Steroid-Refractory Acute Severe Ulcerative Colitis in Infliximab-Experienced Patients.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis (UC) that can lead to significant morbidity and mortality, with a substantial number of patients needing colectomy. Infliximab (IFX) has been increasingly used as a rescue therapy for patients who have failed intravenous steroids and has been more frequently used as an induction and maintenance therapy in moderate-to-severe UC. Therefore, the number of patients admitted with ASUC previously exposed to IFX has been increasing, raising additional challenges in the medical management of these patients to avoid emergent colectomy. This narrative review intends to summarise the most recent evidence in the medical management of steroid-refractory ASUC patients previously exposed to IFX and to propose a treatment algorithm for approaching this difficult-to-treat group of patients.

A colite ulcerosa aguda grave (CUAG) é uma complicação potencialmente fatal da colite ulcerosa (CU), que pode levar a significativa morbilidade e mortalidade, com um número substancial de doentes a necessitar de colectomia. O uso de infliximab (IFX) como terapêutica de resgate em doentes sem resposta a corticoterapia endovenosa tem vindo a aumentar, bem como a sua utilização como terapêutica de indução e manutenção em doentes com CU moderada-grave. Assim, o número de doentes hospitalizados com CUAG que já estiveram previamente expostos ao IFX tem vindo a aumentar, levantando novos desafios na abordagem médica destes doentes, de forma a evitar a colectomia emergente. Esta revisão narrativa tem como objetivo sumarizar a evidência mais recente na abordagem médica da CUAG refratária aos corticoides em doentes previamente expostos ao IFX e propor um algoritmo terapêutico para abordar este grupo desafiante de doentes.

Immunosuppressants in women with repeated implantation failure in assisted reproductive techniques: a systematic review and meta-analysis.

Objective: To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone. Data source: Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023. Study Selection: Randomized clinical trials and observational studies with the outcomes of interest were included. Data collect: We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy. Data synthesis: Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42). Conclusion: Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure. PROSPERO: CRD42023449655.

Topical Application of 0.05% Cyclosporine for the Treatment of Neurotrophic Keratopathy Secondary to Herpes Simplex Keratitis.

PURPOSE: The purpose of this study was to assess the effectiveness and tolerability of 0.05% cyclosporine A (CsA) eye drops for neurotrophic keratopathy (NK) secondary to herpes simplex keratitis (HSK). METHODS: Fifteen patients (15 eyes) with prior HSK and secondary NK, classified as stage 2 or 3 on the basis of the Mackie classification, were enrolled. All patients received a combined treatment regimen of 0.05% CsA eye drops (1 drop 4 times daily), a silicone hydrogel bandage contact lens, and 0.15% ganciclovir ophthalmic gel (1 drop 3 times daily). For patients achieving corneal healing, CsA was continued at a reduced dosage of twice daily for an additional 2 months and other treatments were discontinued. Follow-ups were scheduled at weeks 1, 2, 3, and 4 and at months 2 and 3 after treatment initiation, followed by a 3-month follow-up period. Key outcomes, including best-corrected visual acuity, Schirmer I test, and corneal sensitivity, were assessed at each visit before and after treatment. FINDINGS: Significant reductions were observed in the area of corneal defects, expressed as proportion of total corneal area, throughout follow-up period. Complete corneal healing was achieved by 13.3% of patients by week 2, 60.0% by week 3, 86.7% by week 4, and 100.0% by week 8, with the mean (SD) time to healing being 3.8 (1.8) weeks (range, 2-8 weeks). Additionally, significant improvements were noted in diseased eyes for best-corrected visual acuity, tear secretion (Schirmer I test values), and corneal sensitivity after treatment. IMPLICATIONS: CsA eye drops, with bandage lenses and ganciclovir, effectively resolve NK from HSK, without adverse effects. This combination therapy shows promise for future clinical use and research. CLINICAL TRIAL REGISTRATION: Our study is a retrospective observational study because it involves the analysis of previously collected data, so the study was not registered prior to its commencement. However, if it is necessary for publication, we are willing to proceed with retrospective registration.

Linear IgA bullous dermatosis in a latin adolescent treated with cyclosporine and prednisone.

