Injection site reactions after dupilumab or tralokinumab for atopic dermatitis.

Background: Injection site reaction (ISR) is a local phenomenon defined as a constellation of symptoms, including swelling, erythema, pruritus, and pain around the site of injection.Objective: ISR is reported as a frequent adverse event after subcutaneous injection (SCI) of several biologics.Methods: We performed an observational real-life study to compare dupilumab and tralokinumab as regards ISR, analysing frequency, duration and intensity of symptoms related to SCI. From January 2023 to June 2023, we enrolled adult patients affected by moderate to severe AD and being on dupilumab or tralokinumab treatment. A 12 items questionnaire was administered to all enrolled patients.Results and conclusions: Three hundred and ninety-two patients were included. ISR was a frequent occurrence in both the treatment groups, with tralokinumab causing ISR more frequently than dupilumab. However, the reactions were generally mild and no patient stopped therapy.

A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections.

BACKGROUND: Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. OBJECTIVE: To summarize injection site reaction data in phase 3 trials of all biologic agents. METHODS: MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. RESULTS: There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). CONCLUSIONS: The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.

Safety of BCG vaccination and revaccination in healthcare workers.

BCG vaccination and revaccination are increasingly being considered for the protection of adolescents and adults against tuberculosis and, more broadly, for the off-target protective immunological effects against other infectious and noninfectious diseases. Within an international randomized controlled trial of BCG vaccination in healthcare workers (the BRACE trial), we evaluated the incidence of local and serious adverse events, as well as the impact of previous BCG vaccination on local injection site reactions (BCG revaccination). Prospectively collected data from 99% (5351/5393) of participants in Australia, Brazil, Spain, The Netherlands and the UK was available for analysis. Most BCG recipients experienced the expected self-limiting local injection site reactions (pain, tenderness, erythema, swelling). BCG injection site itch was an additional common initial local symptom reported in 49% of BCG recipients. Compared to BCG vaccination in BCG-naïve individuals, BCG revaccination was associated with increased frequency of mild injection site reactions, as well as earlier onset and shorter duration of erythema and swelling, which were generally self-limiting. Injection site abscess and regional lymphadenopathy were the most common adverse events and had a benign course. Self-resolution occurred within a month in 80% of abscess cases and 100% of lymphadenopathy cases. At a time when BCG is being increasingly considered for its off-target effects, our findings indicate that BCG vaccination and revaccination have an acceptable safety profile in adults.

Global incidence pattern and factors associated with common cutaneous reactions related to COVID-19 vaccination of 2.55 million participants in real-world settings: A systematic review and meta-analysis.

Background: Understanding the incidence pattern of cutaneous reactions is crucial for promoting COVID-19 vaccination. We aimed to report the global incidence pattern of, and factors associated with common cutaneous reactions related to COVID-19 vaccination in real-world settings. Methods: We searched five databases (PubMed, Web of Science, Embase, CNKI, and Wanfang) from inception to May 13, 2022, for studies reporting the incidence of common cutaneous reactions related to COVID-19 vaccines in real-world settings. The outcomes were the systematic skin reactions (rash and urticaria) and the local injection site reactions (pain, swelling, redness, and erythema). We conducted random-effects meta-analyses and explored associated factors using multi-step statistical analyses. Results: We included 35 studies and assessed 2 549 968 participants from 23 countries. The pooled incidence of overall systemic skin reactions was 3.8% (95% confidence interval (CI) = 2.4%-5.5%) with short duration (about one week). Specifically, the pooled incidence rates of rash and urticaria were 3.0% (95% CI = 2.1%-3.9%) and 1.1% (95% CI = 0.7%-1.5%), respectively. For overall local injection site reactions, the pooled incidence was 72.4% (95% CI = 65.7%-78.7%) with short duration (1 to 4.5 days). Except for local pain (72.2%, 95% CI = 65.3%-78.5%), other localized reactions had low incidence, including swelling (13.3%, 95% CI = 9.5%-17.7%), redness (11.5%, 95% CI = 5.7%-19.0%), and erythema (5.8%, 95% CI = 0.7%-15.4%). Geographically, different distribution patterns were observed for these reactions. Regarding associated factors, mRNA vaccines showed lower incidence of urticaria (P < 0.001). Asia population showed higher incidence of urticaria (P < 0.001). We observed lower incidence rates of overall local injection site reactions and pain among inactivated vaccines (P < 0.001). We found no significant difference among reactions between the first and the second dose of vaccines. Conclusions: We examined the global incidence pattern of common cutaneous reactions related to COVID-19 vaccination and found low incidence and short duration of systemic skin reactions and local injection site reactions (except for pain); discrepancies in these reactions were observed across different vaccine types. The cutaneous side effects related to COVID-19 vaccination do not seem to cause concern. Registration: PROSPERO: CRD42021258012.

