Baseline skin cytokine profiles determined by RNA in situ hybridization correlate with response to dupilumab in patients with eczematous dermatitis.

BACKGROUND: Dupilumab has revolutionized the treatment of atopic dermatitis. However, not all patients respond optimally, and this may relate to underlying molecular heterogeneity. Nevertheless, clinically useful and accessible methods to assess such heterogeneity have not been developed. OBJECTIVE: We assessed whether cytokine staining and/or histologic features correlate with clinical response to dupilumab in patients with eczematous dermatitis. METHODS: We retrospectively analyzed biopsies from 61 patients with eczematous dermatitis treated with dupilumab (90.2% met Hanifin-Rajka criteria for atopic dermatitis). RNA in situ hybridization was used to measure markers of type 2 (interleukin [IL]4, IL13), type 1 (interferon gamma) and type 3 (IL17A, IL17F, IL22) inflammation. Histologic features were also assessed. Patterns were compared among complete (n = 16), partial (n = 37), and nonresponders (n = 8) to dupilumab. RESULTS: We found that increased IL13 expression was associated with optimal response to dupilumab. In contrast, nonresponders tended to express less IL13 and relatively greater levels of type 1 and 3 cytokines. In addition, certain histologic features tended to correlate with improved response to dupilumab. LIMITATIONS: Retrospective approach and small size of the nonresponder group. CONCLUSION: Cytokine RNA in situ hybridization may aid in treatment selection for eczematous disorders. Moreover, personalization of treatment selection for inflammatory skin diseases may be possible.

The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases.

Cutaneous immune-related adverse events encompass a spectrum of dermatological manifestations, including lichenoid reactions, psoriasiform eruptions, eczematous dermatitis, immunobullous disorders, granulomatous reactions, pruritus, vitiligo, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome. The conventional approach to treating high-grade or refractory cutaneous immune-related adverse events has involved high-dose systemic corticosteroids. However, their use is limited owing to the potential disruption of antitumor responses and associated complications. To address this, corticosteroid-sparing targeted immunomodulators have been explored as therapeutic alternatives. Biologic agents, commonly employed for non-cutaneous immune-related adverse events such as colitis, are increasingly recognized for their efficacy in treating various patterns of cutaneous immune-related adverse events, including psoriasiform, immunobullous, and Stevens-Johnson syndrome-like reactions. This review consolidates findings from the English-language literature, highlighting the use of biologic agents in managing diverse cutaneous immune-related adverse event patterns, also encompassing maculopapular, eczematous, and lichenoid eruptions, pruritus, and transient acantholytic dermatosis (Grover disease). Despite the established efficacy of these agents, further research is necessary to explore their long-term effects on antitumor responses.

The Impact of Dermatologic Adverse Events on the Quality of Life of Oncology Patients: A Review of the Literature.

Dermatologic adverse events resulting from oncologic therapy are common and negatively impact patients' quality of life. Dermatologic adverse events include toxicity of the skin, oral mucosa, nails, and hair and are seen with cytotoxic chemotherapy, targeted therapy, immunotherapy, and radiation therapy, with distinct patterns of dermatologic adverse events by drug class. Here, we review the literature on the impact of dermatologic adverse events on quality of life. Studies on quality of life in patients with cancer have relied on scales such as the Dermatologic Life Quality Index and Skindex to demonstrate the association between dermatologic adverse events and declining quality of life. This relationship is likely due to a variety of factors, including physical discomfort, changes to body image, decreased self-esteem, and an effect on social interactions. Addressing such quality-of-life concerns for patients with cancer is critical, not only for patients' well-being but also because decreased satisfaction with treatment can lead to discontinuation of treatment or dose reduction. Prophylactic treatment and early management of dermatologic adverse events by experienced dermatologists can alleviate the negative effects on quality of life and allow continuation of life-prolonging treatment.

Hidradenitis suppurativa and the risk of myocardial infarction, cerebrovascular accident, and peripheral vascular disease: a population-based study.

Previous studies have identified an association between myocardial infarction (MI), cerebrovascular accident (CVA), and peripheral vascular disease (PVD) in patients with hidradenitis suppurativa (HS). To evaluate the risk and prognostic outcomes of MI, CVA, and PVD in patients with HS. A population-based retrospective cohort study using the computerized database of Clalit Health Services (CHS), the largest managed care organization in Israel, was conducted to compare the incidence of MI, CVA, and PVD among patients with HS (N = 6779) with age-, sex- and ethnicity-matched control subjects (N = 33,260). Adjusted hazard ratios (HRs) were estimated by multivariate Cox regression analysis. The overall incidence rates of MI, CVA, and PVD were estimated at 2.9 (2.3-3.4), 1.3 (0.9-1.7), and 0.8 (0.6-1.1) per 1000 person-year, respectively. Patients with HS were at an increased risk of developing MI (fully-adjusted HR 1.33; 95% CI 1.04-1.68; P = 0.021), but the risk of CVA (fully-adjusted HR 0.82; 95% CI 0.59-1.14; P = 0.245) and PVD (fully-adjusted HR 1.22; 95% CI 0.80-1.87; P = 0.355) was comparable relative to controls. Compared to other patients with HS, increased risk of all-cause mortality was observed among patients with HS and comorbid MI (HR 12.56; 95% CI 7.59-20.80; P < 0.001), CVA (HR 13.33; 95% CI 7.29-24.37; P < 0.001), and PVD (HR 7.11; 95% CI 2.61-19.32; P < 0.001). Patients with HS are at an increased risk of MI, but not CVA and PVD. Awareness of these epidemiological findings is of importance for clinicians managing patients with HS.