Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%‐3% of patients receiving nonionic ICM. The diagnosis ...and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re‐exposition or drug provocation test should only be done with skin test‐negative ICMs. The decision for performing either re‐exposition or drug provocation test needs to be taken based on a risk‐benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.
Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near‐daily basis, over >6 weeks; ...many patients experience flare‐ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.
Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H-antihistamines, even at high doses. In phase 2 trials, omalizumab, ...an anti-IgE monoclonal antibody corrected that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients.
In this phase 3, multicenter, randomized, double-blind study, we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H-antihistamine therapy (licensed doses). We randomly assigned 323 patients to receive three subcutaneous injections, spaced 4 weeks apart, of omalizumab at doses of 75 mg, 150 mg, or 300 mg or placebo, followed by a 16-week observation period. The primary efficacy outcome was the change from baseline in a weekly itch-severity score (ranging from 0 to 21, with higher scores indicating more severe itching).
The baseline weekly itch-severity score was approximately 14 in all four study groups. At week 12, the mean (±SD) change from baseline in the weekly itch-severity score was -5.1±5.6 in the placebo group, -5.9±6.5 in the 75-mg group (P=0.46), -8.1±6.4 in the 150-mg group (P=0.001), and -9.8±6.0 in the 300-mg group (P<0.001). Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg group (1% for each).
Omalizumab diminished clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of approved doses of H-antihistamines. (Funded by Genentech and Novartis Pharma; ClinicalTrials.gov number, NCT01292473.).
Chronic spontaneous urticaria (CSU) is defined as the spontaneous development of itchy hives and/or angioedema due to known or unknown causes that last for at least 6 weeks. At any given time, CSU is ...believed to affect 0.5–1% of the global population. Omalizumab (a recombinant, humanized anti-immunoglobulin-E antibody) is the only approved treatment for antihistamine refractory CSU. However, ~ 30% of patients remain symptomatic at licensed doses of omalizumab 150 mg and 300 mg, even after a treatment period of over 6 months. In the recent years, there have been several studies on updosing of the drug, suggesting that the individualized approach for urticaria treatment with omalizumab is useful. In this article, we provide an overview of these studies and the real-world data on omalizumab updosing as it became necessary to obtain complete CSU symptom control in a proportion of patients. Published observational studies (from June 2003 to October 2019) on the updosing of omalizumab in CSU were identified using PubMed and Ovid databases. Reports mainly show that updosing/dose adjustment evaluated with the assessment of disease activity (Urticaria Activity Score) and control (Urticaria Control Test) achieves better clinical response to omalizumab with a good safety profile in a pool of patients with CSU. These real-world data will provide an overview of updosing of omalizumab in CSU and aid in setting informed clinical practice treatment expectations.
Limonene and linalool are among the most common fragrance terpenes used in everyday products. They are pre‐haptens, forming hydroperoxides (Lim‐OOHs, Lin‐OOHs) upon oxidation and inducing frequent ...positive patch test reactions in patients with dermatitis, and yet they are not routinely tested in Europe. This review evaluates current patch testing with Lim‐OOHs and Lin‐OOHs by asking whether hydroperoxide patch testing is warranted, examining the difficulties or challenges related to reading and interpreting hydroperoxide patch test results with currently available material, and assessing their relevance. Studies are increasingly pointing to high percentages of positive reactions in patients consecutively patch tested with these oxidized products. An association between a positive clinical history and a strong patch test reaction has been described, but problems with doubtful/irritant reactions have also been reported. Considering the high frequency of relevant positive reactions, the incorporation of Lim‐OOHs 0.3% and Lin‐OOHs 1% in the baseline series may be justified. Since exposure, sensitization, and elicitation limits of Lim‐OOHs and Lin‐OOHs in the products still need to be better determined, an assessment of previous exposure, possible sensitizations, and reactions may help to improve the clinical assessment.
Summary
The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact ...dermatitis or other delayed‐type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
During a meeting in Munich, Germany, a presymptomatic attendee with severe acute respiratory syndrome coronavirus 2 infected at least 11 of 13 other participants. Although 5 participants had no or ...mild symptoms, 6 had typical coronavirus disease, without dyspnea. Our findings suggest hand shaking and face-to-face contact as possible modes of transmission.
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