Clonal mast cell disorders and elevated basal serum tryptase (BST) levels with unknown cause(s) are associated with severe Hymenoptera venom–triggered anaphylaxis (HVA). However, some individuals ...with clonal disease have a normal BST level (<11.4 ng/mL).
Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy.
We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR.
In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% 24 of 132 vs 1.8% in patients with lower grades 4 of 88 with grade III and 0 of 131 with other grades; P < .001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% 14 of 24 vs 34.3% 37 of 108; P = .03) and absence of skin symptoms (41.7% 10 of 24 vs 15.7% 17 of 108; P = .004). Among patients with a normal BST level, KIT p.D816V (OR = 10.25 95% CI = 3.75-36.14; P < .0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% 15 of 23) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA.
These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients with HVA who are regularly missed when BST level is used alone.
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Summary
Background
Confirmation of the clinical relevance of sensitisation is important for the diagnosis of allergic rhinitis.
Objective
To investigate the usefulness of an in vitro basophil ...activation test and component‐resolved diagnosis in distinguishing between symptomatic allergic rhinitis patients and asymptomatic sensitization to house dust mites (HDMs).
Methods
Thirty‐six subjects with a positive skin prick test (SPT) for HDM were divided into a symptomatic (n = 17) and an asymptomatic (n = 19) group on the basis of their clinical history and a nasal provocation test. A basophil CD63 response to in vitro stimulation with Dermatophagoides pteronyssinus whole allergen extract and the IgE reactivity profiles for Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 were evaluated. Serum IgE and IgG specific to D pteronyssinus whole allergen extract and total IgE were measured.
Results
There were no statistically significant differences in the levels of IgE (IgE levels were higher in symptomatic patients with P = 0.055) and IgG specific to D pteronyssinus and total IgE. Symptomatic patients showed a lower threshold for in vitro basophil activation (3.33 ng/mL vs 33.3 ng/mL), a higher area under the curve (AUC) of basophil activation (171 vs 127) (P = 0.017), a higher response to positive control with anti‐FcεRI stimulation (97% vs 79%) (P < 0.001), a recognition of more HDM allergens (4 vs 2) and more frequent sensitization to rDer p 7 (P = 0.016) and rDer p 23 compared to asymptomatic subjects (P = 0.018). There was a positive correlation (r = 0.63; P < 0.001) between the number of recognized allergens and the AUC of basophil activation.
Conclusion and Clinical Relevance
In the subjects studied, the differences in the basophil response to D pteronyssinus allergen extract, number of recognized HDM allergens and reactivity to rDer p 7 and rDer p 23 distinguish symptomatic from asymptomatic HDM sensitisation better than SPT or allergen extract‐specific IgE. Information regarding the clinical relevance of sensitization is important for the prescription of allergen‐specific immunotherapy.
Abstract Background As of writing, there are no publications pertaining to the prediction of COVID-19-related outcomes and length of stay in patients from Slovene hospitals. Objectives To evaluate ...the length of regular ward and ICU stays and assess the survival of COVID-19 patients to develop better prediction models to forecast hospital capacity and staffing demands in possible further pandemic peaks. Methods In this retrospective, single-site study we analysed the length of stay and survival of all patients, hospitalized due to the novel coronavirus (COVID-19) at the peak of the second wave, between November 18th 2020 and January 27th 2021 at the University Clinic Golnik, Slovenia. Results Out of 407 included patients, 59% were male. The median length of stay on regular wards was 7.5 (IQR 5–13) days, and the median ICU length of stay was 6 (IQR 4–11) days. Age, male sex, and ICU stay were significantly associated with a higher risk of death. The probability of dying in 21 days at the regular ward was 14.4% (95% CI 10.9–18%) and at the ICU it was 43.6% (95% CI 19.3-51.8%). Conclusion The survival of COVID-19 is strongly affected by age, sex, and the fact that a patient had to be admitted to ICU, while the length of hospital bed occupancy is very similar across different demographic groups. Knowing the length of stay and admission rate to ICU is important for proper planning of resources during an epidemic.
Background
The European baseline series (EBS) of contact allergens is subject to change. An allergen is considered for inclusion when routine patch testing of patients with suspected contact ...dermatitis results in ≥0.5% prevalence rate.
Objectives
We aimed to determine the frequency of sensitizations to 30 EBS allergens and 10 locally added allergens. Additionally, we assessed the strength and evolution of reactions to all tested allergens and co‐reactivity of additional allergens.
Methods
Patch testing with our baseline series of 40 allergens was done in 748 consecutive adults. Tests were applied to the upper back and removed by patients after 48 h. Readings were done on Day 3 (D3) and D6 or D7 (D6/7). Positive reactions fulfilled the criteria of at least one plus (+) reaction. A retrospective analysis was done.
Results
Eight allergens not listed in the EBS had ≥0.5% prevalence rate (i.e., cocamidopropyl betaine, thiomersal, disperse blue mix 106/124, 2‐bromo‐2‐nitropropane‐1,3‐diol, diazolidinyl urea, propylene glycol, Compositae mix II and dexamethasone‐21‐phosphate), and 16.6% of positive reactions would have been missed without D6/7 readings.
Conclusion
We propose further studies to evaluate whether cocamidopropyl betaine, disperse blue mix 106/124, 2‐bromo‐2‐nitropropane‐1,3‐diol, diazolidinyl urea and Compositae mix II need to be added to the EBS.
Our study results suggest that cocamidopropyl betaine 1% aq., disperse blue mix 106/124 1% pet., 2‐bromo‐2‐nitropropane‐1,3‐diol 0.5% pet., Compositae mix II 5% pet. and diazolidinyl urea 2% pet. may need to be added to the European baseline series of patch test allergens.
Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe ...reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9/38) of patients, sIgE to alpha-gal was >0.10 kUA/L, and 8/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 n = 4 vs. 1.8% in grade 2 n = 3 or no reaction n = 1 at 3.3 ng/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 µg/mL, 63.2% vs. 4.1% at 100 µg/mL, 58.2% vs. 2.7% at 10 µg/mL, and 32.1% vs. 3.3% at 1 µg/mL of cetuximab, respectively; p ≤ 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab.
In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the ...long-term effectiveness of VIT.
1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.
285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% n = 207 of 610 with Ring-Messmer grade 3-4 vs. 11% n = 78 of 709 with Grade 1-2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% n = 207 in Grade 3-4 vs. 0.001% n = 78 in Grade 1-2; p < .0001), and the majority had normal baseline serum tryptase levels (69% n = 196 of 285). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).
By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
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