A case report of lymphoproliferative disease in brain following therapies with mycophenolate Mofetil and Fingolimod and literature review.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder. With the method of indirect immunofluorescence assay (IIF), more anti-NMDAR encephalitis patients have been discovered when its first onset. But it was rare that anti-NMDAR encephalitis overlapped with multiple sclerosis (MS) documented in literatures. Here, we present a case who initially developed anti-NMDAR encephalitis and MS. Furthermore, we concluded the characteristics of patients who were diagnosed as anti-NMDAR encephalitis overlapping with MS. Additionally, due to the relapsing process, mycophenolate mofetil and sequentially fingolimod for the treatment were taken, which subsequently led to the development of a lymphoproliferative disease in his brain and other organs. This case illustrates the complex role of immunosuppressive agents.

Tailored Polymersomes for Enhanced Oral Drug Delivery: pH-Sensitive Systems for Intestinal Delivery of Immunosuppressants.

Ensuring precise drug release at target sites is crucial for effective treatment. Here, pH-responsive nanoparticles for oral administration of mycophenolate mofetil, an alternative therapy for patients with inflammatory bowel disease unresponsive to conventional treatments is developed. However, its oral administration presents challenges due to its low solubility in the small intestine and high solubility and absorption in the stomach. Therefore, this aim is to design a drug delivery system capable of maintaining drug solubility compared to the free drug while delaying absorption from the stomach to the intestine. Successful synthesis and assembly of a block copolymer incorporating a pH-responsive functional group is achieved. Dynamic light scattering indicated a significant change in hydrodynamic size when the pH exceeded 6.5, confirming successful incorporation of the pH-responsive group. Encapsulation and controlled release of mycophenolate mofetil are efficiently demonstrated, with 90% release observed at intestinal pH. In vitro cell culture studies confirmed biocompatibility, showing no toxicity or adverse effects on Caco-2 cells. In vivo oral rat studies indicated reduced drug absorption in the stomach and enhanced absorption in the small intestine with the developed formulation. This research presents a promising drug delivery system with potential applications in the treatment of inflammatory bowel disease.

An Adolescent Case of Anti-MDA5 Antibody-Positive Juvenile Dermatomyositis With Interstitial Lung Disease Successfully Treated by Multitarget Therapy Avoiding Cyclophosphamide: A Case Report and Literature Review.

Juvenile dermatomyositis (JDM) patients who test positive for the antimelanoma differentiation-associated gene 5 (MDA5) antibody have a poor prognosis because of rapidly progressing interstitial lung disease (ILD). However, agreement on the best treatment for this condition remains elusive. We encountered a 13-year-old girl with anti-MDA5 antibody-positive JDM who presented with arthritis and was already showing signs of ILD when she was admitted to the hospital. While cyclophosphamide (CY) is commonly used, it can cause gonadal disorders and other complications when administered to adolescent females. Consequently, we chose multitarget therapy, which includes tacrolimus and mycophenolate mofetil. Her ILD and skin symptoms gradually improved, and she was able to maintain remission and avoid CY administration for three years. We conducted a thorough literature review to determine the efficacy and safety of multitarget therapy for anti-MDA5 antibody-positive DM and JDM. Multitarget therapy shows promise as a potentially effective and relatively safe treatment. The ability to avoid CY, which is especially important for adolescent patients concerned about fertility preservation, highlights a significant benefit of this multitarget therapy for anti-MDA5 antibody-positive DM and JDM patients.

Therapeutic drug monitoring of mycophenolic acid and azole antifungals on two distinct LC-MS/MS instruments.

Background: As an active metabolite of a commonly prescribed immunosuppressant, mycophenolic acid (MPA) levels are often monitored to prevent organ rejection following a transplant. Triazoles are often prescribed for treatment of invasive fungal infections in immunocompromised patients. Due to the variability in individual pharmacokinetics and drug-drug interactions, therapeutic drug monitoring is recommended for triazole antifungals. A multiplex LC-MS/MS assay has been developed that can quantify both MPA and triazole drugs in serum. Methods: A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument. Results: The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4-48 µg/mL for MPA, 0.1-12 µg/mL for posaconazole, and 0.2-24 µg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 µg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems. Conclusion: A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.

Treatment of Patients with IgA Nephropathy: Evaluation of the Safety and Efficacy of Mycophenolate Mofetil.

