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.

2023 guidelines on the management of psoriasis by the Dermatological Society of Singapore.

Introduction: Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore. Method: The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermato-logical Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence. Results: The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticoste-roids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combina-tion or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implica-tions in special populations, such as pregnant/ lactating women, children, the elderly, those undergo-ing surgery and those suffering from specific infections and cancer were addressed. Conclusion: These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.

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.

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.

Response to Single Agent Cyclosporin in Patients with Non-Severe Aplastic Anaemia.

OBJECTIVE: To determine the effectiveness of cyclosporin A (CSA) monotherapy in treating patients with non-severe aplastic anaemia (NSAA). STUDY DESIGN: A cross-sectional observational study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan, from January 2022 till December 2023. METHODOLOGY: A total of 51 patients of NSAA, classified as aplastic anaemia not satisfying criteria for severe and very severe disease as per Modified Camitta Criteria, were included. Results were evaluated in terms of survival rate (OS) and responses. Responses were assessed as complete response (CR), partial response (PR), overall response (ORR), and no response (NR) by using standard British Committee for standard Haematology (BCSH) response criteria at 3, 6, and 12 months. RESULTS: Out of 51 patients, 34 (67%) were males and 17 (33%) were females. Median age at the time of diagnosis was 25 (IQR 26) years. At follow-up of 12 months, OS was 86.3%. Overall response rates to cyclosporin monotherapy at 3, 6, and 12 months were 49%, 57%, and 59%, respectively. Baseline haemoglobin was associated with responses at 6 and 12 months and a significant association was found between transfusion dependency at 3, 6, and 12 months with overall survival (p = 0.01, 0.005, and 0.04, respectively). Responses at time-defined points also had significant impact on OS (3 months Plog-rank = 0.046, 6 months Plog-rank = 0.01, and 12 months Plog-rank = 0.008). CONCLUSION: Overall response rates at 3, 6, and 12 months indicate the potential of CSA as a viable treatment option, particularly in resource-constrained settings. Despite some patients experiencing treatment-related complications, CSA demonstrated a generally tolerable safety profile. KEY WORDS: Cyclosporin A, Non-severe aplastic anaemia, Survival rate, Response rate, Complete response, Partial response.

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.

Perspective on oral medication adherence among patients with acute graft-versus-host disease: a qualitative descriptive study.

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.

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

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

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.

From Research to Practice: The Latest Data on Evolving Treatments for Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) should be on every dermatology practitioner's radar. CSU is a skin disorder marked by wheals, angioedema, or both for more than 6 weeks. Patients with CSU experience unexplained, itchy wheals that appear and disappear, traveling around the body and lasting less than 24 hours per area. Angioedema accompanies wheals for up to 48 hours in around half of cases. CSU is a diagnosis of exclusion, relying heavily on patient history to differentiate CSU symptoms from other causes of urticaria or angioedema. But reassuringly, CSU has a simple diagnostic algorithm and a clear initial treatment path. First-line strategies include non-pharmacologic approaches, and second-generation antihistamines (2gAH) administered up to 4 times their standard dose. Omalizumab and cyclosporine (off-label) are second- and third-line options, respectively. However, many patients will continue to have CSU symptoms despite consistent maximum-dose treatment. Novel therapies, including biologic agents and small molecule drugs targeting mast cell activation and inflammatory mediators, show promise in treating CSU refractory to standard therapy. However, further research is needed to establish their efficacy and safety in clinical practice. J Drugs Dermatol. 2024;23:9(Suppl 2):s5-14.Access the CME Activity.

The Impact of Psoriasis Treatments on the Risk of Skin Cancer: A Narrative Review.

Several studies have described increased risk ratios of certain types of malignancies in patients with severe psoriasis. Among these, the lymphoproliferative disorders, including non-Hodgkin's lymphoma, cutaneous T-cell lymphoma and non-melanoma skin cancer, have been described most frequently. In addition to traditional cancer risk factors, some psoriasis treatments may also be implicated as potential carcinogens. The aim of this study was to perform a review of current literature on the association between psoriasis, the therapies against this disease and skin cancer, focusing on both epidemiology and the potential mechanism involved. Some psoriasis treatments, such as psoralen and ultraviolet A (PUVA) therapy and cyclosporine, have been associated with increased risk of skin cancer. Variable data have been reported for anti-tumour necrosis factor (TNF) drugs, whereas other class of biologics, like anti-IL17 and IL23, as well as ustekinumab, seem not to be related to skin cancer risk, such as the case of currently available small molecules.

