Cyclosporine Treatment Research Articles

Cyclosporine Treatment in Patients with Kawasaki Disease and Coronary Artery Aneurysms or Treatment Resistance.

To describe the clinical course and outcome of 33 patients with Kawasaki disease (KD) treated with cyclosporine (CSA) for coronary artery abnormalities (CAA) or treatment resistance. Single-center, retrospective study of patients with KD treated from 2013 through 2023 for CAA or treatment resistance. Demographics, laboratory studies, medications, adverse events, and echocardiographic data were analyzed. Of the 33 KD patients treated with CSA, 25 patients received CSA for CAA and 8 for treatment resistance. Four patients received CSA intravenously initially, followed by oral therapy. Since 2014, all patients received CSA orally only. The target 2-hour post-dose level (300-600 ng/ml) was best achieved by dividing 5 mg/kg/day every 12 hours. We developed a standardized treatment protocol based on our experiences with this patient population. The patients treated for CAA all showed improved coronary artery Z-scores at both the 2-week and 6-week follow-up. Two patients experienced significant adverse events. One patient had posterior reversible encephalopathy syndrome, while the other developed EBV-associated lymphoproliferative disorder. Discontinuation of CSA led to complete recovery in both cases. CSA was generally well tolerated in patients with KD and CAA or treatment resistance. Our study contributes to the limited literature on CSA use in KD, providing dosing guidance and advocating for cautious monitoring.

Outcomes of Cyclosporine Treatment in Pediatric Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS): A Retrospective Cohort Analysis.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a rare but severe hypersensitivity reaction. This retrospective cohort study compared the efficacy of systemic corticosteroids, the current first-line therapy, with cyclosporine, an emerging alternative therapy, in pediatric DReSS patients. We analyzed 14 cases of pediatric patients (<18 years) admitted to The Hospital for Sick Children between January 2016 and September 2023. Five patients received cyclosporine, while nine were treated with systemic corticosteroids. Cyclosporine treatment was associated with shorter hospital stays (median 6 days vs. 9 days) and faster normalization of alanine aminotransferase levels (25.0 days vs. 40.0 days) compared to corticosteroids. While cyclosporine was well-tolerated, corticosteroid therapy was linked to adverse events, including corticosteroid-induced diabetes (n=2), disease flares during tapering (n=3), and the need for treatment intensification (n=2). These findings suggest that cyclosporine may be a promising alternative for managing pediatric DReSS.

Which Immunosuppressive Therapy should be used in Primary Membranous Glomerulonephritis?

Background: Different results have been reported on immunosuppressive treatments in patients with primary membranous nephropathy. In recent years, it has been determined that antiPLA2R antibodies can be used for the diagnosis of primary membranous glomerulonephritis. The aim of this study was to investigate the treatment responses of patients with primary membranous glomerulonephritis determined by the presence of PLA2-R antibody. Patients and Methods: Sixty patients (M:29, F:31) with membranous glomerulonephritis were retrospectively investigated. The presence of glomerular PLA2R antibodies were investigated by immunohistochemical method from the pathological specimen. Those patients were treated with immunosuppressants (methylprednisolon, cyclophosphamide, cyclosporine, azathioprine), and angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB). The treatments were carried out with different combinations. The success of the treatment was defined as complete (&lt;0.3g/day), partial (&lt;3.5g/day or at least 50% reduction) or unresponsive (insufficient reduction) according to the reduction in proteinuria. In the patients, progression risks (low, moderate, high) were divided according to proteinuria and creatinine clearance. The results of immunosuppressive treatments were statistically analyzed, and p&lt;0.05 was accepted significant. Results Glomerular PLA2R antibodies were positive in 50 cases (87.7%), negative in 7 cases (12.2%). The mean duration of treatment of the patients was 23 months (6-58 months). With the treatment of PLA2R antibody-positive patients, 29% developed complete remission, 56% partial remission, and 15% did not respond. Complete remission was achieved only by steroid plus cyclophosphamide or cyclosporine combinations. The overall response (complete plus partial) rates were similar (respectively, 91% and 89%) in cyclophosphamide or cyclosporine treatment with steroids. The reduction rates in proteinuria were 70.6% in patients using cyclophosphamide, steroid, and ARB, and 79.5% in patients using cyclosporine, steroid, and ARB; there was no difference between them (P=0.67). In patients with positive PLA2R antibodies, the risk of progression was low in 25%, moderate in 29%, and high in 46%. When the treatment responses were examined, a lower rate of complete remission and higher partial remission were found in the high-risk group than in the low-risk group. However, overall response rates were not different in risk groups. Conclusion In primary membranous glomerulonephritis, only cyclophosphamide or combinations of cyclosporine and steroids provided complete remission. The complete plus partial response rates were similar in all risk groups.

