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Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARBinduced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAEassociated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher’s exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phredscaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusions Telangiectasia is a prominent feature of rosacea leading to a high demand for effective treatment. To ensure consistent clinical and scientific evaluations and assess treatment response accurately, standardized assessment tools are necessary for grading the severity of telangiectasia. However, no validated grading scales for this condition are currently available.To develop and validate a photonumeric scale for assessing the severity of telangiectasia in rosacea patients.The five‐point photonumeric Telangiectasia in Rosacea Severity Assessment (TRoSA) scale was developed for the severity of telangiectasia in rosacea. Sixteen experts participated in the validation process, evaluating 50 images of rosacea patients in two rounds. Interrater and intrarater reliability were analyzed using the intraclass correlation coefficient (ICC) and weighted kappa, respectively.Interrater reliability was found to be “almost perfect” in both validation rounds (Round 1: ICC 0.847; Round 2: ICC 0.828). The mean weighted kappa indicated “substantial” intrarater reliability between the two rounds with a weighted kappa of 0.719. A bubble plot of the two rounds illustrated a diagonal order, confirming the consistency of the intrarater agreement.The TRoSA scale demonstrated high interrater and intrarater reliability indicating that it is a consistent and reproducible tool for grading the severity of telangiectasia in rosacea. This scale can standardize clinical assessments, assisting in diagnosis, treatment planning, and evaluation of therapeutic efficacy. [ABSTRACT FROM AUTHOR]