INTRODUCTION: Linear IgA bullous dermatosis (LABD) is a rare autoimmune disease. Although dapsone is the initial treatment, other immunomodulators are used in resistant cases or when dapsone is unavailable. CASE REPORT: A 12-year-old Mexican child, with no relevant medical history, developed in May 2023 a disseminated dermatosis affecting all body segments, including mucous membranes, characterized by erythematous patches and plaques evolving into the formation of serous and serosanguinous blisters and vesicles, distributed in a "string of pearls" pattern. LABD was suspected and confirmed by skin biopsy, which showed a subepidermal blister with neutrophilic infiltration and linear Immunoglobulin A deposits at the dermo-epidermal junction by direct immunofluorescence. Treatment with prednisone (2 mg/kg/day) and cyclosporine (5 mg/kg/day) resulted in improvement and lesion remission within 2 weeks. Both drugs needed to be discontinued for 3 months due to intermittent blistering. Cyclosporine was continued as maintenance therapy at a dose of 4 mg/kg/day for 8 months. CONCLUSIONS: The report highlights the use of cyclosporine as an alternative immunomodulator for DAAL, an immunosuppressive agent used in autoimmune disorders. Few cases, including this one, have described complete remission and control of the dermatosis with cyclosporine, accompanied by prednisone at the start of treatment.

INTRODUCCIÓN: La dermatosis ampollosa por IgA lineal es una enfermedad autoinmunitaria rara. Aunque la dapsona es el tratamiento inicial, se usan otros inmunomoduladores en casos resistentes o cuando la dapsona no está disponible. CASO CLÍNICO: Un niño mexicano de 12 años, sin antecedentes relevantes, desarrolló en mayo de 2023 una dermatosis diseminada a todos los segmentos corporales, incluyendo las mucosas, caracterizada por manchas y placas eritematosas que evolucionaron hacia la formación de ampollas y vesículas serosas y serohemáticas, distribuidas en forma de «cadena de perlas¼. Se sospechó dermatosis ampollosa por IgA lineal y se confirmó mediante biopsia cutánea, que mostró una ampolla subepidérmica con infiltrado neutrófilo y depósitos lineales de IgA en la unión dermoepidérmica mediante inmunofluorescencia directa. El tratamiento con prednisona (2 mg/kg al día) y ciclosporina (5 mg/kg al día) resultó en mejoría y la remisión de las lesiones a las 2 semanas. Fue necesario dejar ambos fármacos durante 3 meses debido a la aparición intermitente de ampollas. Se dejó ciclosporina como terapia de mantenimiento a dosis de 4 mg/kg al día por 8 meses. CONCLUSIONES: El reporte destaca el uso de ciclosporina como inmunomodulador alternativo para la dermatosis ampollosa por IgA lineal, un agente inmunosupresor utilizado en trastornos autoinmunitarios. Pocos casos, incluido este, han descrito la remisión completa y el control de la dermatosis con ciclosporina, acompañada de prednisona al inicio del tratamiento.

Efficacy of Topical Cyclosporine Combined with Punctal Plugs in Treating Dry Eye Disease and Inflammation.

PURPOSE: To evaluate the effect of punctal plugs combined with cyclosporine eye drops on dry eye disease (DED) and ocular surface inflammation. METHODS: In a clinical trial, 73 patients were randomly allocated into three groups: punctal plug group, combination therapy group, and cyclosporine group. At the baseline and four weeks after treatment, the Schirmer I test score, fluorescein tear film break-up time (FBUT), ocular surface staining score and dry eye symptoms were assessed. Tear samples were collected to detect the level of inflammatory factors (interleukins, matrix metalloproteinase 9 (MMP-9) and tumor necrosis factor alpha (TNF-α)). In an animal experiment, a New Zealand rabbit dry eye model was induced. The rabbits were randomly divided into control group, punctal plug group, and combination therapy group (n = 6). Conjunctival goblet cell density, protein level of MMP-9 in conjunctiva and mRNA levels of inflammatory factors in conjunctiva and cornea were measured before and after treatment. RESULTS: In combination therapy group of the clinical trial, the following results were observed: significant improvement in Schirmer I test scores and FBUT compared to the cyclosporine group and punctal plug group, respectively; a decrease in the tear levels of IL-6, IL-1, and MMP-9 compared to the punctal plug group; and a decrease in the tear levels of IL-1α, IL-6, and IL-17 compared to the baseline (all p < 0.05). In the animal experiment, rabbits in combination therapy group had a higher goblet cell density (p < 0.01) and lower mRNA levels of IL-16 (p < 0.05), IL-17 (p < 0.05), and MMP-9 (p < 0.01) in conjunctiva and that of MMP-9 (p < 0.01) in cornea compared to punctal plug group. CONCLUSION: Cyclosporine eye drops combined with degradable punctal plugs is a more optimized clinical treatment strategy for DED compared with degradable punctal plugs or cyclosporine eye drops alone, considering the influence of comprehensive clinical efficacy and ocular surface inflammation.