Cyclosporin for the treatment of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN): a systematic review of observational studies and clinical trials focusing on single therapy, combination therapy, and comparative assessments.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe, and potentially life-threatening skin and mucous membrane disorders. They are characterized by widespread skin and mucosal detachment and necrosis, and are classified based on the percentage of total body surface area (TBSA) affected. Given the severe and often life-threatening nature of these conditions, the identification and implementation of effective treatments is crucial. Notably, cyclosporin has demonstrated efficacy in managing these challenging conditions. A systematic search was carried out through the PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases until May 2024. Additionally, a manual search was conducted through the reference lists of the included studies to minimize the risk of missing reports. Overall, 17 studies involving 4761 patients were included in our analysis. The majority of the included studies suggested favorable outcomes for the use of cyclosporin in SJS/TEN patients. The use of cyclosporin was associated with improved survival rates, early arrest of disease progression, faster re-epithelialization, reduced length of hospital stays, and lower rates of multi-organ failure. However, a few studies did not find a survival advantage with cyclosporin and even reported an increased risk of mortality, as well as an increased TBSA detachment and risk of infection. Most studies indicate positive outcomes with cyclosporin treatment in SJS/TEN patients. This is likely due to cyclosporin's immunomodulatory properties, which may help attenuate the severe inflammatory response associated with these conditions.

Maintenance therapy in moderate to severe chronic plaque psoriasis: Role of weekend cyclosporin treatment

Maintenance therapy in moderate to severe chronic plaque psoriasis: Role of weekend cyclosporin treatment

Comparison of cyclosporine and tacrolimus after liver transplantation for primary biliary cholangitis: A propensity score–matched intention-to-treat registry study

The optimal calcineurin inhibitor after liver transplantation (LT) for primary biliary cholangitis (PBC) remains debated. We compared tacrolimus with cyclosporine in a propensity score–matched intention-to-treat analysis from the Scientific Registry of Transplant Recipients. We included adults with PBC who underwent primary LT from 1995 to 2022. Patients with initial cyclosporine treatment were 1:3 matched with those with initial tacrolimus treatment, ensuring exact calendar-period match. Primary outcomes were patient and graft survival. After matching, 579 patients with PBC and initial cyclosporine and 1348 with tacrolimus were well balanced for baseline characteristics. During a median follow-up of 11.1 years, 1044 (54%) deaths and 124 (6%) re-LTs occurred. In the overall matched sample, no significant survival difference emerged between cyclosporine and tacrolimus. However, tacrolimus conferred a survival advantage in some secondary analysis, such as LT after year 2000 and women, and in a 6-month landmark analysis excluding early postoperative events and calcineurin inhibitor switches. Cyclosporine did not reduce graft loss from PBC recurrence or affect laboratory markers of recurrence. In conclusion, we found no benefit of starting immunosuppression with cyclosporine after LT for PBC.

