IgG4-related sclerosing cholangitis (IgG4-SC) is an IgG4-related disease charac-terized by bile duct wall thickening and luminal stricture. Its pathogenesis involves complex multi-dimensional regulation, including immune imbalance, genetic epigenetic regulation, microbial ecolo-gical abnormalities, and activation of fibrotic pathways. Due to the lack of specificity in clinical mani-festations, IgG4-SC is easily misdiagnosed as biliary tract diseases such as cholangiocarcinoma and primary sclerosing cholangitis in the early stage, leading to diagnostic difficulties. At present, gluco-corticoids are the preferred treatment option. Although most patients can quickly recover in the early stages, high recurrence rates and hormone dependence limit the long-term effectiveness of treatment. The authors combine the latest research progress at home and abroad to deeply analyze the pathogenesis, clinical manifestations, and diagnosis of IgG4-SC, focusing on treatment strategies and cutting-edge advances, in order to provide reference and inspiration for clinical practice.

IgG4-related sclerosing cholangitis (IgG4-SC) is an IgG4-related disease charac-terized by bile duct wall thickening and luminal stricture. Its pathogenesis involves complex multi-dimensional regulation, including immune imbalance, genetic epigenetic regulation, microbial ecolo-gical abnormalities, and activation of fibrotic pathways. Due to the lack of specificity in clinical mani-festations, IgG4-SC is easily misdiagnosed as biliary tract diseases such as cholangiocarcinoma and primary sclerosing cholangitis in the early stage, leading to diagnostic difficulties. At present, gluco-corticoids are the preferred treatment option. Although most patients can quickly recover in the early stages, high recurrence rates and hormone dependence limit the long-term effectiveness of treatment. The authors combine the latest research progress at home and abroad to deeply analyze the pathogenesis, clinical manifestations, and diagnosis of IgG4-SC, focusing on treatment strategies and cutting-edge advances, in order to provide reference and inspiration for clinical practice.

Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:An ambispective study was conducted on 123 AD patients treated with dupilumab in Department of Dermatology, the Second Xiangya Hospital of Central South University from July 2020 to March 2022, clinical data were collected, and efficacy and safety of dupilumab were evaluated. Primary outcomes included scores of eczema area and severity index (EASI) , patient-oriented eczema measure (POEM) , peak pruritus numerical rating scale (NRS) and dermatology life quality index (DLQI) before and after 4-, 8-, 12- and 16-week treatment, and adverse reactions and events were recorded. Comparison of scores before and after treatment was performed using paired t test or repeated measures analysis of variance, Mann-Whitney U test was used for the comparison of efficacy among patients with different types of skin lesions or different IgE levels, and multiple regression model based on robust standard errors was used to analyze factors influencing the efficacy. Results:Among the 123 AD patients, 107 were enolled into the efficacy analysis, and 85 (79.44%) completed at least 4 weeks of treatment, including 6 (7.06%) achieving EASI75 and 23 (27.06%) achieving EASI50, and the EASI, NRS, POEM, DLQI scores (10.41 ± 6.72, 4.12 ± 1.74, 8.60 ± 4.29, 7.81 ± 4.38, respectively) significantly decreased compared with those before treatment (18.08 ± 10.69, 7.21 ± 2.01, 16.88 ± 5.74, 12.95 ± 5.95, respectively; all P < 0.001) in the 85 patients. Among the 107 patients, 47 (43.93%) completed at least 16 weeks of treatment. Among the 47 patients, 23 (82.14%) of 28 adults and 17 (89.47%) of 19 adolescents and children achieved 75% or greater improvement in EASI score; the EASI, NRS, POEM and DLQI scores before the treatment all significantly differred from those 4, 8, 12, 16 weeks after the treatment (all P < 0.001) , and all the scores were significantly lower at weeks 4, 8, 12 and 16 than at the previous adjacent time points (all P < 0.05) . At week 4 during the treatment, the EASI improvement rate was significantly lower in the AD patients with prurigo nodularis than in those without ( U = 151.00, P = 0.006) , while there was no significant difference in the EASI improvement rate between the AD patients with xeroderma and those without ( P > 0.05) ; at week 16 during the treatment, there was no significant difference in the EASI improvement rate between patients with prurigo nodularis or xeroderma and those without (both P > 0.05) . Multiple regression analysis based on robust standard errors at week 16 showed that the improvement degree in the EASI score was not correlated with the type of skin lesions ( β = 3.20, P = 0.075) , but correlated with age ( β = -0.22, P = 0.030) , whether patients were in adulthood ( β = 9.54, P = 0.049) , immediate family history ( β = 7.46, P = 0.017) ; the improvement degree in the NRS score was correlated with the type of skin lesions ( β = 0.55, P = 0.032) , age ( β = -0.04, P = 0.033) , weight ( β = -0.05, P = 0.020) , whether patients were in adulthood ( β = 2.06, P = 0.003) and whether patients received combined treatment with antihistamines ( β = -1.91, P = 0.001) . Adverse reactions: among the 123 patients, 6 (4.88%) developed conjunctivitis, and 2 (1.63%) developed facial erythema. Adverse events: vitiligo-like changes occurred on the right forehead of 1 patient, and 3 patients discontinued the treatment with dupilumab due to Henoch-Sch?nlein purpura, distal axonal damage in peripheral nerves in both upper limbs, and epilepsy, respectively. The causal relationship between these adverse events and dupilumab was unclear. Conclusion:Dupilumab is effective in the treatment of AD with high overall safety, and can serve as a new treatment option for AD patients with an unsatisfactory response to traditional treatment.