[Diagnosis and treatment of aplastic anemia and lower-risk myelodysplastic neoplasms].

Myelodysplastic neoplasms (MDS) are clonal hematological malignancies arising from gene mutations. Immunosuppressive therapies (IST) are effective in lower-risk MDS (LR-MDS) with characteristics such as hypoplastic marrow with low blasts or low ring sideroblasts, and with a small increase of PNH clones or decrease of megakaryocytes. Differential diagnosis of these LR-MDS cases from AA can be difficult, and precise diagnosis requires careful evaluation of bone marrow cellularity and dysplasia. To decide on an appropriate treatment strategy for LR-MDS, it is important to evaluate the underlying pathology, and preferentially select IST as first-line therapy in patients with features that indicate immune-mediated bone marrow failure.

Defining the Etiology of Renal Allograft Dysfunction Using Banff 2019 Classification: Correlation with Post-Transplant Duration and Creatinine Levels-A Comprehensive Analysis of 200 Renal Biopsies at a Tertiary Care Medical Center Hospital.

OBJECTIVE: Chronic kidney disease is a growing global health issue, contributing significantly to morbidity and mortality. The incidence of end-stage renal disease (ESRD) is approximately 100 per million population. Renal transplantation remains the cornerstone treatment for ESRD, with a projected 20-year survival rate of 60%. We aim to define the etiology of renal allograft dysfunction using the Banff 2019 classification by analyzing 200 renal allograft biopsies in correlation with creatinine levels across post-transplant time frames. METHODOLOGY: 200 renal allograft biopsies are analyzed using the recent Banff 2019 classification with creatinine levels and post-transplant duration correlation. RESULTS: The study included 150 (75%) male patients and 50 (25%) female patients, with the majority 78 (39%) representing the age group of 16-30 years. 36 (18%) biopsies were within 3-month post-transplant, while 92 (46%) were 2-year post-transplant. According to the Banff 2019 classification, 92 (46.0%) transplant rejection biopsies were identified, with most 54 (27%) exhibiting antibody-mediated rejection (Category 2), including 40 (20%) active acute antibody-mediated rejection (ABMR) and 14 (7.0%) chronic active ABMR. T-cell-mediated rejection (TCMR; Category 4) represented 12 (6%) biopsies, including 10 (5%) acute TCMR and 2 (1%) chronic active TCMR. Category 5, the miscellaneous group, represented 100 (50%) biopsies, out of which 32 (16%) exhibited calcineurin inhibitor (CNI) toxicity, 38 (19%) acute tubular necrosis, and 8 (4%) thrombotic microangiopathy. A notable variation in the dysfunction distribution across different post-transplant time frames indicated a temporal evolution in the underlying causes of allograft dysfunction. Specific Banff categories showed a robust association with renal dysfunction, potentially contributing to the elevation of creatinine levels and renal function deterioration. CONCLUSION: Our study highlights the intricate pathophysiology of renal allograft dysfunction. Most biopsies were attributed to ABMR whereas one-third of biopsies exhibited mixed lesions (ABMR and TCMR or ABMR and calcineurin inhibitor toxicity (CNIT)). Additionally, this study suggests that renal allograft rejection remains a significant contributor to graft dysfunction. A complex interplay between histological findings, Banff classification, and renal function is noted. A significant difference in the distribution of dysfunction across post-transplant time frames is noted suggesting a temporal evolution in the etiology of allograft dysfunction. Certain Banff categories demonstrate a stronger association with renal dysfunction that may influence creatinine level increase and renal function deterioration. In correspondence to the recent Banff 2019 guidelines for diagnosing ABMR, we emphasize the role of C4d staining on immunofluorescence or immunohistochemistry in allograft biopsies as imperative for timely diagnosis and immunosuppressant therapy adjustment, ultimately enhancing graft survival. Further research is needed to elucidate the underlying mechanisms driving renal dysfunction in different Banff categories, ultimately informing personalized management strategies for patients with renal allograft dysfunction. In line with the Banff 2019 guidelines for diagnosing ABMR, this study highlights the critical role of C4d staining through immunofluorescence or immunohistochemistry in allograft biopsies for early diagnosis and timely adjustment of immunosuppressive therapy, ultimately improving graft survival.

