高甲基化SIM2基因在子痫前期诊断和严重程度及妊娠结局评估中的价值

目的探讨高甲基化SIM2基因在子痫前期诊断和严重程度及妊娠结局评估中的价值。方法选取2016年7月至2018年7月天门市妇幼保健院和荆州市中心医院诊治的168例子痫前期孕妇、74例正常妊娠孕妇和30例健康未妊娠女性作为研究对象。并将其分别设为子痫前期组、正常妊娠组和未妊娠对照组。采用实时荧光定量PCR检测三组成员高甲基化SIM2基因含量。结果子痫前期组孕妇高甲基化SIM2阳性检出率明显高于正常妊娠组孕妇,其中重度子痫前期和晚发型子痫前期孕妇高甲基化SIM2阳性检出率分别高于轻度子痫前期和早发型子痫前期孕妇,其差异均具有统计学意义(均P<0.05)。治疗后不同严重程度和临床分期子痫前期组孕妇高甲基化SIM2基因水平与治疗前比较明显降低;治疗前后重度子痫前期和晚发型子痫前期孕妇高甲基化SIM2基因水平分别高于轻度子痫前期和早发型子痫前期孕妇,其差异均具有统计学意义(均P<0.05)。早产儿孕妇和低出生体重儿孕妇高甲基化SIM2基因相对表达水平明显高于非早产儿孕妇和非低出生体重儿孕妇,其差异均具有统计学意义(均P<0.05)。经Logistic回归分析得知,重度子痫前期、晚发型子痫前期和高甲基化SIM2基因含量是导致子痫前期妊娠不良结局的关键危险因素(P<0.05)。结论高甲基化SIM2基因在子痫前期组孕妇外周血浆中含量明显高于正常妊娠组孕妇,且与临床分期、严重程度和妊娠不良结局呈明显正相关,有望成为子痫前期临床诊疗的有效评估指标。     

妊娠期脂代谢异常与子痫前期发生的相关性研究

目的分析妊娠期脂代谢异常与子痫前期发生的关系。方法回顾性选取2019年1月至2020年1月于新疆医科大学第一附属医院产检并分娩的53例子痫前期产妇作为观察组,并选取同期医院产检并分娩的53例正常产妇作为对照组。记录两组产妇妊娠早、中、晚期的脂代谢指标,分析其与子痫前期发生的关系。结果两组早、中、晚期的甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平比较,差异具有统计学意义(P<0.001);进一步两两比较发现,两组晚期TG、HDL-C、LDL-C分别与两组早期及中期比较,差异具有统计学意义(P<0.001),两组中期TC与观察组早期及对照组晚期比较,差异具有统计学意义(P<0.001),但观察组中期与晚期TC及对照组早期与中期TC比较,差异无统计学意义(P>0.05)。经Logistic回归分析结果显示,不同妊娠期脂代谢水平与子痫前期的发生有关,妊娠早、中、晚期TG、TC、LDL-C升高及HDL-C降低可能是子痫前期发生的风险因子(P<0.05);绘制受试者工作特征(ROC)曲线结果显示,妊娠早、中...     

Systemtherapie der Vitiligo

Systemic drug treatment of vitiligo is currently limited to predominantly adjuvant measures for increasing the effectiveness of UV light therapy. We here present new approaches for the systemic treatment of vitiligo currently under clinical investigation. These include the α?MSH-analogue afamelatonide and oral immunosuppressants such as the Janus kinase (JAK) inhibitors which target interferon-α-dependent autotoxic inflammatory reactions. In 2015 the first publications on the successful systemic use of Janus kinase (JAK) inhibitors in vitiligo appeared. The effectiveness was experimentally supported by animal models of vitiligo and by the characterization of new biomarkers in the serum of vitiligo patients. This may significantly expand the range of treatment options for vitiligo. Topical antiinflammatory and UV therapies are still the main components of vitiligo treatment, often in combination. The main outcome parameters include the extent and duration of repigmentation, cessation of spreading, avoidance of side effects and improvement in the quality of life of patients.     

