Abrocitinib, tralokinumab and upadacitinib for treating moderate-to-severe atopic dermatitis.

Background: Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus). Objectives: To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib). Data sources: Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review. Methods: A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources. Results: Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost. Conclusions: The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations. Future work and limitations: The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective. Study registration: This study is registered as PROSPERO CRD42021266219. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in Health Technology Assessment; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.

Atopic dermatitis is one of the most common skin conditions in children but can also develop in adulthood. People with atopic dermatitis have dry, red (inflamed) skin that is also extremely itchy (pruritus). There is no cure for atopic dermatitis. Therapy starts with topical treatments that are applied to the skin, such as emollients. Severe forms of atopic dermatitis are often treated with systemic treatments, which are drugs that are provided as tablets or an injection. Ciclosporin A is often the first systemic therapy given. If atopic dermatitis does not get better with ciclosporin A, options available in the National Health Service are dupilumab and baricitinib. New therapies that have been evaluated in clinical trials for atopic dermatitis but have not been assessed for use in the National Health Service are abrocitinib, tralokinumab and upadacitinib. The aim of this project is to review the medical benefits, risks and value for money for the National Health Service of abrocitinib, tralokinumab and upadacitinib for the treatment of moderate-to-severe atopic dermatitis in a multiple technology appraisal. Our review found that: For children aged between 12 and 18 years, abrocitinib and a low dose of upadacitinib (15 mg) are good value for money for the National Health Service. For adults who need a first systemic treatment, upadacitinib is unlikely to be good value for money for the National Health Service. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, upadacitinib 15 mg and tralokinumab could be good value for money for the National Health Service if they are used on their own. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, but need to take it with steroid cream, abrocitinib 100 mg, upadacitinib 15 mg and tralokinumab could all be good value for money for the National Health Service.

Adalimumab induced exacerbation of psoriasis in patients with combined pemphigus: A case report.

RATIONALE: Psoriasis is an immune-related disease caused by genetic factors, abnormalities in the immune system and environmental factors, while pemphigus is an autoimmune disease caused by the autoimmune system attacking the skin and mucosal tissues. Herein, we aimed to report a rare case of adalimumab induced exacerbation of psoriasis patients with pemphigus. The rare disease causes considerable challenges for clinical diagnosis and treatment. PATIENT CONCERNS: The patient was a 43-year-old man with intermittent erythema and scaling all over the body for more than 20 years, and blisters and vesicles on the trunk and limbs for 1 month. Half a year ago, the patient had blisters on the limbs, and was diagnosed with deciduous pemphigus in a hospital, and the blisters subsided after being given traditional Chinese medicine orally. Half a month ago, the erythema area was enlarged, and adalimumab 80 mg intramuscular injection was given for 1 time after consultation in the hospital. On the following day, the area of erythema and scales was suddenly enlarged obviously compared with the previous 1, and obvious blisters and vesicles appeared on the limbs, neck, and trunk, which were aggravated progressively and accompanied by obvious itching and pain. DIAGNOSES: The patient was diagnosed with psoriasis in patients with combined pemphigus. INTERVENTION: After combined treatment with methylprednisolone and cyclosporine, the skin lesions have basically recovered. OUTCOMES: The skin lesions have basically healed. Follow up for 6 months without recurrence. LESSONS: Methylprednisolone combined with cyclosporine may be an option in treating patients with psoriasis patients with pemphigus.

Immunosuppressive and immunomodulating therapy for atopic dermatitis in pregnancy: an appraisal of the literature.

Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course and the fact that the therapy needs to be safe for both the mother and the fetus. Here we present an up-to-date appraisal of the literature on the treatment options available for AD in patients planning pregnancy, during pregnancy, and during breastfeeding. All patients with AD are recommended to supplement any medical treatment with daily applications of emollients. The first step in the medical treatment for AD during pregnancy are topical corticosteroids, and/or topical tacrolimus. If required, UV-light therapy can also be considered. Treatment with systemic therapy during pregnancy should always rely on a careful risk-benefit assessment and be based on shared-decision making between the treating physician and patient. The first-line systemic treatment option is cyclosporine A, whereas azathioprine may be considered in patients already receiving this treatment prior to pregnancy. Systemic glucocorticoids may also be used. Treatment with systemic JAK inhibitors is not recommended, whereas treatment with mycophenolate mofetil and methotrexate is contraindicated. Targeted therapy with dupilumab is not generally recommended, due to lack of experience in human pregnancies, yet some case-reports on their use are emerging. These recommendations are based on the authors appraisal of existing literature and the current recommendation from the European Task Force on Atopic Dermatitis. It is always the responsibility of the treating physician to stay updated on the newest guidelines and literature when treating patients with AD during pregnancy.

Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. OBJECTIVE: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. LIMITATIONS: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. CONCLUSIONS: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Executive summary: Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications. CONCLUSIONS: The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Treatment of ocular rosacea: A practical review from an interdisciplinary approach.

Rosacea is a chronic and inflammatory disease that primarily affects the skin, although more than half of cases also present with ocular symptoms ranging from blepharitis to conjunctivitis and keratitis. It represents a frequent reason for consultation with a psychosocial impact, affecting quality of life, and requires management involving ophthalmologists, dermatologists, and primary care physicians. For this paper, a search was conducted in several databases, including Medline, Embase, Cochrane, and Google Scholar, using the MeSH term "rosacea" in conjunction with other relevant keywords such as "ocular rosacea", "management", "treatment", and "guidelines". Available articles were reviewed. International and local guidelines recommend initiating the management of rosacea with lifestyle changes, including ocular hygiene and avoidance of triggers. Topical or oral treatment is recommended as the next step, with topical cyclosporine, topical azithromycin, topical tacrolimus, and oral doxycycline being the treatments most supported by evidence. Combination treatments are also recommended. Current management guidelines mainly focus on cutaneous manifestations, generating few guidelines on ophthalmologic treatment, and most recommendations are issued by experts. This work compares local and international treatment guidelines for rosacea, as well as other available medical literature, and suggests a practical and interdisciplinary treatment scheme for ocular involvement based on the reviewed bibliography.

An update on therapeutic options for palmoplantar pustulosis: a narrative review and expert recommendations.

INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease belonging to the localized form of pustular psoriasis. It is characterized by sterile pustule formation in palms and soles and a recurrent disease course. Although we have many treatments for PPP, there is no authoritative guidance. AREAS COVERED: A thorough search of PubMed was conducted to identify studies in PPP from 1973 onwards, with additional references to specific articles. Any treatment methods were outcomes of interest, including topical treatment, systemic treatment, biologics, other targeted treatments, phototherapy, and tonsillectomy. EXPERT OPINION: Topical corticosteroids are suggested as first-line therapy. Oral acitretin has become the most applied systemic retinoid recommended in PPP without joint involvement. For patients with arthritis, immunosuppressants like cyclosporin A and methotrexate are more recommended. UVA1, NB-UVB, and 308-nm excimer laser are effective phototherapy options. The combinations of topical or systemic agents and phototherapy may enhance the efficacy, particularly in recalcitrant cases. Secukinumab, ustekinumab, and apremilast are the most investigated targeted therapies. However, heterogeneous reported outcomes in clinical trials provided low-to-moderate quality evidence of their efficacy. Future studies are required to address these evidence gaps. We suggest managing PPP based on the acute phase, maintenance phase, and comorbidities.

Insights into atopic dermatitis pathogenesis lead to newly approved systemic therapies.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by scaly, oozing skin and itch. In moderate-to-severe AD, treatment options have been historically very limited and off-label use has been a common method for disease management. For decades, ciclosporin A was the only systemic immunosuppressive drug approved in most European countries to address this major unmet medical need. However, increased understanding of the pathophysiology of AD has led to a revolution in the treatment of this potentially debilitating disease. Following the approval of the first biological therapy for AD in 2017, there has been a rapid expansion of compounds under development and four additional systemic therapies have been approved in Europe and the USA within the past 3 years alone. In this review, we underscore how key breakthroughs have transformed the therapeutic landscape of AD, leading to a major expansion of type 2 immunity-targeted biological therapies, exploration of neuroimmune modulatory agents, and interest in Janus kinase inhibition.

Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain. / [Artículo traducido] Características de los pacientes, patrones de tratamiento, uso de recursos y costes en adultos con dermatitis atópica moderada-grave en la práctica habitual en España: Estudio Derma-Atopic.

BACKGROUND: Moderate-severe atopic dermatitis (AD) has a significant impact on patients' lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. METHODS: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. RESULTS: Patients (N = 1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. CONCLUSIONS: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD.