Outcomes of kidney transplantation in recipients with SARS-cov-2 infection: a 282-case single-center experience in Japan.

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a global epidemic. There are concerns regarding the severity of SARS-CoV-2 infections in kidney transplant (KTx) recipients. However, there is limited data on how the epidemic has affected the treatment and prognosis of these patients. Therefore, we aimed to report the changes in the treatment and outcomes of KTx recipients infected with SARS-CoV-2 during each wave at our institution. METHODS: A total of 282 KTx recipients who were infected with SARS-CoV-2 during the study period were followed up at Tokyo Women's Medical University between March 2020 and August 2022. We investigated the outcomes and treatments of infected KTx recipients. RESULTS: Nineteen (6.7%) patients showed severe outcomes, including eight SARS-CoV-2 infection-related deaths. Risk factors associated with severe outcomes included underlying conditions, such as diabetes mellitus, heart disease, and liver disease (odds ratios, 2.09, 2.88, and 5.52, respectively). Treatment strategies changed throughout the epidemic in response to changes in the SARS-CoV-2 variants. Antiviral drugs were gradually administered as soon as they were approved for use. CONCLUSIONS: Treatment strategies for KTx recipients were gradually established over the course of the epidemic. Although the proportion of infected KTx recipients decreased compared to that of the general population throughout the epidemic, many patients still followed a severe course.

The role of immune cells in the pathogenesis of connective tissue diseases-associated pulmonary arterial hypertension.

Connective tissue diseases-related pulmonary arterial hypertension (CTD-PAH) is a disease characterized by an elevated pulmonary artery pressure that arises as a complication of connective tissue diseases. The number of patients with CTD-PAH accounts for 25.3% of all PAH patients. The main pathological features of CTD-PAH are thickening of intima, media and adventitia of pulmonary arterioles, increased pulmonary vascular resistance, autoimmune activation and inflammatory reaction. It is worth noting that abnormal immune activation will produce autoantibodies and release cytokines, and abnormal immune cell recruitment will promote inflammatory environment and vascular remodeling. Therefore, almost all forms of connective tissue diseases are related to PAH. In addition to general therapy and targeted drug therapy for PAH, high-dose glucocorticoid combined with immunosuppressant can quickly alleviate and stabilize the basic CTD-PAH disease. Given this, the development of therapeutic approaches targeting immune dysregulation and heightened inflammation is recognized as a promising strategy to prevent or reverse the progression of CTD-PAH. This review explores the potential mechanisms by which immune cells contribute to the development of CTD-PAH and examines the clinical application of immunosuppressive therapies in managing CTD-PAH.

Cyclosporine may reduce the risk of symptomatic COVID-19 in patients with systemic lupus erythematosus: a retrospective cohort study.

This study aimed to explore the effect of cyclosporine (CsA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in systemic lupus erythematosus (SLE) patients to provide a valuable reference for clinical treatment strategies in the context of the long-term risk of SARS-CoV-2 infection. SLE patients who visited the Rheumatology Outpatient Department of Fujian Medical University Union Hospital between 1 May and 31 October 2022 were included. Data on SARS-CoV-2 infection in patients between 1 November 2022 and 31 July 2023 were obtained by telephone follow-up. Patients were divided into two groups according to whether CsA was used during the observation period: the glucocorticoid or hydroxychloroquine group and the CsA group. To assess the robustness of the results, Data sets 1 and 2 were established to be analyzed independently. Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for symptomatic coronavirus disease (COVID-19). A total of 184 patients were included, among whom 129 were definite symptomatic COVID-19 patients; 29 were presumptive symptomatic COVID-19 patients; and 4 had signs and symptoms of COVID-19, but tested negative for SARS-CoV-2 in a virological test. According to the multivariable-adjusted models, CsA was associated with lower odds of symptomatic COVID-19 (P = 0.042, OR = 0.316, 95% CI: 0.104-0.959 in Data set 1 and P = 0.021, OR = 0.257, 95% CI: 0.081-0.812 in Data set 2). CsA is associated with lower odds of contracting symptomatic COVID-19. The use of CsA may be considered an appropriate therapeutic option for disease management in patients with rheumatic diseases who have severe disease activity and persistent SARS-CoV-2 infection. IMPORTANCE: Our study indicated that cyclosporine may reduce the risk of symptomatic COVID-19 in systemic lupus erythematosus patients in spite of its immunosuppressive effects. This study provides a reference for clinical treatment strategies for AIIRD patients in the context of the long-term risk of SARS-CoV-2 infection.

