BACKGROUND: Systemic sclerosis (SSc) is a heterogenous, multi-system autoimmune disease that causes progressive fibrosis of the skin and internal organs, resulting in high morbidity and mortality. Intravenous Immunoglobulin (IVIG) is a therapeutic option for SSc; however, reports of its efficacy have been variable, and its use across multiple organ manifestations of SSc has not been comprehensively reviewed.
OBJECTIVE: The aim of this study was to systematically assess the existing literature on the role of IVIG use across a range of SSc manifestations.
METHODS: Medline, Embase, Cochrane, Web of Science and Scopus were searched from 01/01/2003-15/04/2024 using terms related to SSc and IVIG. Included studies were English-language full texts, where ≥5 adults with SSc received IVIG, and where a reportable outcome was documented.
RESULTS: Of 418 potentially relevant records, 12 were included in this review, comprising 266 patients across one randomised control trial, two pilot studies, one open label study, seven retrospective studies and one case control study. Eighteen outcomes were documented across five different organ systems: cutaneous, respiratory, musculoskeletal, gastrointestinal, and other (clinical improvement and corticosteroid sparing benefit). Results showed a favourable effect of IVIG in reducing the extent of skin thickening, muscle and joint pain, gastrointestinal symptoms, steroid dosing and improving patient/physician reported quality of life. Whilst IVIG may appear to be less beneficial for respiratory disease, the stabilisation in pulmonary function tests and radiological features may be considered a positive outcome in itself. Limitations included a lack of high-quality studies, and the use of concomitant therapies in many studies, rendering the efficacy of IVIG alone difficult to ascertain.
CONCLUSIONS: IVIG showed benefit in treating some manifestations of SSc, however there was a lack of convincing evidence for the efficacy in others. The lack of high-quality data highlights the need for further well-designed clinical trials to confirm these findings and inform guidelines for IVIG use.

Acquired hemophilia A (AHA) is a rare autoimmune disease resulting from the development of autoantibodies directed against endogenous factor (F)VIII, leading to bleeding manifestations that can be life-threatening. The current standard hemostatic treatment involves the use of bypassing agents that circumvent FVIII (recombinant activated FVII, activated prothrombin complex concentrate, and recombinant porcine FVIII) that must be administered intravenously and possess a short half-life. These limitations and the risk of potentially fatal bleeding complications justify the early initiation of immunosuppressive treatment (IST) aimed at promptly eradicating the autoantibodies. IST is not without side effects, sometimes severe and possibly fatal, especially in persons with AHA who are generally older and have multiple comorbidities. Emicizumab, a bispecific antibody that mimics the action of FVIII, has emerged as an effective hemostatic therapy among persons with congenital hemophilia, whether complicated by the presence of anti-FVIII antibodies or not. Numerous arguments from recent clinical experiences suggest positioning emicizumab as a first-line treatment for AHA. This strategy has the potential to reduce bleeding complications and, importantly, the side effects associated with IST, which can be delayed and tailored to each patient.

Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells. Both recipient- and donor-derived DCs play a critical role in the rejection process, infiltrating the transplanted organ and sustaining T-cell responses. The use of immunosuppressive drugs represents the predominant approach to control this immunological barrier in transplanted organs. Evidence has shed light on the immunopharmacology of these drugs and novel strategies for manipulating DCs to promote allograft survival. Therefore, comprehending the mechanisms underlying this intricate microenvironment and the effects of immunosuppressive therapy on DCs is crucial for developing targeted therapies to reduce graft failure rates. This review will delve into the fundamental immunobiology of DCs and provide a detailed exploration of their clinical significance concerning alloimmune responses and posttransplant malignancies.

The role of the immune system in myocarditis onset and progression involves a range of complex cellular and molecular pathways. Both innate and adaptive immunity contribute to myocarditis pathogenesis, regardless of its infectious or non-infectious nature and across different histological and clinical subtypes. The heterogeneity of myocarditis etiologies and molecular effectors is one of the determinants of its clinical variability, manifesting as a spectrum of disease phenotype and progression. This spectrum ranges from a fulminant presentation with spontaneous recovery to a slowly progressing, refractory heart failure with ventricular dysfunction, to arrhythmic storm and sudden cardiac death. In this review, we first examine the updated definition and classification of myocarditis at clinical, biomolecular and histopathological levels. We then discuss recent insights on the role of specific immune cell populations in myocarditis pathogenesis, with particular emphasis on established or potential therapeutic applications. Besides the well-known immunosuppressive agents, whose efficacy has been already demonstrated in human clinical trials, we discuss the immunomodulatory effects of other drugs commonly used in clinical practice for myocarditis management. The immunological complexity of myocarditis, while presenting a challenge to simplistic understanding, also represents an opportunity for the development of different therapeutic approaches with promising results.

