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Purpose: Despite the importance of adherence to immunosuppressants (IMMs) after an allogeneic haematopoietic stem cell transplant (HSCT) for the treatment of acute graft-versus-host disease (aGvHD), no studies to date have reported the experiences of such patients concerning medication adherence (MA). Therefore, the aim of the study was to explore the perspective on MA to immunosuppressive oral therapy among allogeneic HSCT patients with aGvHD., Methods: A qualitative descriptive study following a reflexive thematic analysis methodological approach was performed involving a purposive sample of 16 patients with aGvHD who were being cared for in the outpatient setting of a bone marrow transplant centre and were willing to participate. Semi-structured audio-recorded interviews were conducted, transcribed verbatim and thematically analysed; member checking was performed. COnsolidated criteria for REporting Qualitative research (COREQ) and the ESPACOMP Medication Adherence Reporting Guideline were followed., Results: Participants aged 25-74 years and mostly males (62.5%) were recruited for this study; 56.2% developed grade I, 37.5% grade II and 6.3% grade III aGvHD; 56.2% were receiving treatment with both cyclosporine and prednisone. Patients' perspectives have been summarised into four themes, named: "Transiting from an external obligation to a habit"; "Being in the middle between the negative and positive effects of the IMMs"; "Failure to systematically respect the rules"; and "Adopting personal strategies to become adherent". After difficulties with the perception of feeling obliged, patients became used to adhering to IMMs. Although there were failures in systematically taking the medication correctly and there were episodes of non-adherence, the adoption of personal strategies helped patients to become adherent to their medication schedules., Conclusions: MA in patients with aGvHD is a complex behaviour and is often a challenge. These results can help healthcare professionals and centres to understand how best to design tailored strategies and behavioural interventions to maximise patients' MA to IMMs., (© 2024. The Author(s).)

Eltrombopag combined with immunosuppressive therapy (IST) was superior to IST alone for severe aplastic anemia (SAA) in the previous studies. But in China, horse antithymocyte globulin (hATG) is not available, instead, we use rabbit ATG (rATG). Here, we compared the efficacy and safety of IST (rATG combined with cyclosporine) combined with or without eltrombopag for the first-line treatment of SAA and very severe aplastic anemia (VSAA). A total of 371 patients in ten institutions in China from April 1, 2017 to December 1, 2022 were enrolled. The overall response (OR) rate at 3 months (54.2% vs. 41%; P = 0.046), the complete response (CR) (31.3% vs. 19.4%; P = 0.041) and OR (78.3% vs. 51.1%; P < 0.0001) rates at 6 months were significantly higher with IST combined with eltrombopag than with IST alone in SAA patients. While in VSAA patients, the addition of eltrombopag to IST only increased the CR rate at 6 months (29.8% vs. 9.43%; P = 0.010). Liver injury increased significantly in groups treated with IST combined with eltrombopag (P < 0.05). Serious treatment-related toxicities were similar (P > 0.05). In patients with SAA, 3-year failure-free survival (FFS) of eltrombopag combined with IST group was significantly higher than that of IST group (70.7 ± 5.3% vs. 50.3 ± 3.9%; P = 0.007). In patients with VSAA, the addition of eltrombopag significantly improved 3-year overall survival (OS) (82.2 ± 5.7% vs. 57.3 ± 7.2%; P = 0.020). Our findings suggested that IST combined with eltrombopag could improve the hematological recovery of newly diagnosed SAA without increasing severe toxicities. But in VSAA, the addition of eltrombopag seemed to show no other improvement to efficacy except the CR rate at 6 months., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A 6-year-old spayed female domestic short-hair cat was presented for primary complaints of anorexia and lethargy. The cat was being treated with cyclosporine (25 mg/cat, PO q24h) and prednisolone (1 mg/kg, PO q12h) for feline hypersensitivity dermatitis and inflammatory bowel disease for 1 year, wherein prednisolone was withdrawn 2 weeks prior to presentation. At presentation, dehydration, hyperglycaemia, ketonaemia, increased fructosamine, glucosuria, ketonuria and metabolic acidosis were observed. The cat was diagnosed with diabetic ketoacidosis (DKA). Immediate treatments with insulin continuous-rate infusion and intravenous fluid therapy were initiated. A serum cyclosporine concentration was >2100 ng/mL, indicating cyclosporine toxicity. Cyclosporine was discontinued immediately. The cat's acidosis and ketonaemia were resolved within a week, allowing a switch from insulin continuous-rate infusion to subcutaneous glargine (1 IU/cat), which was eventually discontinued due to persistent normoglycaemia 12 days after initial presentation. Hyperglycaemia was not observed for 28 days thereafter without insulin, indicating remission of diabetes mellitus. This report suggests that using prednisolone, particularly immune suppressive doses, could be problematic in cats receiving long-term cyclosporine therapy. Additionally, diabetic cats receiving immune-suppressive agents can possibly achieve diabetic remission after surviving DKA through regular monitoring of blood glucose concentration, elimination of prednisolone and intensive blood glucose management., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Bullous pemphigoid (BP), an autoimmune bullous dermatosis, occurs predominantly in older individuals. Nemolizumab, a humanized monoclonal antibody against the interleukin (IL)-31 receptor A, is used to treat severe atopic dermatitis (AD) in Japan. However, it can cause several adverse events, such as exacerbation of AD, erythema, and eosinophilia. Herein, we describe a case of prurigo-type AD developing BP after nemolizumab administration. A 62-year-old man with prurigo-type AD and asthma presented with serious, refractory itching. After nemolizumab injection, his pruritus was relieved for 2 days. However, on day 3, erythema with blisters and erosions suddenly appeared throughout his body. Pathological examination showed typical BP and the patient's serum anti-BP180-NC16a antibody level was 882.5 U/mL. Oral prednisolone (PSL) was initiated and nemolizumab was never used again. Despite high-dose PSL, new blisters continued to develop, with a rapid elevation of anti-BP180-NC16a antibodies to 6930 U/mL. Adding high-dose cyclosporine and intravenous gamma globulin reduced new blister formation after 9 weeks, and PSL and cyclosporine were gradually tapered. Dupilumab, an anti-IL-4 receptor antibody, was initiated after 16 weeks, resulting in continued remission without PSL and cyclosporine. The sudden occurrence of BP in this case suggested that the patient had occult BP before the nemolizumab initiation and that nemolizumab exacerbated BP and made it overt. Blocking the IL-31 pathway may exacerbate inflammation in AD or BP, resulting in the acceleration of blister formation. This may be countered by blocking the IL-4/13 pathway with dupilumab. To our knowledge, this is the first case of nemolizumab-exacerbated BP., (© 2024 Japanese Dermatological Association.)