Parvovirus B19-Induced Lower Motor Neuron Facial Nerve Palsy and Cutaneous Small-Vessel Vasculitis: A Case Report.

Parvovirus B19, commonly associated with erythema infectiosum in children, can also present with various clinical manifestations in adults, including arthropathy, myocarditis, vasculitis, and neurological complications. This case report describes a 39-year-old male who presented with fever, rash, and polyarthralgia, followed by the sudden onset of left-sided facial weakness and slurred speech. Clinical examination revealed lower motor neuron facial nerve palsy and signs consistent with cutaneous small-vessel vasculitis. Extensive laboratory investigations confirmed the presence of parvovirus B19 DNA, while tests for other common viral infections and autoimmune markers were negative. The patient was treated with oral prednisolone, resulting in significant improvement in his symptoms over the course of one month. This case highlights the rare but important association between parvovirus B19 infection and both neurological and dermatological manifestations. It underscores the need for healthcare providers to consider viral etiologies in the differential diagnosis of facial nerve palsy and vasculitis, particularly when presented with concurrent symptoms of systemic infection. Early diagnosis and appropriate management are crucial for improving patient outcomes in such atypical presentations. This report adds to the growing body of literature on the diverse clinical manifestations of parvovirus B19, emphasizing the importance of recognizing and treating these rare complications promptly.

Interstitial Pneumonia with Autoimmune Features: Aiming to Define, Refine, and Treat.

Interstitial pneumonia with autoimmune features (IPAF) was defined for research purposes as interstitial lung disease (ILD) associated with features of autoimmunity without diagnosed rheumatic disease. Since publication of the IPAF criteria in 2015, there have been multiple studies of IPAF. However, much remains unknown regarding pathogenesis, prognosis, and treatment in IPAF. This narrative review details the history and classification of IPAF, lists challenges associated with classifying patients as IPAF, and explores the prevalence, epidemiology and presentation of IPAF. We also examine prognosis and important features determining IPAF clinical course, outline pathogenesis, and review treatment strategies.

La neumonía intersticial con características autoinmunes (IPAF) se definió para fines de investigación como enfermedad pulmonar intersticial (EPI) con hallazgos de autoinmunidad sin evidencia de enfermedad reumática (ER) diagnosticada. Desde la publicación de los criterios de clasificación de IPAF en 2015, se han venido realizando múltiples estudios acerca de esta enfermedad. Sin embargo, aún queda mucho por conocer sobre la patogénesis, el pronóstico y el tratamiento de la IPAF. Esta revisión narrativa detalla la historia y la clasificación de la IPAF, enumera los desafíos asociados con la clasificación de los pacientes como IPAF y explora la prevalencia, la epidemiología y manifestaciones clínicas de la enfermedad. Asimismo, explicamos la patogenia, el pronóstico junto con las características importantes que determinan el curso clínico de IPAF y revisamos las estrategias de tratamiento.

A Presentation of Neisseria meningitidis in a Patient Taking Adalimumab as Immunosuppressive Therapy for Hidradenitis Suppurativa.

Neisseria meningitidis is common within the human population. Most patients with N. meningitidis colonization are asymptomatic, but invasive disease can result in meningitis, fulminant septicemia, and disseminated intravascular coagulation. This case report describes a patient who presented with symptoms of sepsis and was later diagnosed with N. meningitidis. The cause of her infection was believed to be immunosuppression from adalimumab, which she was taking for systemic hidradenitis suppurativa.

Rates and predictors for sustained ventricular tachycardia in patients with cardiac sarcoidosis and AV block as first cardiac presentation: Implications for device implantation.

