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Background: Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome of suspected SARS‐CoV‐2 vaccine hypersensitivity. Methods: Totally, 334 individuals underwent an allergy work up regarding SARS‐CoV‐2 vaccination (group A: 115 individuals suspected to be at increased risk for vaccine‐related reactions before vaccination and group B: 219 patients with reactions after COVID vaccination). The large majority of the SPT/IDT with the vaccines were negative; however, we identified in 14.1% (n = 47) a possible sensitization to the SARS‐CoV‐2 vaccine and/or its ingredients defined as one positive skin test. Of the 219 individuals (group B) who experienced symptoms suspicious for a hypersensitivity reaction after vaccination, 214 were reported after the first vaccination with a mRNA vaccine (157 mRNA (Comirnaty®, 38 Spikevax®) and 18 with a vector vaccine (Vaxzevria®), 5 cases were after the second vaccination. Results: The symptom profile in group B was as follows: skin symptoms occurred in 115 cases (n = 59 angioedema, n = 50 generalized urticaria and n = 23 erythema/flush. Seventy individuals had cardiovascular, 53 respiratory and 17 gastrointestinal symptoms. Of the overall 334 individuals, 78 patients tolerated (re)‐vaccination (out of skin test positive/negative 7/19 from group A and 17/35 from group B). Conclusion: Proven IgE‐mediated hypersensitivity to SARS‐CoV‐2 vaccines is extremely rare and not increased in comparison with reported hypersensitivity to other vaccines. The value of skin tests is unclear and nonspecific reactions, in particular when intradermal testing is applied, should be considered. [ABSTRACT FROM AUTHOR]

Background: Patch test (PT) readings are recommended after 48 h and 72 h (D3). An additional day 7 (D7) reading has been suggested by some, although data on efficient patient selection are scarce. We investigated positive D7 reactions regarding (i) allergens in the baseline series and additional PT series of the German Contact Dermatitis Research Group (DKG) and (ii) characteristics of the patients tested. Methods: Retrospective, multicentre analysis of 190 allergens derived from 17 DKG test series in 4687 patients with an additional D7 reading. Patients were patch tested with the baseline series and additional series, if required. Occurrence of novel D7 reactions as well as increasing skin reactions from D3 to D7 was analysed separately. Results: Depending on the allergen tested, waiving D7 readings would have missed 4.4–26.8% of positive PT results. Patch test series with the highest number of novel D7 reactions were baseline series, metal series, and leather/shoe series. New positive reactions on D7 were associated with age over 50 years and with a negative irritant control containing sodium lauryl sulphate. Of note, application of the PT allergens for 48 h instead of 24 h was positively associated with late PT reactions. Conclusion: Within the most frequently tested allergens, without late readings, on average 11.7% of sensitizations would have been missed. Novel late reacting allergens were identified. This study comprehensively dissects patient‐, allergen‐ and test‐dependent parameters in support for D7 readings. We propose to always consider late readings individually based on effort‐benefit considerations. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood. Methods: To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE‐inhibitor induced (ACE‐AE), and 12 mast cell‐mediated without wheals in chronic spontaneous urticaria (CSU‐AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin‐lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme‐linked immunosorbent assay. Results: New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin‐mediated (BK‐) AE (ie, HAE and ACE‐AE) from mast cell‐/histamine‐mediated CSU‐AE. However, FAP‐α and tPA were significantly increased in all AE compared to controls. In HAE, FAP‐ α, tPA, uPAR, pentraxin‐3, Tie‐2, sE‐selectin, and VE‐cadherin were significantly increased compared to controls. In HAE compared to CSU‐AE and ACE‐AE, sE‐Selectin, Tie‐2, and VE‐Cadherin were significantly increased, whereas for Ang‐2 the difference was significant compared to CSU‐AE only. Tie‐2 correlated strongly negatively with C4, C1‐INH activity, and C1‐INH function. Conclusions: This study is the first to compare HAE, ACE‐AE, and CSU‐AE. Although significance is limited by small sample size, Tie‐2 was identified as a new promising biomarker candidate for HAE. FAP‐ α and tPA might serve as a marker for AE in general, whereas sE‐selectin and Ang‐2 were increased in BK‐AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes. [ABSTRACT FROM AUTHOR]

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss‐of‐function mutations of these genes constitute a risk factor for atopic dermatitis and eczema‐related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double‐deficient (FlgHrnr−/−) mouse model lacking both genes including the intergenomic sequence. Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr−/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr−/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady‐state conditions, FlgHrnr−/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions: Together, our FlgHrnr−/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions. [ABSTRACT FROM AUTHOR]

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss-of-function mutations of these genes constitute a risk factor for atopic dermatitis and eczema-related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation., Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double-deficient (FlgHrnr -/- ) mouse model lacking both genes including the intergenomic sequence., Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr -/- mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr -/- mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady-state conditions, FlgHrnr -/- mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions., Conclusions: Together, our FlgHrnr -/- mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)