Preeclampsia and eclampsia: Etiopathogenesis and perioperative management

Preeclampsia is a pregnancy specific syndrome of elusive etiology, developing in 2nd trimester and associated with high maternal and perinatal morbidity and mortality. The spectrum ranges from mild preeclampsia with no systemic involvement to multi-system involvement. The course is unpredictable and delivery is the only curative treatment. Elevated blood pressure( 160/110 mm Hg) should be reduced gradually to a safe level(140/90) using antihypertensive drugs. Prophylaxis and treatment of convulsions using Mg SO4 is indicated for severe preeclampsia. Fluid therapy is controversial due to potential delicate balance between constricted plasma volume and risk of fluid overload and pulmonary oedema secondary to increased capillary permeability and reduced colloid osmotic pressure. Single shot spinal anaesthesia is the technique of choice for caesarean delivery unless contraindicated. General anaesthesia is indicated in patients with coagulopathy or eclampsia but is associated with risk of difficult airway and exaggerated sympathetic response during laryngoscopy. Epidural analgesia and anaesthesia is safe in absence of coagulopathy.     

Patient‐reported outcomes (PROs) in chronic urticaria

Chronic urticaria is an itching skin disease which persists for more than 6 weeks. Chronic urticaria has great impact on the daily life of the patient, and the fluctuating nature of the symptoms complicates the monitoring and treatment of the disease. Currently, there are no reliable biomarkers to identify and measure disease activity in chronic spontaneous urticaria. Consequently, use of patient‐reported outcomes (PROs) is crucial when evaluating and monitoring different aspects of chronic urticaria such as disease activity/severity, disease control, and quality of life. We present an overview of seven different PROs used in chronic urticaria and highlight their strengths, limitations, and use in clinical practice and research.     

Iranian guideline for rituximab therapy in pemphigus patients

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and/or mucosa. Rituximab (RTX) has been approved recently by US FDA as an effective and safe treatment of PV. The high incidence of PV in Iran encouraged our team to prepare a consensus guideline for RTX administration based on literature review and a decade experience of an expert panel. RTX is recommended for the treatment of new cases of PV as well as patients not responding to conventional therapy. Contraindications include history of anaphylaxis or IgE‐mediated hypersensitivity to murine proteins of RTX, severe active infections, pregnancy, breastfeeding, severe heart failure, and arrhythmia. Prophylactic antiviral therapy is recommended in patients at risk of reactivation of HBV and isoniazid for those at risk of reactivation of tuberculosis. Concomitant use of systemic corticosteroids is recommended as a rule. Except for methotrexate, the combination with other immunosuppressive drugs is discouraged. Intravenous immunoglobulin is recommended for those at risk of infections or with extensive disease. The recommended dosage of RTX for the first cycle is 2 g either 500 mg weekly or 1 g biweekly. There is no general consensus whether the next doses of RTX be administered upon relapse or as maintenance therapy. We strongly recommend RTX sooner in the course of pemphigus.     

Leprosy treatment during pregnancy and breastfeeding: A case report and brief review of literature

Leprosy is a chronic disease which primarily affects the skin, mucous membranes and peripheral nerves due to Mycobacterium leprae. It is now infrequent in Europe and is rarely reported during pregnancy. Leprosy can be exacerbated during pregnancy, and without treatment it can permanently damage the skin, nerves, limbs and eyes. Therefore, it is important to treat leprosy during pregnancy. This article describes a patient with multibacillary lepromatous leprosy who was treated with multidrug therapy during pregnancy and breastfeeding. The patient delivered a healthy baby girl without perinatal complications, and the infant's growth and development were normal during the 1‐year follow‐up period. Multidrug therapy consisting of dapsone, rifampicine, and clofazimine is highly effective for people with leprosy and considered safe, both for the mother and the child. Antileprosy drugs are excreted into human milk but there is no report of adverse effects except for skin discoloration of the infant due to clofazimine. Multidrug therapy for leprosy patients should be continued unchanged during pregnancy and breastfeeding.     

Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate‐to‐severe psoriasis undergoing anti‐tumor necrosis factor‐α therapy

Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate‐to‐severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti‐tumor necrosis factor (TNF)‐α therapy in these patients. This was a prospective study on a series of consecutive non‐diabetic patients with moderate‐to‐severe psoriasis who completed 6 months of therapy with anti‐TNF‐α‐adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m² or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty‐nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6‐month BSA change compared with baseline results. In patients with moderate‐to‐severe psoriasis, ADMA levels correlate with clinical markers of disease severity.     