INTRODUCTION AND AIM: Immunoglobulin A nephropathy (IgAN), characterized by aberrant IgA immune complex deposition, is the most prevalent primary glomerular disease and the main cause of end-stage renal disease, causing a significant physical and psychological burden on people worldwide. Conventional therapeutic approaches, such as renin-angiotensin-aldosterone system inhibitors and corticosteroids, may not achieve sufficient effectiveness and may produce major side events in the past. The previous data in Asian populations indicated that mycophenolate mofetil (MMF) might significantly advance the development of a new therapy strategy for IgAN. The effectiveness and safety of MMF in patients with IgAN will be investigated in this study. METHODS: A literature search was conducted on June 30th, 2023, by searching the following databases: PubMed and the Cochrane Library according to predefined criteria. To investigate the renoprotective benefits and safety of MMF, statistical analyses were performed using Cochrane's Review Manager Version 5.3. RESULTS: The meta-analysis included nine randomized controlled studies that fulfilled the inclusion criterion. In the Asian population, the results revealed a substantial difference in remission rates between the MMF group and the control group (OR: 2.53, 95% CI: 1.02, 6.30, P = 0.05). MMF can increase the rate of decrease in proteinuria in IgAN patients when compared with controls in Asians (OR: 7.34, 95% CI: 2.69, 20.08, P = 0.0001), and MMF can reduce the urinary protein in patients with IgAN in Asians (WMD: -0.61, 95% CI: -1.15, -0.08, P = 0.02). Interestingly, these studies on Asians were conducted in China. However, the differences in remission rate, rate of decrease in proteinuria, and urinary protein reduction between the MMF group and control group were not found in overall populations and in the Caucasian population. The differences in complete remission rate, partial remission rate, serum creatinine (SCr) doubling rate, rate of 50% increase in SCr, and rate of need for renal replacement treatment between the MMF group and control group were not found in Asians, Caucasians, and overall populations. The difference in the rate of side effects between the MMF group and the control group was not found. CONCLUSION: MMF protects renal function and is a safe medication for treating Chinese IgAN patients. MMF might significantly advance the development of a new therapy strategy for IgAN in the Chinese population

Unraveling the Clinical Features and Outcomes of IgG4-Related Ophthalmic Disease.

Background/Objectives: IgG4-related ophthalmic disease (IgG4-ROD), characterized by lymphoplasmacytic infiltration, fibrosis, and elevated IgG4 levels, presents diagnostic challenges while offering insights into immune-mediated inflammatory disorders. The aim of this study was to comprehensively examine the clinical features and outcomes of IgG4-ROD. Materials and Methods: A retrospective study was conducted on 33 patients diagnosed with IgG4-ROD, fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. The demographic characteristics of the IgG4-ROD patients were compared with those of 37 patients diagnosed with IgG4-related disease (IgG4-RD) in departments other than ophthalmology (IgG4-nonROD) at the same hospital during the same period. The patients diagnosed with IgG4-ROD were initially treated with glucocorticosteroid (GCS) monotherapy, GCS combined with steroid-sparing agents (SSAs; mycophenolate mofetil, azathioprine, hydroxychloroquine), biologic agent (rituximab) monotherapy, or watchful waiting. The primary outcome was the assessed treatment response at 6 months, and the secondary outcome was the evaluation of recurrence at 1 year after initial treatment. A response was evaluated as the absence of ocular signs and symptoms, either clinically or radiologically. Results: Eyelid swelling (17 patients, 51.5%) was the most common symptom, and lacrimal gland (17 patients, 51.5%) was the most frequent site of involvement. The response rate for GCS monotherapy was 33.3% (3 out of 9 patients), while the response rate for GCS combined with SSA was 60.0% (9 out of 15 patients). The lacrimal gland group demonstrated a significantly higher treatment response compared to the non-lacrimal gland group (66.7% vs. 20.0%, p = 0.013), and the combination of GCS and SSA resulted in a significantly higher treatment response than the GCS monotherapy (77.8% vs. 33.3%, p = 0.045). The group including hydroxychloroquine (HCQ), which comprised 5 out of 33 patients (15.2%), showed no recurrence at 1 year. Conclusions: The combination therapy of GCS and SSA for IgG4-ROD can be considered an effective treatment approach and HCQ could be considered as a potential adjunctive therapy for IgG4-ROD.