Abstract: Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although in vivo lymphodepletion for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced-intensity conditioning (RIC) are not well described. Patients (N = 83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to 2 GVHD prophylaxis arms: alemtuzumab and cyclosporine (AC; n = 44) or tacrolimus, methotrexate, and sirolimus (TMS; n = 39), with the primary end point of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%; overall, P = .0002), as well as any grade (P = .003) and moderate-severe (P < .0001) cGVHD. AC was associated with higher rates of grade 3 to 4 infections (P = .02) and relapse (52% vs 21%; P = .003) with no difference in 5-year GVHD-free-, relapse-free-, or overall survival. AC severely depleted naïve T-cell reconstitution, resulting in reduced T-cell receptor repertoire diversity, smaller populations of CD4Treg and CD8Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile, which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. This trial was registered at www.ClinicalTrials.gov as #NCT00520130., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Liang, Zhang, Chen, Shi, Hao, Zhao, Gong, Wei, He, Jiang, Han, Zhang and Feng.)

Background and Aims: Ciclosporin (CSA) is an immunosuppressive agent that requires therapeutic drug monitoring (TDM). High partitioning in erythrocytes indicates that whole blood (WB) is a suitable matrix for CSA determination. Alternative sampling strategies, such as volumetric absorptive microsampling (VAMS), are novel possibilities for blood collection during TDM for various analytes, including immunosuppressants. This technique is attractive for vulnerable pediatric patients, including home-based self-sampling, remote therapy, and adherence control., Materials and Methods: This study aimed to develop and validate a new method for CSA determination based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) of WB and VAMS samples. Additionally, these methods were applied for CSA determination in clinical samples from pediatric transplant recipients. A strong point of this study is the assessment of an external proficiency testing scheme., Results: Both methods were successfully validated within the 1-2000 ng/mL calibration range, with LOD 0.5 and 1 ng/mL for WB and VAMS methods, respectively. All the validation parameters fulfilled the international acceptance criteria for bioanalytical methods. Cross-validation confirmed the interchangeability of the LC-MS/MS method developed in this study., Conclusion: This study developed and validated novel methods for CSA determination in whole blood and VAMS using LC-MS/MS. Clinical validation and proficiency testing confirmed their utility in routine clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The therapeutic arsenal for atopic dermatitis (AD) has increased in recent years. The use of biologics or Janus kinase inhibitors (JAKi) is advocated following failure or contraindication to cyclosporine (CSA), however, it is not known whether treatment with CSA can impact the response to biologics or JAKi. The aim of this study was to evaluate the effect of previous treatment with CSA on response to biologics or JAKi in patients with AD. This was a retrospective observational study including patients with AD treated for 16 weeks with a biologic or JAKi, who had previously received cyclosporine for at least four weeks. Thirty patients with AD, with a mean age of 25.07±9.91 years, of whom 18 (60%) were women, were included. The mean duration of CSA treatment was 43.39±31.32 weeks. After 16 weeks of biologic or JAKi treatment, 17 (56.7%) patients achieved EASI75. These patients had a higher cumulative dose of CSA (3,6815 vs.76,993.33 mg; p=0.022) and a longer treatment duration (24.5 vs.57.4 weeks; p=0.003). Additionally, a negative correlation was observed between cumulative dose of CSA and EASI or SCORAD at 16 weeks. Previous cumulative dose and longer duration of CSA treatment does not appear to have a negative impact on response to biologics and JAKi in patients with AD.

Nano-delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral-mimicking ternary polyplexes system for the controlled delivery of the anti-inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44-mediated targeting. By mimicking the Trojan Horse strategy employed by viruses, these polyplexes undergo a stepwise process of deshielding and disintegration within the inflamed joints. This process leads to the release of CsA within the cells and the scavenging of pathogenic factors. This study demonstrates that these viral-mimicking ternary polyplexes exhibit rapid targeting, high accumulation, and prolonged persistence in the joints of RA mice. As a result, they effectively reduce inflammation and alleviate symptoms. These results highlight the potential of viral-mimicking ternary polyplexes as a promising therapeutic approach for the targeted and programmed delivery of drugs to treat not only RA but also other autoimmune diseases., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Systemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection (SSI) and complication., Objective: To evaluate the risk of SSI and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alfa [TNF-α] inhibitors, interleukin [IL] 12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte-associated antigen-4 costimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine (CsA), and methotrexate [MTX]) undergoing surgery., Methods: We performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery., Results: We examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease., Conclusion: For low-risk procedures, TNF-α inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, MTX, CsA, and apremilast can safely be continued. For intermediate- and high-risk surgery, MTX, CsA, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib., Competing Interests: Conflicts of interest Dr Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alvotech, vTv Therapeutics, Bristol Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, LEO Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate, and the National Psoriasis Foundation and is a founder and part owner of Causa Research and holds stock in Sensal Health. Dr Wu is or has been an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, and Zerigo Health. Dr Hsu has served on the advisory board for Boehringer Ingelheim, LEO Pharma, and Sanofi and has served on the registries/clinical trials for CorEvitas, PROSE, Argenx, and Cabaletta. Dr Armstrong has served as a research investigator, scientific adviser, and/or speaker to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, and Pfizer. Dr Wallace has served as a research investigator, scientific adviser, and/or speaker to Pfizer, Target RWE, Kyowa, Amgen, Arcutis, and Argenx. Dr Lee has served as a research investigator, scientific adviser, and/or speaker to Eli Lilly, Sanofi, Regeneron, Pfizer, Trevi Therapeutics, AbbVie, Mayne Pharmaceuticals, Incyte Corp, Castle Creek, Pyramid Bioscience, Amyrt, Krystal Biotech, Arcutis, Celgene, Target Pharma, Amgen, Novartis, UCB, Galderma, Kiniksa, Avita, Janssen, MoonLake Pharmaceuticals, and Timber Pharmaceuticals. Dr Merola is a consultant and/or investigator for Amgen, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi Regeneron, Sun Pharma, Biogen, Pfizer, and LEO Pharma. Dr Schwartzman has served as a speaker and/or consultant to AbbVie, Janssen, Lilly, Pfizer, UCB, Myriad, Novartis, Sanofi/Regeneron, Stelexis, Jubilant, and Teijin and has served as a board member to the National Psoriasis Foundation. Dr Gladman has received consulting fees from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB and has received research support from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Dr Liu has served as a research investigator, scientific adviser, and/or speaker to for AbbVie, Janssen, Lilly, Sanofi Regeneron, Arcutis, Dermavant, Pfizer, Bristol Myers Squibb, UCB, Incyte, Amgen, and Evelo. Dr Koo has served on the advisory board/consultant for AbbVie, Arcutis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Castle, Dermavant, Incyte, Janssen, Eli Lilly, EPI, Leo, Novartis, Ortho Dermatologics/Valeant, Pfizer, Regeneron/Sanofi, Sun Pharma, and UCB. Dr Hawkes has served on the advisory board/consultant for AbbVie, Arcutis, Boehringer Ingelheim, BMS, Janssen, LearnSkin, LEO, Lilly, Novartis, Pfizer, Regeneron-Sanofi Genzyme, and UCB, has served on the medical/scientific board for the National Psoriasis Foundation and International Psoriasis Council (IPC), and has stock ownership/equity in Regeneron Pharmaceuticals. Dr Reddy has served on the advisory board/consultant UCB, Novartis, Fresenius, Amgen, AbbVie, Janssen, and Pfizer. Dr Prussick has served as a scientific adviser and/or speaker to of Amgen, Janssen, AbbVie, and Novartis and has served as a board member to the National Psoriasis Foundation. Dr Yamauchi has served as a research investigator, scientific adviser, and/or speaker to AbbVie, Amgen, Lilly, Janssen, Sun Pharma, BMS, UCB, Ortho Dermatologics, and Novartis. Dr Lewitt has received grants/research support from Novan, Galderma, Leo, Lilly, DermTech, and Amgen and has served as a speaker’s bureau/consultant/advisory board for AbbVie, Janssen, Lilly, Galderma, Pfizer, UCB, Ortho Dermatologics, Dermavant, and Bristol Myers Squibb. Dr Soung has served as a research investigator, scientific adviser, and/or speaker to Celgene, Amgen, Eli Lilly, AbbVie, Pfizer, Ortho Dermatologics, National Psoriasis Foundation (non-profit), LEO, Novartis, Regeneron/Sanofi, UCB, Janssen, Kyowa Kirin, Dermavant, Bristol Myers Squibb, Arcutis, KoBioLabs, and Castle Biosciences. Dr Weinberg has served as a speaker for AbbVie, Dermavant, Lilly, Janssen, BMS, Amgen, and UCB and has received research grants from Arcutis, Dermavant, AbbVie, UCB, Janssen, and Lilly. Dr Lebwohl is an employee of Mount Sinai, has received research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc, and is a consultant for AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Avotres Therapeutics, BioMX, Boehringer Ingelheim, Brickell Biotech, Cara Therapeutics, Castle Biosciences, CorEvitas, Dermavant Sciences, Evommune, Inc, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima Ltd, Incyte, Meiji Seika Pharma, Mindera, National Society of Cutaneous Medicine, New York College of Podiatric Medicine, Pfizer, Seanergy, SUN Pharma, Verrica, and Vial. Dr Glick has served as a research investigator, scientific adviser, and/or speaker to AbbVie, AstraZeneca, Amgen, Janssen, Galderma, Sun Pharma, LEO Pharma, Lilly, Novartis, Dermavant Sciences, Incyte, EPI/Novan, BMS, Nimbus Lakshmi, Cara Therapeutics, Dermira, Sanofi/Genzyme, Regeneron, Pfizer, ChemoCentryx, Ortho Dermatologics, UCB, Brickell, Biotech, CorEvitas Registry PSO, CorEvitas Registry AD, PROSE Registry for AD. Dr Kircik has served as a research investigator, scientific adviser, board member, and/or speaker to Abbott Laboratories, AbbVie, Allergan, Inc, Almirall, Amgen, Inc, Arcutis, Biogen-Idec, BMS, Boehringer Ingelheim, Breckinridge Pharma, Celgene, Centocor, Inc, Cellceutix, Cipher, Combinatrix, Connetics Corporation, Coria, Dermavant, Dermira, Dow Pharmaceutical Sciences, Inc, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Genentech, Inc, GlaxoSmithKline, PLC, Idera, Johnson & Johnson, Leo, Maruho, Merck, Medicis Pharmaceutical Corp, Novartis AG, Promius, PharmaDerm, Pfizer, Serono (Merck Serono International SA), Stiefel Laboratories, Inc, Sun Pharma, Taro, UCB, Valeant Pharmaceuticals Intl, and XenoPort. Dr Desai has served on the Medical Board of the National Psoriasis Foundation and holds multiple other leadership positions in dermatologic organizations, and has served as a researcher and/or consultant for Pfizer, Lilly, AbbVie, Bristol Myers Squibb, Galderma, and other organizations. Drs James and Zaino and Author Rosenberg have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