BACKGROUND: Atrioventricular block (AVB) is a frequent initial presentation of cardiac sarcoidosis (CS), but dangerous ventricular arrhythmias (VA) can occur. Despite the scarcity of data, guidelines recommend implantable cardioverter-defibrillator (ICD) rather than a pacemaker implantation whenever a device is needed. OBJECTIVE: In this study, we aimed to establish predictors for sustained VA in patients with CS presenting with pacing indication because of an AVB. METHODS: We prospectively enrolled 112 patients with CS. Excluding those with VA, 82 patients remained and were divided into 2 groups: 34 individuals with AVB as initial presentation and 48 with other symptoms as first presentation (OSF). Both groups were compared for clinical characteristics, rates of VA, left ventricular assist device (LVAD) implantation, heart transplantation, and mortality. RESULTS: During follow-up, VA was detected in 50% in the AVB and 10.4% in the OSF group (P = .001). Death, LVAD implantation, and heart transplantation occurred in 11.8% in AVB group vs 10.4% in the OSF group (P = .847). Late gadolinium enhancement (LGE) was equally observed in both groups: 70% vs 70.5% (P = .966), whereas more patients in the AVB group exhibited abnormal positron emission tomography (PET) uptake: 86.2% vs 54.3% (P = .007). In multivariate analysis, AVB (hazard ratio [HR], 25.15), right ventricular (RV) LGE in cardiovascular magnetic resonance (CMR) (HR, 7.39) were predictors for VA occurrence, whereas the use of immunosuppressive therapy was associated with less VA (HR, 0.26). CONCLUSIONS: Patients with CS presenting with AVB have a high risk of sustained VA. Although immunosuppressive drugs may reduce the occurrence of VA, ICD implantation is reasonable, especially in case of RV LGE.

Assessment of the humoral immune status of varicella-zoster virus in patients with diffuse connective tissue diseases.

Background: Diffuse connective tissue diseases (DCTDs) require long-term immunosuppressive treatment, increasing the risk of varicella-zoster virus (VZV) infection. This study aims to evaluate the humoral immune status against VZV in DCTD patients and explore factors that may influence their immune levels. Methods: This is a retrospective cohort study that collected data from adult DCTD patients (≥18 years) attending our outpatient clinic. The geometric mean concentration (GMC) of VZV-specific IgG antibodies in the patients' sera was measured using the enzyme-linked immunosorbent assay (ELISA). Results: A total of 280 RA patients, 272 SLE + MCTD patients and 280 healthy controls were included. SLE + MCTD patients had significantly higher VZV IgG antibody levels than RA patients (p < 0.05) but showed no significant difference compared to healthy controls (p > 0.05). Notable differences were observed particularly among female patients and those aged 30-49 years, (p < 0.05). SLE + MCTD patients in an active disease state had significantly higher VZV IgG antibody titers than RA patients (p < 0.05). Additionally, patients with a history of herpes zoster, regardless of being in the SLE + MCTD, RA, or control group, exhibited higher VZV IgG titers (p < 0.05). Conclusion: Although DCTD patients, particularly those with SLE and MCTD, exhibit higher VZV IgG antibody levels, they still face a higher risk of developing herpes zoster (HZ), which may be related to their underlying disease and immunosuppressive treatment. The presence of antibodies alone may not provide complete protection, necessitating consideration of cellular immune mechanisms. It is recommended to enhance monitoring of VZV antibody levels in high-risk patients and consider herpes zoster vaccination to reduce HZ-related complications.

Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center.

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19] years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4 months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.

The Diagnostic Challenge of a Dyshidrosiform Bullous Pemphigoid: A Palmar Puzzle.

We present a unique case of an 89-year-old male with Alzheimer's disease who developed hemorrhagic blisters on his palms, which ruptured with time and were followed by pruritic erythematous lesions across his chest, upper back, lower abdomen, and thighs. The patient was diagnosed with dyshidrosiform bullous pemphigoid (DBP), an uncommon variant of the autoimmune condition bullous pemphigoid characterized by cutaneous and mucosal blistering, which commonly appears as vesiculobullous eruptions in the palmoplantar areas and may spread to other parts of the body. Less than 100 cases of DBP have been documented in the medical literature. Since DBP is difficult to identify and treat due to its clinical appearance similar to pompholyx, we reviewed the treatment of DBP and included clinical images and direct immunofluorescence (DIF) staining technique images to better establish the diagnosis.

Case Report: A case of immune hemolytic anemia after liver transplantation: passenger lymphocyte syndrome is the culprit.

