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Addressing COVID19 vaccine hesitancy and minimizing potential vaccine contraindications are critical to combat the ongoing pandemic. We describe a practical approach to immediate adverse events after the first dose of the SARS-CoV2 mRNA vaccines, focusing on allergic reactions with respect to their diagnosis and management.

Summary Background The formation of neutralizing antibodies (inhibitors) directed against human coagulation factor VIII (hFVIII) is a life-threatening pathogenic response that occurs in 20–30% of severe congenital hemophilia A patients and 0.00015% of remaining population (i.e. acquired hemophilia A). Interspecies amino acid sequence disparity among FVIII orthologs represents a promising strategy to mask FVIII from existing inhibitors while retaining procoagulant function. Evidence for the effectiveness of this approach exists in clinical data obtained for porcine FVIII products, which have demonstrated efficacy in the setting of congenital and acquired hemophilia. Objectives In the current study, recombinant (r) ovine FVIII (oFVIII), was evaluated for antigenicity and procoagulant activity in the context of human patient-derived and murine model-generated FVIII inhibitors. Methods The antigenicity of roFVIII was assessed using i) inhibitor patient plasma samples, ii) murine anti-FVIII MAbs, iii) immunized murine hemophilia A plasmas, and iv) an in vivo model of acquired hemophilia A Results Overall, roFVIII demonstrated reduced reactivity to, and inhibition by, anti-hFVIII immunoglobulin in patient plasmas. Additionally, several hFVIII epitopes were predicted and empirically shown not to exist within roFVIII. In a murine hemophilia A model designed to mimic clinical inhibitor formation, it was demonstrated that inhibitor titers to roFVIII were significantly reduced compared to the orthologous immunogens, rhFVIII or rpFVIII. Furthermore in a murine model of acquired hemophilia A, roFVIII administration conferred protection from bleeding following tail transection. Conclusion These data support the investigation of FVIII orthologs as treatment modalities in both the congenital and acquired FVIII inhibitor settings.

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Mast cells (MC) have recently been demonstrated to play an integral role in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). When activated, MCs release pre-formed granules of many pro-inflammatory mediators, including histamine, serotonin, and various chemokines and cytokines including tumor necrosis factor (TNF)-α, interferon ɣ (IFN ɣ), macrophage inhibitory factor, transforming growth factor, interleukin (IL) 1, 3-6, 9, 10, 13 and 16. These mediators promote inflammation in AERD by recruiting or activating a network of cells involved in acute and chronic inflammatory pathways, such as endothelial, epithelial, stromal, and other immune cells. Several studies have implicated multifactorial pathways for MC activation in AERD beyond classical IgE mediated mechanisms. The elucidation of these complex networks therefore represents important targets for innovative patient therapeutics. This review summarizes classic and alternative pathways of MC activation in AERD with a special focus in relation to new and emerging treatment strategies.

Ocular allergy is recognized as a heterogeneous collection of immunoglobulin E (IgE) and noneIgE-mediated diseases. IgE-mediated ocular allergies include seasonal allergic conjunctivitis, perennial allergic conjunctivitis, 1 vernal keratoconjunctivitis, and atopic keratoconjunctivitis. NoneIgE-mediated ocular allergies and hypersensitivities include contact blepharoconjunctivitis, giant papillary conjunctivitis, irritative conjunctivitis, and blepharitis.The following 4 cardinal symptoms characterize ocular allergies: redness, itchiness, swelling, and watering (tearing), with several symptoms overlapping with dry eye disease.Allergological workup (skin prick testing, serum-specific IgE measurements, conjunctival provocation testing, and patch testing) is helpful in confirming a causative allergic mechanism.Newer topical corticosteroid formulations such as loteprednol have not been found to increase the risk of cataracts unlike older corticosteroids.Successful treatment usually involves a combination of avoidance of allergic triggers, medications (topical, oral, or both), and in some cases, allergy immunotherapy.

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