American Journal of Clinical Dermatology最新文献

Drug reaction with eosinophilia and systemic symptoms (DReSS) is known to cause mortality and long-term sequelae in the pediatric population, however there are no established clinical practice guidelines for the management of pediatric DReSS. We conducted a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the currently available data on treatment, mortality, and long-term sequelae of DReSS in children (aged 0–18 years). Data from 644 individuals revealed that various treatment strategies are being used in the management of pediatric DReSS, and strategies were often used in combination. The diversity in treatment approaches cannot be solely attributed to age or disease severity and reflects the lack of evidence-based management guidelines for DReSS. Children are also at risk of developing autoimmune sequelae following DReSS, most commonly thyroid disease and type 1 diabetes mellitus. We found that the eventual development of autoimmune disease was more often associated with DReSS caused by antibiotics, especially minocycline and sulfamethoxazole, in comparison with individuals who did not develop sequelae. In this study, we identify strengths and weaknesses in the currently available literature and highlight that future prospective studies with structured and long-term follow-up of children with DReSS are needed to better understand potential risk factors for mortality and development of sequelae after DReSS.

Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions.

The heterogeneity of atypical wounds can present diagnostic and therapeutic challenges; however, as the prevalence of atypical wounds grows worldwide, prompt and accurate management is increasingly an essential skill for dermatologists. Addressing the underlying cause of an atypical wound is critical for successful outcomes. An integrated approach with a focus on pain management and patient engagement is recommended to facilitate enduring wound closure. Advances in treatment, in addition to further research and clinical training, are necessary to address the expanding burden of atypical wounds.

Background

Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management.

Objectives

The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE.

Methods

In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg).

Results

Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0–5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator’s Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores.

Conclusions

Consistent with results seen in adults, adolescents, and older children (aged 6–11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population.

Trial Registration

ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

Merkel cell carcinoma (MCC) is a rare skin cancer characterized by neuroendocrine differentiation. Its carcinogenesis is based either on the integration of the Merkel cell polyomavirus or on ultraviolet (UV) mutagenesis, both of which lead to high immunogenicity either through the expression of viral proteins or neoantigens. Despite this immunogenicity resulting from viral or UV-associated carcinogenesis, it exhibits highly aggressive behavior. However, owing to the rarity of MCC and the lack of epidemiologic registries with detailed clinical data, there is some uncertainty regarding the spontaneous course of the disease. Historically, advanced MCC patients were treated with conventional cytotoxic chemotherapy yielding a median response duration of only 3 months. Starting in 2017, four programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors—avelumab, pembrolizumab, nivolumab (utilized in both neoadjuvant and adjuvant settings), and retifanlimab—have demonstrated efficacy in treating patients with disseminated MCC on the basis of prospective clinical trials. However, generating clinical evidence for rare cancers, such as MCC, is challenging owing to difficulties in conducting large-scale trials, resulting in small sample sizes and therefore lacking statistical power. Thus, to comprehensively understand the available clinical evidence on various immunotherapy approaches for MCC, we also delve into the epidemiology and immune biology of this cancer. Nevertheless, while randomized studies directly comparing immune checkpoint inhibitors and chemotherapy in MCC are lacking, immunotherapy shows response rates comparable to those previously reported with chemotherapy but with more enduring responses. Notably, adjuvant nivolumab has proven superiority to the standard-of-care therapy (observation) in the adjuvant setting.

Background

Ultrasound surveillance has become the new standard of care in stage III melanoma after the 2017 Multicenter Selective Lymphadenectomy Trial II (MSLT-II) demonstrated non-inferior 3-year survival compared with complete lymph node dissection.

Objective

We aimed to quantify diagnostic performance and adherence rates of ultrasound surveillance for melanoma locoregional metastasis, offering insights into real-world applicability.

Methods

Conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we systematically searched the Medline, Embase, Cochrane Library, CINAHL, Scopus, and Web of Science databases from inception until 11 October 2023. All primary studies that reported data on the diagnostic performance or adherence rates to ultrasound surveillance in melanoma were included. R statistical software was used for data synthesis and analysis. Sensitivity and specificity were aggregated across studies using the meta-analytic method for diagnostic tests outlined by Rutter and Gatsonis. Adherence rates were calculated as the ratio of patients fully compliant to planned follow-up to those who were not.

Results

A total of 36 studies including 18,273 patients were analysed, with a mean age of 56.6 years and a male-to-female ratio of 1:1.11. The median follow-up duration and frequency was 36 and 4 months, respectively. The pooled sensitivity of ultrasound examination was 0.879 (95% confidence interval [CI] 0.878–0.879) and specificity was 0.969 (95% CI 0.968–0.970), representing a diagnostic odds ratio of 224.5 (95% CI 223.1–225.9). Ultrasound examination demonstrated a substantial improvement in absolute sensitivity over clinical examination alone, with a number needed to screen (NNS) of 2.95. The overall adherence rate was 77.0% (95% CI 76.0–78.1%), with significantly lower rates in the United States [US] (p <  0.001) and retrospective studies (p <  0.001).

Conclusion

Ultrasound is a powerful diagnostic tool for locoregional melanoma metastasis. However, the real applicability to surveillance programmes is limited by low adherence rates, especially in the US. Further studies should seek to address this adherence gap.

Secondary bacterial infections of common dermatoses such as atopic dermatitis, ectoparasitosis, and varicella zoster virus infections are frequent, with Staphylococcus aureus and Streptococcus pyogenes being the bacteria most involved. There are also Gram-negative infections secondary to common dermatoses such as foot dyshidrotic eczema and tinea pedis. Factors favoring secondary bacterial infections in atopic dermatitis, ectoparasitosis, and varicella zoster virus infections mainly include an epidermal barrier alteration as well as itch. Mite-bacteria interaction is also involved in scabies and some environmental factors can promote Gram-negative bacterial infections of the feet. Furthermore, the bacterial ecology of these superinfections may depend on the geographical origin of the patients, especially in ectoparasitosis. Bacterial superinfections can also have different clinical aspects depending on the underlying dermatoses. Subsequently, the choice of class, course, and duration of antibiotic treatment depends on the severity of the infection and the suspected bacteria, primarily targeting S. aureus. Prevention of these secondary bacterial infections depends first and foremost on the management of the underlying skin disorder. At the same time, educating the patient on maintaining good skin hygiene and reporting changes in the primary lesions is crucial. In the case of recurrent secondary infections, decolonization of S. aureus is deemed necessary, particularly in atopic dermatitis.