A 42-year-old female patient was admitted to hospital due to acute neurological symptoms (dysarthria, disorientation). After exclusion of cerebral ischemia and hemorrhage an autoimmune encephalitis was diagnosed. Shortly before as an outpatient the suspicion of the presence of systemic lupus erythematosus (SLE) was voiced. The patient showed a constellation of high levels of inflammatory laboratory parameters and within a few days developed a severe pancytopenia. In the presence of all diagnostic criteria a secondary hemophagocytic lymphohistiocytosis (sHLH) was diagnosed and confirmed by a kidney biopsy during the course of the underlying SLE. The immunosuppressive treatment with etoposide and high-dose dexamethasone according to the HLH-94 protocol only showed temporary success. After 3 weeks of treatment with a protocol-conform dose reduction, under running treatment a new exacerbation of symptoms was confirmed. A renewed dose escalation of the drugs used did not lead to control of the symptoms. The inflammatory activity could only be sustainably controlled by the use of cyclosporin A in combination with mycophenolate mofetil (MMF) and dexamethasone. After stabilization of the condition of the patient, an outpatient follow-up care was possible., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus; up to 30% of patients with LN will develop end-stage kidney disease (ESKD). One of the main treatment goals for LN is preservation of kidney function, with early decreases in proteinuria associated with improved long-term outcomes. Voclosporin, a second-generation calcineurin inhibitor, was approved in the United States in 2021 for the treatment of active LN combined with background immunosuppression. The AURORA 1 study found that the use of voclosporin with low doses of mycophenolate mofetil and glucocorticoids yielded significant reductions in proteinuria. The AURORA 2 study showed long-term efficacy and safety of voclosporin over a 3-year period with kidney function preservation. The Institute for Clinical and Economic Review (ICER) is a nonprofit organization that evaluates medical evidence to help improve patient outcomes and control costs. In 2021, ICER published an economic model to estimate the impact and cost-effectiveness of LN therapies. From a US health care perspective, voclosporin was cost-effective at $149,260 per quality-adjusted life-year (QALY) and $131,528 per equal value of life-years gained (evLYG). At the time of the LN cost-effectiveness model (CEM) development, voclosporin was not yet approved in the United States and the cost of treating patients with LN with ESKD was not captured in the literature., Objective: To evaluate the cost-effectiveness of voclosporin given the emergence of new data., Methods: The LN CEM uses a short-term trial-based Markov model and long-term extrapolation using partitioned survival modeling data assuming adults with LN start with active disease, transitioning to complete or partial renal response, kidney failure, or death. In the current analysis, clinical data for voclosporin, duration of voclosporin treatment for nonresponders, and drug costs reflecting the 2023 price of voclosporin were updated. Additionally, health care payer costs of disease management were incorporated based on real-world claims data on the costs of treating patients with LN., Results: Using the LN CEM with inputs reflecting the latest and most relevant evidence, the incremental cost of voclosporin per QALY was $88,076 and per evLYG was $77,643. For a subpopulation of Black, Hispanic, and Latino patients, the incremental cost of voclosporin per QALY was $77,435 and per evLYG was $67,828., Conclusions: Following the inclusion of updated data in the cost-effectiveness analysis, voclosporin remains a cost-effective therapy for the treatment of active LN including in a Black, Hispanic, and Latino subpopulation, substantially below the ICER willingness-to-pay threshold of $150,000/QALY.

