Delayed cutaneous hypersensitivity reactions following the use of infliximab or adalimumab in patients with coronavirus disease 2019.

Recent evidence has emerged concerning delayed cutaneous hypersensitivity reactions after infliximab or adalimumab applications in patients with coronavirus disease 2019 (COVID-19). A few real-world studies compared the events, clinical features, and prognosis of infliximab- or adalimumab-related delayed cutaneous hypersensitivity reactions in COVID-19 patients. Disproportionality analysis and Bayesian analysis were utilized to determine the suspected adverse events of delayed cutaneous hypersensitivity reactions after infliximab or adalimumab use based on the Food and Drug Administration's Adverse Event Reporting Systems (FAERS) from May 2020 to December 2021. Additionally, the times to onset and fatality rates of delayed cutaneous hypersensitivity reactions following infliximab or adalimumab were compared. In total, 475 reports of delayed cutaneous hypersensitivity reactions were associated with infliximab or adalimumab. Females were affected almost twice more than males. Among the two therapies, infliximab had the highest association with delayed cutaneous hypersensitivity reactions based on the highest reporting odds ratio (2.14, 95% two-sided confidence interval [CI] = 1.2-3.81), proportional reporting ratio (1.95, χ2 = 7.03), and empirical Bayesian geometric mean (1.94, 95% one-sided CI = 1.2). Infliximab-related delayed cutaneous hypersensitivity reactions had earlier onset (0 [interquartile range (IQR): 0-0] days vs. 166.5 (IQR: 18-889.5) days, p < 0.05), while adalimumab-related delayed cutaneous hypersensitivity reactions have higher fatality rate (0.44% vs. 0.00%). Based on the FAERS database, we profiled delayed cutaneous hypersensitivity reactions related to infliximab or adalimumab application in patients with COVID-19 with more points of occurrences, clinical characteristics, and prognosis.

Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives.

Atopic dermatitis is a chronic inflammatory skin disease in which the overproduction of reactive oxygen species plays a pivotal role in the pathogenesis and persistence of inflammatory lesions. Phototherapy represents one of the most used therapeutic options, with benefits in the clinical picture. Studies have demonstrated the immunomodulatory effect of phototherapy and its role in reducing molecule hallmarks of oxidative stress. In this review, we report the data present in literature dealing with the main signaling molecular pathways involved in oxidative stress after phototherapy to target atopic dermatitis-affected cells. Since oxidative stress plays a pivotal role in the pathogenesis of atopic dermatitis and its flare-up, new research lines could be opened to study new drugs that act on this mechanism, perhaps in concert with phototherapy.

The need of an updated culture of "occupational" atopic hand dermatitis in children at the time of COVID-19.

During the COVID-19 outbreak, handwashing emerged as an essential tool to prevent the spread of SARS-CoV-2 virus. It can put into practice using warm water and soap or, if not available, alcohol-based hand sanitizers (ABHS). Anyway, the use of warm water and soap is not always possible. On the contrary, ABHS are frequently used for their versatility, but can represent a risk factor for atopic dermatitis exacerbations in the pediatric age. At the same time, the Italian Ministry of Health established a school regulation, asking the students to periodically disinfect hands with sanitizing gel, or soap and water, especially before entering classrooms and laboratories, immediately after contact with everyday objects, after using the toilet, after throwing away the handkerchief and before and after eating. No rules have been personalized in this statement for children affected by atopic dermatitis attending the school. Based on this observation, we reported two case reports, involving children with a known diagnosis of atopic dermatitis, who attended our Pediatric Allergy Unit in Mantua, Italy. They experienced a worsening of symptoms related to AD on their hands in the last year for an intensive handwashing with ABHS before entering all classrooms and laboratories every day at school. Avoiding ABHS at school and washing their hands with a non-alcohol and additives soap and water solved their problem and brought their atopic dermatitis back to good control. So, it seems appropriate to consider ABHS as a "school trigger" and the low-controlled atopic dermatitis of these two patients as an "occupational dermatitis". An adequate pediatric culture of atopic dermatitis at the time of COVID 19 is needed.

Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink.