Exploring the Impact of Pre-existing Allergic Conjunctivitis on the Efficacy of Refractory Medications in Chronic Spontaneous Urticaria: A TrinetX Database Analysis

Chronic Spontaneous Urticaria, often characterized by pruritic hives, can significantly impact quality of life [1][4]. Standard treatment involves second-generation antihistamines, but some cases may become refractory, requiring stronger medications such as cyclosporine A [2]. Purpose: To investigate the association of allergic conjunctivitis alongside CSU and use of cyclosporine A compared to those without pre-existing AC in treating CSU, using TrinetX database. Methods: Analysis included ICD-10 codes ‘urticaria, unspecified, ‘idiopathic urticaria,’ or ‘other urticaria’ for patients seen during 2020-2024, with at least two consecutive visits at least 4-6 weeks apart, in addition to receiving a second-generation H1-antihistamine treatment. Compare prevalence of cyclosporine use between two cohorts: AC (+) x urticaria x pretreated with H1 and AC (-) x urticaria x pretreated with H1 and patients with and without AC, requiring the addition of cyclosporine A to H1 for treatment of CSU over an observation period of 5 years. Propensity score matching to pair the two cohorts for age, sex, and race [3]. Results: In AC (+) x urticaria x pretreated with H1 group, there were 38,530 patients, out of which 446 required the addition of cyclosporine treatment, resulting in a risk percentage of 1.158%. In AC (-) x urticaria x pretreated with second-generation antihistamine group, with 415,786 patients, 2,812 required the addition of cyclosporine treatment, resulting in a lower risk percentage of 0.676%. Risk Ratio (RR) is calculated as 1.711, with a 95% confidence interval of (1.55, 1.89). Conclusion: A greater proportion of CSU patients with AC required cyclosporine compared to those without AC.

The evolution of cyclosporine treatments for treatment of ocular surface diseases.

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. 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. 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.

Dupilumab treatment decreases MBC2s, correlating with reduced IgE levels in pediatric atopic dermatitis

BackgroundA preference for type 2 immunity plays a central role in the pathogenesis of atopic dermatitis (AD). Dupilumab, a monoclonal antibody targeting the IL-4α receptor subunit, inhibits IL-4 and IL-13 signaling. These cytokines contribute significantly to IgE class switch recombination in B-cells, critical in atopic diseases. Recent studies indicate IgG+CD23hiIL-4RA+ memory B-cells (MBC2) as IgE-producing B-cell precursors, linked to total IgE serum levels in atopic patients. Total IgE serum levels decreased during dupilumab treatment in previous studies. ObjectiveTo assess the effects of dupilumab treatment in comparison to alternative therapies on the frequency of MBC2 and the correlation to total IgE levels in pediatric patients with AD. MethodsPediatric patients with AD, participating in an ongoing trial, underwent randomization into three treatment groups: dupilumab (n=12), cyclosporine (n=12), or topical treatment (n=12). Plasma and Peripheral Blood Mononuclear Cells (PBMCs) were collected at baseline (T0) and after 6 months (T6). Flow cytometry was employed for PBMC phenotyping, ELISA was utilized to assess total IgE levels in plasma. For detailed Methods, please see the Methods section in this article's Online Repository at www.jacionline.org ResultsOur findings revealed a significant reduction in MBC2 frequency and total IgE levels among patients treated with dupilumab. Additionally, a significant correlation was observed between MBC2s and total IgE levels ConclusionSystemic blocking of the IL-4RA subunit leads to a decrease in circulating MBC2 cells and total IgE in pediatric AD patients. Our findings unveil a novel mechanism through which dupilumab exerts its influence on the atopic signature.

Systemic Treatment With Cyclosporine A in Children With Severe Vernal Keratoconjunctivitis.