Background: Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children. We performed this study to report histopathological findings, the correlation between clinical and histopathological features, and the response to steroids and other immunosuppressive drugs and outcomes in Syrian children with INS., Methods: A single-center retrospective observational cohort study was conducted at Children's University Hospital in Damascus, and included all patients aged 1-14 years, admitted from January 2013 to December 2022, with INS and who underwent kidney biopsy., Results: The study included 109 patients, with a male/female ratio of 1.13:1, and a median age of 5 years with interquartile range (2.8-10). The main indication of kidney biopsy was steroid-resistant nephrotic syndrome (SRNS) (57.8%). The main histopathological patterns were minimal change disease (MCD) (45%) and focal segmental glomerulosclerosis (FSGS) (37.6%). FSGS was the most common histopathological pattern in SRNS (44.3%). In SRNS, we used calcineurin inhibitors to induce remission. Tacrolimus was used in 49 patients with response rate (complete remission of proteinuria) of 69.4% and cyclosporine in 20 patients with response rate of 50%. In steroid-dependent nephrotic syndrome (SDNS), we used mycophenolate mofetil (MMF) and cyclophosphamide to prevent relapses; MMF was used in 9 patients with response rate (maintaining sustained remission) of 89% and cyclophosphamide in 3 patients with response rate of 66.7%. Rituximab was used in four patients with FSGS, two SRNS patients and two SDNS patients, with sustained remission rate of 100%. Fifteen patients (13.7%) progressed to chronic kidney disease stage 5. Of them, 7 patients had FSGS and 8 patients had focal and global glomerulosclerosis;14 of them were steroid-resistant and one patient was steroid-dependent with persistent relapses. The most common outcome was sustained remission (47%) in MCD and frequent relapses (31.7%) in FSGS., Conclusions: FSGS was the most common histopathological pattern in idiopathic SRNS and had the worst prognosis. Calcineurin inhibitors could be an effective therapy to induce complete remission in SRNS. Rituximab may be an effective treatment to achieve sustained remission in SDNS and frequently relapsing NS and may have a potential role in SRNS with further studies required., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Perianal fistulas are painful ulcers or sinus tracts that disproportionately affect German shepherd dogs and are proposed as a spontaneous animal model of fistulising Crohn's disease., Objectives: To characterise the rectal and cutaneous microbiota in German shepherd dogs with perianal fistulas and to investigate longitudinal shifts with lesion resolution during immunomodulatory therapy., Animals: Eleven German shepherd dogs with perianal fistulas and 15 healthy German shepherd dogs., Materials and Methods: Affected dogs were evaluated and swabbed at three visits, 30 days apart, while undergoing treatment with ciclosporin and ketoconazole. Healthy German shepherd dogs were contemporaneously sampled. Sites included the rectum, perianal skin and axilla. The microbiome was evaluated following sequencing of the V4 hypervariable region of the 16S ribosomal RNA (rRNA) gene., Results: Alpha diversity was not significantly different between healthy and affected dogs at each of the three body sites (p > 0.5), yet rectal and perianal beta diversities from affected dogs differed significantly from those of healthy dogs at Day 0 (p = 0.004). Rectal and perianal relative abundance of Prevotella spp. increased and perianal Staphylococcus spp. relative abundance decreased in affected dogs over time, coincident with lesion resolution., Conclusions and Clinical Relevance: Changes in lesional cutaneous and rectal microbiota occur in German shepherd dogs with perianal fistulas and shift over time with lesion resolution during immunomodulatory therapy. Further investigations of the role of cutaneous and enteric microbiota in the pathogenesis of perianal fistulas, and whether manipulation of microbial populations may ameliorate disease, are needed., (© 2024 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

We present a 70-year-old female patient diagnosed with epidermal growth factor receptor-mutated metastatic non-small cell lung cancer (T4N2M1a), who developed afatinib-induced toxic epidermal necrolysis (TEN). We have also performed a PubMed/Medline literature review to detect other possible cases of TEN/Stevens-Johnson syndrome associated with afatinib treatment and found only 5 other cases reported. To our best knowledge, this is the first case of afatinib-induced TEN successfully treated with cyclosporine., (© 2024 British Pharmacological Society.)

Background: Chronic inducible urticaria (CIndU) management often follows chronic spontaneous urticaria (CSU) guidelines, but a step-by-step evaluation of their effectiveness in CIndU is lacking., Objective: To assess the clinical impact of adapting CSU international guidelines for CIndU management., Methods: We conducted a prospective cohort study involving patients diagnosed with CIndU based on challenge tests and a Urticaria Control Test (UCT) score of ≤11 points. Following the guidelines, a stepwise approach was used: avoidance measures, antihistamines, omalizumab, and cyclosporine. Treatment steps were added based on individual response, with control defined as UCT ≥12 points. Pharmacological steps were evaluated for at least 1 month, with the next step initiated in case of a UCT score ≤11 points., Results: We enrolled 194 patients with CIndU. Of them, 134 patients had CIndU with concomitant CSU and 60 had CIndU only. Following the step-by-step approach outlined in the guidelines, a total of 159 (81.9%) patients reach a UCT ≥12 points, with avoidance measures 23 (11.8%) patients, antihistamines 84 (43.2%), omalizumab 35 (18%), and cyclosporine 17 (8.7%)., Conclusions: This study supports the use of a stepwise approach based on CSU guidelines for CIndU management. However, a significant proportion of patients, particularly those with CIndU only, did not achieve adequate control. This highlights the heterogeneity within CIndU and the need for further research to develop new therapies for patients with CIndU who remain uncontrolled., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

We retrospectively evaluated the incidence, factors, and clinical outcomes of the discontinuation of immunosuppressive treatment (IST) after single-unit unrelated cord blood transplantation (CBT) in adults receiving cyclosporine-based graft-versus-host disease (GVHD) prophylaxis at our institute. Among the 309 patients who achieved engraftment, 247 were able to discontinue IST with a median follow-up of 121 months for survivors. The cumulative incidence of the discontinuation of IST was 46.2% at 180 days, 72.8% at 2 years, and 79.3% at 5 years post-CBT. In the multivariate analysis, discontinuation of IST after CBT was significantly associated with the requirement for steroid therapy (hazard ratio [HR]: 0.46; P < 0.001) and the recent calendar year of CBT (HR: 1.79; P < 0.001). In the conditional landmark analysis at 180 days, discontinuation of IST was not associated with the development of extensive chronic GVHD (HR: 1.00; P = 0.989), non-relapse mortality (HR: 0.49; P = 0.122), relapse (HR: 1.46; P = 0.388), or overall survival (HR: 1.91; P = 0.065). Our data showed that successful discontinuation of IST is common after single-unit CBT in adults. Discontinuation of IST did not affect subsequent outcomes, suggesting that discontinuation of IST is both feasible and safe in adults undergoing single-unit CBT., (© 2024. The Author(s).)