Response to biological drugs and JAK inhibitors following cyclosporine in patients with atopic dermatitis.

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.

Unpredictable Cyclosporine Clearance in a Korean Patient With Aplastic Anemia With Adverse Effects: A Case Study.

ABSTRACT: A 29-year-old Korean woman with chronic aplastic anemia presented with seizures due to cyclosporine-induced posterior reversible encephalopathy syndrome, caused by unpredictable oral cyclosporine (CS) accumulation and prolonged elimination. This case demonstrates the need to monitor CS drug levels with careful dose adjustments.

Other Immunomodulatory Treatment for Cytokine Storm Syndromes.

Cytokine storm syndromes (CSS) include different entities such as macrophage activation syndrome, primary and secondary hemophagocytic lymphohistiocytosis (HLH), and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. An effective management strategy is critical in CSS. While biologics have become an essential part of CSS treatment, hematopoietic stem cell transplantation (HSCT) has changed the fate of primary HLH patients. This chapter will focus on the available alternative immunomodulatory therapies in CSS, which include corticosteroids, cyclosporine A, intravenous immunoglobulin, interleukin 18 binding protein, therapeutic plasmapheresis, HSCT, and mesenchymal stromal cell-based therapies.

Improvement in signs and symptoms of severe dry eye disease after dual therapy with high-potency steroids and 0.05% cyclosporine.

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.

High-potency steroid plus CsA is more effective than CsA monotherapy in alleviating the signs and symptoms of DED.Dual therapy has acceptable safety particularly in terms of IOP and cataract risk.Dual therapy is a viable option for patients with severe DED without contraindications.

Comparison of efficacy of eltrombopag combined with immunosuppression in the treatment of severe aplastic anemia and very severe aplastic anemia: real-world data and evidence.

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.

Post-transplantation cyclophosphamide and cyclosporine A versus methotrexate and cyclosporine A for graft-versus-host disease prophylaxis after allogeneic peripheral stem cell transplantation in adult acute myeloid leukemia patients.

BACKGROUND: Different prophylactic protocols are available for preventing graft-versus-host disease (GVHD) after matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to compare the effectiveness of post-transplantation cyclophosphamide plus cyclosporine A (PT-CY/CSA) versus methotrexate plus CSA (MTX/CSA) as GVHD prophylaxis protocols in adult acute myeloid leukemia (AML) patients who received peripheral blood stem cells (PBSC) from fully matched donors. METHODS: The 1-year outcomes of 89 patients treated with PT-CY/CSA and 90 patients treated with MTX/CSA who had MSD allo-HCT for AML using unmanipulated mobilized PBSC were examined and compared. RESULTS: The cumulative incidence of acute GVHD at 100 days was considerably lower in the PT-CY/CSA group (4% vs 19.3%, p = 0.002), however there were no statistically significant difference in the cumulative incidence of chronic GVHD at 1-year (19.6% vs 37.4%, p = 0.053). Significant delays in neutrophil and platelet engraftments were reported in the PT-CY/CSA group (17 vs 12 days) and (13 vs 12 days), respectively (p < 0.001). The cumulative incidences of relapse (19.1% vs 13.7%, p = 0.470), overall survival (79.1% vs 77.3%, p = 0.986), non-relapse mortality (16.5% vs 16.8%, p = 0.837), and the GVHD and relapse-free survival (GRFS) (53.7% vs 46.6%, p = 0.478) did not differ statistically at 1-year. CONCLUSION: PT-CY/CSA demonstrated a significant decrease in the rate of acute GVHD. However, it was associated with engraftment delay.

Remission of diabetes mellitus induced by prednisolone in combination with cyclosporine toxicity in a cat.

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.

Chronic urticaria: unmet needs, emerging drugs, and new perspectives on personalised treatment.

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.