Real-World Treatment Patterns, Resource Use and Costs in Adult Patients With Atopic Dermatitis Receiving Systemic Treatment: Derma-Atopic Study in Spain.

BACKGROUND: Moderate-severe atopic dermatitis (AD) has a significant impact on patients' lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. METHODS: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. RESULTS: Patients (N=1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. CONCLUSIONS: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD.

Treatment options for moderate to severe atopic dermatitis.

Background: The treatment of chronic refractory moderate-to-severe atopic dermatitis (AD) has traditionally relied on broad-spectrum systemic anti-inflammatory agents. With the introduction of biologics and Janus kinase inhibitors (Jakinib), the step management of moderate-to-severe AD is rapidly changing; however, guidelines have yet to provide formal recommendations for how to best incorporate these agents into the treatment plan. Objective: To summarize the updated evidence-based medical treatment for AD, including a proposed position for biologics and Jakinibs in the treatment algorithm. Methods: A literature search of several medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from 2012 to 2022 on the treatment of moderate-to-severe AD was conducted to prepare this narrative review. Results: Emollients and topical corticosteroids are the mainstay for treating acute flares and for maintaining chronic control. Second-line topical agents include calcineurin inhibitors, e.g., tacrolimus and pimecrolimus; crisaborole; and ruxolitinib. For acute flares, cyclosporine is preferred over systemic corticosteroids. For chronic treatment, phototherapy should be considered before systemic anti-inflammatory agents. Of the traditional anti-inflammatory agents, cyclosporine is the first-line choice, with methotrexate and azathioprine equal secondary choices. Although abrocitinib may have better efficacy then dupilumab based on indirect comparisons, abrocitinib requires closer monitoring for adverse events. Based on package labeling, Jakinibs, e.g., abrocitinib and upadacitinib, should be used only after failure with other systemic agents, including biologics (e.g., dupilumab and tralokinumab). Biologics and Jakinibs should be considered before the traditional systemic anti-inflammatory agents. Conclusion: Clinicians should consider a modified step management for AD as they await the development of national and international guideline recommendations for how best to position the biologics and Jakinibs into the AD treatment algorithm.

Annual Trends in Medicare Part D Prescription Claims for Dupilumab 2017 to 2019.

Disease control for moderate to severe atopic dermatitis (AD) has been primarily achieved with phototherapy and non-specific immunomodulators, cyclosporine, and methotrexate. These treatments have, however, been associated with many unfavorable side effects.

European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

Reassessment of mitochondrial cyclophilin D as a target for improving cardiac arrest outcomes in the era of therapeutic hypothermia.

Uncertainty exists regarding whether cyclophilin D (CypD), a mitochondrial matrix protein that plays a key role in ischemia-reperfusion injury, can be a pharmacological target for improving outcomes after cardiac arrest (CA), especially when therapeutic hypothermia is used. Using CypD knockout mice (CypD-/-), we investigated the effects of loss of CypD on short-term and medium-term outcomes after CA. CypD-/- mice or their wild-type (WT) littermates underwent either 5 minute CA followed by resuscitation with and/or without hypothermia at 33°C-34°C (targeted temperature reached within minutes after resuscitation), or a sham procedure. Brain and cardiac injury were assessed using echocardiography, neurological scores, MRI and biomarkers. Seven day survival was compared using Kaplan-Meier estimates. The rate of restoration of spontaneous circulation was significantly higher in CypD-/- mice (with shorter cardiac massage duration) than in WT mice (P < 0.05). Loss of CypD significantly attenuated CA-induced release of troponin and S100ß protein, and limited myocardial dysfunction at 150 minutes after CA. Loss of CypD combined with hypothermia led to the best neurological and MRI scores at 24 hours and highest survival rates at 7 days compared to other groups (P < 0.05). In animals successfully resuscitated, loss of CypD had no benefits on day 7 survival while hypothermia was highly protective. Pharmacological inhibition of CypD with cyclosporine A combined with hypothermia provided similar day 7 survival than loss of CypD combined with hypothermia. CypD is a viable target to improve success of cardiopulmonary resuscitation but its inhibition is unlikely to improve long-term outcomes, unless therapeutic hypothermia is associated.

Current concepts regarding Graves' orbitopathy.

