Background: Recent studies indicated that fish-allergic patients may safely consume certain fish species. Multiplex IgE testing facilitates the identification of species tolerated by individual patients. Methods: Sera were collected from 263 fish-allergic patients from Austria, China, Denmark, Luxembourg, Norway and Spain. Specific (s) IgE to parvalbumins (PVs) from 10 fish species along with IgE to 7 raw and 6 heated fish extracts was quantified using a research version of the ALEX 2 assay. IgE-signatures of individual patients and patient groups were analyzed using SPSS and R. Results: sIgE to alpha-PV from ray, a cartilaginous fish, was not detected in 78% of the patients while up to 41% of the patients, depending on their country of origin, tested negative for at least one beta-PV. sIgE values were highest for mackerel and tuna PVs (>10 kUA/L) and significantly lower for cod (4.9 kUA/L) and sole PVs (2.55 kUA/L). 17% of the patients, although negative for PVs, tested positive for the respective fish extracts. Based on the absence of IgE to PVs and extracts, up to 21% of the patients were identified as potentially tolerating one or more bony fish. Up to 90% of the patients tested negative for ray. The probability of negativity to one fish based on negativity to others was calculated. Negativity to tuna and mackerel emerged as a good marker of negativity to additional bony fish. Conclusion: Measuring sIgE to PVs and extracts from evolutionary distant fish species indicates bony and cartilaginous fish species for tolerance-confirming food challenges.

LETTER TO THE EDITORNo apparent impact of incremental dosing on eliciting dose at double-blind, placebo-controlled peanut challengeOlaya Álvarez García,1,2 Joan Bartra,1,3 Monica Ruiz-Garcia,1Isabel J. Skypala,1,4 Stephen R. Durham,1,4 Robert J. Boyle,1 E.N. Clare Mills,5 Paul J. Turner1

Background: Although ibuprofen and other arylpropionic acid derivatives (APs) are among the non-steroidal anti-inflammatory drugs (NSAIDs) most consumed worldwide at all age ranges, little is known about hypersensitivity to this group of drugs. Our aim was to characterise in detail patients reporting hypersensitivity reactions induced by APs. Methods: We prospectively evaluated patients with symptoms suggestive of hypersensitivity to APs and analysed their clinical characteristics, the reported reactions, and the diagnosis approach. Results: A total of 662 patients confirmed as hypersensitive to APs were included: 489 as cross-reactive (CR) hypersensitivity type (73.86%) and 173 as selective responders (26.13%) (SR). The percentage of subjects reporting reactions induced by ibuprofen and dexketoprofen was higher in CRs (p=0.005 and p=0.01, respectively), whereas reactions induced by naproxen and ketoprofen were more frequent in SRs (p=0.0002 and p=0.00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria combined or not with angioedema in both NIUA and SNIUAA. NPT-LASA was positive in 156 cases (77.14% of NERD and 68.18% of blended) and DPT to ASA was needed in 246 (50.3%) CR patients. In 28 SR cases (25 SNIUAA and 3 SNIDR), DPT with the culprit AP was required. Conclusions: Skin is the most common organ involved in hypersensitivity to APs, in both CR and SR, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are needed to clarify the underlying mechanism in DHR induced by APs.