Clinical data of the subjects confirmed as DHR
The 662 subjects confirmed as of DHR to APs had a median age at
diagnosis of 38 [interquartile range (IR): 26–49] years, and 402
(60.73%) were female. A total of 284 had underlying rhinitis (42.9%);
161 had asthma (24.32%); 61 had nasosinusal polyposis (9.21%); 49 CSU
(7.4%), and 24 food allergy (3.63%) (3 to nuts, 7 to shellfish, 6 to
melon, 5 to peach, 2 to apple, 1 to kiwi, and 1 to banana). The
percentage of rhinitis, asthma, nasosinusal polyposis, and CSU was
higher in CRs compared with SRs (Table 1). A total of 440 patients were
atopic (66.46%), being most frequently detected sensitisations toDermatophagoides pteronyssinuss (264; 39.87%), Olea
europaea (217; 32.77%), and Lolium perenne (175; 26.43%) No
differences were observed comparing CRs and SRs (Table 1 and
Supplemmentary Table 1).
Patients confirmed as blended were the youngest (p=0.01), being the
percentage of females higher in NERD and SNIDR (p=0.01). The percentage
of cases with underlying rhinitis, asthma, and nasosinusal polyposis was
higher in NERD cases, followed by blended cases (p<0.0001,
respectively). The percentage of atopy was higher in NIUA, NECD,
blended, and SNIUAA (p<0.0001), being the percentage of
sensitisations to D. pteronyssinus higher in NIUA and SNIUAA
(p=0.0003) and to Alternaria and Pru p 3 in blended (p<0.0001
and p=0.01, respectively) compared with the other clinical entities
(Table 2 and Supplemmentary Table 2).
Cases reported a total of 1946 episodes induced by NSAIDs, being 1341
induced by APs, with a median of 2 [IR: 1-2] episodes induced by APs
intake per patient, being the median higher in SRs compared with CRs (2
[IR: 2-3] vs 1 [IR: 1-2]; p<0.0001). In most subjects
(601; 90.78%), reported reactions were induced by ibuprofen, followed
by dexketoprofen (96; 14.5%), naproxen (64; 9.66%), and ketoprofen (9;
1.35%). In 100 cases (73 CRs and 27 SRs), 2 different APs were involved
in the reactions, and in 4 cases 3 different APs were reported, all of
them CRs. Comparing CRs and SRs, the percentage of subjects reporting
reactions induced by ibuprofen (CR: 453 (92.63%) vs SR: 148 (85.54%);
p=0.005) and dexketoprofen (CR: 81 (16.56%) vs SR: 15 (8.67%), p=0.01)
was higher in CRs, and patients reporting reactions induced by naproxen
(CR: 37 (7.15%) vs SR: 29 (16.76%); p=0.0002) and ketoprofen (CR: 1
(1.84%) vs SR; 8 (4.62%); p=0.00001) were more frequent in SRs. All
APs were administered orally, except for 27 cases in which dexketoprofen
was administered by parenteral route (intravenous and intramuscular) and
6 cases in which ketoprofen were administered topically. In 147 cases
confirmed as CRs, 605 episodes were induced by others NSAIDs different
from APs: 180 (36.8%) cases reported reactions induced by pyrazolones
(175 by metamizol and 5 by propifenazone), 164 (33.53%) by ASA, 82
(16.76%) by arylacetic acid derivatives (73 by diclofenac, 6 by
ketorolac and 3 by aceclofenac), 66 (13.49%) by paracetamol, 9 (1.84%)
by oxicams (7 by meloxicam and 2 by piroxicam), 5 (1.02%) by lysine
clonixinate, 2 (0.4%) by etoricoxib, 2 (0.4%) by indomethacin, and 1
(0.2%) by nimesulide.
According to the clinical entity, a total of 225 cases were confirmed as
NIUA (33.98%), 150 as SNIUAA (22.65%), 110 as blended (16.61%), 105
as NERD (15.86%), 49 as NECD (7.4%), and 23 as SNIDR (3.47%) (Figure
1). Ibuprofen and dexketoprofen induced NIUA more commonly than other
APs (34.8%, p<0.0001; and 42.7%, p=0.02, respectively),
whereas naproxen induced more frequently SNIUAA (34.4%, p=0.0004), and
ketoprofen induced SNIDR (77.8%, p<0.0001) (Table 3).
The most frequent symptoms induced by ibuprofen, dexketoprofen, and
naproxen were isolated AE and urticaria combined or not with AE in both
NIUA and SNIUAA, and the most frequent ones induced by ketoprofen were
contact eczema and maculopapular exanthema (MPE) in SNIDR (Table 4). No
differences were found in the percentage of atopic patients comparing
the clinical symptoms induced by each AP (data not shown).
The time interval between the AP intake and the onset of the reaction
was shorter for NERD (30 [IR:15-50] minutes), blended (30 [IR:
10-60] minutes), and SNIUAA (30 [IR: 30-120] minutes,
respectively) compared with NECD (60 [IR: 30-120] minutes), NIUA (60
[IR: 15-120] minutes) and SNIDR (2160 [IR: 510-7200] minutes)
(p<0.0001). No differences were found comparing the APs
involved in each clinical entity (data not shown).