Membranous nephropathy (MN) management poses challenges, particularly in selecting appropriate immunosuppressive treatments (IST) and monitoring disease progression and complications. This article highlights 10 key tips for the management of primary MN based on current evidence and clinical experience. First, we advise against prescribing IST to patients without nephrotic syndrome (NS), emphasizing the need for close monitoring of disease progression. Second, we recommend initiating IST in patients with persistent NS or declining kidney function. Third, we suggest prescribing rituximab (RTX) or RTX combined with calcineurin inhibitors in medium-risk patients. Fourth, we propose cyclophosphamide-based immunosuppression for high-risk patients. Fifth, we discourage the use of glucocorticoid monotherapy or mycophenolate mofetil as initial treatments. Sixth, we underscore the importance of preventing infectious complications in patients receiving IST. Seventh, we emphasize the need for personalized monitoring of IST by closely measuring kidney function, proteinuria, serum albumin and anti-M-type phospholipase A2 receptor levels. Eighth, we recommend a stepwise approach in the treatment of resistant disease. Ninth, we advise adjusting treatment for relapses based on individual risk profiles. Finally, we caution about the potential recurrence of MN after kidney transplantation and suggest appropriate monitoring and treatment strategies for post-transplantation MN. These tips provide comprehensive guidance for clinicians managing MN, aiming to optimize patient outcomes and minimize complications.

OBJECTIVE: To describe the long-term outcomes, overall survival, progression-free survival, and prognostic factors in dogs with necrotizing encephalitis (NE).
METHODS: 37 client-owned dogs clinically diagnosed with NE.
METHODS: All dogs underwent MRI and CSF analysis. Cox proportional hazards regression was used to examine factors related to the risk of relapse and death, including signalment, history, diagnostic investigation results, and treatments before the first relapse.
RESULTS: The medians of the overall and progression-free survival times were 639 days (IQR, 342 to 1,482 days) and 233 days (IQR, 111 to 775 days), respectively. Overall survival was highly correlated with progression-free survival. Four dogs (11%) died or were euthanized within 3 months of diagnosis. Relapse within 6 months was associated with a shorter overall survival. However, no prognostic factors for overall survival were found. The category of patients with presenting clinical signs that lasted 29 days to 6 months (OR, 3.26; 95% CI, 1.35 to 7.90) was associated with a higher risk of relapse. Seizures were presented in 75.7% of dogs, with a recurrence rate of 100%.
CONCLUSIONS: This report provides comprehensive follow-up information for dogs with NE, revealing a fair prognosis and low early mortality rate. Seizure is a very common clinical sign with a high recurrence rate.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA.
METHODS: The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient\'s symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence.
CONCLUSIONS: For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

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BACKGROUND: Lead dislodgement is a severe complication in cardiac implantable electronic device (CIED) implantation. Inflammation after CIED implantation results in the development of adhesions between lead and tissues, resulting in the lead becoming fixed in the body. In patients with immunosuppressive therapy, however, adhesion is inhibited by anti-inflammatory effects. However, the association between lead dislodgement and immunosuppressive therapy has not been clarified. The purpose of this study was to investigate the association between lead dislodgement and immunosuppressive therapy.
OBJECTIVE: We hypothesized that lead dislodgement more frequently occur in patients with immunosuppressive therapy than those without.
METHODS: In total, 651 consecutive patients who underwent CIED implantation or lead addition (age, 76 ± 11 years; and males, 374 [58%], high voltage device, 121 [19%], lead addition 23 [4%]) were retrospectively enrolled. Immunosuppressive therapy was with regular steroids or immunosuppressants. Lead placement was guided by fluoroscopy, and active fixation leads were used. Restraint of the upper limb by chest tape was performed for 1 week after the procedure. Lead dislodgement was defined as a change in lead position and/or lead failure requiring reoperation.
RESULTS: Twenty (3.1%) patients received immunosuppressive therapy. Among these, 15 (2.3%) patients regularly took steroids and 8 (1.2%) took immunosuppressants. Lead dislodgement occurred in 10 (1.5%) patients. Lead dislodgement was more frequent in patients with immunosuppressive therapy than in those without (3 [15%] vs. 7 [1%], p = 0.003).
CONCLUSIONS: In patients with CIED implantation or lead addition, lead dislodgement is more frequent in patients with immunosuppressive therapy than in those without.

A case of a late-onset Rasmussen\'s encephalitis (RE) presenting with drug-refractory focal epilepsy and progressive hemispheric cerebral atrophy noted on a serial radiologic head scan done on a gentleman in his 30s is presented. A positive antinuclear ribonucleoprotein antibody test, a weak-positive antinuclear antibody test, an elevated C3 complement, and possible trauma were identified as potential causative or promoting factors for RE in this patient. Literature evidence regarding the challenges with the aetiopathogenesis description, diagnosis, and management of this rare condition has been reviewed in this article. Exploring an aetiological-based diagnosis of this condition could open research and interventional opportunities into aetiology-guided management opportunities in this condition.