Lower injection-site reactions and long-term safety, immunogenicity, and efficacy of etanercept biosimilar YLB113: Results from a post-hoc analysis of a double-blind, randomized, phase III comparative study and its open-label extension in patients with rheumatoid arthritis.

AIM: YLB113 biosimilar was evaluated in an open-label extension single-arm study to assess long-term safety, efficacy, and immunogenicity in patients with rheumatoid arthritis (RA). We also report post-hoc results on the incidence of injection-site reactions (ISRs) and injection-site erythema (ISE) from a phase III study. METHOD: Participants from the phase III, double-blind, randomized, 96 week equivalence study who completed the final visit received 50 mg YLB113 subcutaneously every 2 weeks. Key safety end points were assessed through adverse events (AEs), ISRs, ISE, and anti-drug antibody (ADA) incidence. The efficacy end point was change from baseline in Disease Activity Score 28-joint count (DAS28) over time. RESULTS: Of 201 participants, 184 (91.5%) completed the study. Treatment-emergent AEs were experienced by 93.5% and severe AEs by 10.0% of participants. The discontinuation rate due to AEs was 2.0%. Overall, 20.0% of participants reported an incidence of ISRs throughout the open-label extension study. Two participants developed ADAs, and none developed neutralizing ADAs at any time after study drug administration. The overall DAS28 (mean ± SD) change was 2.22 ± 0.95 at the study transition, 2.10 ± 0.91 at week 72, and 2.06 ± 0.89 at the end of the study. In the post-hoc analysis, YLB113 showed a statistically significant lower incidence of ISRs (10 [3.8%], P < 0.0001) and ISE (5 [1.9%], P < 0.0001) compared with the reference product Enbrel®. CONCLUSION: YLB113 demonstrated long-term safety and sustained efficacy for up to 96 weeks. Patients on YLB113 experienced significantly lower ISRs and ISE in a post-hoc analysis of the phase III study when compared with reference product.

Cutaneous adverse events following 771 doses of the inactivated and mRNA COVID-19 vaccines: A survey study among health care providers.

INTRODUCTION: As Coronavirus disease 19 (COVID-19) still continues to affect humanity worldwide, different types of COVID-19 vaccines are being administered to maintain immunization against COVID-19. As both the inactivated and mRNA vaccines are now being applied prevalently, systemic adverse events along with cutaneous side effects are frequently being reported in the literature. AIM: In our study, we aimed to determine the cutaneous adverse effects of the inactivated (Sinovac-CoronaVac) and mRNA (Pfizer-BioNTech) vaccines in healthcare providers in a tertiary referral hospital. METHODS: A web-based survey consisting of 26 questions related to the systemic and cutaneous side effects of the inactivated and mRNA COVID-19 vaccines, was formed. The online questionnaire was spread among the healthcare professionals working in a tertiary referral hospital via common instant messaging groups and e-mail. FINDINGS: A total number of 234 participants were included in the study. One hundred fifty-seven were female whereas 77 were male. The mean age was 31.51 years. Eighty-nine respondents reported to have at least one cutaneous side effect after COVID-19 vaccination. Most commonly observed cutaneous side effects were local injection site reactions. Pfizer-BioNTech vaccine at the first and second doses, was shown to have statistically significantly higher rates of systemic and cutaneous adverse events compared to the Sinovac-CoronaVac vaccine. RESULTS: Our study shows that both inactivated and mRNA COVID-19 vaccines are associated with transient local injection site reactions, no severe systemic or cutaneous adverse events were observed in our study population.

Cutaneous adverse reactions to coronavirus vaccines: A Saudi nationwide study.