A Comprehensive and Practical Approach to the Management of Lupus Nephritis in the Current Era.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is one of the leading causes of morbidity and mortality in patients with SLE. It is estimated that up to 60% of individuals with SLE will develop LN, which can manifest at any stage of a patient's life; however, it commonly emerges early in the course of SLE and tends to exhibit a more aggressive phenotype in men compared to women. Black and Hispanic patients are more likely to progress to kidney failure than white patients. LN is characterized by kidney inflammation and chronic parenchymal damage, leading to impaired kidney function and potential progression to kidney failure. This article provides a comprehensive overview of the epidemiology, pathogenesis, clinical presentation, diagnosis, and management of LN, highlighting the importance of early recognition and treatment of LN to prevent progressive, irreversible kidney damage and improve patient outcomes. Additionally, the article discusses current and emerging therapies for LN, including traditional immunosuppressive agents, biological agents, and novel therapies targeting specific pathways involved in LN pathogenesis, to provide a practical guide for clinicians in properly diagnosing LN and determining a patient-centered treatment plan.

Efficacy and Safety of Pharmacokinetically-Driven Dosing of Mycophenolate Mofetil for the Treatment of Pediatric Proliferative Lupus Nephritis-A Double-Blind Placebo Controlled Clinical Trial (The Pediatric Lupus Nephritis Mycophenolate Mofetil Study).

Background: The safety and efficacy of mycophenolate mofetil (MMF) for lupus nephritis (LN) treatment is established in adults and in some children. MMF is rapidly converted to the biologically active metabolite mycophenolic acid (MPA) whose pharmacokinetics (PK) is characterized by large inter- and intra-individual variability. Methods/Design: This randomized, double-blind, active comparator, controlled clinical trial of pediatric subjects with proliferative LN compares pharmacokinetically-guided precision-dosing of MMF (MMFPK, i.e. the dose is adjusted to the target area under the concentration-time curve (AUC0-12h) of MPA ≥ 60-70 mg*h/L) and MMF dosed per body surface area (MMFBSA, i.e. MMF dosed 600 mg/m2 body surface area), with MMF dosage taken about 12 hours apart. At baseline, subjects are randomized 1:1 to receive blinded treatment with MMFPK or MMFBSA for up to 53 weeks. The primary outcome is partial clinical remission of LN (partial renal response, PRR) at week 26, and the major secondary outcome is complete renal response (CRR) at week 26. Subjects in the MMFBSA arm with PRR at week 26 will receive MMFPK from week 26 onwards, while subjects with CRR will continue MMFBSA or MMFPK treatment until week 53. Subjects who achieve PRR at week 26 are discontinued from study intervention. Discussion: The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) study will provide a thorough evaluation of the PK of MMF in pediatric LN patients, yielding a head-to-head comparison of MMFBSA and MMFPK for both safety and efficacy. This study has the potential to change current treatment recommendations for pediatric LN, thereby significantly impacting childhood-onset SLE (cSLE) disease prognosis and current clinical practice.

Low dose glucocorticoids, mycophenolate mofetil and hydroxychloroquine in IgA nephropathy, an update of current clinical trials.

This mini-review explores glucocorticoids, mycophenolate mofetil (MMF), and hydroxychloroquine (HCQ) in IgA nephropathy (IgAN). It discusses conflicting findings from pivotal trials like TESTING and STOP-IgAN regarding glucocorticoid efficacy, emphasizing reduced-dose protocols as potentially safer options. MMF's effectiveness varies among populations, demonstrating promise in Chinese cohorts but yielding inconclusive results elsewhere. HCQ shows potential in reducing proteinuria, with ongoing trials investigating its long-term benefits.

Timing of immunotherapeutic strategies for first-episode Isolated Anti-Myelin Oligodendrocyte Glycoprotein-IgG Associated Optic Neuritis: A single-centre retrospective study.