To report our experience with systemic cyclosporine as a treatment for severe vernal keratoconjunctivitis (VKC) in pediatric patients who did not respond to previous treatments. We analyzed the medical records of 6 patients, aged 4 to 15 years, with severe VKC treated with systemic cyclosporine for VKC at Shamir Medical Center in Zerifin, Israel, between the years 2000 and 2023. The average treatment duration was 18 months. In all patients, previous treatments with antihistamines, mast cells stabilizers, topical steroids and topical cyclosporine, and systemic steroids did not result in sufficient improvement. The severity of inflammation was evaluated during clinical examinations and the patients' subjective assessment of their quality of life. In all 6 patients, signs and symptoms showed significant improvement within 2 to 4 weeks of initiating systemic cyclosporine treatment. All patients were able to discontinue regular steroids use and reported a significant improvement in their quality of life. No significant side effects were observed in any of the patients. Systemic cyclosporine is a safe and effective treatment for severe VKC. It is a steroid-sparing treatment that allows good quality of life, while keeping the disease latent.

The treatment journey of children with moderate to severe atopic dermatitis in Türkiye: unmet needs.

Atopic dermatitis (AD) substantially burdens individuals, families, and healthcare systems. We aimed to document the treatment journey of pediatric patients with moderate-to-severe AD in a referral center based in our country. This retrospective study reviewed patients aged 1-18 years diagnosed with AD, seeking systemic treatment recommendations from the "pediatric allergy and dermatology multidisciplinary team meeting". Over the 14-month study period, 30 (12.5%) of 240 AD patients were evaluated in the pediatric dermato-allergy team meetings. The median age of the patients was 13.66 years (Q1-Q3: 7.94-17.27), of whom 60% were male. The median annual healthcare visits for AD were 4 (Q1-Q3: 1.00-8.75). Among the study group, 70% were sensitized to aeroallergens, and admission markers included total IgE (median: 1980 IU/mL, Q1-Q3: 794.50-5446), and eosinophil counts (median: 650, Q1-Q3: 275-1275). All patients utilized intermittent and/or continuous topical corticosteroids (CS), with 56.6% employing short-term/long-term topical tacrolimus. Over the past two years, systemic CSs were utilized in 93.3% of the patients, whereas 57.1% received more than one course. Approximately 43.3% of the patients agreed to receive systemic cyclosporine treatment, with only 30.8% benefiting and 3.3% reporting adverse effects (hypertrichosis and cellulitis). Three patients self-funded dupilumab, all benefiting without adverse effects. Omalizumab, mycophenolate mofetil and narrow-band ultraviolet (UV) treatments were used in one patient each, with limited benefit observed. Health insurance did not grant approval for a Janus kinase inhibitor for one patient. Managing moderate to severe AD is complex and costly, considering disease heterogeneity, comorbidities, care pathways, and health system challenges. Addressing the unmet needs should be a priority in Türkiye's healthcare systems.

Efficacy and safety of weekend cyclosporine treatment as maintenance therapy for preventing frequent disease exacerbations in moderate to severe chronic plaque psoriasis patients - A retrospective cohort study.

Background Psoriasis is a chronic, inflammatory, systemic disease with predominant manifestations in the skin and joints impairing patient's quality of life. A proportion of patients have frequent severe disease exacerbations requiring repeated systemic treatments. There is a scarcity of literature evaluating the role of systemic maintenance therapy in psoriasis patients in preventing such frequent disease flares. Objective To evaluate the efficacy and safety of weekend cyclosporine treatment (WCT) as maintenance therapy in moderate to severe chronic plaque psoriasis patients for the prevention of frequent disease exacerbations. Methods In this retrospective cohort study, 22 psoriasis patients with a history of frequent disease exacerbations (≥ 3 in the last 1 year) who were administered WCT (group A) were compared with the same number of matched patients (age and gender) not on WCT or any systemic maintenance therapy (group B). Results Four patients (18.2%) in group A had disease exacerbations which was significantly lower (p = 0.00, Fisher's exact test) as compared to 21 patients (95.5%) in group B during the study period. Also, patients in group A had significantly lower number of overall exacerbations [mean ± SD: 0.23 ± 0.53 vs 2.95 ± 1.43) p = 0.00, Mann-Whitney U test] as compared to group B. Four (9.1%) patients in group A encountered adverse effects (acneiform eruptions - two, mild gingival hyperplasia - one, myalgia - one) as compared to three (acneiform eruptions - two, headache - one) in group B (p = 1.00). Conclusion WCT significantly reduced the number of disease exacerbations and is a safe and effective mode of maintenance therapy in such subset of psoriasis patients.