BACKGROUND: The Centers for Disease Control and Prevention's Vaccine Safety Datalink (VSD) has been performing safety surveillance for COVID-19 vaccines since their earliest authorization in the United States. Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. This study's objective was to use this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S) COVID-19 vaccines. METHODS: VSD enrollees receiving a first booster of COVID-19 vaccine through April 2, 2022 were followed for 56 days. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the follow-up period. The self-controlled tree-temporal scan statistic was used, conditioning on the total number of cases for each diagnosis. P-values were estimated by Monte Carlo simulation; p = 0.01 was pre-specified as the cut-off for statistical significance of clusters. RESULTS: More than 2.4 and 1.8 million subjects received Pfizer-BioNTech and Moderna boosters after an mRNA primary series, respectively. Clusters of urticaria/allergy/rash were found during Days 10-15 after the Moderna booster (p = 0.0001). Other outcomes that clustered after mRNA boosters, mostly with p = 0.0001, included unspecified adverse effects, common vaccine-associated reactions like fever and myalgia, and COVID-19. COVID-19 clusters were in Days 1-10 after booster receipt, before boosters would have become effective. There were no noteworthy clusters after boosters following primary Janssen vaccination. CONCLUSIONS: In this untargeted data-mining study of COVID-19 booster vaccination, a cluster of delayed-onset urticaria/allergy/rash was detected after the Moderna booster, as has been reported after Moderna vaccination previously. Other clusters after mRNA boosters were of unspecified or common adverse effects and COVID-19, the latter evidently reflecting immunity to COVID-19 after 10 days.

Incidence of Asthma, Atopic Dermatitis, and Allergic Rhinitis in Korean Adults before and during the COVID-19 Pandemic Using Data from the Korea National Health and Nutrition Examination Survey.

The prevalence of allergic diseases has been increasing globally prior to COVID-19. The pandemic resulted in changes in lifestyle and personal habits such as universal mask-wearing and social distancing. However, there is insufficient information on the impact of the COVID-19 pandemic on the prevalence of allergic conditions such as asthma, atopic dermatitis, and allergic rhinitis. We analyzed the incidence rate for self-reported and doctor-diagnosed cases of allergic diseases of asthma, atopic dermatitis, and allergic rhinitis. A total of 15,469 subjects were registered from a national cohort dataset of the National Health and Nutrition Examination Survey. Using multiple logistic regression analysis, we calculated the adjusted odds ratio (OR) for each disease in 2020 compared to 2019. Subgroup analyses were performed according to age and sex. There were no statistically significant differences between the incidence of doctor-diagnosed and current allergic diseases in 2019 and 2020 (asthma, p = 0.667 and p = 0.268; atopic dermatitis, p = 0.268 and p = 0.973; allergic rhinitis, p = 0.691 and p = 0.942, respectively), and subgroup analysis showed consistent results. Among the Korean population from 2019 to 2020, the incidence of the allergic diseases asthma, atopic dermatitis, and allergic rhinitis did not decrease as expected.

Genetic causal correlations between allergic diseases and COVID-19: A systematic two-sample and bidirectional MR study (preprint)

Background: Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation remains controversial. We therefore systematically investigated the genetic causal correlations of various ADs with COVID-19 infection/severity. Methods: : We systematically performed a two-sample, bidirectional Mendelian randomization (MR) study of five ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also validated the significant causal correlations and further elucidated underlying molecular mechanisms. Results: : The most suitable MR method, for the first time, revealed significant causal effects of COVID-19 infection/severity on an increased asthma prevalence (OR>4.21), which obtained further validations. In contrast, asthma consistently demonstrated causally protective effects on critically ill and hospitalized COVID-19 cases upon adopting multiple MR methods (OR, 0.96–0.99). Our MR analyses also observed potential causal correlations of COVID-19 severity with atopic dermatitis, shrimp and peach allergy. Regarding underlying molecular mechanisms, we observed that COVID-19 phenotypes, especially those critically ill cases, were causally correlated to hematological traits and count data of immune-related cells. In contrast, ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting ACE2 protein expression. Conclusions: : Our MR analyses suggest a bidirectional causal effect between COVID-19 phenotypes and ADs, especially asthma. The potential underlying molecular mechanisms of the causal effects may be beneficial in developing effective therapeutic strategies for allergy patients with COVID-19 infection and call for more attention to their physical characteristics upon showing long-term COVID-19 symptoms.

Outcomes of COVID-19 and Vaccination in Patients With Moderate to Severe Atopic Dermatitis Treated With Tralokinumab.

This case series describes the outcomes of COVID-19 and SARS-CoV-2 vaccination in patients with atopic dermatitis who have been treated with tralokinumab.

The use of azathioprine in atopic dermatitis: A review.