Chronic urticaria is a common and debilitating mast cell-driven skin disease presenting with itchy wheals, angio-oedema, or both. Chronic urticaria is classified as spontaneous (without definite triggers) and inducible (with definite and subtype-specific triggers; eg, cold or pressure). Current management guidelines recommend step-up administration of second-generation H1-antihistamines to four-fold the approved dose, followed by omalizumab and ciclosporin. However, in many patients, chronic urticaria does not respond to this linear approach due to heterogeneous underlying mechanisms. A personalised endotype-based approach is emerging based on the identification of autoantibodies and other drivers of urticaria pathogenesis. Over the past decade, clinical trials have presented promising options for targeted treatment of chronic urticaria with the potential for disease modification, including Bruton's tyrosine kinase inhibitors, anti-cytokine therapies, and mast cell depletion. This Therapeutics article focuses on the evidence for these novel drugs and their role in addressing an unmet need for personalised management of patients with chronic urticaria., Competing Interests: Declaration of interests TZ has received honoraria for lectures from Amgen, AstraZeneca, AbbVie, ALK–Abelló, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES Farma, HAL Allergy, Henkel, Kryolan, Leti, L'Oreal, Meda, Menarini, Merck Sharp & Dohme, Novartis, Nuocor, Pfizer, Sanofi, Stallergenes, Takeda, Teva, Union Chimique Belge, and Uriach; fees for industry consulting from Abivax, Almirall, Bluprint, Celldex, Celltrion, Novartis, and Sanofi; he declares unpaid organisational affiliations: is a committee member of Allergic Rhinitis and its Impact on Asthma, is a member of the board of the German Society for Allergy and Clinical Immunology (DGAKI), head of the European Centre for Allergy Research Foundation (ECARF), President of the Global Allergy and Asthma European Network (GA(2)LEN), member of the committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). LFE reports honoraria for lectures from Novartis, Sanofi, and Abbvie; and participation on an advisory board for Sanofi. AG-A reports grants from Uriach Pharma, Novartis, Instituto Carlos III-FEDER (PI11/00108); consulting fees from Uriach Pharma, Neucor, Genentech, Novartis, FAES Farma, GlaxoSmithKline, Sanofi–Regeneron, Amgen, Thermo Fisher Scientific, Almirall, Leo Pharma, Mitsubishi Tanabe, and Servier; honoraria for lectures and education from Uriach Pharma, Novartis, Genentech, Menarini, LEO-PHARMA, GlaxoSmithKline, Merck Sharp & Dohme, Almirall, Sanofi, and Avene; and participates on an advisory board for Celldex Therapeutics. CG has a consultancy with Celltrion and is on steering committees for AB Science and Blueprint Medicines. EK reports honoraria for lectures and consulting from Novartis. KK reports grants from Novartis (NCT05032157, NCT05513001, NCT06042478); and personal fees from Novartis, Menarini, and Takeda, outside the submitted work. PK reports personal fees from Novartis, Roche, and ValenzaBio, outside the submitted work. MM is or recently was a speaker, advisor, or both, for Allakos, Alexion, Almirall, Alvotech, Amgen, Aquestive, Arcensus, argenX, AstraZeneca, Astria, BioCryst, Blueprint, Celldex, Celltrion, Clinuvel, Cogent, CSL Behring, Escient, Evoemmune, Excellergy, GlaxoSmithKline, Incyte, Jasper, Kashiv, Kalvista, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Mitsubishi Tanabe Pharma, Moxie, Noucor, Novartis, Orion Biotechnoloy, Pharvaris, Resonance Medicine, Sanofi–Regeneron, Santa Ana Bio, Septerna, Servier, Takeda, Teva, Third HarmonicBio, Valenza Bio, Vitalli Bio, Yuhan Corporation, and Zurabio; and he received institutional research funding from Allakos, Alexion, Amgen, AstraZeneca, Astria, BioCryst, Blueprint, Celldex, Clinuvel, Cogent, CSL Behring, Escient, Evommune, Incyte, Jasper, Kalvista, Kyowa Kirin, Leo Pharma, Lilly, Mitsubishi Tanabe Pharma, Noucor, Novartis, Pharvaris, Sanofi–Regeneron, Santa Ana Bio, Septerna, Servier, Takeda, ThirdHarmonicBio, and Yuhan Corporation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like perforin and FasL ) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants., Competing Interests: The authors declare no conflict of interest.

Kikuchi-Fujimoto disease (KFD) is an inflammatory disease of unknown aetiology characterised by fever and cervical lymphadenopathy. Although KFD is a self-limiting disease, patients with severe or long-lasting course require glucocorticoid therapy. We presently report a 17-year-old boy with KFD who had seven relapses since the onset at 4 years old. He suffered from hypothermia, bradycardia, and hypotension during the treatment with prednisolone or methylprednisolone. All of his vital signs recovered after cessation of the drug in addition to fluid replacement and warming. Thus, glucocorticoid was effective but could not be continued because of the adverse event. Although hypothermia developed during the treatment with 5 mg/kg/day of cyclosporine A (CsA) at his second relapse, he was successfully treated with lower-dose CsA (3 mg/kg/day). Thereafter, he had five relapses of KFD until the age of 12 years and was treated by 1.3-2.5 mg/kg/day of CsA. Hypothermia accompanied by bradycardia and hypotension developed soon after concomitant administration of ibuprofen at his fifth and sixth relapses even during low-dose CsA therapy. Conclusively, glucocorticoid, standard dose of CsA, or concomitant use of non-steroidal anti-inflammatory drugs may cause hypothermia, bradycardia, and hypotension and needs special attention. Low-dose CsA could be a choice for such cases with KFD., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Introduction: Posterior leukoencephalopathy syndrome (PRES) is a rare neurological disease possibly associated with the use of calcineurin inhibitors like cyclosporine A (CSA). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the outbreak of coronavirus disease 19 (COVID-19) can cause neurological manifestations. We described a case of CSA-related PRES whose diagnosis was difficult due to a concurrent infection with SARS-CoV-2., Observation: The 16-year-old patient was known to have corticosteroid-resistant nephrotic syndrome secondary to minimal change disease. CSA was introduced, and on the fifth day of treatment, the patient presented with seizures followed by fever. Biological and magnetic resonance imaging data were in favor of SARS-CoV-2 encephalitis. Relief of immunosuppression by discontinuation of CSA was decided and the patient was put on anticonvulsants. After being declared cured of COVID-19, which was without other clinical signs, the CSA was reintroduced but the patient presented with seizures the next day. This allowed the physicians to rectify the diagnosis and relate the seizures to a CSA-related PRES., Conclusion: Infection with SARS-CoV-2 could be a differential diagnosis of a PRES related to calcineurin inhibitors.

BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.