Choline-based ionic liquids enhance the dermal delivery of cyclosporine a for potential treatment of psoriasis.

Psoriasis is a prevalent chronic disease affecting 2-3% of the global population. Cyclosporine A (CyA) has been widely used with great promise in the treatment of moderate to severe psoriasis despite various side effects associated with its systemic administration. Topical administration of CyA circumvents systemic side effects; however, the poor water solubility and large molecular weight of CyA pose challenges for dermal delivery. In this study, choline-based ionic liquids (ILs) were used to enhance the dermal delivery of CyA for the potential treatment of psoriasis. All four ILs tested significantly improved the solubility of CyA, which was greater than that of the control group with dimethyl sulfoxide (DMSO) as a solubilizer (20%, w/w). The saturated solubility of CyA in two of the ILs, choline geranate ([Ch][Ge]) and choline ricinoleate ([Ch][Ra]), reached more than 90 mg/mL, and the solubilization capability of the ILs except [Ch][Ci] was resistant to water dilution. The negligible change in CyA content determined by high-performance liquid chromatography and the secondary structure detected by circular dichroism spectroscopy confirmed the stability of CyA in the ILs. At 4 h in the in vitro penetration test, the amount of CyA retained in the skin in the IL groups was slightly greater than that in the control group (20% DMSO). The water content of the ILs significantly affected their penetration ability. When the water content increased from 10 to 70%, the dermal delivery of CyA first increased, peaked at a water content of 30%, and then decreased. The dermal delivery ability of [Ch][Ge] and [Ch][Ra] with a water content of 70% was still comparable to that of 20% DMSO. Moreover, CyA-loaded ILs (0.5%, w/w) significantly relieved the symptoms of psoriasis in an imiquimod (IMQ)-induced mouse model, and the levels of inflammatory factors, including tumor necrosis factor α, interleukin 22 and interleukin 17, in the affected area were reduced by 71.7%, 75.6%, and 89.3%, respectively. The IL tested, choline sorbate ([Ch][So]), showed low cytotoxicity to human immortalized epidermal cells (HaCaT). After 7 days of consecutive application, [Ch][So] did not cause significant irritation. In conclusion, ILs demonstrate promising potential for the dermal delivery of CyA for the treatment of psoriasis.

Cyclosporine-induced alopecia:a case report, FDA adverse event reporting system analysis and literature assessment.

Cyclosporine is a potent immunosuppressive drug for various immune-mediated diseases in children. Cyclosporine's expected therapeutic effect also carries a wide range of side effects. One of the most common and intriguing dermatological side effects is hypertrichosis. However, recent reports have recognized alopecia as a potential adverse effect of cyclosporine. Here, we report a case of a 29-month-old boy diagnosed with aplastic anemia. During cyclosporine therapy, the patient presented with hair loss on the scalp, which and subsequently spread to the eyebrows and eyelashes. The alopecic symptoms were not relieved following topical minoxidil liniment interventions. When the cyclosporine was discontinued, a remarkable improvement was observed in the scalp, with complete hair regrowth. Data concerning cyclosporine from the FDA Adverse Event Reporting System (FAERS) database were extracted from January 2004 to January 2023. Within FAERS, our post-marketing pharmacovigilance analysis detected the reporting association of cyclosporine and alopecia. In monotherapy, cyclosporine-induced alopecia was observed in 118 cases, and tacrolimus-induced alopecia signals were detected in 197 cases. Although the potential mechanism of medication-induced hair loss is unclear, we identified a potential correlation between alopecia and cyclosporine, and it is still necessary to adequately recognize and clinically monitor this paradoxical reaction.

In vitro mechanistic study on mycophenolate mofetil drug interactions: effect of prednisone, cyclosporine, and others.