Evaluation of the Factors Influencing Mortality in Patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Multicenter Study of 166 Patients.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening acute mucocutaneous disorders usually triggered by drugs. In this study, we aimed to evaluate the factors affecting mortality in patients with SJS-TEN. Our study is a retrospective cohort study, analyzing data collected from a total of 12 tertiary care centers between April 2012 and April 2022. The study included 59 males and 107 females, a total of 166 patients, with an average age of 50.91 ± 21.25years. Disease classification was TEN in 50% of cases, SJS in 33.1%, and SJS-TEN overlap in 16.9%. The average SCORTEN within the first 24h was 2.44 ± 1.42. Supportive care was provided to 99.4% of patients. The most commonly used systemic immunomodulatory treatments were systemic steroids (84.3%), IVIG (intravenous immunoglobulin) (49.3%), and cyclosporine (38.6%). Plasmapheresis was administered to five patients. While 66.3% of patients were discharged, 24.1% resulted in exitus. Our comparative analysis of survivors and deceased patients found no effect of systemic steroids, IVIG, and cyclosporine treatments on mortality. Univariate analysis revealed that the SCORTEN scores on days 1 and 3 as well as the rates of detachment at the onset and during follow-up were significantly higher in deceased patients compared to survivors. The rates of fever, positive blood cultures, and systemic antibiotic use were higher in deceased patients compared to survivors. The presence of comorbidities, diabetes, and malignancy were significantly more common in deceased patients. Multivariate regression analysis indicated that over SCORTEN 2, the mortality risk exponentially rose with each SCORTEN increment, culminating in an 84-fold increase in mortality at SCORTEN 5-6 (odds ratio [95% confidence interval]: 13.902-507.537, p < 0.001) compared to SCORTEN 0-1. Additionally, the utilization of plasmapheresis was associated with a 22-fold increase in mortality (odds ratio [95% confidence interval]: 1.96-247.2, p = 0.012). Our study found that a high SCORTEN score within the first 24h and the use of plasmapheresis were related to increased mortality, while systemic steroids, IVIG, and cyclosporine treatments had no impact on mortality. We believe that data gathered from one of the most comprehensive studies which we conducted on SJS-TEN will enrich the literature, although additional research is warranted.

Effect of Early Cyclosporine Treatment on Survival in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Early cyclosporine administration is a potentially useful treatment in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, previous studies have reported conflicting results regarding the survival benefits. Therefore, in this study, we evaluated the survival of patients with SJS/TEN according to whether they received early cyclosporine administration. This retrospective cohort study was conducted using a Japanese national administrative claims database. Data on patients admitted to the hospital with SJS/TEN between April 1, 2016, and March 31, 2021, were extracted. Patients with missing data, those discharged within two days of admission, pregnant women, and children aged <16 years were excluded. Patients who received cyclosporine on the day of admission (early cyclosporine group) were compared with those who did not (comparison group). The primary endpoint was in-hospital mortality. Secondary endpoints were 30- and 50-day mortality and length of hospital stay. The effect of early cyclosporine treatment was evaluated after baseline adjustment using doubly robust estimation. Among 3807 enrolled patients (mean age, 65.5 years; 53.8% women), the early cyclosporine and comparison groups included 115 and 3692 patients, respectively. After adjustment, cyclosporine treatment decreased in-hospital mortality by 6.03% (95% confidence interval (CI), 5.27-6.82%), 30-day mortality by 2.94% (95% CI, 2.43-3.50%), and 50-day mortality by 4.38% (95% CI, 3.70-5.04%), but increased the length of hospital stay by 9.45 days (95% CI, 1.00-20.23 days). Early cyclosporine administration can improve the survival of patients with SJS/TEN but is associated with a longer hospital stay.