Graves' orbitopathy (GO) is an orbital autoimmune disorder and the main extrathyroidal manifestation of Graves' disease, the most common cause of hyperthyroidism. GO affects about 30% of Graves' patients, although fewer than 10% have severe forms requiring immunosuppressive treatments. Management of GO requires a multidisciplinary approach. Medical therapies for active moderate-to-severe forms of GO (traditionally, high-dose glucocorticoids) often provide unsatisfactory results, and subsequently surgeries are often needed to cure residual manifestations. The aim of this review is to provide an updated overview of current concepts regarding the epidemiology, pathogenesis, assessment, and treatment of GO, and to present emerging targeted therapies and therapeutic perspectives. Original articles, clinical trials, systematic reviews, and meta-analyses from 1980 to 2021 were searched using the following terms: Graves' disease, Graves' orbitopathy, thyroid eye disease, glucocorticoids, orbital radiotherapy, rituximab, cyclosporine, azathioprine, teprotumumab, TSH-receptor antibody, smoking, hyperthyroidism, hypothyroidism, thyroidectomy, radioactive iodine, and antithyroid drugs. Recent studies suggest a secular trend toward a milder phenotype of GO. Standardized assessment at a thyroid eye clinic allows for a better general management plan. Treatment of active moderate-to-severe forms of GO still relies in most cases on high-dose systemic-mainly intravenous-glucocorticoids as monotherapy or in combination with other therapies-such as mycophenolate, cyclosporine, azathioprine, or orbital radiotherapy-but novel biological agents-including teprotumumab, rituximab, and tocilizumab-have achieved encouraging results.

Cyclosporin A alleviates trophoblast apoptosis and senescence by promoting autophagy in preeclampsia.

INTRODUCTION: Abnormal extravillous trophoblast (EVT) function is closely related to preeclampsia (PE) and may be caused by inadequate autophagy, apoptosis, and senescence. Cyclosporin A (CsA) is an effective immunosuppressant that has been reported to stimulate autophagy and exert benign biological effects on EVTs. Therefore, we hypothesized that CsA may display therapeutic efficacy against PE by activating autophagy. METHODS: We established the nitro-l-arginine methyl ester (l-NAME)-induced preeclamptic mice model and a hypoxia-reoxygenation (H/R) model in vitro. The effects of CsA on autophagy were evaluated by western blotting (WB). The effects of CsA on apoptosis were analyzed by Hematoxylin-eosin (H&E) staining, cell apoptosis assay and WB. Senescence-associated ß-galactosidase (SA-ß-gal) staining, RT-qPCR and WB were used to examine the senescence level. RT-qPCR were used to detect the senescence-associated secretory phenotype (SASP) level. DCFH-DA fluorescent probe, dihydroethidium (DHE) staining and mitochondrial membrane potential (ΔΨm) were used to detect senescence-associated mitochondrial dysfunction (SAMD). RESULTS: CsA alleviated PE-like symptoms and reduced placental necrosis and senescence in mice injected with l-NAME. CsA ameliorated placental SASP and SAMD level induced by l-NAME. CsA also upregulated the expression of autophagic proteins in mouse placentas disrupted using l-NAME. In vitro, we found that CsA reversed H/R-induced apoptosis and senescence, as well as decreasing SASP and SAMD levels and upregulating autophagic proteins levels. Notably, 3-methyladenine (3-MA), an early phase inhibitor of autophagosome formation, abolished the protective effects of CsA against H/R. DISCUSSION: CsA may display some therapeutic effects against PE by activating autophagy in vivo and in vitro.