Most patients with atopic dermatitis (AD) have a good response to topical treatment. However, some need systemic therapy in order to satisfactorily control the disease. Azathioprine is an accessible drug for patients in many countries, including underdeveloped countries, and therefore it is used by many dermatologists in moderate and severe AD. It is important to have a deep knowledge and understanding about this drug since it is an alternative therapy as a steroid-sparing agent and an affordable one. However, when it comes to systemic therapy for AD, it is not always clear its indications and it is necessary to have a closer follow-up of the patient. In this paper, we describe thoroughly its indications in AD, the mechanism of action of the drug, as well as the interactions, adverse effects, adequate monitoring, and precautions in special population that must be considered when prescribing azathioprine. This review will help dermatologists prescribe it safely to all patients who require it.

Effectiveness and Safety of Upadacitinib in the Treatment of Moderate-Severe Atopic Dermatitis: A Multicentric, Prospective, Real-World, Cohort Study.

BACKGROUND: The efficacy and safety of upadacitinib in atopic dermatitis (AD) have been defined in clinical trials, but no real-world data are currently available. We aimed to assess the safety and effectiveness of upadacitinib in a real-world AD patient cohort that mostly included patients who failed the available systemic therapies, including dupilumab. METHODS: Prospective cohort study collecting data on upadacitinib-treated AD adult patients completing at least 16 weeks of therapy. RESULTS: Forty-three patients showed rapid and marked response to upadacitinib with significant reduction of all disease severity scores since the first follow-up visit. At week 16, Eczema Area and Severity Index (EASI) 75, EASI 90, and EASI 100 response was observed in 97.5%, 82.1%, and 69.2% of patients, respectively. EASI 90 response reflected the achievement of a clear or almost clear condition (POEM 0-2), self-evaluated by 79.5% of patients. Patients' quality of life improved as suggested by the achievement of DLQI 0/1 by 38.5% of patients at week 4, and by 76.9% at week 16. CONCLUSION: Elevated effectiveness and favorable safety of upadacitinib were confirmed in patients unresponsive to dupilumab, who were not included in upadacitinib trials.

Social isolation: main dermatosis and the impact of stress during the COVID-19 pandemic.

OBJECTIVE: To analyze the pattern of triggering and exacerbation of dermatological diseases between March and July 2020 and to compare this pattern to the corresponding period of 2019. METHODS: This was a quantitative, descriptive, comparative and documentary study that was carried out through the retrospective analysis of medical records (March to July 2019 and 2020) of individuals assisted at a private dermatology practice service located in the southern area of the city of São Paulo (SP). RESULTS: We evaluated 992 medical consultations in 2019 and 1,176 in 2020. In 2020, we observed a significant increase in cases of telogen effluvium (276%), psoriasis (1,400%), atopic dermatitis (178%), seborrheic dermatitis (200%), herpes zoster (1,200%) and vitiligo (433%). All diseases had stress as a possible initial trigger. In addition, fragile nail syndrome and contact dermatitis, pathologies associated with behavioral measures, also had an important increase in the prevalence (6,400% and 5,500%, respectively). However, the number of aesthetic procedures decreased by approximately 54% during the pandemic period. CONCLUSION: During the pandemic period, the pattern of incidence of dermatoses had changed compared with the previous year. An emphasis was observed on diseases triggered by a psychological component, as well as those pathologies that have behavioral measures as the main cause. For this reason, the impacts of COVID-19 is greater than only among those infected.

Immunotherapy in atopic dermatitis.

In the past decade, the emergence of biologics targeting human cytokine networks has advanced a new era in atopic dermatitis therapy. Dupilumab, in particular, the most widely studied and used IL-4/IL-13 inhibitor, has been considered a milestone in the treatment of patients with moderate-to-severe atopic dermatitis. In addition to the IL-4 and IL-13 pathways, many other cytokines and receptors have been newly targeted as therapeutic options. In this review, the authors provide an overview of the approved and tested biologics and JAK inhibitors for the treatment of atopic dermatitis, including their advantages and limitations.