[Translated article] Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP)

BackgroundThe past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. Material and methodMulticenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. ResultsWe analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). ConclusionDrug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.

Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A

ABSTRACT Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes encoding MAPKs and microRNA (miRNA) molecules potentially regulating their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes exposed to bacterial lipopolysaccharide A (LPS) and cyclosporine A (CsA). HaCaT cells were treated with 1 µg/mL LPS for 8 h, followed by treatment with 100 ng/mL cyclosporine A for 2, 8, or 24 h. Untreated cells served as controls. The molecular analysis consists of microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay analyses. The statistical analysis of the obtained results was performed using Transcriptome Analysis Console and STATISTICA 13.5 PL with the statistical significance threshold of p < 0.05. Changes in the expression profile of six mRNAs: dual-specificity phosphatase 1 (DUSP1), dual-specificity phosphatase 4 (DUSP4), mitogen-activated protein kinase kinase 2 (MAP2K2), mitogen-activated protein kinase kinase 7 (MAP2K7), mitogen-activated protein kinase kinase kinase 2 (MAP3K2) and mitogen-activated protein kinase 9 (MAPK9) in cell culture exposed to LPS or LPS and the drug compared to the control. We observed that under the LPS and cyclosporine treatment, the expression o/ miR-34a, miR-1275, miR-3188, and miR-382 changed significantly (p < 0.05). We demonstrated a potential relationship between DUSP1 and miR-34a; DUSP4 and miR-34a, miR-382, and miR-3188; MAPK9 and miR-1275, MAP2K7 and mir-200-5p; MAP3K2 and mir-200-5p, which may be the subject of further research in the context of psoriasis.

Conjunctival and nasal microflora in patients on topical cyclosporine for dry eye.

Introduction: Dry eye is a common ocular condition causing discomfort and visual disturbances. Anti-inflammatory agents like Cyclosporine A (CsA) are often used in its treatment. However, the impact of CsA on ocular flora remains understudied. This research aimed to evaluate changes in conjunctival and nasal microflora in patients receiving topical cyclosporine for dry eye. Methods: In this cross-sectional study, conjunctival and nasal samples were collected from two groups of dry eye patients. Group 1 consisted of 38 patients using CsA eye drops, while Group 2 included 34 patients using preservative-free artificial tear drops. Bacterial cultures were grown from the samples, and the identified organisms underwent antibiotic susceptibility testing. Additionally, alpha diversity metrics were employed to assess the diversity of bacterial species in the samples. Results: Bacterial growth was observed in 75% of conjunctival samples and 97.22% of nasal samples. Staphylococcus epidermidis was the predominant organism in both groups. Alpha diversity analysis showed no significant differences in Shannon diversity and OTU richness between the groups for most bacterial species. Antibiotic susceptibility tests revealed no substantial variations in resistance patterns between the groups. Conclusion: This study provides valuable insights into the impact of CsA eye drops on conjunctival and nasal flora in dry eye patients. The findings suggest that CsA does not significantly influence the composition, diversity, or antibiotic resistance patterns of ocular flora. Long-term topical cyclosporine treatment for dry eye does not significantly impact conjunctival microflora or lead to antibiotic resistance. These results have important implications for the safe use of CsA in patients undergoing ocular treatments, particularly those at risk of intraocular infections.

Risk of Developing Hypertension in Atopic Dermatitis Patients Receiving Long-term and Low-dose Cyclosporine: A Nationwide Population-based Cohort Study.