Objectives: To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system., Methods: A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons., Results: In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE., Conclusions: The base-case results for all evidence groups are consistent with the different sensitivity analyses., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the use of calcineurin inhibitors (CNIs), specifically tacrolimus, in unplanned pregnancies with active lupus disease among patients with systemic lupus erythematosus (SLE)., Materials and Methods: The study includes data from pregnancies in women diagnosed with SLE at Gazi University Hospital in Ankara, Türkiye, between January 2010 and July 2022. The study categorized pregnancies into planned and unplanned groups based on lupus nephritis presence, emphasizing the need for inactive lupus disease for at least 6 months before attempting conception in planned pregnancies. The outcomes of pregnancies involving CNIs, particularly tacrolimus, were assessed., Results: In our cohort comprising 632 SLE patients, 39 individuals reported 42 pregnancies. Among the 42 pregnancies, 14 have a history of lupus nephritis. We observed that 8 of 14 patients with a history of lupus nephritis had unplanned pregnancies. Three patients used cyclosporine and 2 used tacrolimus during their pregnancy; their pregnancies were completely healthy, and no lupus flare was observed during their pregnancies. The pregnancy of 2 patients who used azathioprine and 1 last patient who used no immunosuppressive treatment ended in abortion., Conclusion: This study reveals that tacrolimus can be effectively used in unplanned pregnancies with active lupus disease, providing favorable maternal and fetal outcomes. The findings emphasize the importance of considering CNIs, particularly tacrolimus, in the management of SLE pregnancies, even in cases of unplanned pregnancies with a history of lupus nephritis.

Competing Interests: The authors have no conflicts of interest to declare.

Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm., Competing Interests: Disclosure Dr J. James has no conflicts of interest. Dr J. Gao received fellowship funding from Abbvie and Janssen. She is an investigator for Abbvie, Bristol Meyers Squibb, UCB, and Novartis. Dr T. Otto is an investigator for Abbvie, Bristol Meyers Squibb, UCB, and Novartis. Dr M.L. Porter is a consultant and/or an investigator for Abbvie, Bristol Meyers Squibb, Eli Lilly, Regeneron, Pfizer, UCB, Moonlake, Acelyrin, Incyte, Trifecta Clinical, and Novartis. She has previously received fellowship funding and honoraria from the National Psoriasis Foundation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effectiveness and safety of combining 0.05% cyclosporine A (CsA) with high-potency steroids for treating severe dry eye disease (DED)., Materials and Methods: This retrospective comparative case series included 93 patients treated with 0.05% CsA for severe DED. Among them, we included data from 54 eyes of 27 patients who received high-potency steroids in the study group and from 132 eyes of 66 patients who did not receive high-potency steroids in the control group. Data on demographic characteristics, comorbidities, medications and intraocular pressure (IOP) were recorded. The primary outcomes were changes in symptom and sign scores. The ocular surface disease index was used as the symptom score, whereas tear break-up time, Schirmer I test without anaesthesia, ocular surface staining scores and presence of meibomian gland dysfunction were considered as sign scores. Repeated one-way ANOVA and generalized linear mixed models were used to evaluate differences., Results: In the control group, symptom scores decreased from 1 to 2 months and from 2 to 3 months after treatment ( p  = .002 and .049). In the high-potency steroid group, symptom scores improved during these intervals ( p  = .003 and .005). The sign score in the control group remained unchanged (all p  > .05), while the high-potency steroid group exhibited progressive improvement in sign scores (all p  < .05). The high-potency steroid group had more favourable symptom ( p  = .035) and sign ( p  < .001) scores than did the control group. However, multiple systemic diseases were associated with poor symptom ( p  = .025) and sign ( p  = .014) scores. The risks for glaucoma and cataract formation were similar between the two groups (all p  > .05)., Conclusions: Dual therapy combining high-potency steroids and 0.05% CsA significantly improved the signs and symptoms of severe DED compared with 0.05% CsA monotherapy, without severe complications.

Background: Cyclosporine A (CsA) and regular doses of recombinant human thrombopoietin (rhTPO) can accelerate platelet recovery in patients with non-severe aplastic anemia (NSAA). However, it is unclear whether CsA plus rhTPO at a higher dose can further increase the efficacy., Methods: Data from patients with newly diagnosed NSAA, who had been treated with CsA in combination with different doses of rhTPO between February 2021 and August 2021 at Peking Union Medical College Hospital, were reviewed. All the enrolled patients had been treated with CsA at 3-5 mg/(kg/d), and patients were further classified into high-dose (with rhTPO 30000U qd × 14 days for 2 months) group or regular-dose (with rhTPO 15000U qd × 7days for 3 months) group. The treatment response and therapy-related adverse events were compared., Results: 36 patients including 16 (44.4%) in the high-dose and 20 (55.6%) in the regular-dose group were enrolled. The baseline characteristics were compatible between the two groups. The platelet counts were significantly higher at 1/3/6 months in the high-dose group ( p  = 0.028, 0.0063 and p  = 0.040, respectively). The high-dose group had a significantly shorter time to platelet transfusion independence ([1 (0.5-6) months vs 2.5 (1-12) months, p  = 0.040]). There was no significant difference in overall response and complete response rate between the two groups at 1/3/6/12 months ( p  > 0.05). Treatment-related morbidities were similar between the two groups ( p  > 0.05)., Conclusions: Adding a higher dose of rhTPO can further accelerate platelet recovery and platelet transfusion independence in patients with newly diagnosed NSAA.

Background: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities., Methods: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines., Results: Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria., Conclusions: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.

Purpose of Review: Cyclosporine is a versatile immunomodulatory drug commonly employed in modern medicine. Although cyclosporine was initially used to prevent solid organ transplant rejection, its indications have extended to treat many inflammatory or autoimmune diseases. Cyclosporin is available for use in oral, intravenous, and topical forms, including eye drops to treat corneal and ocular surface conditions. It is naturally advantageous to administer cyclosporin directly into the eye, avoiding potential and dose limiting systemic adverse effects. However, the transition from systemic to topical administration has been a challenging one. This report reviews the evolution of ophthalmic cyclosporine treatment and explores its clinical impacts and future research directions., Recent Findings: Latest advancements in formulations - from oil-based solutions to nanomicelle and gel systems and waterless formulations - have improved the therapeutic efficacy and tolerability of topically applied cyclosporine, demonstrating greater effectiveness in treating ocular surface parameters compared to oil-based solution., Summary: Cyclosporine continues to be a safe and effective immunomodulatory drug in the field of ophthalmology to treat various chronic inflammatory ocular surface diseases and dry eye. Currently, there are several commercially available topical preparations available for ophthalmic use each with unique formulation and clinical outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Chronic spontaneous urticaria (CSU) patients sometimes do not respond to second-generation antihistamine, and 10-50% patients do not even respond to four-fold the usual dose of nonsedating H1 antihistamine, which further leads to repeated courses of oral corticosteroids to abate the symptoms. There are third-line agents approved by EAACI guidelines, which include omalizumab and cyclosporine. Certain patients are even resistant to the third-line agents. In this review, various other treatment options will be discussed in patients of refractory CSU., Recent Findings: Recently, we demonstrated azathioprine as a possible third-line option, which was found noninferior to cyclosporine in antihistamine refractory CSU. There have been trials, studies, case series and reports, which suggest other putative options for refractory CSU management., Summary: Studies on the management of refractory CSU are accumulating thereby expanding the armamentarium of dermatologists and allergologist against difficult-to-treat urticaria patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH is characterized by uncontrolled immune activation leading to fever, cytopenias, hepatosplenomegaly, coagulation abnormalities, and elevated typical markers. This condition can be genetic or secondary, with the latter often triggered by infections. Here, we present a unique case of HLH secondary to acute otitis media (AOM), a common ear infection., Patient Concerns: We describe a 4-year-old boy who initially presented with a high fever and otalgia, later diagnosed with bilateral AOM. Despite antibiotic treatment, his condition deteriorated., Diagnosis: The patient fulfilled diagnostic criteria for HLH., Interventions: Aggressive treatment by using combination therapy with immunoglobulins, intravenous steroids (dexamethasone), cyclosporine, and etoposide was performed., Outcomes: After 1 month of treatment, improvement in the otologic symptoms was observed, and hematological findings gradually improved and normalized., Lessions: The link between AOM and HLH may be associated with inflammatory responses and immunological mechanisms, highlighting the importance of considering HLH in severe infection cases. This case emphasizes the need for prompt diagnosis and management, especially in secondary HLH scenarios, to improve patient outcomes. It is imperative to be aware of the potential correlation between these 2 conditions, and healthcare professionals should consider the likelihood of HLH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN)., Methods: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion., Results: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy., Conclusion: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil., (© 2024. The Author(s).)