The coronavirus vaccine was developed to help overcome the COVID-19 crisis. This study aimed to identify the cutaneous side effects secondary to Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines in the general population of Saudi Arabia and to list the risk factors for the development of cutaneous side effects. This cross-sectional study was conducted in 2021, self-administered surveys were distributed electronically through social media, and telephonic interviews were conducted with a sample size of 1000 participants. Data analysis was performed using Statistical Package for the Social Sciences. A total of 1021 patients (229 male and 722 female) aged 12 years or older were included. While 833 participants were medically free, 188 had chronic illnesses. While 802 participants were not taking any medications, 219 were taking medications regularly. Oxford-Astra Zeneca and Pfizer BioNTech vaccines were administered to 319 and 702 participants, respectively. One-hundred and twenty-five participants previously had COVID-19 infection and 407 were exposed to a PCR positive case of COVID. Six hundred and fifty-nine patients (64.5%) reported experiencing injection site reactions: 606 (59.4%) had injection site pain, 168 (16.5%) had injection site swelling, and 107 (10.5%) had injection site redness. Only 51 patients (5%) experienced cutaneous side effects after injection. A significant association was found between chronic illnesses and cutaneous side effects post-vaccine (9% vs. 4.1%; p value = 0.005). Patients on medications showed a higher rate of symptoms (8.2% vs. 4.1%; p value = 0.005). Age, gender, vaccine types, and history of COVID-19 infection were not significantly associated with cutaneous side effects post-vaccine.

Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB). METHODS: A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan-Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy. RESULTS: Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil. CONCLUSIONS: In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.

Incidence and Characteristics of Delayed Injection Site Reaction to the mRNA-1273 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine (Moderna) in a Cohort of Hospital Employees.

BACKGROUND: mRNA SARS-CoV-2 vaccines are administered to 2 million individuals per day in the United States under US Food and Drug Administration emergency use authorization. METHODS: Observational cohort study of hospital employees who received their first SARS-CoV-2 mRNA vaccination between 14 December 2020 and 8 January 2021, including employees who reported onset of an injection site reaction ≥48 hours after administration of their first or second dose to an employee hotline. RESULTS: Thirteen female employees who received the mRNA-1273 vaccine (Moderna) during the first 3 weeks of the SARS-CoV-2 vaccine rollout at San Francisco General Hospital reported a pruritic rash at the injection site appearing 3 -9 days after receipt of their initial dose. Five had milder or similar reactions with earlier onset after the second dose. One additional female employee reported this delayed reaction only after the second dose. None reported serious adverse events or had symptoms severe enough to seek medical attention. These cases represented 1.1% of the 1275 female employees who received their first mRNA-1273 dose and 2.0% of the 557 who were aged 31 -45 years during this initial vaccine rollout. None of 675 males who initiated mRNA-1273 or 3612 employees of any sex who initiated BNT162b (Pfizer) vaccination during this period reported delayed-onset reactions. CONCLUSIONS: These results suggest that delayed-onset, injection site pruritic rashes after mRNA-1273 SARS-CoV-2 vaccine administration, lasting up to 1 week, occur commonly in females, do not lead to serious sequela, and should not deter receipt of the second vaccine dose.

Harm reduction for the treatment of patients with severe injection-related infections: description of the Jackson SIRI Team.

INTRODUCTION: Hospitalizations for severe injection-related infections (SIRI), such as endocarditis, osteomyelitis, and skin and soft tissue infections (SSTI) are increasingly common. People who inject drugs (PWID) experiencing SIRIs often receive inadequate substance use disorder (SUD) treatment and lack of access to harm reduction services. This translates into lengthy hospitalizations with high rates of patient-directed discharge, readmissions, and post-hospitalization mortality. The purpose of this study was to describe the development of an integrated "SIRI Team" and its initial barriers and facilitators to success. MATERIALS AND METHODS: The Jackson SIRI Team was developed to improve both hospital and patient-level outcomes for individuals hospitalized with SIRIs at Jackson Memorial Hospital, a 1550-bed public hospital in Miami, Florida, United States. The SIRI Team provides integrated infectious disease and SUD treatment across the healthcare system starting from the inpatient setting and continuing for 90-days post-hospital discharge. The team uses a harm reduction approach, provides care coordination, focuses on access to medications for opioid use disorder (MOUD), and utilizes a variety of infection and addiction treatment modalities to suit each individual patient. RESULTS: Over the initial 8-months of the SIRI Team, 21 patients were treated with 20 surviving until discharge. Infections included osteomyelitis, endocarditis, bacteraemia/fungemia, SSTIs, and septic arthritis. All patients had OUD and 95% used stimulants. All patients were discharged on MOUD and 95% completed their prescribed antibiotic course. At 90-days post-discharge, 25% had been readmitted and 70% reported taking MOUD. CONCLUSIONS: A model of integrated infectious disease and SUD care for the treatment of SIRIs has the potential to improve infection and addiction outcomes. Providing attentive, patient-centered care, using a harm reduction approach can facilitate engagement of this marginalized population with the healthcare system.KEY MESSAGESIntegrated infectious disease and addiction treatment is a novel approach to treating severe injection-related infections.Harm reduction should be applied to treating patients with severe injection-related infections with a goal of facilitating antibiotic completion, remission from substance use disorder, and reducing hospital readmissions.