Background: There is no consensus on the timing of immunotherapeutic strategies for the first-episode anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) associated disorders (MOGAD) presenting with isolated optic neuritis (ON). Objective: To investigate the optimal timing of intravenous methylprednisolone therapy (IVMP) and necessity of immunosuppressive therapy for the first-episode isolated MOG-IgG associated ON (iMOG-ON). Methods: Adult patients with the first-episode iMOG-ON were enrolled. Primary outcomes were best-corrected visual acuity (BCVA) at last follow-up (i.e. final BCVA) and relapse, and their predictors were assessed by multivariate analysis. Results: 62 patients were included. Logistic regression analysis revealed BCVA at the time of IVMP (odds ratio: 0.463 (95 % confidence interval (CI) 0.310-0.714) was a factor predictive of regaining a final BCVA of 0.0 logMAR vision, and its Youden optimal criterion was <0.175 logMAR by plotting the receiver operating characteristic curve. The time-dependent cox proportional hazards model exhibited MMF therapy was not associated with a high likelihood of relapse-free survival (HR = 1.099, 95 % CI 0.892-1.354, P = 0.376) after adjusting for age of onset, gender, and baseline MOG serum titers. Similar analysis exhibited evidently negative association between high MOG-IgG serum titers at baseline and relapse-free survival after adjusting for age of onset, gender, and MMF therapy (HR = 0.339, 95 % CI 0.155-0.741, P = 0.007). Conclusions: During the first episode of iMOG-ON, the optimal timing of IVMP may be a short timeframe before visual acuity decreasing to 0.175 logMAR, and MMF therapy may not be recommended for patients with low MOG-IgG serum titers. Further long-term follow-up studies are required to validate these findings.

Use of mycophenolate mofetil for the treatment of fibrotic hypersensitivity pneumonitis.

INTRODUCTION: The optimal treatment of fibrosing hypersensitivity pneumonitis (fHP) is not well understood. The aim of the study was to obtain information about the usefulness of mycophenolate mofetil (MMF) in its treatment. MATERIAL AND METHODS: Quasi-experimental analysis of patients diagnosed with fHP and treated with MMF for one year, in a single centre. From the start of treatment, data collection was prospective. RESULTS: 73 were included and 58 completed the study. FVC% and DLCO% decreased until starting MMF (year -1 to year 0). After completion of treatment (year 1), FVC% stabilised (p=0.336) and DLCO% improved significantly (p=0.004) compared to year 0. Dyspnoea, number of patients without corticosteroids and mean corticosteroid dose also improved significantly (p<0.001 in all cases). Being male and having a history of tuberculosis were predictors of poor drug response [AUC = 0.89 (95% CI: 0.80-0.98)]. 45 adverse effects were observed in 34 patients (46.6%). In 4 cases (5.5%), the adverse effect was severe and required discontinuation of treatment. CONCLUSIONS: In patients with fHP, MMF improves lung function and dyspnoea and reduces both the number of patients requiring oral corticosteroids and their mean dose in those who completed 1 year of treatment. The model constructed predicts which patients will respond poorly to treatment, with good discriminative ability and only a small percentage of patients will not tolerate treatment. Further prospective, randomised clinical trials are needed to define the role of this treatment in fHP.

Adeno-associated viral vector gene therapy: Challenges for the paediatric hepatologist.

Hepatoxicity associated with recombinant adeno-associated virus gene therapy is being increasingly encountered by hepatologists in tertiary and quaternary referral units due to the recent increase of these therapies for neuromuscular and haematological disorders. The challenges in managing the condition stem from a lack of good-quality evidence on the appropriate protocols for immunosuppressants due to lack of representative animal models. There is a need for protocols for diagnosing and treating hepatotoxicity and this possible with further research to understand the problem and its management. The review also highlights the importance of a multidisciplinary team in managing hepatotoxicity and recommends further research to better identify at-risk individuals, define the extent of the problem and assess the long-term effects of liver injury and immunosuppressants.

Influence of interruption of oral mycophenolate mofetil for graft-versus-host disease prophylaxis on outcomes after single cord blood transplantation.

Mycophenolate mofetil (MMF), in combination with a calcineurin inhibitor, is used as the prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Compared to intravenous methotrexate (MTX), MMF is associated with a lower incidence of mucositis and shorter time for hematopoietic engraftment but comparable incidence of acute GVHD, resulting in the preferred use of MMF for GVHD prophylaxis in elderly patients or those undergoing cord blood transplantation (CBT). Although several studies have evaluated the clinical impact of MTX omission due to toxicity after allogeneic HCT, the impact of oral MMF interruption for GVHD prophylaxis on transplant outcomes remains unclear. Therefore, in this study, we retrospectively analyzed the consecutive data of adult patients who underwent single-unit unrelated CBT and received oral MMF in combination with cyclosporine for GVHD prophylaxis at our hospital. Among the 53 patients, the planned dose of MMF was interrupted in 14 with a median of 19.5 d (range, 3-27 d) of CBT. In multivariate analysis, MMF interruption, which was treated as a time-dependent covariate, was significantly associated with poorer overall survival (hazard ratio [HR], 5.41; 95% confidence interval [CI], 2.03-14.43; P < 0.001) and higher non-relapse mortality (HR, 7.56; 95% CI, 1.99-28.79; P = 0.002). Further studies with larger cohorts are necessary to confirm the clinical significance of oral MMF interruption in GVHD prophylaxis.