Passenger lymphocyte syndrome (PLS) is most commonly observed after solid organ transplantation with minor ABO blood group incompatibility. It consists of a set of clinical symptoms brought on by the remaining lymphocytes of the donor organ developing antibodies against the recipient's antigens. Here, we describe a typical case of PLS in a type A+ recipient receiving a liver transplant from a type O+ donor. She suffered from jaundice, abnormally decreased hemoglobin level, and severe hemolytic anemia without bleeding. During hemolysis, we detected a positive direct antiglobulin test (DAT), and the thermal elution test revealed the presence of IgG anti-A antibodies in her serum. When immunosuppressive agents and blood transfusion were used together, cross-matched O+ washing red blood cells led to an expected outcome without side effects.

Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

A Systematic Review and Meta-Analysis of Eltrombopag Efficacy Combined With Immunosuppressive Drugs in Treatment of Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a life-threatening disorder with high mortality. The only curative treatment is hematopoietic stem cell transplantation (HSCT), but it is mainly for young patients with suitable donors. The alternative is immunosuppressive therapy (IST), which can improve blood counts in about 58% of patients, but many relapse after discontinuation. Recently, eltrombopag, a thrombopoietic receptor agonist, was tested. As a single drug, it improved blood counts in 40-50% of patients. However, combining eltrombopag and IST proved more effective and safer. A review of 20 randomized controlled trials with 2,469 patients showed that the group receiving eltrombopag and IST had a significantly higher overall response rate (86% vs. 74%) after six months. After two years, 54% of the experimental group had relapsed compared to 39% in the control group. Despite this, eltrombopag tends to increase relapse rates over time. In conclusion, combining eltrombopag with IST is a superior treatment for SAA.

Plasmapheresis, immunosuppressive therapy and anti-GBM disease prognosis: a cohort study of 107 patients.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease presents with rapidly progressive glomerulonephritis and alveolar hemorrhage, requiring urgent management. In this study, we analyzed the relationship between plasmapheresis strategy, immunosuppressive therapy and the prognosis of anti-GBM disease patients. METHOD: We screened newly diagnosed anti-GBM disease patients at West China Hospital of Sichuan University from 2010 to 2021. The primary outcome was a composite endpoint of in-hospital death or dialysis dependency upon discharge. RESULTS: This study enrolled 107 anti-GBM disease patients. The use of plasmapheresis was independently associated with a reduced risk of primary outcome (OR: 0.179, 95% Cl: 0.051-0.630, p = 0.007), better 2-year (HR: 0.146; 95% CI: 0.038-0.553; p = 0.005) and 8-year patient survival (HR: 0.309; 95% CI: 0.112-0.850; p = 0.023). Restricted cubic spline regression suggested that patients with 5-10 sessions of plasmapheresis had already achieved maximum risk reduction in the primary outcome. Patients who started plasmapheresis at lower serum creatinine (42.9% vs. 96.2%, p < 0.001) or lower anti-GBM antibody levels (44.4% vs. 93.3%, p = 0.030) had lower risk of primary outcome than those at higher levels. Use of high-dose methylprednisolone (p = 0.505), pulsed cyclophosphamide (p = 0.343) or ANCA positivity (p = 0.115) were not related to primary outcome in anti-GBM disease. CONCLUSION: Plasmapheresis was protective for both in-hospital outcome and long-term survival in anti-GBM disease. Patients who initiated plasmapheresis early had a better prognosis and might only need 5-10 plasmapheresis sessions to achieve maximal risk reduction. Use of high-dose methylprednisolone or cyclophosphamide pulses was not related to improved short- or long-term outcomes in anti-GBM disease.

Infectious Disease Prophylaxis During and After Immunosuppressive Therapy.

Immune-mediated renal diseases are a diverse group of disorders caused by antibody, complement, or cell-mediated autosensitization. Although these diseases predispose to infection on their own, a growing array of traditional and newer, more targeted immunosuppressant medications are used to treat these diseases. By understanding their mechanisms of action and the infections associated with suppression of each arm of the immune system, nephrologists can better anticipate these risks and effectively prevent and recognize opportunistic infections. Focusing specifically on nonkidney transplant recipients, this review discusses the infections that can be associated with each of the commonly used immunosuppressants by nephrologists and suggest interventions to prevent infectious complications in patients with immune-mediated renal disease.