Cyclosporine (CS) is a first-line immunosuppressive agent used to manage moderate to severe atopic dermatitis (AD). To date, the risk of developing hypertension associated with the long-term use of low-dose CS in AD patients is understudied. To determine the cumulative dose-dependent effect of CS on the risk of developing hypertension in patients with AD. A nationwide population-based retrospective cohort with 1,844,009 AD patients was built from the Korean National Health Insurance System database from 2005 to 2009. A Cox proportional-hazard regression analysis was performed according to patients' CS treatment history adjusted for potential confounders. Current use of CS was associated with an increased risk of developing hypertension (adjusted hazard ratio, 4.442; 95% confidence interval, 3.761-5.247). Among the current CS users, a higher cumulative dose of CS (≥39,725 mg) or longer cumulative use of CS (≥182 days), was significantly associated with an increased risk of developing hypertension. The incidence of CS-associated hypertension is very low when using low-dose treatment regimens for AD. However, the current use or a high cumulative dose of CS for treating patients with AD increases the risk of developing hypertension. Precaution is needed when prescribing CS for long-term treatment of AD.

Review of two immunosuppressants: tacrolimus and cyclosporine.

Immunosuppressants are vital in organ transplantation including facial transplantation (FT) but are associated with persistent side effects. This review article was prepared to compare the two most used immunosuppressants, cyclosporine and tacrolimus, in terms of mechanism of action, efficacy, and safety and to assess recent trials to mitigate their side effects. PubMed and Google Scholar queries were conducted using combinations of the following search terms: "transplantation immunosuppressant," "cyclosporine," "tacrolimus," "calcineurin inhibitor (CNI)," "efficacy," "safety," "induction therapy," "maintenance therapy," and "conversion therapy." Both immunosuppressants inhibit calcineurin and effectively down-regulate cytokines. Tacrolimus may be more advantageous since it lowers the likelihood of acute rejection, has the ability to reverse allograft rejection following cyclosporine treatment, and has the potential to reinnervate nerves. Meanwhile, graft survival rates seem to be comparable for the CNIs. To avoid nephrotoxicity, various immunosuppressants other than CNIs have been studied. Despite averting nephrotoxicity, these medications show increases in acute rejection or other types of adverse effects compared to CNIs. FT has been a topic of interest for oral and maxillofacial surgeons, and the postoperative usage of immunosuppressants is crucial for the long-term prognosis of FT. As contemporary transplantation regimens incorporate novel medications along with CNIs, further research is required.

Long-term outcomes of cyclosporin induction and ustekinumab maintenance combination therapy in patients with steroid-refractory acute severe ulcerative colitis.

Effective management of patients with acute severe ulcerative colitis (ASUC) is a major challenge and there remains a paucity of available maintenance treatment options after efficacious cyclosporin induction therapy. We investigated the long-term effectiveness and safety of cyclosporin and ustekinumab combination therapy in patients with steroid refractory ASUC. Monocentric, prospective study. We included patients with steroid refractory ASUC with multiple failed prior advanced therapies, who were treated with cyclosporin and ustekinumab combination therapy. Among the 11 included patients, 10 had prior failure to infliximab and 8 failed at least three previous biological therapies. The mean baseline Mayo and Lichtiger scores were 10.9 (9-12) and 13.3 (11-14), respectively. Ustekinumab was initiated 3.2 weeks (1-8) after initiation of cyclosporin treatment and combination therapy was continued for a mean of 11.5 (4-20) weeks. Clinical response was achieved in six patients at week 16 and clinical steroid-free clinical remission in five patients at week 48. Endoscopic remission was achieved in five patients at week 16 and together with histological remission in five patients at week 52. Intestinal ultrasound demonstrated mean bowel wall thickening in the sigmoid colon of 5.5 mm at baseline and 3.5 mm at week 52, respectively. Two patients had to undergo colectomy (mean 4.5 months, range 3-6) and three stopped ustekinumab therapy due to ineffectiveness. Overall, combination therapy was well tolerated. Combination of cyclosporin and ustekinumab therapy allowed nearly half of ASUC patients to reach clinical and endoscopic remission after 52 weeks, warranting further studies. Not applicable.