Manifestation of Crohn's disease in a young woman during the course of treatment for severe form of chronic plaque psoriasis with etanercept

With the growing number of patients with immune‐modulated diseases treated with tumor necrosis factor (TNF) alpha inhibitors, we are more frequently encountering the occurrence of so‐called paradoxical drug reactions. These are basically situations where during the course of the treatment of one disease, the manifestation of another with similar etiopathogenesis occurs, although under normal conditions this newly developed disease responds well to treatment with TNF alpha inhibitors and is indicated for this treatment. Skin reactions are most frequently recorded in the form of induced psoriasis and psoriasiform exanthems. A less common paradoxical reaction is the induction of Crohn's disease, which is most often described in association with the treatment of inflammatory joint diseases with etanercept. We present a case of induction of Crohn's disease during therapy with etanercept, where the primary disease being treated was psoriasis. In the literature, similar cases have only been described sporadically.     

Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema

Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized.     

Biomarkers of psoriasis severity and therapy monitoring

Psoriasis is a chronic, recurrent inflammatory cutaneous disease. Psoriasis patients alternate between periods of remission and periods of exacerbation of the disease. Usually, psoriasis severity is clinically evaluated using tools like Psoriasis Area and Severity Index that present some limitations and subjectivity. Clinicians select the therapy according to psoriasis severity, aiming that patients achieve longer remission periods and improve their quality of life. Biological markers for diagnosis and prognosis of psoriasis help to establish its severity and to monitor the therapeutic response; moreover, biomarkers of psoriasis assist clinicians in their therapeutic decision to treat psoriasis and to choose earlier and more adequate therapeutic strategies, avoiding or minimising worsening of psoriasis. With these markers, they would be able to monitor therapeutics, avoiding unnecessary therapeutic surcharge or changes to a more aggressive therapy. As any attempt to identify these biomarkers should be encouraged, in this review, we will debate published data concerning the proposal of biomarkers to evaluate severity and response to treatment of psoriasis vulgaris.     

Practical compendium for psoriasis management

Psoriasis management is complex and challenging. It should be tailored for each patient. Treatment strategy differs according to patient's age, sex, disease type, disease severity, burden on patient's quality of life, comorbidities, involvement of specific sites, and pregnancy. The choice of the appropriate therapeutic must take into consideration the availability, the price, and the patient's preferences. It is very important that the chosen treatment is not more unpleasant, intolerable, or dangerous than the disease itself. According to the disease type, severity, and effect on patient's quality of life, dermatologist chooses whether to start with topical therapy, phototherapy or systemic therapy, or a combination of two or more of them. Under each category, there are different types of therapies that can be the first line therapeutics, second line, or even contraindicated. In this compendium, we provide dermatologists with different treatment plans considering all the mentioned variables so that a dermatologist can choose the optimum plan for the patient.     

Management of severe epidermolysis bullosa by haematopoietic transplant: principles,perspectives and pitfalls

People with severe forms of epidermolysis bullosa (EB) develop widespread blistering and progressively debilitating multisystem complications that may result in a shortened lifespan. As some wounds in EB individuals are difficult or impossible to access with topical therapy, we examined the potential of systemic therapy with normal haematopoietic stem cells. In both animal models and children with EB, healthy donor cells from the haematopoietic graft migrated to the injured skin; simultaneously, there was an increase in the production of skin‐specific structural proteins deficient in EB, increased skin integrity and reduced tendency to blister formation. Even though the majority of evaluable individuals have had a positive response in skin healing, frequently changing their quality of life, the improvement in lifestyle has been varied and the overall clinical response incomplete. To change the current amelioration of disease into a full cure, we propose to (i) increase safety as well as efficacy of haematopoietic cell transplant (HCT) using co‐infusion of mesenchymal stromal/stem cells with haematopoietic stem cells and non‐myeloablative conditioning for transplant; (ii) optimize homing of donor cells into the skin erosions in animal models of EB; and (iii) discover and test new drugs for EB therapy using patient‐specific induced pluripotent stem cells. We conclude that although HCT has always been a risky treatment restricted to those with serious life‐threatening or debilitating diseases, by most benchmarks, the results of HCT in EB have shown that HCT has the potential of being a durable, systemic therapy for people with severe forms of EB.     

Psoriasis: evolution of pathogenic concepts and new therapies through phases of translational research

Psoriasis is perhaps unique for a disease studied through translational science in that there is not an accepted animal model, yet many rounds of bidirectional translation have taken place that have helped to define disease pathogenesis and to advance therapy. In this review, we illustrate the evolution of new pathogenic concepts and the testing of new therapeutic agents through translational research in humans. We present a current view of disease pathogenesis that stems from research in patients and animal models, but with the perspectives (i) that disease models can advance or hinder the overall translational enterprise and (ii) that the research process must be firmly grounded in the pathophysiology of the actual human condition.     