Vogt-Koyanagi-Harada Syndrome: A Case Report.

Vogt-Koyanagi-Harada disease (VKH) is a neurological disorder that impacts vision and hearing by causing the immune system to attack melanocytes. Symptoms of the condition include flu-like symptoms, eye pain, headache, and dizziness, which may progress to vitiligo and hearing impairment. The diagnostic criteria include ocular involvement, generalized choroiditis, tinnitus, meningitis, and skin depigmentation. The treatment includes corticosteroids and immunosuppressive drugs. VKH is believed to be an autoimmune condition, possibly triggered by hereditary factors and cross-reactivity with cytomegalovirus. VKH is common in East Asia and India and has a genetic link to certain alleles. Inflammation generated by Th1 in melanocytes results in the production of granulomas. An analysis of a 48-year-old female with VKH disease revealed symptoms of anterior uveitis and subsequent glaucoma. The treatment involved the administration of systemic steroids and intratympanic steroid injections. Biochemical indicators showed signs of inflammation. Timely identification and therapy are essential for managing VKH. Further research is necessary to enhance outcomes for patients with VKH disease.

Frequency of Topical Immunomodulatory and Immunosuppressive Therapies for Ocular Chronic Graft-versus-Host Disease.

Introduction: The purpose of the study was to evaluate the frequency of topical immunomodulatory and immunosuppressive therapies in patients with ocular chronic graft-versus-host disease (cGVHD) in consideration of inflammatory activity and systemic immunosuppressive therapies in a tertiary care university hospital setting. Methods: We included 95 adult patients (48 male, 47 female) with ocular chronic graft-versus-host disease (cGVHD) after alloHSCT (median age 49.5 years). Clinical ophthalmological findings and the grade of ocular cGVHD according to the NIH eye score and the German-Austrian-Swiss Consensus (GAS) Grading were analyzed. Systemic GVHD manifestations as well as the prevalence of topical and systemic (immunomodulatory) therapies were assessed. Results: A total of 74 of 95 patients (77.8%) had manifestations of systemic chronic graft-versus-host disease other than ocular GVHD. 68.42% (65/95) of patients were under systemic immunosuppressive therapy with at least one immunosuppressive medication. All patients (95/95) received lid-margin hygiene and phosphate- and preservative-free lubricating eye drops. Twenty-five percent of the cohort (24/95) were treated with autologous serum eye drops (ASEDs). In total, 80% (76/95) of patients required topical steroid therapy to treat acute exacerbation of inflammation at least once; continuous topical steroid therapy was only necessary for a minor part (12%) with refractory chronic inflammation. A total of 92.63% (88/95) were primarily treated with ciclosporin A 0.1% as Ikervis®, of whom at least one third did not continue the therapy because of intolerable side effects during follow-up and received alternative topical formulations. Conclusions: Our data show that patients with ocular cGVHD mostly need topical therapy including anti-inflammatory agents despite systemic immunosuppressive therapy. In our cohort, 80% of patients received topical steroids, and more than 90% received topical ciclosporin A eye drops, which were tolerated by only two thirds of patients due to side effects.

Delayed peak antibody titers after the second dose of SARS-CoV-2 vaccine in solid organ transplant recipients: Prospective cohort study.

Poor post-vaccination production of antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a concern among solid organ transplant (SOT) recipients. Furthermore, the timing and kinetics of antibody titers after the second vaccine dose are unknown. We conducted a multicenter prospective observational study that included 614 SOT recipients: 460 kidney, 53 heart, 50 liver, 20 lung, and 31 simultaneous pancreas-kidney (SPK). The participants received two doses of the mRNA vaccine (Pfizer BNT162b2 or Moderna mRNA-1273), as indicated. Serum samples were collected before the first and second vaccinations and at 1, 3, and 6 months after the second vaccine dose, which were then assessed for SARS-CoV-2 antibodies. The overall seropositivity rate was 43% at 1 month after administration of the second vaccine dose; it gradually increased to 68% at 3 months after second dose administration and to 70% at 6 months. In addition, recipient of kidney, lung or SPK transplants had lower antibody titers at the 3- and 6-month time points than did the other recipients. SOT recipients acquired SARS-CoV-2 S-IgG antibodies slowly, and the peak titer differed significantly from that of the general population.