Clinical profile of idiopathic angioedema based on severity and treatment response is independent of the presence of concomitant wheals

Background: Idiopathic angioedema varies in disease severity and treatment response, possibly due to different pathophysiological mechanisms. The presence of wheals is an indicator for histamine-mediated angioedema. Idiopathic angioedema patients are treated in accordance with chronic spontaneous urticaria guidelines. Little is known about treatment effectiveness in idiopathic angioedema patients without wheals in comparison to idiopathic angioedema patients with concomitant wheals. Objective: To describe the disease severity profile in patients with angioedema of unknown cause in relation to prophylactic treatment and the presence or absence of concomitant wheals. Methods: In this retrospective cohort study, all records of angioedema patients visiting the outpatient clinic of the UMC Utrecht between January 2015 and March 2020 were screened. Patients with idiopathic angioedema, including those with concomitant wheals, were included. Attack frequency, patient-reported disease control and attack treatment as indicator for severity were analysed in relation to prophylactic treatment at follow-up and outcomes were compared between patients with and without concomitant subordinary wheals. Results: Two hundred thirty-six patients were included: 95% (139/236) with angioedema only and 41% (97/236) with angioedema and concomitant subordinary wheals. No prophylactic treatment was prescribed in 27% (64/236), with well-controlled disease in 86% (25/29) of patients. Antihistamine monotherapy was used in 59% (139/236) of patients and resulted in well-controlled disease in 68% (62/92). Add-on treatment was prescribed in 14% (33/236) of patients, omalizumab in 9% (22/236) specifically, with complete response in 38% (6/16) of patients and low attack frequency in another 18% (3/16). Difficult-to-treat disease was seen in 8% (18/236), with no response to a fourfold dose of antihistamines or omalizumab. All findings were independent from the presence of concomitant wheals. Conclusion: Angioedema is well manageable in the majority of patients without prophylactic therapy or antihistamine monotherapy, but a substantial proportion does not respond to antihistamines and/or omalizumab. Treatment response was independent of the presence or absence of concomitant wheals

Assessment of allelic diversity in intron-containing Mal d 1 genes and their association to apple allergenicity

<p>Abstract</p> <p>Background</p> <p>Mal d 1 is a major apple allergen causing food allergic symptoms of the oral allergy syndrome (OAS) in birch-pollen sensitised patients. The <it>Mal d 1 </it>gene family is known to have at least 7 intron-containing and 11 intronless members that have been mapped in clusters on three linkage groups. In this study, the allelic diversity of the seven intron-containing <it>Mal d 1 </it>genes was assessed among a set of apple cultivars by sequencing or indirectly through pedigree genotyping. Protein variant constitutions were subsequently compared with <b>S</b>kin <b>P</b>rick <b>T</b>est (SPT) responses to study the association of deduced protein variants with allergenicity in a set of 14 cultivars.</p> <p>Results</p> <p>From the seven intron-containing <it>Mal d 1 </it>genes investigated, <it>Mal d 1.01 </it>and <it>Mal d 1.02 </it>were highly conserved, as nine out of ten cultivars coded for the same protein variant, while only one cultivar coded for a second variant. <it>Mal d 1.04</it>, <it>Mal d 1.05 </it>and <it>Mal d 1.06 A, B </it>and <it>C </it>were more variable, coding for three to six different protein variants. Comparison of <it>Mal d 1 </it>allelic composition between the high-allergenic cultivar Golden Delicious and the low-allergenic cultivars Santana and Priscilla, which are linked in pedigree, showed an association between the protein variants coded by the <it>Mal d 1.04 </it>and <it>-1.06A </it>genes (both located on linkage group 16) with allergenicity. This association was confirmed in 10 other cultivars. In addition, <it>Mal d 1.06A </it>allele dosage effects associated with the degree of allergenicity based on prick to prick testing. Conversely, no associations were observed for the protein variants coded by the <it>Mal d 1.01 </it>(on linkage group 13), -<it>1.02</it>, -<it>1.06B, -1.06C </it>genes (all on linkage group 16), nor by the <it>Mal d 1.05 </it>gene (on linkage group 6).</p> <p>Conclusion</p> <p>Protein variant compositions of Mal d 1.04 and -1.06A and, in case of <it>Mal d 1.06A</it>, allele doses are associated with the differences in allergenicity among fourteen apple cultivars. This information indicates the involvement of qualitative as well as quantitative factors in allergenicity and warrants further research in the relative importance of quantitative and qualitative aspects of <it>Mal d 1 </it>gene expression on allergenicity. Results from this study have implications for medical diagnostics, immunotherapy, clinical research and breeding schemes for new hypo-allergenic cultivars.</p

Thresholds of allergenic proteins in foods

Threshold doses or Estimated Eliciting Doses (EEDs) represent an important new field of research in food allergy. Clinicians and regulators have embraced some toxicological concepts such as LOAEL and NOAEL and applied them to an area of significant clinical uncertainty and interest. The impact of intrinsic human factors (e.g., asthma and exercise) and extrinsic event factors (e.g., season, location and especially dose of allergen) on a future allergic reaction in the community needs to be considered carefully when interpreting results of clinical and research low-dose food challenges. The ongoing cooperation of food allergy research groups in medicine, food science and government will surely deliver results of the highest importance to the wider communities of allergology, food science and technology and the increasing number of allergic consumers