Prevalence of COVID-19 vaccines (Sputnik V, AZD-1222, and Covaxin) side effects among healthcare workers in Birjand city, Iran.

BACKGROUND: The prevalence of vaccine side effects plays an important role in public perception about vaccination programs. This study was designed to investigate the side effects of the first dose of COVID-19 vaccine; Sputnik-V, AZD-1222, and Covaxin. METHODS: A study was performed to evaluate the side effects of these vaccine among 503 health care workers in Birjand (Iran). Our study used the questionnaire consisted of 4 main categories including demographic data, previous COVID-19 infection, vaccine information, and local and systemic side effects of vaccines. RESULTS: 81.9%, 88.8%, and 92.9% of people who have been vaccinated with Sputnik-V, AZD1222, and Covaxin vaccines, respectively, have reported at least one side effect. The prevalence of systemic side effects in AZD-1222 vaccine was higher than Sputnik V and Covaxin vaccines. Injection site pain (62.1%), fatigue (43.9%), muscle pain (42.5%), and fever (40.6%) were the most common side effects in all three vaccines. Side effect frequency was higher in the female group (90.6%) than the male group (79.5%). The prevalence of side effects with Sputnik V and Covaxin vaccines was reduced in the elderly. Moreover, the prevalence of side effects was higher in the case of convalescent patients (92.4 %) than in the group with no history of infection. The prevalence of side effects was higher in person with a BMI above 25 in the AZD-1222 and Covaxin vaccines. CONCLUSIONS: The most common side effects of the Sputnik-V, AZD-1222, and Covaxin vaccine among Birjand (Iran) healthcare workers were injection site pain, muscle pain, fatigue, fever, and headache. Age and gender were the most important variables in the prevalence of vaccine side effects.

Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine: A Case Series.

Importance: In response to the coronavirus disease 2019 (COVID-19) pandemic, 2 mRNA vaccines (Pfizer-BioNTech and Moderna) received emergency use authorization from the US Food and Drug Administration in December 2020. Some patients in the US have developed delayed localized cutaneous vaccine reactions that have been dubbed "COVID arm." Objective: To describe the course of localized cutaneous injection-site reactions to the Moderna COVID-19 vaccine, subsequent reactions to the second vaccine dose, and to characterize the findings of histopathologic examination of the reaction. Design, Setting, and Participants: This retrospective case series study was performed at Yale New Haven Hospital, a tertiary medical center in New Haven, Connecticut, with 16 patients referred with localized cutaneous injection-site reactions from January 20 through February 12, 2021. Main Outcomes and Measures: We collected each patient's demographic information, a brief relevant medical history, clinical course, and treatment (if any); and considered the findings of a histopathologic examination of 1 skin biopsy specimen. Results: Of 16 patients (median [range] age, 38 [25-89] years; 13 [81%] women), 14 patients self-identified as White and 2 as Asian. The delayed localized cutaneous reactions developed in a median (range) of 7 (2-12) days after receiving the Moderna COVID-19 vaccine. These reactions occurred at or near the injection site and were described as pruritic, painful, and edematous pink plaques. None of the participants had received the Pfizer-BioNTech vaccine. Results of a skin biopsy specimen demonstrated a mild predominantly perivascular mixed infiltrate with lymphocytes and eosinophils, consistent with a dermal hypersensitivity reaction. Of participants who had a reaction to first vaccine dose (15 of 16 patients), most (11 patients) developed a similar localized injection-site reaction to the second vaccine dose; most (10 patients) also developed the second reaction sooner as compared with the first-dose reaction. Conclusions and Relevance: Clinical and histopathologic findings of this case series study indicate that the localized injection-site reactions to the Moderna COVID-19 vaccine are a delayed hypersensitivity reaction. These reactions may occur sooner after the second dose, but they are self-limited and not associated with serious vaccine adverse effects. In contrast to immediate hypersensitivity reactions (eg, anaphylaxis, urticaria), these delayed reactions (dubbed "COVID arm") are not a contraindication to subsequent vaccination.

