Objectives Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum. Its current treatments involve long-term uptake of glucocorticoids (e.g., prednisone) for controlling inflammation; however, side effects are common. We strived for an improved therapy for fibrosis remission while reducing side effects. Methods We surveyed gene-disease-drug databases and discovered that mammalian target of rapamycin (mTOR) was a key signalling protein in RPF and the mTOR inhibitor compound sirolimus affected many RPF pathways. We designed a therapy combining a gradual reduction of prednisone with a long-term, stable dosage of sirolimus. We then implemented a single-arm clinical trial and assessed the effects in eight RPF patients at 0, 12 and 48 weeks of treatment by measuring fibrous tissue mass by CT, markers of inflammation and kidney functions by lab tests, immune cell profiles by flow cytometry and plasma inflammatory proteins by Olink proteomics. Results With the combined therapy, fibrous tissue shrunk about by half, markers of acute inflammation reduced by 70% and most patients with abnormal kidney functions had them restored to normal range. Molecularly, fibrosis-related T cell subsets, including T_H2, T_H17 and circulating T_FH cells, were reduced and tumour necrosis factor and related cytokines restored to healthy levels. No severe long-term side effects were observed. Conclusions Our combined therapy resulted in significant fibrosis remission and an overall regression of the immune system towards healthy states, while achieving good tolerance. We concluded that this new therapy had the potential to replace the steroid monotherapy for treating RPF.

Objectives: To evaluate the differences in efficacy and safety between two therapeutic approaches: glucocorticoids monotherapy and combined therapy of glucocorticoids and immunosuppressants, in patients with retroperitoneal fibrosis (RPF). Methods: Systematic searches of PubMed, EMBASE, Cochrane Library, Web of Science and ProQuest were performed. Randomized controlled trials, quasi-experimental designs and observational cohort studies that reported the efficacy or recurrence on RPF patients treated with glucocorticoid monotherapy or glucocorticoids combined with specified immunosuppressants therapy were included. Subsequently, a meta-analysis was conducted, followed by an independent bioinformatics analysis to elucidate the mechanisms by which glucocorticoids combined with immunosuppressants potentiate therapeutic effects in the treatment of RPF. Results: A total of 11 studies comprising 224 patients were identified. Compared with glucocorticoid monotherapy, combined therapy demonstrated a significant higher response rate (98.9% vs. 85.1%, P  = 0.08) and a trend toward more frequent disappearance of hydronephrosis (97.1% vs. 90.0%, P = 0.29). Moreover, while recurrence rates were comparable between the two groups within the first year (5.7% vs. 4.9%, P = 0.92), recurrence in the monotherapy group surpassed that in the combined therapy group beyond 1 year of continuous follow-up (10.6% vs. 7.4% at 24 months, 21.1% vs. 10.7% at 36 months, and 26.1% vs. 12.5% overall), although without significant difference. Bioinformatic analysis revealed that prednisone targets overlapping with RPF-associated genes are mainly involved in acute inflammatory responses and cytokine regulation, whereas immunosuppressants act on a broader range of pathogenic genes implicated in key immunological and fibrotic pathways in RPF. This complementary targeting provides a mechanistic rationale for the role of immunosuppressants in promoting fibrotic tissue remodeling and alleviating mechanical obstruction in RPF. The use of immunosuppressants was associated with a low incidence of adverse events (7.2%), and no severe side effects were reported. Conclusions: Clinical evidence from literature and mechanistic insights from bioinformatics both suggest a potential benefit of combination therapy in RPF. However, the evidence remains associative and exploratory. Further randomized controlled trials are warranted to evaluate the potential benefits and risks associated with the addition of immunosuppressants in patients with RPF.

Objective: About 40% of IgG4-related disease (IgG4-RD) patients face recurrence, severely impacting their quality of life. We aimed to explore the characteristics of the perception of recurrence risk in patients with IgG4-RD. Methods: A qualitative study design with a descriptive phenomenological approach was used. Fourteen patients with IgG4-RD were recruited via purposive sampling, including six patients with first onset and eight patients experiencing recurrence. Semi-structured interviews were conducted to collect data, and transcripts were analysed by two independent researchers using Colaizzi’s descriptive analysis framework. The COREQ checklist was followed. Results: Data analysis identified nine subthemes falling into four themes: (a) perception of differential susceptibility to recurrence; (b) perception of crucial recurrence risk factors; (c) perception of recurrence warning signs and medical behaviours; (d) perception of multiple recurrence outcomes. We found that susceptibility perception formed the basis of recurrence risk perception. For patients with first onset, the main manifestations were misconception or evasion of the risk of recurrence, whereas patients experienced recurrence demonstrated a clear perception of recurrence risk and feelings of fear. Based on this, other themes emerged. Conclusions: Since the absence of accurate knowledge related to recurrence, the perception of recurrence risk in patients with IgG4-RD primarily manifested as misconception, evasion or feeling fear. Ultimately, they couldn’t take appropriate actions to prevent recurrence. Healthcare professionals should develop comprehensive interventions for patients with IgG4-RD, integrating health education, disease consultation and psychological support, with the aim of enhancing awareness of recurrence risk and empowering them to manage their conditions in the long term.

Objective: Retroperitoneal fibrosis ( RPF ) complicated by mediastinal fibrosis ( MF ) is rare but fatal. We aimed to explore the features and indicators of poor prognosis for the population of those affected. Methods: Patients with idiopathic RPF were recruited in Peking University International Hospital. Literature related to RPF with MF was searched from PubMed , Web of Science, and Embase until September 2024. Systematic review and case‐control studies were conducted. Results: One patient with RPF and MF from our center and nine cases identified through literature search formed the study group. The remaining 51 patients with RPF who did not have MF were enrolled as the control group. Patients with RPF and MF were more likely to present specific symptoms, including emaciation (30% vs 2%), fever (20% vs 0), pericardial effusion (30% vs 0), pleurisy (20% vs 0) and dyspnea (40% vs 0) (all P < 0.05). Hyperglobulinemia (elevated IgG levels) was also more predominant in the study group, whereas low back pain (20% vs 56.9%, P = 0.043) was less prevalent. Four of 10 patients in the study group died, but none died in the control group. A second case‐control study was performed among patients with RPF and MF, with the three patients who died of fibrosis disease as the study group and the surviving six patients as the control group. It was found that pleural effusions (100% versus 16.7%, P = 0.048) and the absence of glucocorticoid treatment were risk factors for death in patients with RPF and MF. Conclusion: RPF with MF has specific clinical features and poor prognosis. Early detection and glucocorticoids‐based treatment could improve the outcome.