Objective: The metabolism- and transporter-based drug-drug interactions (DDIs) between mycophenolate mofetil (MMF) and co-administered medications may be key factors for the high individual variability in MMF exposure. This study systematically assessed the influence of co-medications on the mycophenolic acid (MPA) pharmacokinetic (PK) process in vitro, particularly to provide mechanistic evidence of the metabolic interaction among steroids, cyclosporine (CsA), and MMF. Methods: Based on a previous study, we hypothesized that there are three main DDI pathways affecting MMF PK in vivo. A human hepatocyte induction study, transporter substrate/inhibition study using human embryonic kidney 293 cells, and multidrug resistance-associated protein 2 (MRP2) substrate/inhibition study using vesicle membrane were conducted to assess the mechanistic evidence of the metabolic interaction in triple therapies. The potential DDI risks associated with seven medications commonly co-administered with MMF in clinical practice were further evaluated. Results: The in vitro results suggested that prednisolone, the active metabolite of prednisone, induces the enzymatic activity of uridine 5'-diphospho-glucuronosyltransferase (UGT), particularly the UGT1A9 and UGT2B7 isoforms, resulting in increased metabolism of MPA to MPA glucuronide (MPAG). This induction potential was not observed in CsA-treated human hepatocytes. CsA inhibits organic anion-transporting polypeptide (OATP) 1B1- and OATP1B3-mediated MPAG. Prednisolone and CsA showed no inhibitory effect on MRP2-mediated MPAG efflux. Salvia miltiorrhiza significantly inhibited organic anion-transporting polypeptide and OAT 3 activities, suggesting that it affects the hepatic uptake and renal excretion of MPAG, causing increased MPAG exposure in vivo. Conclusion: These identified factors may contribute to the high inter-individual variability in MMF exposure and facilitate further development of mechanistic MMF PK models and individualized therapies.

Kaempferol attenuates cyclosporine-induced renal tubular injury via inhibiting the ROS-ASK1-MAPK pathway.

Cyclosporine (CSA) is a widely used immunosuppressive medication. CSA nephrotoxicity severely limits its application. Kaempferol (KPF), a naturally occurring phenolic compound, has a promising protective effect in reducing CSA-induced renal tubular injury, but the mechanism remains unknown. Our study aimed to determine the protective role of KPF against CSA-induced renal tubular injury. C57/B6 mice and the NRK-52E cell line were employed. CSA worsened renal function in mice, causing detachment and necrosis of tubular cells, leading to tubular vacuolation and renal interstitial fibrosis. CSA caused the detachment, rupture, and death of tubular cells in vitro, resulting in cell viability loss. KPF mitigated all these injurious alterations. KPF hindered CSA-induced ROS generation and protected renal tubular epithelial cells, similar to the antioxidant NAC. CSA lowered SOD activity and GSH levels while increasing MDA levels, and KPF ameliorated these changes. CSA caused phosphorylation of ASK1, JNK, and p38, similar to H2O2, whereas KPF significantly inhibited these changes. In conclusion, KPF reduces CSA-induced tubular epithelial cell injury via its antioxidant properties, inhibits the phosphorylation of ASK1, and inhibits the phosphorylation of p38 and JNK, implying that the synergistic use of KPF in CSA immunotherapy may be a promising option to reduce CSA-evoked renal injury.

Asymptomatic COVID-19 Infection-Induced Rhabdomyolysis in the Backdrop of Statin-Cyclosporine Drug Interaction.

Rhabdomyolysis involves skeletal muscle breakdown leading to high serum creatine kinase (CK) levels and myoglobinuria. Here, we report the case of a middle-aged man who developed rhabdomyolysis, resulting in acute kidney injury (AKI) over pre-existing chronic kidney disease (stage 3a) secondary to focal segmental glomerulosclerosis (primary FSGS), during an asymptomatic COVID-19 infection. The patient had been on treatment with cyclosporine and statin, among other drugs, for his comorbidities. He had initially presented to the hospital after a fall due to difficulty walking in the setting of increasing edema. Lab workup revealed elevated CK and AKI. Urinalysis showed "large" blood on a dipstick with only two RBCs per high-power field on microscopy, suggesting myoglobinuria. A standard respiratory pathogen polymerase chain reaction panel revealed positive SARS-CoV-2. The chest X-ray and oxygenation were normal, and he had no respiratory symptoms. He was treated with intravenous fluids and albumin, with a steady improvement in renal function. Our case underlines that rhabdomyolysis can occur in asymptomatic COVID-19 infection. Therefore, it may be worth monitoring CK levels in COVID-19-positive patients with risk factors for rhabdomyolysis, such as the concurrent usage of statins and cyclosporine, even if they are otherwise asymptomatic.

