Anaphylactic reactions were observed after Singapore’s national coronavirus disease 2019 (COVID-19) vaccination programme started in December 2020. We report the clinical and laboratory features of three patients in our institution who developed anaphylactic reactions after receiving the Pifzer BNT162b2 vaccine. IgM and IgG antibodies, but not IgE antibodies to the Pfizer BNT162b2 vaccine, were detected in all subjects. Similarly, mild to high elevated levels of anti-polyethylene glycol (PEG) IgG (1035–19709 U/mL, vs. vaccine-naive < 265 U/mL, vaccine-tolerant < 785 U/mL) and IgM (1682–5310 U/mL, vs. vaccine-naive < 1011 U/mL, vaccine-tolerant < 1007 U/mL) were detected in two out of three patients via commercial ELISA. High levels of serum anaphylatoxin C3a (79.0 ± 6.3 μg/mL, mean ± SD, vs. normal < 10 μg/mL) were observed in all three patients during the acute phase of the reaction, while tryptase levels, a marker of mast cell activation, were not elevated. Finally, one patient with the highest levels of anti-PEG IgG, IgM, and anti-Pfizer BNT162b2 IgG and IgM exhibited an enhanced Th2 cytokine serum profile during an acute reaction, with high levels of IL-4 (45.7 pg/mL, vs. vaccine-naive/tolerant < 2.30 pg/mL), IL-33 (86.4 pg/mL, vs. vaccine-naive/tolerant < 5.51 pg/mL) and IL-10 (22.9 pg/mL, vs. vaccine-naive/tolerant < 12.49 pg/mL) diminishing over time following corticosteroid treatment. Taken together, we propose these cases of anaphylaxis described are driven by a complement activation-related pseudoallergy (CAPRA), rather than classical IgE-mediated mechanisms.

The aim of the European Journal of Rheumatology is to cover various aspects of rheumatology for its readers, encompassing the spectrum of diseases with arthritis, musculoskeletal conditions, autoinflammatory diseases, connective tissue disorders, osteoporosis, translational research, the latest therapies and treatment programs. European Journal of Rheumatology publishes original articles, invited reviews, case based reviews, letters to the editor and images in rheumatology. The publication language of the journal is English. Accepted manuscripts are copy-edited for grammar, punctuation, and format. Once the publication process of a manuscript is completed, it is published online on the journal's webpage as an aheadof-print publication before it is included in its scheduled issue. A PDF proof of the accepted manuscript is sent to the corresponding author and their publication approval is requested within 2 days of their receipt of the proof.

Background Major challenges in large scale genetic association studies include not only the identification of causative single nucleotide polymorphisms (SNPs), but also accounting for SNP-SNP interactions. This study thus proposes a novel feature engineering approach integrating potentially functional coding haplotypes (pfcHap) with machine-learning (ML) feature selection to identify biologically meaningful, possibly causative genetic factors, that take into consideration potential SNP-SNP interactions within the pfcHap, to best predict for methotrexate (MTX) response in rheumatoid arthritis (RA) patients.Methods Exome sequencing from 349 RA patients were analysed, of which they were split into training and unseen test set. Inferred pfcHaps were combined with 30 non-genetic features to undergo ML recursive feature elimination with cross-validation using the training set. Predictive capacity and robustness of the selected features were assessed using six popular machine learning models through a train set cross-validation and evaluated in an unseen test set.Findings Significantly, 100 features (95 pfcHaps, 5 non-genetic factors) were identified to have good predictive performance (AUC: 0.776-0.828; Sensitivity: 0.656-0.813; Specificity: 0.684-0.868) across all six ML models in an unseen test dataset for the prediction of MTX response in RA patients.Interpretation Majority of the predictive pfcHap SNPs were predicted to be potentially functional and some of the genes in which the pfcHap resides in were identified to be associated with previously reported MTX/RA pathways.

The purpose of study was to assess the validity, reliability and acceptability of the English version of the Asthma Quality of Life Questionnaire in a multi-ethnic Asian population. The English version of the Standardized Asthma Quality of Life Questionnaire (AQLQ-S) and the Asthma Control Questionnaire (ACQ) were self-completed by 119 English-speaking Chinese, Malay and Indian asthmatic subjects, aged 17-78. Spirometric measurements, peak expiratory flow rate, current clinical symptoms and treatment requirements were documented. Reliability and responsiveness were analyzed in a subgroup of 57 patients who were reassessed 6 weeks later. The Cronbach alpha reliability coefficient for internal consistency of the AQLQ-S was 0.97 (0.96-0.98) for the overall score. The intraclass correlation coefficient (ICC) overall score was 0.97 (95% CI: 0.94-0.99) while the responsiveness index was 1.29 with strong longitudinal validity for clinical and spirometric measures of asthma severity and asthma control score (p < 0.001). The results of this study showed that the English version of the AQLQ-S is a sensitive and valid instrument for measuring health-related quality of life in asthmatic subjects from a multi-ethnic Asian population.

We describe a 35-year-old Chinese woman with Behçet disease complicated by recurrent gastrointestinal flares. During admission for acute lower abdominal pain, a computed tomographic scan of the abdomen showed thrombosis of the left ovarian vein. She was treated with increased immunosuppressant and oral anticoagulant. Although she was not compliant to oral anticoagulant with her international normalized ratio frequently subtherapeutic, her symptoms abated and the thrombosis resolved. There has been only 1 reported case of a patient with Behçet disease presenting with postpartum ovarian vein thrombosis and pulmonary embolism and no reported case of Behçet disease with ovarian vein thrombosis occurring outside pregnancy and the puerperium. Ovarian vein thrombosis is a rare cause of abdominal pain that should be considered in patients with Behçet disease.