Effect of a combination of Korean red ginseng extract and probiotics on the prevention of atopic dermatitis in a murine model.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A.Mey. (Korea red ginseng) has been used in Asia to treat inflammatory skin diseases. Recently, Korea red ginseng (KRG) is emerging as a good candidate for treating atopic dermatitis (AD) because of its anti-allergic and anti-inflammatory effects. AIM OF THE STUDY: Despite much effort, no systemic prevention strategy has been established for AD currently. Therefore, the aim of this study was to determine the preventive effect of a combination of KRG extract and probiotics on AD-like skin lesions of mice. MATERIALS AND METHODS: Forty NC/Nga mice were randomly divided into eight groups: Sham, AD control, Cyclosporine, KRG, Duolac ATP® (ATP), BYO Plant Origin Skin Probiotics (BYO), KRG + ATP, and KRG + BYO. Mice were administered orally with KRG and/or other agents using a gastric tube for 5 days prior to challenge with 1-chloro-2,4-dinitrobenzene (DNCB). AD-like skin lesions were induced by percutaneous challenge with DNCB on ears and backs of NC/Nga mice. Effects of each treatment were evaluated based on the following: Clinical severity score, ear thickness, transepidermal water loss (TEWL), total serum Immunoglobulin E (IgE) level, mRNA expression levels and immunohistochemistry analysis of IFN-γ, IL-4, and TSLP in cutaneous lesions. RESULTS: TEWL, serum IgE level, and expression of immunohistopathologic markers were more improved in the group using KRG combined with probiotics than in the group using KRG or probiotics alone. ATP, KRG + ATP, and KRG + BYO groups showed reduced TEWL increase (ΔTEWL) at 48 h (p < 0.005). KRG + ATP showed a preventive effect on the increase of serum IgE level (p = 0.009). In immunohistopathologic analysis, KRG, ATP, BYO, KRG + ATP, and KRG + BYO groups showed significantly reduced expression levels of IFN-γ at 1 h, 6 h, and 48 h (all p < 0.05). KRG, ATP, BYO, and KRG + BYO groups showed reduced expression levels of IL-4 compared to the AD control group at 6 h and 24 h. KRG, ATP, BYO, KRG + ATP, and KRG + BYP groups showed significantly lower expression levels of TSLP than the AD control group at 1 h and 24 h. CONCLUSION: KRG can suppress increases of allergic and inflammatory cytokines and increase of TEWL. A combination of KRG and probiotics might have better effects than KRG or probiotics alone for preventing an AD flare-up.

Treating the skin with biologics in patients with psoriasis decreases the incidence of psoriatic arthritis.

OBJECTIVES: To compare the incidence of psoriatic arthritis (PsA) in patients with psoriasis (PsO) according to different treatments for their skin: topics/no treatment, conventional disease-modifying antirheumatic drugs (DMARDs) (cDMARDs) or biological DMARDs (bDMARDs). METHODS: Patients with PsO without PsA followed at a university hospital were included in this retrospective cohort study. Patients were classified according to their treatment in topics (topics, phototherapy or no treatment), cDMARDs (methotrexate and cyclosporine) and bDMARDs (tumour necrosis factor inhibitors (TNFi), interleukin 17 inhibitors (IL-17i) and IL-12-23i ((interleukin (IL) 12/IL-23 inhibitor))) groups. Incident cases of PsA were attributed to one treatment if developed during the administration of that treatment. A Cox proportional hazards model was used to evaluate the adjusted risk of PsA development by treatment group. RESULTS: 1719 patients with PsO contributed a total of 14 721 patient/years (py). 1387 (81%) patients were in the topics, 229 (13%) in cDMARDs and 103 (6%) in the bDMARDs group. During follow-up, 239 patients (14%) developed PsA (231 under topics, six under cDMARDs and two under bDMARDs). Global incidence was 1.6 per 100 py. The risk of developing PsA in patients with PsO treated with bDMARDs was significantly lower (incidence rate ratio (IRR)=0.26; 95% CI 0.03 to 0.94; p=0.0111), compared with topics, but not compared with cDMARDs (IRR=0.35; 95% CI 0.035 to 1.96; p=0.1007). Adjusted Cox proportional hazards regression analysis showed that male sex, nail involvement and higher body max index were associated with increased risk of developing PsA, while biologics use was protective (HR: 0.19; 95% CI 0.05 to 0.81). CONCLUSION: Treatment with biologics in patients with PsO reduced the risk of PsA development.

[Diagnosis and treatment for aplastic anemia].

Treatments of aplastic anemia comprise supportive therapy and aplastic anemia-specific therapy to recover from hematopoiesis. Supportive therapy includes transfusion, granulocyte colony-stimulating factor, and iron chelation therapy in addition to symptomatic treatment. Aplastic anemia-specific treatments that aim to achieve hematopoietic recovery are immunosuppressive therapy, thrombopoietin receptor agonist (TPO-RA) treatment, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although the transplantation achieves complete recovery of hematopoiesis (healing), there is a risk of death from transplant-related complications. The most effective drug therapy is the combination of TPO-RA and the immunotherapy combined with anti-thymocyte globulin and cyclosporine. This treatment is also effective against secondary, drug-induced, or hepatitis-associated aplastic anemia. In the treatment of aplastic anemia, the treatment choice is made based on the disease severity and patient ages.