Infection risk in patients with autoimmune cytopenias and immune dysregulation treated with mycophenolate mofetil and sirolimus.

Introduction: Autoimmune cytopenias (AICs) are a group of disorders characterized by immune-mediated destruction of blood cells. In children, they are often secondary to immune dysregulation that may require long-lasting immunosuppression. Mycophenolate mofetil and sirolimus represent two well-tolerated options to treat these disorders, often as a steroid-sparing option. However, no data are available on the infection risk for patients undergoing long-lasting treatments. Patients and methods: The rate of severe infective events was calculated in episodes per 100 persons/months at risk (p/m/r) documented by the analysis of hospitalization charts between January 2015 and July 2023 of patients treated with mycophenolate mofetil or sirolimus given for isolated AIC or AICs associated with autoimmune lymphoproliferative syndrome (ALPS)/ALPS-like syndromes in two large Italian pediatric hematology units. Results: From January 2015 to July 2023, 13 out of 96 patients treated with mycophenolate mofetil or sirolimus developed 16 severe infectious events requiring hospitalization. No patients died. Overall infection rate was 0.24 person/*100 months/risk (95% CI 0.09-0.3). Serious infectious events incidence was higher in patients with ALPS-like compared to others (0.42 versus 0.09; p = 0.006) and lower in patients who underwent mycophenolate treatment alone compared to those who started sirolimus after mycophenolate failure (0.04 versus 0.29, p = 0.03). Considering only patients who started treatment at the beginning of study period, overall cumulative hazard was 18.6% at 60 months (95% CI 3.4-31.4) with higher risk of infectious events after 5 years in ALPS-like patients (26.1%; 95% CI 3.2-43.5) compared to other AICs (4%; 95% CI 0-11.4; p = 0.041). Discussion: To the best of our knowledge, this is the first study to describe the infectious risk related to mycophenolate and sirolimus chronic treatment in patients with AICs and immune dysregulation. Our data highlight that infection rate is very low and mainly related to the underlying hematological condition. Conclusions: Mycophenolate and sirolimus represent a safe immunosuppressive therapy in AICs and immune dysregulation syndromes.

Population pharmacokinetics of mycophenolate in patients treated for interstitial lung disease (EVER-ILD study).

BACKGROUND: Mycophenolate mofetil (MMF) has been used to treat interstitial lung disease (ILD), but mycophenolate (MPA) pharmacokinetics was not reported for this use. This ancillary study of the EVER-ILD protocol aimed at describing the pharmacokinetic variability of MPA using population modelling in ILD. METHODS: Concentrations of MPA were measured during an 8-h course for 27 ILD patients treated with 1000 mg MMF b.i.d. Absorption, distribution and elimination of MPA were described using population compartment models with first-order transfer and elimination rate constants, while accounting for both absorption peaks using gamma absorption models. RESULTS: The pharmacokinetics of MPA was best described using a two-compartment model and two gamma absorption models, model performances of this model were still similar to those of a one gamma absorption model. This pharmacokinetics seemed to be notably influenced by body weight, renal function and inflammatory status. The distribubtion value area under the concentration curve between two administrations of MMF was AUC12 = 52.5 mg.h/L in median (interquartile range: 42.2-58.0 mg.h/L). CONCLUSION: This is the first study reporting MPA pharmacokinetics in ILD. This pharmacokinetics appears to be similar to other indications and should be further investigated in future studies.

Mycophenolate Metabolite Trough Concentrations Are Not Well Correlated With Dosing or Adverse Outcomes in Pediatric Heart Transplant Recipients.