The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60-35.40) vs. 22.95 mg/dL (17.60-33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678-1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG-33.8%, GA-50.2%, and AA-16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure ( p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.

Background: TAFRO syndrome is a rare disorder that causes thrombocytopenia, generalized oedema, fever, organ enlargement, and renal impairment. Few reports have suggested an association with vaccines, and few cases have undergone renal biopsy. TAFRO syndrome is often severe and fatal, and its cause is unknown. We report a case of TAFRO syndrome that occurred after vaccination with the coronavirus disease 2019 (COVID-19) vaccine., Case Presentation: An 82-year-old woman received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Two weeks later, she was admitted to the hospital with oedema, accompanied with renal failure and thrombocytopenia. After close examination, she was diagnosed with TAFRO syndrome. She was treated with steroids, cyclosporine, and thrombopoietin receptor agonists. The patient was discharged after several months in remission., Conclusions: Although an incident of TAFRO syndrome after COVID-19 vaccination has been previously reported, this is a rare case in which the patient went into remission and was discharged. A renal biopsy was also performed in this case, which was consistent with previous reports. The favorable treatment course for TAFRO syndrome provides valuable insights., (© 2024. The Author(s).)

Introduction: Cyclosporine-A (CsA) and post transplantation cyclophosphamide (PTCy) are common agents used for graft versus host disease (GVHD) prophylaxis in Haploidentical hematopoietic cell transplantation (haplo-HCT). However, the impact of CsA cessation timing in the posttransplant setting on clinical outcomes is uncertain. We aimed to investigate the impact of a novel approach that integrated early CsA cessation with PTCy utilization., Patients and Methods: This study was a single arm retrospective study carried out at a tertiary referral hospital hematology and bone marrow transplantation center between 2009 and 2022. The patients who received haplo-HCT with ATG, PTCy and CsA as GVHD prophylaxis were included. CsA was planned for cessation starting at day 45 to day 60. Acute and chronic GVHD were evaluated and graded. CsA blood concentrations and its impact on acute and chronic GVHD was evaluated., Results: Thirty-one patients composed of 19 (61.3%) male and 12 (38.7%) female patients with a median age of 31 years (20-58). Busulfan and TBI based conditioning regimens were the most utilized regimens. The majority of donors were first degree relatives. Stem cell origin was peripheral blood for all patients. GVHD prophylaxis consisted of ATG, CsA and PTCy. Acute GVHD was observed in 9 (29%) cases, whereas chronic GVHD was seen in 3 (9.7%) cases, with 2 of them having overlapping GVHD. Age, gender, number of chemotherapy lines, transplant characteristics, infused CD34 cell count, and engraftment durations were similar among patients with and without GVHD. Patients with GVHD had similar 1st, 2nd, 3rd and 4th week CsA concentrations compared to patients without GVHD (p > 0.05). The presence of GVHD was not associated with worse progression free survival and overall survival (p = 0.6, p = 0.5, respectively). CMV reactivation was more common in the GVHD group., Conclusion: In the current study, we did not find an impact of CsA concentration on GVHD and post-transplant outcomes in Haplo-HCT setting. Therefore, together with the use of PTCy, early CsA cessation can be an option; further studies are needed to understand all aspects of this approach., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA)., Methods: The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated., Results: Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference ( P < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor ( P =0.008, P =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×10 9 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST ( P =0.020, OR =0.062), and high PLT count was a protective factor ( P =0.044, OR =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence ( P =0.001, 0.031)., Conclusion: The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.

Pure red cell aplasia (PRCA) is a rare bone marrow disorder characterized by a severe reduction or absence of erythroid precursor cells, without affecting granulocytes and megakaryocytes. Immunosuppressive therapies, particularly cyclosporine, have demonstrated efficacy as a primary treatment. This study aims to develop a predictive model for assessing the efficacy of cyclosporine in acquired PRCA (aPRCA). This retrospective study encompasses newly treated aPRCA patients at the General Hospital of Tianjin Medical University. Diagnosis criteria include severe anemia, and absolute reticulocyte count below 10 × 10 9 /L, with normal white blood cell and platelet counts, and a severe reduction in bone marrow erythroblasts. Cyclosporine therapy was administered, with dose adjustments based on blood concentration. Response to cyclosporine was evaluated according to established criteria. Statistical analysis involved logistic multi-factor regression, generating a predictive model. The study included 112 aPRCA patients with a median age of 63.5 years. Patients presented with severe anemia (median Hb, 56 g/L) and reduced reticulocyte levels. Eighty-six patients had no bone marrow nucleated erythroblasts. Primary PRCA accounted for 62 cases (55.4%), and secondary PRCA accounted for 50 cases (44.6%). Univariate analysis revealed that ferritin, platelet to lymphocyte ratio (PLR), and CD4/CD8 ratio influenced treatment response. Multivariate analysis further supported the predictive value of these factors. A prediction model was constructed using ferritin, PLR, and CD4/CD8 ratio, demonstrating high sensitivity and specificity. The ferritin, PLR, and CD4/CD8-based nomogram showed good predictive ability for aPRCA response to cyclosporine. This model has potential clinical value for individualized diagnosis and treatment of aPRCA patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Omalizumab is a safe and effective treatment for antihistamine-refractory chronic spontaneous urticaria (CSU) but is insufficient in one-third of patients. For serious cases in which omalizumab is ineffective, cyclosporine or methotrexate may be preferred. Most drug trials in CSU have focused on omalizumab or cyclosporine monotherapy., Objective: This retrospective study evaluated responses to monotherapy or combined therapy and real-life data on the effectiveness and safety of omalizumab in antihistamine-refractory CSU., Methods: A total of 133 patients who received omalizumab due to antihistamine-refractory CSU were evaluated in terms of 7-day urticaria activity score, total IgE, anti-thyroid peroxidase, C-reactive protein, skin prick test with aeroallergens and disease duration. Partial or nonresponders to omalizumab monotherapy were given antihistamine, omalizumab, cyclosporine, and methotrexate as combined or monotherapy., Results: Ninety-eight (73.7%) of the 133 patients were female and the mean age was 40.7 ± 14.4 years; 70.6% of the patients received omalizumab monotherapy and the others received combined or non-omalizumab monotherapy. Omalizumab monotherapy was effective in 66.9% of the patients. Of those with complete response to omalizumab monotherapy, 65.4% had early recurrence after discontinuing treatment. Treatment response was significantly better in patients who had high total IgE (p = 0.001). Patients with longer disease duration had significantly higher likelihood of early recurrence (p = 0.035)., Conclusions: Omalizumab monotherapy was as effective in real life as in placebo-controlled trials. Omalizumab was well tolerated by all patients. Treatment responses were comparable in patients treated with combined therapy and those who received monotherapy.