Transition from Intravenous to Subcutaneous Daratumumab Formulation in Clinical Practice.

INTRODUCTION: Daratumumab is an anti-CD38 monoclonal antibody widely used for treating patients with newly diagnosed or relapsed/refractory multiple myeloma. The subcutaneous formulation of daratumumab was developed with the purpose of minimizing the treatment burden (to patients and health care system) associated with intravenous daratumumab. Given its recent approval, there is a knowledge gap regarding the best practices that should be instituted for safe administration of subcutaneous daratumumab. METHODS: A retrospective chart review was performed from August 2020 until November 2020 to identify patients either switched to or treated upfront (daratumumab naive) with any subcutaneous daratumumab-based treatment regimen. All patients received appropriate premedications per institutional standards of care. The study end points were to report real-world data regarding administration-related reaction rates (at or following discharge from infusion center), as well as compare their incidence rates to those noted in the COLUMBA study (historical cohort). RESULTS: The study included 58 patients, of whom 38% (n = 22) were daratumumab naive. The majority (84%, n = 49) received subcutaneous daratumumab in combination with various antimyeloma regimens. There were no cases of administration-related reactions at infusion center or after discharge irrespective of previous exposure to intravenous daratumumab. None of the patients included herein required rescue home medications or visited the emergency department within 24 to 48 hours after subcutaneous daratumumab administration. These translated into a significant difference in incidence of administration-related reactions compared with historical cohort (0% vs. 13%, P = .003). CONCLUSION: Subcutaneous daratumumab was extremely well tolerated and could be safely administered without need for monitoring or rescue home medications.

Infections associated with diabetic-care devices.

BACKGROUND AND AIMS: There are more than 463 million people living with diabetes with this number expected to increase to 700 million people by 2045. Diabetes is a risk factor for patients developing various comorbidities including, but not limited to, diabetic neuropathy, retinopathy, chronic kidney disease, vascular impediments, and infections. Due to the continuous invasiveness of monitoring and/or treatment of this disease, site for infections are elevated. METHODS: Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Key search words employed were: diabetes, insulin site infection, lancing infections, insulin pump associated infections, and continuous glucose monitoring infections. RESULTS: Diabetic care devices used for blood glucose monitoring and insulin administration are an integral part of the disease management and/or treatment in various settings including patient homes, assisted living facilities, community centers, and hospitals. These invasive devices leave a diabetic patient with a small open wound which may get infected or aid in blood borne pathogen transmission. Since diabetes itself has a morbidity and mortality burden, it is important to also study complications arising from the management of diabetes. CONCLUSION: Although cases exist of infections, either by pathogen transmission or direct inoculation of the prick site, these are a very small percentage and thus should not undermine the confidence in diabetes management. This review highlights the instances of these infections and where they most often occur.

Effectiveness and Safety of Long-Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real-Life Observational Study.

OBJECTIVE: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks. METHODS: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52. RESULTS: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent. CONCLUSIONS: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults.

Importance: Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. Objective: To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. Design, Setting, and Participants: This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. Exposure: One or more doses of rituximab. Main Outcomes and Measures: Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. Results: We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Conclusions and Relevance: Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.

Immunogenicity and Safety of Reduced-Dose Intradermal vs Intramuscular Influenza Vaccines: A Systematic Review and Meta-analysis.