Transplant-Acquired Food Allergy in Children.

BACKGROUND: Organ transplantation in children is a vital procedure for those with end-stage organ failure, but it has been linked to the development of post-transplant allergies, especially food allergies. This phenomenon, known as transplant-acquired food allergy (TAFA), is becoming increasingly recognized, though its mechanisms remain under investigation. Pediatric transplant recipients often require lifelong immunosuppressive therapy to prevent graft rejection, which can alter immune function and heighten the risk of allergic reactions. Our review aimed to gather the latest evidence on TAFA. METHODS: We conducted a PubMed search from 25 June to 5 July 2024, using specific search terms, identifying 143 articles. After screening, 36 studies were included: 24 retrospective studies, 1 prospective study, 2 cross-sectional researches, and 9 case reports/series. RESULTS: Most studies focused on liver transplants in children. The prevalence of food allergies ranged from 3.3% to 54.3%. Tacrolimus, alongside corticosteroids, was the most commonly used immunosuppressive therapy. In addition to food allergies, some patients developed atopic dermatitis, asthma, and rhinitis. Allergic symptoms typically emerged within a year post-transplant, with common allergens including milk, eggs, fish, nuts, soy, wheat, and shellfish. Both IgE-mediated and non-IgE-mediated reactions were observed, with treatment often involving the removal of offending foods and the use of adrenaline when necessary. CONCLUSIONS: Consistent immunological monitoring, such as skin prick tests and IgE level assessments, is essential for early detection and management of allergies in these patients. Understanding the link between transplantation and allergy development is crucial for improving long-term outcomes for pediatric transplant recipients.

Anterior Segment Optical Coherence Tomography for the Tailored Treatment of Mooren's Ulcer: A Case Report.

Background: Mooren's ulcer (MU) is a rare and debilitating form of peripheral ulcerative keratitis (PUK), characterized by a crescent-shaped ulcer with a distinctive overhanging edge at the corneal periphery. If left untreated, MU can lead to severe complications such as corneal perforation and blindness. Despite various treatment approaches, including anti-inflammatory and cytotoxic drugs, as well as surgical interventions, there is no clear evidence of the most effective treatment due to the lack of randomized controlled trials. AS-OCT is a non-invasive imaging technique that provides high-resolution cross-sectional images of the anterior segment, allowing for accurate evaluation of corneal ulcer characteristics, including depth, extent, and disease progression. Methods: We present the case of a 20-year-old male patient with MU managed using a stepladder approach, which included local and systemic corticosteroids, limbal conjunctival resection, and Cyclosporine A 1% eye drops. The patient underwent consecutive AS-OCT examinations and strict follow-up to tailor systemic and topical therapy. Results: Complete healing of the corneal ulcer with resolution of the inflammatory process was achieved. There was no recurrence of the disease at the 7-month follow-up. AS-OCT demonstrated progressive reorganization and thickening of the stromal tissue until the complete recovery of stromal thickness. Conclusions: The AS-OCT imaging modality allowed for the accurate evaluation of corneal ulcer characteristics, facilitating informed decision-making regarding the use of systemic immunosuppression, surgical interventions, and local immunomodulation and providing detailed and precise assessment of disease progression. This approach enabled a tailored and effective treatment strategy for the patient and played a critical role in guiding the therapeutic approach.

Effectiveness of cyclosporine nanoemulsion eye drops in patients with mild-to-moderate dry eyes: objective and subjective evaluation.

BACKGROUND: To compare and evaluate objective and subjective clinical parameters between 0.05% cyclosporine nanoemulsion (CsN) and 0.15% hyaluronic acid (HA) administration in patients with mild-to-moderate dry eyes. METHODS: In this prospective, randomized, double-masked, single-center, and placebo-controlled parallel study, patients with mild-to-moderate dry eyes were randomly allocated to be treated with 0.05% CsN or 0.15% HA twice daily. Patients were followed-up at 4, 8, and 12 weeks. Objective and subjective parameters were evaluated during each visit. RESULTS: A total of 35 patients were enrolled in this study. Compared with baseline, tear film break-up time and fluorescein staining scores at 4, 8, and 12 weeks significantly improved in the CsN group. However, the Schirmer I test showed no statistically significant change until week 12. Using the Symptom Assessment in Dry Eye (SANDE) score, both groups gradually showed significant improvement compared with baseline values. However, the Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) showed no statistically significant change during the treatment period. CONCLUSIONS: Both 0.05% CsN and 0.15% HA administration twice a day effectively improved the objective signs and subjective symptoms of patients with mild-to-moderate dry eyes. However, patients treated with 0.05% CsN experienced greater and faster improvement.