Recent developments in the immunopathology of COVID-19 (preprint)

There has been an important change in the clinical characteristics and immune profile of COVID-19 patients during the pandemic thanks to the extensive vaccination programs. Here, we highlight recent studies on COVID-19, from the clinical and immunological characteristics to the protective and risk factors for severity and mortality of COVID-19. The efficacy COVID-19 vaccines and potential allergic reactions after administration are also discussed. The occurrence of new variants of concerns such as Omicron BA.2, BA.4 and BA.5 and the global administration of COVID-19 vaccines have changed the clinical scenario of COVID-19. Multisystem inflammatory syndrome in children (MIS-C) has been identified as an important cause of death of children with COVID-19. Perturbations in immunity of T cells, B cells, and mast cells, as well as autoantibodies and metabolic reprogramming may contribute to the long-term symptoms of COVID-19. Atopic diseases, such as allergic asthma and rhinitis, have been shown to be associated with a lower susceptibility and better outcomes of COVID-19. At the beginning of pandemic, EAACI developed guidelines that provided timely information for the management of allergic diseases and preventive measures to reduce transmission in the allergic clinics. The global distribution of COVID-19 vaccines and emerging SARS-CoV-2 variants with reduced pathogenic potential dramatically decreased the morbidity, severity, and mortality of COVID-19. Nevertheless, breakthrough infection remains a challenge for disease control. Hypersensitivity reactions (HSR) to COVID-19 vaccines are low compared to other vaccines, and these were addressed in EAACI statements that provided indications for the management of allergic reactions, including anaphylaxis to COVID-19 vaccines. We have gained a depth knowledge and experience in the over 2 years since the start of the pandemic, and yet a full eradication of SARS-CoV-2 is not on the horizon. Novel strategies are warranted to prevent severe disease in high-risk groups, the development of MIS-C and long COVID.

Incidence of immediate allergic reactions to mRNA COVID-19 vaccines in adults with drug allergies and other allergic disorders.

Concerns have been raised about allergic reactions to messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccines. A history of allergic reactions, including anaphylaxis to drugs, has been frequently reported in individuals with anaphylaxis to mRNA vaccines. To estimate the rate of immediate allergic reactions in patients with a history of drug allergy or other allergic disorders. We included adult patients who had received at least 1 dose of an mRNA COVID-19 vaccine at the Special Hospital for Pulmonary Diseases between March 1, 2021, and October 1, 2021, and who reported a history of drug allergy or other allergic diseases (asthma, allergic rhinitis, atopic dermatitis, food or insect venom allergy, mastocytosis, idiopathic anaphylaxis, acute or chronic urticaria, and/or angioedema). Immediate allergic reactions, including anaphylaxis, occurring within 4 hours of vaccination were recorded. Six immediate allergic reactions were noted in the cohort of 1679 patients (0.36%). One patient experienced anaphylaxis (0.06%), which resolved after epinephrine administration, and the other reactions were mild and easily treatable. Most patients with a history of allergies can safely receive an mRNA COVID-19 vaccine, providing adequate observation periods and preparedness to recognize and treat anaphylaxis.

General and Skin-Specific Health-Related Quality of Life in Patients With Atopic Dermatitis Before and During the COVID-19 Pandemic.

BACKGROUND: Few studies have investigated health-related quality of life (HRQoL) in patients with atopic dermatitis (AD) during the COVID-19 pandemic. OBJECTIVES: The objectives of this study were to compare HRQoL in adult AD patients before and during the pandemic and to assess measurement performance of 4 HRQoL measures. METHODS: Between 2018 and 2021, a multicenter, cross-sectional survey was conducted, involving 218 adult AD patients. Health-related quality of life outcomes included the EQ-5D-5L, Skindex-16, Dermatology Life Quality Index (DLQI), and DLQI-Relevant (DLQI-R). Severity was measured using objective SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Investigator Global Assessment. RESULTS: The mean ± SD EQ-5D-5L utility, Skindex-16, DLQI, and DLQI-R scores were 0.82 ± 0.22, 56.84 ± 27.46, 13.44 ± 8.46, and 13.76 ± 8.60, respectively. The patients reported more problems during the pandemic ( P < 0.05) regarding pain/discomfort (odds ratio [OR], 1.78), worrying (OR, 1.89), concerns about persistence/reoccurrence of disease (OR, 1.88), and social relationships (OR, 1.69). The HRQoL outcomes showed strong correlations with each other (range of rs , |0.69| to |0.99|). The Skindex-16, DLQI, and DLQI-R were able to discriminate between severity groups with large (η 2 = 0.20-0.23), whereas the EQ-5D-5L with moderate effect sizes (η 2 = 0.08-0.11). CONCLUSIONS: Atopic dermatitis patients experienced significantly more problems in some areas of HRQoL during the pandemic. The EQ-5D-5L, Skindex-16, DLQI, and DLQI-R demonstrated good convergent and known-group validity and can be suitable instruments for HRQoL assessment in clinical and research settings.