Management of immune-related cutaneous adverse events with dupilumab.

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70-90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.

Self-Reported Prevalence of Allergies in the USA and Impact on Skin-An Epidemiological Study on a Representative Sample of American Adults.

BACKGROUND: The rising prevalence of allergies can substantially impact the skin, which is one of the largest targets for allergic and immunologic responses. OBJECTIVE: Here, we describe the results of an online survey assessing self-reported allergy prevalence in Americans, outline the populations who report allergies, and characterize the skin conditions associated with allergy. METHODS: An online survey was conducted in the USA of 2,008 adults as a representative sample of the general American population. RESULTS: 41.7% of American adults (mean age 44.7 ± 15.3 years old) reported having allergies. Reported allergies included respiratory allergies (45.2%), skin allergies (41.4) and food allergies (33.9%). 47.7% of those who reported allergies also reported experiencing associated skin reactions. In addition, those who reported allergies were 2 to 4.5 times more likely to report a cutaneous skin disease, 7 times more likely to report sensitive skin, and twice as likely to report experiencing skin reactions when using skincare products compared to those who did not report allergies. CONCLUSIONS: It is estimated that over 100 million American adults have allergies. These results will help raise awareness about the burden of allergies and the need to develop solutions to mitigate their impact on health.

The Promise of Electronic Health Records to Promote Shared Decision Making: A Narrative Review and a Look Ahead.

BACKGROUND: Shared decision making (SDM) involves the sharing of best available evidence between patients and providers in the face of difficult decisions. We examine outcomes that occur when electronic health records (EHRs) are purposefully used with the goal of improving SDM and detail which EHR functions can benefit SDM. METHODS: A systematic search of PubMed yielded 1369 articles. Studies were included only if they used EHR interventions to support SDM and included results that showed impact on SDM. Articles were excluded if they did not measure the impact of the intervention on SDM or did not discuss how SDM had been supported by the EHR. RESULTS: Five studies demonstrated improved clinical outcomes, positive lifestyle behavior changes, more deliberation from patients regarding use of imaging, and less decisional conflict about medication use among patients with use of EHRs aiding SDM. DISCUSSION: Few EHRs have integrated SDM, and even fewer evaluations of these exist. EHRs have potential in supporting providers during all steps of SDM. The promise of EHRs to support SDM has yet to be fully exploited.

HIV Alters Gap Junction-Mediated Intercellular Communication in Human Brain Pericytes.

Despite successful control of viremia by combined antiretroviral therapy, brain infection and its resulting neurocognitive impairment remain a prevalent comorbidity in HIV infected individuals. HIV invades the brain early in the course of infection via penetration through the blood-brain barrier (BBB). While the impact of HIV on BBB astrocytes and endothelial cells is relatively well studied, the role of pericytes in BBB regulation during HIV infection remains unclear; however, it is known that a selective population of pericytes is prone to infection. In the present study, we hypothesize that injury signals are propagated from infected pericytes to neighboring cells via gap junction (GJ)-mediated intercellular communication. Among a variety of studied GJ proteins, HIV infection of human brain pericytes specifically increased expression of connexin 43 as determined by immunoblotting and immunostaining. This effect was confirmed in the brains of mice infected with EcoHIV, a mouse-specific HIV strain. In addition, HIV infection enhanced functional GJ-mediated intercellular communication in pericytes. The importance of this process was confirmed in experiments in which inhibition of GJs by carbenoxolone attenuated HIV infection. In addition to GJs, an extracellular ATP release assay revealed that HIV may also play a role in opening of connexin (Cx)-containing hemichannels (HCs). Overall, these findings indicate an important role of GJs in the propagation of HIV infection in human brain pericytes that may contribute to BBB dysfunction in brain infection and the pathogenesis of NeuroAIDS.