Objective: Atopic dermatitis (AD) is an allergic inflammatory skin disease. Changes in circulating inflammatory proteins are reflected in the entire process of AD progression, and its pathophysiology is still unclear. This Mendelian randomization study was conducted to further evaluate the role of circulating inflammatory proteins in AD. Methods: This study investigated the potential causal relationship between circulating inflammatory proteins and AD. We used a two-sample Mendelian randomization (MR) method to analyze data from a large-scale genome-wide association study to explore the relationship between 91 circulating inflammatory proteins, 41 inflammatory factors, and CRP and AD. The inverse variance weighted method was mainly used to evaluate the causal relationship between exposure and outcome based on the effect indicator odds ratio (OR) and 95% confidence interval (CI). In addition, MR-Egger, weighted median, simple model, weighted model and MR-PRESSO multiple sensitivity analyses were applied to strengthen the final results. The leave-one-out method, heterogeneity test, and horizontal gene pleiotropy test were used to verify the stability and reliability of the results. Results: Forward MR analysis showed that there was a significant correlation between AD risk and changes in the levels of multiple inflammatory proteins at different p-value thresholds, among which increased levels of interleukin-18 receptor 1 were found to increase the risk of AD, which was significant in all three groups of analysis (P IVW<0.05); increased levels of C-X-C motif chemokine 9 and Fms-related tyrosine kinase 3 ligand were found to reduce AD risk at P<5×10-8 and p<5×10-7 thresholds; increased levels of C-X-C motif chemokine 11 were found to be associated with a reduced risk of AD at P<5×10-8 and P<5×10-6 thresholds (P IVW<0.05). Reverse MR analysis showed that increased AD risk was associated with decreased levels of AXIN-1, natural killer cell receptor 2B4, interleukin-1 receptor subunit α, and interleukin-33 (P IVW<0.05). In addition, increased AD risk was associated with increased Cystatin D levels (P IVW<0.05). In the 41 inflammatory factor data sets, increased AD risk may be associated with increased IL18 levels (P IVW=0.036) and MIG levels (P IVW=0.046). No significant heterogeneity and horizontal pleiotropy were observed in the analysis. After verification MR analysis, it was found that there was a significant association between the levels of inflammatory proteins such as Fms-related tyrosine kinase 3 ligand, interleukin 18 receptor 1, C-X-C motif chemokine 9, and tumor necrosis factor ligand superfamily member 14 and AD risk, and there was consistency between different P value thresholds. Bidirectional MR showed that there was a complex bidirectional causal relationship between interleukin 18 receptor 1 levels and AD. The leave-one-out analysis showed that the results were stable, there were no instrumental variables that had a strong impact on the results, and the leave-one-out method verified the robustness of the results. There was heterogeneity test and horizontal pleiotropy in the reverse causal relationship between the level of tumor necrosis factor ligand superfamily member 14 and the AD validation set. Conclusion: The results of MR analysis indicate a potential causal relationship between circulating inflammatory proteins and AD. This study provides a new approach for exploring the biological mechanisms of AD in the future and proposes possible therapeutic targets. Further research is needed to confirm these results and understand the specific role of these proteins in AD, and to provide reference value for future studies on the relationship between circulating inflammatory proteins and AD.

Primary membranous nephropathy (MN) is a rare autoimmune cause of kidney failure. Observational studies have suggested some relationship between virus infection and primary MN, but the association remains unclear. The current study performed a two‑sample Mendelian randomization (MR) analysis to explore the causal association between varicella‐zoster virus (VZV) infection (chickenpox and shingles) and primary MN using genome‑wide association studies (GWASs) summary statistics. The exposure datasets containing chickenpox and shingles were obtained from the GWASs conducted by the 23andMe cohort. And summary‐level statistics for primary MN were used as the outcome dataset, comprising 2150 cases and 5829 controls from European Ancestry. The inverse variance weighted method was adopted as the main analysis. As a result, we found that both genetically determined chickenpox (odds ratio [95% confidential interval] = 3.61 [1.74–7.50], p = 5.59e−04) and shingles (p = 7.95e−03, odds ratio [95% confidential interval] = 2.49 [1.27–4.91]) were causally associated with an increased risk of developing primary MN. In conclusion, our MR findings provided novel genetic evidence supporting the causal effect of VZV infection on primary MN. Further studies are needed to elucidate the underlying mechanisms mediating the causal association.

Severe cutaneous adverse reactions (SCARs) to drugs are associated with morbidity, mortality, healthcare costs, and challenges in drug development. It is important to identify the SCAR type early by using strict diagnostic criteria because they may require different treatments, follow-ups, and short- or long-term prognoses. A 68-year-old woman admitted to our hospital presented with fever and rashes for 10 days. This case exhibited many features that suggested acute generalized exanthematous pustulosis (AGEP). However, the course of treatment and verified clinical features led to a diagnosis of AGEP and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome that was induced by carbamazepine and levofloxacin after a herpes zoster infection. AGEP combined with DRESS syndrome is a complicated and rare drug-induced dermatological eruption that follows a course similar to DRESS syndrome and more recalcitrant than the course seen with typical AGEP. The associated factors for the SCARs in our patient included age, history of allergy, viral infection, and drugs interacting with specific HLA loci. Improving our understanding of these factors can improve the treatment and prevention of SCARs in these patients.