Elucidating acceptance and clinical indications to support the rational design of drug-eluting contact lenses.

The advent of drug-eluting contact lenses (DECLs) has opened up new avenues for the treatment of eye diseases. DECLs is expected to partially overcome the shortcomings of eye drops due to single-dose packaging, accurate dosing, prolonged drug elution behavior, and simplified dosing procedures. Currently, a significant proportion of the DECLs design effort has been directed towards enhancing the compatibility of contact lenses with drugs. The appropriate elution time for the drug remains unclear. Additionally, it is ambiguous for which ophthalmic diseases DECLs offers the greatest therapeutic advantage. To rationally design DECLs in practice, it is necessary to understand the acceptance of DECLs by patients and practitioners and to clarify the indications for DECLs. This review will first focus on the acceptance of DECLs by different patients and practitioners and discuss the factors that influence its acceptance. Secondly, this review presents an overview of the current effectiveness of DECLs treatments in animals and in the clinical phase, with a particular focus on the suitability of DECLs for the treatment of ophthalmic diseases. Overall, patients and practitioners expressed positive attitudes towards DECLs. However, this is related to factors such as DECLs' treatment cycle, safety, and price. In addition, DECLs has good application prospects for ocular wound healing, postoperative management, and treatment of contact lenses-related complications. Furthermore, chronic diseases such as glaucoma that necessitate long-term medication and intraocular diseases that require implants or injections represent additional potential applications for DECLs. It is hoped that this review will facilitate a deeper understanding of DECLs acceptance and indications, thereby supporting the rational design of DECLs. At the same time, this review provides a reference for the design of other drug-device combination products.

Demystifying drug reaction with eosinophilia and systemic symptoms (DRESS): a review of the literature and guidelines for management.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, adverse drug reaction that is notoriously complex in both its presentation and treatment. Although early diagnosis and cessation of the causative agent are universally accepted as the initial interventions for DRESS, the subsequent management lacks a standardized approach. Historically, systemic steroids have been used as first-line treatment, but there is debate about the optimal dosing and route of administration, and evidence persists on the long-term complications associated with steroid use. Novel treatment approaches with targeted therapy, cyclosporine, intravenous immunoglobulin, and plasmapheresis have been gaining interest as alternative mono- and adjuvant therapies, but their use has yet to be supported by clinical trials. This narrative review provides a summary of the current knowledge of DRESS, with a focus on clinical management. The various mono- and adjuvant therapy options are discussed, with literature-supported suggestions for their optimal use in clinical practice. The risks for relapses, viral reactivation, and long-term complications are also considered. The PubMed and Medline databases were searched for articles on DRESS, published between January 1, 2008, and May 1, 2023. 334 articles met the inclusion criteria. Based on the literature, a DRESS management tool with step-by-step guidance is provided. Further suggestions for management are woven throughout this review, giving clinicians a toolbelt of resources with which to approach diagnosis, treatment, and follow-up.

Efficacy of tacrolimus versus cyclosporine after lung transplantation: an updated systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials.

BACKGROUND: Little data supports using tacrolimus versus cyclosporin for immunosuppression concerning acute rejection and bronchiolitis obliterans syndrome/Chronic Lung Allograft Dysfunction CLAD complications following lung transplantation (LTx). Our goal was to evaluate the use of tacrolimus versus cyclosporine in preventing these complications after LTx. METHODS: We included randomized controlled trials (RCTs) by searching PubMed, Web of Science, SCOPUS, and Cochrane through January 10th, 2024. We pooled dichotomous data using the risk ratio (RR) and continuous data using the mean difference (MD) with a 95% confidence interval (CI). RESULTS: We included Four RCTs with a total of 677 patients. Tacrolimus was significantly associated with decreased risk of acute rejection (RR: 1.21, 95% CI [1.03, 1.42], I2 = 25%, P = 0.02) compared with cyclosporine, bronchiolitis obliterans syndrome/CLAD (RR: 1.87, 95% CI [1.26, 2.77], I2 = 52%, P = 0.002), and treatment withdrawal (RR: 3.11, 95% CI [2.06, 4.70], I2 = 0%, P = < 0.00001). However, tacrolimus significantly increased the risk of new-onset diabetes (RR: 0.33, 95% CI [0.12, 0.91], I2 = 0%, P = 0.03), and kidney dysfunction (RR: 0.79, 95% CI [0.66, 0.93], I2 = 0%, P = 0.006). In contrast, there was no difference in the incidence of all-cause mortality (RR: 91, 95% CI [0.68, 1.22], I2 = 0%, P = 0.53), arterial hypertension (RR: 2.40, 95% CI [0.41, 14.21], I2 = 92%, P = 0.33), and new cancer (RR: 1.57, 95% CI [0.79, 3.10], I2 = 4%, P = 0.20). CONCLUSION: Tacrolimus has decreased acute rejection episodes and CLAD rate than cyclosporine, but it increased the risk of new-onset diabetes and kidney dysfunction.