Competing Interests: We declare no competing interests.

Neurologic complications (NCs), especially those of the central nervous system (CNS), represent a severe complication after allogeneic stem cell transplantation (allo-HSCT) and are associated with relevant morbidity and mortality. We aimed to characterize the potential risk factors for the development of CNS-NC, with a special focus on the role of calcineurin inhibitors (CNIs) as a predisposing factor. For this purpose, we compared cyclosporin A (CsA) versus tacrolimus (TAC) with respect to their influence on the incidence and type of CNS-NC after allo-HSCT. We retrospectively analyzed the incidence, risk factors, and impact on outcomes of CNS-NC diagnosed during the post-transplantation follow-up in patients with different high-risk hematologic malignancies who underwent allo-HSCT at our institution over a 20-year period. All patients included in the analysis received CNI (CsA or TAC) as graft-versus-host disease (GVHD) prophylaxis. We evaluated a total of 739 consecutive patients who underwent transplantation between December 1999 and April 2019. During a median follow-up of 6.8 years, we observed a CNS-NC incidence of 17%. The development of CNS-NC was associated with decreased overall survival (OS) and increased transplantation-related mortality (TRM). The most frequent CNS-NCs were infections (30%) and neurologic adverse events related to the administration of CNI, TAC, or CsA as GVHD prophylaxis (42%). In the multivariable analysis, age, total body irradiation (TBI), and severe acute GVHD and chronic GVHD were significant risk factors in the development of CNS-NCs. TAC compared with CsA emerged as an independent predisposing factor for CNS-NCs. The TAC-associated risk of CNS-NCs was related mostly to the occurrence of transplantation-associated thrombotic microangiopathy (TA-TMA) with neurologic manifestations (neuro-TA-TMA), although the general TA-TMA incidence was comparable in the 2 CNI subgroups. CNS-NCs are associated with poor prognosis after allo-HSCT, with TAC emerging as a potential yet insufficiently characterized predisposing factor., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Herein, we describe a case of severe anemia presenting with myelodysplastic syndrome with cold agglutinin disease that was successfully treated by a moderate dose of steroids followed by cyclosporine. In patients with myelodysplastic syndrome, autoimmunity in erythroid cells is occasionally demonstrated, and autoimmune hemolytic anemia is seen in some patients. However, hemolytic anemia with cold agglutinin in patients with myelodysplastic syndrome is less common, and the effect of corticosteroids for autoimmune hemolytic anemia caused by cold agglutinin is thought to be limited. Although the elevated levels of reticulocytes and LDH are usually caused by ineffective hematopoiesis in myelodysplastic syndrome, clinicians should be aware of latent cold agglutinin disease. In the present case, in addition to the improvement of erythroid dysplasia, the corticosteroid-sparing effect on cold agglutinin disease may have played a role in the mechanism underlying the effectiveness of cyclosporine., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The severity of coronavirus disease 2019 (COVID-19) is known to be high in kidney transplant recipients; however, the risk factors for COVID-19 infection in these patients has not been studied extensively. Therefore, we explored the predictors of COVID-19 infection and severity in kidney transplant recipients in Japan., Methods: This study included kidney transplant recipients who were regularly followed-up at our hospital from February 2021 to March 2023. We retrospectively reviewed the patients' medical charts; obtained their clinical information, including comorbidities, immunosuppressant usage, and presence of COVID-19 infection; and assessed the risk of COVID-19 infection and severity. Severe illness was defined as a decrease in oxygen saturation., Results: Among the 155 patients, 50 (32.3%) were infected with COVID-19. Multivariate analysis revealed that recipients taking >5 mg of prednisolone or taking tacrolimus instead of cyclosporine were at higher risk of infection (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.01-5.40; OR 2.29, 95% CI 1.03-5.07, respectively). Furthermore, of the 50 infected recipients, 42 had minor illness and eight had severe illness. Multivariate analysis revealed that recipients taking >5 mg of prednisolone were at a higher risk of severity (OR, 11.60, 95% CI 1.19-113.00)., Conclusion: In kidney transplant recipients, the infection rate and severity of COVID-19 tended to increase with higher maintenance doses of steroids. Recipients taking >5 mg of prednisolone should be considered a switch from tacrolimus to cyclosporine because cyclosporine may inhibit viral replication and reduce the risk of infection., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Chronic active Epstein-Barr virus (CAEBV) disease is more likely to occur when a patient is on immunosuppressive therapy for any disease or is susceptible to infection, and the prognosis is poor without appropriate treatment, including hematopoietic stem cell transplantation (HSCT). In addition to HSCT, several other chemotherapy regimens have been reported, but all of them are difficult to maintain in remission. Without HSCT, survival rates have been reported to be 50% in 5 years and 25% in 15 years. This is a report of a 13-year-old boy who developed CAEBV disease during cyclosporine A (CyA) treatment for the steroid-dependent nephrotic syndrome (SDNS). Since SDNS precluded HSCT or chemotherapy, CyA was tapered off based on the belief that alleviating his immunosuppressed state would decrease the CAEBV disease. We decided to gradually reduce the CyA dose to activate T-cell immunity, while periodically monitoring the EBV viral load. Finally, we found an appropriate dose that could suppress both CAEBV disease and SDNS, and it lasted for more than 9 years. No case has been reported to date in which a patient developed CAEBV disease while receiving immunosuppressive drugs for the primary disease, and both diseases were controlled only by reducing the dose of immunosuppressive drugs. In this report, we show that dose reduction of immunosuppressive agents without chemotherapy or HSCT is an effective option for the treatment of CAEBV disease in patients receiving immunosuppressive agents., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)