Midkine plays a critical role in angiogenesis by regulating the vascular endothelial growth factor (VEGF) signalling pathway, which is known to be associated with psoriasis pathogenesis. However, research on midkine-psoriasis relationship remains limited. The objective of this study was to detect midkine expression in psoriasis and investigate its potential role in the disease. Midkine expression was measured using immunohistochemistry and ELISA. Effects of midkine on HaCaT cell proliferation, VEGF-A production and signalling pathways were assessed using CCK8, RT-PCR and WB. Scratch and in vitro tube formation tests were used to evaluate the effects of HaCaT-cell-activated midkine on the migration and tube formation of human dermal microvascular endothelial cells. Murine psoriasiform models were injected with midkine recombinant protein and midkine monoclonal antibody to investigate skin lesions, tissue sections and dermal microvessel density. Levels of midkine significantly increased in both lesions and serum of patients with psoriasis. Serum expression of midkine decreased after treatment and a positive correlation was found between midkine and disease severity. Midkine promoted HaCaT cell proliferation and VEGF-A production. The Notch2/HES1/JAK2-STAT5A pathway expression increased after midkine treatment of HaCaT cells. The supernatant of HaCaT cells treated with midkine promoted HMEC-1 migration and angiogenesis in vitro. Recombinant midkine protein exacerbated psoriasiform lesions with increased expressions of VEGF-A and microvessel density, while midkine monoclonal antibody alleviated psoriasis lesions. Midkine may have a significant impact on psoriasis angiogenesis by regulating VEGF-A expression through the Notch2/HES1/JAK2-STAT5A pathway, highlighting a potential therapeutic target for psoriasis treatment.

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I2 = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I2 = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones.

Dermatologic TherapyVolume 35, Issue 11 e15852 LETTER Wet-wrap therapy combined with compound glycyrrhizin and oral antihistamines as a therapy option for two cases of papuloerythroderma of ofuji Li Lin, Li Lin orcid.org/0000-0002-6525-9844 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorMojun Chen, Mojun Chen orcid.org/0000-0003-4233-6699 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorLinfeng Li, Corresponding Author Linfeng Li zoonli@sina.com orcid.org/0000-0002-8736-6464 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China Correspondence Linfeng Li, Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, No.95 Yong'an Road, Xicheng District, Beijing, China. Email: zoonli@sina.comSearch for more papers by this author Li Lin, Li Lin orcid.org/0000-0002-6525-9844 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorMojun Chen, Mojun Chen orcid.org/0000-0003-4233-6699 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorLinfeng Li, Corresponding Author Linfeng Li zoonli@sina.com orcid.org/0000-0002-8736-6464 Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China Correspondence Linfeng Li, Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, No.95 Yong'an Road, Xicheng District, Beijing, China. Email: zoonli@sina.comSearch for more papers by this author First published: 24 September 2022 https://doi.org/10.1111/dth.15852 Li Lin and Mojun Chen should be considered joint first author. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume35, Issue11November 2022e15852 RelatedInformation

Some biological therapies for psoriasis can cause the reactivation of viral infections. Although recent studies suggest no increased rate of reactivation with biological therapies, some life-threatening cases have been reported. Therefore, this meta-analysis examined the rate of virus reactivation in patients with psoriasis with biological therapies and concurrent hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. PubMed, Embase, and the Cochrane Library were searched for available papers from inception to December 2021. The outcome was the number of patients with virus reactivation after using biological therapies. The random-effect model was used in all analyses. Fourteen reports (1033 patients) were included. The pooled overall rate of virus reactivation was 0.04 (95

Background: This research aimed to assess the potential association of gestational diabetes (GDM) with early trimester hematological parameters including hemoglobin (Hb), red blood cell (RBC), white blood cell (WBC), and platelet count (PLT) through a prospective cohort study. Methods: The prospective cohort included pregnant women subjected to prenatal examination at Shantou and Beijing hospitals in China from March 2014 to December 2015. Data were collected since the first perinatal visit in obstetrics clinics, and then participants were followed up at 24, 32, 36 gestational weeks and the time of delivery, respectively. Multivariable adjusted logistic regression models were conducted to estimate odds ratio (OR) and its corresponding 95% confidence interval (95% CI). Results: A total of 1004 pregnant women with singletons, less than 12 gestational weeks, and without history of chronic disease were eligible for analysis. The incidence of GDM was 18.82%, and the mean age was 29.50 ± 3.84 years. Total of 187 (18.63%) women who had abnormal RBC level and 222 (22.11%) had abnormal Hb in the first trimester of pregnancy. After multivariable adjustment, each unit increment in numeric RBC or Hb was associated with 177% and 4% increased risk for GDM. The risk for GDM was significantly increased with higher RBC (OR: 2.00 for RBC>4.55×1012 /L) and Hb (OR: 2.14 for Hb>139 g/L) levels in the first trimester. Conclusions: Elevated RBC and Hb in the first trimester are associated with increasing risk of GDM. Further evidence are warranted to confirm these possible causal relationships.