been propagated especially in the United States (13, 18, 19).
With our study, we would like to stress the point, that aiming for such
an extreme standpoint puts patients at unnecessary risks while roughly a
third of DHR cases can be solved with a safer and cheaper approach.
It may be argued that looking at sIgE and skin tests separately results
in only low positivity rates and that these tests may be regarded as
dispensable, therefore. Rightly, the low rate of 4.3% drug-specific IgE
to β-lactams on the ImmunoCAP® system nearly replicated the 3.4% that
we had already described 14 years ago (29). However, these tests are
cheap and can be applied on a large patient group (14). Tweaking read
out parameters such as lowering the threshold to 0.1 kU/l could have
doubled or calculating sIgE/total IgE ratios could have even quadrupled
the positivity rates in our patients, but this would have come at the
price of a lowered specificity (25). Basophil activation tests are
reported as having superior sensitivity and specificity (30, 31).
However, they are more expensive, require especially trained personal,
expensive laboratory equipment and consume a lot of laboratory time.
This makes them a difficult system for use on a broader routine
dimension.
Positive skin tests in our study occurred nearly in twice as many
patients (7.8%) than drug-sIgE (4.3%). Generally, skin tests tend to
be more sensitive than blood tests at an also high specificity with good
negative predictive value (32). Our study underlines the role of skin
testing and we performed them successfully even in 98 children ≤10
years. However, also their specificity had been challenged (33) while
later studies confirmed the high specificity of IDTs especially to
cephalosporins (34). IDTs are the most useful skin tests with early and
late readings. They cause a little bit of pain, which is usually
tolerated by all patients, and they are safe as we experienced no
systemic reaction in 1697 IDTs. When a late reading of the IDT is
available, PTs added only little additional value and might be omitted
in the routine setting. Still, PTs to β-lactams may have a role in the
history of severe cutaneous adverse reactions or in other situations,
where IDTs are impossible due to patient-specific factors.
Interestingly, the higher rate of confirmed reactions to cephalosporins
was just based on the immediate reaction pattern. This had already been
described by Romano et al. who confirmed a lot of immediate but hardly
any delayed type reactions by skin testing (35).
DPTs are the golden standard to rule out or confirm a DHR (36, 37). This
is especially true for the non-immunologically mediated reactions to
non-steroidal anti-inflammatory drugs (38). While representing the
gold-standard, they are not perfect tests, as numerous studies described
false-positive reactions even upon placebo tests (29, 39) and
false-negative tests (40). DPTs put patients at risks, are an expensive
and resource-consuming measure and are a limited resource, even in
well-developed health care systems. In Austria, one of the top-ten
countries concerning access to healthcare (41), there is currently no
reimbursement scheme for DPTs neither by public nor private healthcare
insurances. Because of this lacking financial incentive for hospitals
and outpatient facilities, Austria is faced with scarce resources for
performing DPTs. The metropolitan area of the Austrian capital city
Vienna counts around 3 million inhabitants. Four dermatological and two
paediatric wards are the only institutions offering DPTs with a long
waiting list. In a personal communication with these institutions, the
yearly capacity turns out to be at an astonishingly low 465 DPTs / year.
The majority of these (300) are offered by the department of dermatology
at the Medical University of Vienna. In an own reference study at this
institution (29), only 130/291 (44.7%) DHR evaluations were reserved
for antibiotics, the rest for other drugs e.g. NSAIDs. Assuming, that
this ratio has not changed much over time, the yearly capacity for
performing DPTs with antibiotics in greater Vienna can be estimated at
around 207/year. Of the 932 patients in our 2-year study, 37.1% of the
cases were solved by the application of the diagnostic algorithm with a
clear yes/no outcome. While these 346 individuals already received an
allergy passport (27) or the instruction that they can safely
re-introduce β-lactams in their antibiotic regimen, the majority of
62.9% cases remained unsolved with an ongoing need for DPTs. These 586
patients/2 years (=269/year) of our single allergy outpatient clinic
alone, would have greatly overwhelmed all DPT capacities of Eastern
Austria. To up the ante, there are 4 additional Viennese allergy
outpatient clinics and many more specialists for dermatology and
paediatrics who see additional cases. Hence, the full conventional
allergy workup of an allergy outpatient clinic can help to reduce the
pressure on underpowered DPT capacities.