OBJECTIVE: Although mycophenolate metabolite trough concentrations in serum are routinely obtained for pediatric orthotopic heart transplant (OHT) recipients, limited data support this practice. We sought to investigate the relationship of mycophenolic acid (MPA) and MPA glucuronide (MPAG) serum concentrations to dosing and adverse outcomes among pediatric OHT patients. METHODS: This retrospective study included OHT recipients ages 0 to 21 years who received mycophenolate mofetil (MMF) with MPA and MPAG serum trough concentration monitoring. The primary outcome was the relationship between MPA and MPAG serum concentrations and dosing. Secondary outcomes included the relationship of adverse outcomes to either MPA and MPAG concentrations or dosing. RESULTS: A total of 98 patients with 1287 MPA and MPAG trough serum concentrations (each) were included. The median initial MMF dose was 40.3 mg/kg/day (IQR, 35.12-51.83) and 1164.4 mg/m2/day (IQR, 1080.77-1206.86). There was no correlation between either MPA or MPAG serum concentrations and mg/kg dosing, or mg/m2 dosing. When comparing the adverse effect of bone marrow suppression with no adverse effect, the median MPA serum trough concentration was 2 (IQR, 1.1-3.2) versus 1.6 (IQR, 0.8-2.5), p = 0.003. When comparing the adverse effect of infection with no adverse effect, median MPA serum trough concentration was 0.9 (IQR, 0.49-1.7) versus 1.6 (IQR, 0.8-2.5), p < 0.001. The clinical utility of this finding is of uncertain benefit. There was no association between MPAG serum concentrations and any adverse outcome (p = 0.053). CONCLUSIONS: We did not identify a correlation between mycophenolate serum trough concentrations and either adverse outcomes or dosing. Based on these results, we discourage routine monitoring of mycophenolate trough concentrations.

Breaking Out of the Hive: A Case Report on Hypocomplementemic Urticarial Vasculitis Syndrome.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disorder characterized by chronic urticaria, systemic vasculitis, and hypocomplementemia, posing significant diagnostic challenges due to its overlap with common conditions and varied systemic manifestations. We report the case of a 36-year-old female with a history of post-birth cerebral hemorrhage and seizure disorder, who presented with abdominal pain, diarrhea, and subtle urticarial lesions. Initial investigations by gastroenterology suggested inflammatory bowel disease (IBD), but persistent symptoms and evolving cutaneous signs prompted further evaluation. A skin biopsy demonstrated leukocytoclastic vasculitis, while serological tests showed hypocomplementemia and positive antineutrophil cytoplasmic antibodies (ANCA), confirming HUVS. The patient's management included high-dose corticosteroids and mycophenolate mofetil, with partial symptom relief. Subsequent introduction of rituximab markedly improved her gastrointestinal and dermatological symptoms, highlighting its effectiveness in treating refractory HUVS. This case emphasizes the necessity for vigilance, interdisciplinary collaboration, and personalized treatment adaptations in managing HUVS.

Mechanisms of gastrointestinal toxicity in neuromyelitis optica spectrum disorder patients treated with mycophenolate mofetil: insights from a mouse model and human study.

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial ß-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The ß-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF. IMPORTANCE: Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

Clinical Characteristics and Outcomes of Interstitial Lung Disease in Primary Sjögren's Syndrome: A Retrospective Cohort Study.

Objectives: To describe the characteristics of primary Sjögren's syndrome (pSS) patients with interstitial lung disease (ILD) and to assess treatment response. Methods: All patients of pSS from 2010 to 2019 were retrospectively identified. Lung function tests, high resolution computed tomography (HRCT) findings, and treatment outcomes were analysed. Results: Out of 550 patients with pSS, ILD was detected in 33 patients (frequency of 6 %). The mean(±SD) age at the diagnosis of pSS was 50 (± 9.3) years. 28/33(84.8%) were females. ILD onset preceded pSS diagnosis in 2 (6%) patients, simultaneously diagnosed in 21 (63.6%) patients and developed after pSS onset in 10 (30.3%) patients. 5 patients (15.15 %) were asymptomatic for ILD. Non-specific interstitial pneumonia (NSIP) accounted for the most frequent ILD subtype, in 15 patients (45.5%). Mycophenolate mofetil (MMF) was the most frequently used steroid sparing agent, in 25 patients (75.7%). 7 patients were lost to follow up. Response was seen in 22 patients, whereas 3 patients were non responders. There was one mortality due to lower respiratory tract infection-related sepsis. Presence of sicca symptoms [91.5% vs 8.7% (p<0.001)], NSIP pattern of ILD [90% vs 10% (p = 0.002)], and absence of Raynaud's phenomenon [91.7% vs 8.3% (p<0.001)] were significantly associated with responder status when compared to non-responders. Conclusion: ILD in primary Sjögren's syndrome is not an uncommon entity, and immunosuppression with steroids along with steroid-sparing agents led to good clinical outcomes of ILD in a majority of the patients in our cohort.