Methods & Patients
Patients
From January 1st, 2016 to December
31st, 2017 a cohort of 48.629 routine patients or sera
of routine patients were referred to the Floridsdorf Allergy Center with
91.438 diagnoses (many had more than one referral diagnosis). Of these,
3.875 (8.0%) carried a diagnosis compatible with a history of a DHR. In
1.532 individuals (1085 female / 447 male; 40.6 years ± 22.1) the
suspected drug belonged to penicillin and/or cephalosporine antibiotics
and a serological test was made. As the laboratory of the allergy clinic
also serves as a tertiary referral centre for external serological
tests, clinical data was not available for 76 patients that were
eliminated leaving 1456 patients for the intention-to-treat analysis
(Figure 1). A significant proportion of 523 patients had to be excluded
from the per-protocol population because they did not show up for their
scheduled skin tests and another single patient stepped down from skin
testing on the day of the test (low compliance). This resulted in 932
individuals (669 female / 263 male; 42.5 years old ± 22.1) available for
the per-protocol analysis (Table 1 and Figure 1).
Supplementary Figure 2 depicts the standard algorithm, which was a
modified approach according to the guideline of the German speaking
countries (21) adapted for the needs of our allergy outpatient clinic
without a possibility for performing DPTs. The attending physician could
deviate from the algorithm according to individual patient-specific
factors. The primary outcome (DHR ‘confirmed’, or ‘possible’, or
‘unresolved’) depended on the interpretation of the summary of all
available tests by the attending physician.
Materials & Methods
Specific IgE, total IgE and serum tryptase were measured on an ImmunoCAP
250 laboratory robot with commercially available tests from ThermoFisher
(Uppsala, Sweden): Penicilloyl G (c1) & V (c2), Amoxicilloyl (c6),
Ampicillin (c5), Minor determinate mixture (MDM) (U233), Cefaclor (c7).
Due to production limits of the manufacturer and the high demand at our
centre, not all test reagents were available during the whole study
period (especially c5, c6, c7 and U233).
Skin prick (SPT), intradermal (IDT) and patch tests (PT) were performed
with nationally licensed drugs for intravenous use in nationally
recommended concentrations and read accordingly (21, 22): Penicillin G,
Amoxicillin/Clavulanic Acid, Cefazolin and Ceftriaxon: “Penicillin
G-Natrium Sandoz”, “Curam®”, “Cefazolin Sandoz”, “Ceftriaxon
Sandoz”, all from Sandoz, Kundl, Austria; Ampicillin/Sulbactam:
“Unasyn®”, Pfizer, Borgo San Michele, Italy; Cefuroxim: “Cefuroxim
MIP”, Cephasaar, Sankt Ingbert, Germany). The commonly used penicillin
derivatives MDM & PPL for skin tests marketed by Diater, Madrid, Spain
are not licensed in Austria and cannot be used in routine settings
outside academic hospitals. PTs were performed using Curatest® (Lohman
und Rauscher, Vienna, Austria) and read after 24 hours together with the
late reading of the IDT.
Generally, skin tests were performed in the following order:
1st) all SPTs at once, when negative after 20 min
followed by
2nd) all IDTs at once, when negative after 20 min
followed by
3rd) all PTs at once followed by
4th) late readings of all tests after 24 hours.
Ethics and Statistics
The study was approved by the ethics committee of the Medical University
of Vienna, Austria, during Christian Ostermayer’s medical diploma thesis
according to the Helsinki Declaration of Human Rights (ECS 1103/2018).
Χ²-tests were calculated using MedCalc Statistical Software version 19.2
(MedCalc Software Ltd, Ostend, Belgium; https://www.medcalc.org; 2020).