Analyze interleukin-1ß, interleukin-6, and tumor necrosis factor-α levels in dry eye and the therapeutic effect of cyclosporine A.

BACKGROUND: Dry eye is a common eye disease. Artificial tears supplements are widely used for the treatment of dry eyes. However, multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears, which may affect the therapeutic effect. AIM: To analyze the characteristics of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A. METHODS: A total of 124 dry eye patients treated at The First People's Hospital of Xining from April 2020 to April 2022 were selected as the observation group, while 20 healthy individuals served as the control group during the same period. Levels of inflammatory markers, including IL-1ß, IL-6, and TNF-α, were analyzed. The observation group was further divided into a study group and a control group, each consisting of 62 patients. The control group received artificial tears, whereas the study group received a combination of artificial tears and cyclosporine A. Inflammatory markers, Schirmer's test (SIT), tear break-up time (TBUT), corneal fluorescein staining (CFS), National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) scores, and adverse events (AEs) were compared between the two groups. RESULTS: The observation group exhibited significantly elevated serum levels of IL-1ß, IL-6, and TNF-α in comparison to the healthy group. Following treatment, the study group demonstrated substantial reductions in IL-1ß, IL-6, and TNF-α levels relative to the control group. Moreover, after treatment, the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group. Additionally, significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia, foreign body sensation, fatigue, red eye, and burning sensation within the study group. Furthermore, post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group (P < 0.05). It is noteworthy that significant AEs were reported in both groups throughout the treatment period. CONCLUSION: Cyclosporine A combined with artificial tears is effective in treating dry eye, yielding enhanced outcomes by improving SIT and TBUT levels, reducing CFS scores, and ameliorating vision-related quality of life.

Comparison of the effects of 0.05% topical cyclosporine A versus 0.1% topical cyclosporine A on recurrence and clinical parameters following pterygium surgery.

Background/aim: To compare the efficacy of topical 0.05% cyclosporine A (CsA) and 0.1% topical cyclosporine A (CsA) over a 6-month period following pterygium surgery, specifically evaluating their effects on postoperative recurrence and clinical parameters. Material and methods: This clinical study enrolled 245 patients with pterygium who underwent surgery using the conjunctival autograft technique with mitomycin C (MMC) were enrolled. Participants were divided into three groups: Group 1 (0.05% CsA) (n = 80), Group 2 (0.1% CsA) (n = 80), and a control group (n = 85). They were examined at postoperative first day, first week, first month and sixth month. The examination included best corrected visual acuity (BCVA), intraocular pressure (IOP), presence of inflammation, and ptergium recurrence, all of which were compared across the groups. Results: The mean age of the patients was 63.22 ± 9.39 years, with 53.3% male and 46.7% female. The three groups were similar in terms of demographic characteristics and pterygium size. Inflammation in surgical area significantly regressed in all groups at 6 months postoperatively (p < 0.05). Inflammation in the first and sixth months was not different between the groups (p = 0.118, p = 0.580, and p = 0.435, respectively). The recurrence rate was not different between groups (p = 0.890). There was no statistically significant difference between groups regarding IOP (p = 0.818). A significant increase in BCVA after surgery was observed in three groups compared to preoperative levels (p < 0.05). Conclusion: This study showed that there was no difference between the efficacy of 6 month topical 0.05% CsA and 0.1% CsA application after pterygium surgery with the conjunctival autograft technique with MMC on postoperative outcomes. Including postoperative recurrence, IOP changes, BCVA changes and surgical area inflammation.