Importance: Low-dose intradermal influenza vaccines could be a suitable alternative to full intramuscular dose during vaccine shortages. Objective: To compare the immunogenicity and safety of the influenza vaccine at reduced or full intradermal doses with full intramuscular doses to inform policy design in the event of vaccine shortages. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published from 2010 until June 5, 2020. Study Selection: All comparative studies across all ages assessing the immunogenicity or safety of intradermal and intramuscular influenza vaccinations were included. Data Extraction and Synthesis: Data were extracted by a single reviewer and verified by a second reviewer. Discrepancies between reviewers were resolved through consensus. Random-effects meta-analysis was conducted. Main Outcomes and Measures: Primary outcomes included geometric mean titer, seroconversion, seroprotection, and adverse events. Results: A total of 30 relevant studies were included; 29 studies were randomized clinical trials with 13 759 total participants, and 1 study was a cohort study of 164 021 participants. There was no statistically significant difference in seroconversion rates between the 3-µg, 6-µg, 7.5-µg, and 9-µg intradermal vaccine doses and the 15-µg intramuscular vaccine dose for each of the H1N1, H3N2, and B strains, but rates were significantly higher with the 15-µg intradermal dose compared with the 15-µg intramuscular dose for the H1N1 strain (rate ratio [RR], 1.10; 95% CI, 1.01-1.20) and B strain (RR, 1.40; 95% CI, 1.13-1.73). Seroprotection rates for the 9-µg and 15-µg intradermal doses did not vary significantly compared with the 15-µg intramuscular dose for all the 3 strains, except for the 15-µg intradermal dose for the H1N1 strain, for which rates were significantly higher (RR, 1.05; 95% CI, 1.01-1.09). Local adverse events were significantly higher with intradermal doses than with the 15-µg intramuscular dose, particularly erythema (3-µg dose: RR, 9.62; 95% CI, 1.07-86.56; 6-µg dose: RR, 23.79; 95% CI, 14.42-39.23; 9-µg dose: RR, 4.56; 95% CI, 3.05-6.82; 15-µg dose: RR, 3.68; 95% CI, 3.19-4.25) and swelling (3-µg dose: RR, 20.16; 95% CI, 4.68-86.82; 9-µg dose: RR, 5.23; 95% CI, 3.58-7.62; 15-µg dose: RR, 3.47 ; 95% CI, 2.21-5.45). Fever and chills were significantly more common with the 9-µg intradermal dose than the 15-µg intramuscular dose (fever: RR, 1.36; 95% CI, 1.03-1.80; chills: RR, 1.24; 95% CI, 1.03-1.50) while all other systemic adverse events were not statistically significant for all other doses. Conclusions and Relevance: These findings suggest that reduced-dose intradermal influenza vaccination could be a reasonable alternative to standard dose intramuscular vaccination.

Botulinum toxin type A versus 5-Fluorouracil in treatment of keloid.

Most therapeutic approaches for keloids remain clinically unsatisfactory. In the last years, intralesional botulinum toxin-A (IL BTX-A) was proposed for treatment of keloids. Our aim of the study was to compare the clinical efficacy of IL BTX-A and IL 5-Fluorouracil (IL 5-FU) in treatment of keloids. A total of 50 patients with keloids were included in the study, 22 patients (with 26 keloids) were treated with IL BTX-A monthly for up to 6 months and other 22 patients (with 27 keloids) were treated with IL 5-FU weekly for up to 6 weeks, while the remaining 6 patients, each having multiple keloids, were treated with both IL BTX-A for some lesions (8 keloids) and IL 5-FU for their remaining lesions (8 keloids). The clinical improvement was assessed according to flattening of the lesions. Side effects were recorded. A significantly better therapeutic response of keloids was detected after IL BTX-A than IL 5-FU (P = 0.041). IL BTX-A achieved excellent and good flattening of the lesions (58.8% and 20.6%) compared to (31.4% and 17.1%) after IL 5-FU, respectively. In BTX-A treated group, there was no statistically significant difference between the clinical response in small lesions compared to medium and large ones (P = 0.476). While in 5-FU treated group, small and medium lesions showed significantly better response than larger ones (P = 0.009). IL BTX-A caused fewer side effects than IL 5-FU, less pain, itching, no hyperpigmentation and less recurrence. Both IL BTX-A and IL 5-FU showed positive results in treatment of keloids. However, IL BTX-A showed higher clinical efficacy even in large size keloids with less side effects.