Sodium thiosulfate in the treatment of non‐uremic calciphylaxis

Calciphylaxis is a metastatic calcification‐induced vasculopathy that results in the occlusion of small blood vessels. Although calciphylaxis is normally associated with end‐stage renal disease, calciphylaxis from non‐uremic origin occurs as well. While the number of reports continues to increase, a standard treatment for non‐uremic calciphylaxis has yet to be established. Sodium thiosulfate (STS), which has been proven to be effective in the treatment of uremic calciphylaxis, shows promise; however, reports of its use in non‐uremic cases are limited. We describe a case of non‐uremic calciphylaxis in a patient with normal renal and parathyroid function who had complete resolution of disease after treatment with STS, and we review similar cases in the published work. Based on the successful outcomes detailed in this case series, STS appears to be an effective therapy for non‐uremic calciphylaxis.     

Psoriasis and the pregnant woman: what are the key considerations?

Pregnancy is characterized by multiple physiologic changes. During the entire gestational period, both mother and infant are vulnerable to a variety of external and internal factors. Maternal disease, use of certain medications, drugs, alcohol, smoking, and radiation exposure can have devastating effects on the fetus. Pregnancy-related complications in women with psoriasis can be caused by both the disease and the treatment. The response of the maternal placenta to psoriasis-induced inflammation and comorbid conditions, such as obesity, hypertension, and depression, may also influence the pregnancy. Herein, we review the relationship between psoriasis and undesirable pregnancy outcomes.     

Biomarkers of psoriasis severity and therapy monitoringSusa

Psoriasis is a chronic, recurrent inflammatory cutaneous disease. Psoriasis patients alternate between periods of remission and periods of exacerbation of the disease. Usually, psoriasis severity is clinically evaluated using tools like Psoriasis Area and Severity Index that present some limitations and subjectivity. Clinicians select the therapy according to psoriasis severity, aiming that patients achieve longer remission periods and improve their quality of life. Biological markers for diagnosis and prognosis of psoriasis help to establish its severity and to monitor the therapeutic response; moreover, biomarkers of psoriasis assist clinicians in their therapeutic decision to treat psoriasis and to choose earlier and more adequate therapeutic strategies, avoiding or minimising worsening of psoriasis. With these markers, they would be able to monitor therapeutics, avoiding unnecessary therapeutic surcharge or changes to a more aggressive therapy. As any attempt to identify these biomarkers should be encouraged, in this review,we will debate published data concerning the proposal of biomarkers to evaluate severity and response to treatment of psoriasis vulgaris.     

Exposure to biological therapies during conception and pregnancy: a systematic review

Biologic therapies are effective treatments for psoriasis and are often used in women of childbearing age. Regulatory authorities state that there are no adequate studies to evaluate the safety of biologics at conception or during pregnancy and therefore advise against their use at these times. However, in practice these situations are challenging given the clinical need to treat on‐going psoriasis. To evaluate the safety of biologic therapy in conception and/or pregnancy, the authors of this study, from the U.K., performed a systematic review of studies of women exposed to biologic therapy for the treatment of psoriasis during conception and/or pregnancy. The authors identified four studies involving 1300 women exposed to biologics (called TNFi) 3 months prior to or during the first 3 months of pregnancy. These studies showed a trend towards drug‐specific harm with TNFi exposure in women with different inflammatory diseases (i.e. not just psoriasis), with an increased risk of congenital malformations in three of the studies, and pre‐term birth in one of the studies. However, the risk was low and there is uncertainty about the causal role of TNFi. The authors conclude that the potential effect of biologics on pregnancy outcomes specifically in women with psoriasis has not been adequately studied to quantify accurately. Data on use of biologics in other diseases is limited. Women of childbearing potential should be routinely advised to use regular contraception, however, when planning conception the risk and benefits of continuing versus stopping therapy should be discussed case‐by‐case. A large study is required, taking into account other factors that may influence pregnancy such as disease activity, other therapies and maternal demographics.     

Outcomes of pregnancies among women and partners of men with a history of exposure to methoxsalen photochemotherapy (PUVA) for the treatment of psoriasis

Because oral methoxsalen and UV-A radiation (PUVA) therapy is mutagenic, concern exists about the potential for teratogenic effects resulting from the use of this therapy at the time of conception and during pregnancy. After 12.8 years of prospective study, we documented the pregnancy outcomes among 1380 patients (892 men and 488 women) who received PUVA treatments. Ninety-four men reported 167 pregnancies in their partners, and 93 women reported 159 pregnancies. For 34% of pregnancies among partners of male patients, the man received PUVA therapy near the time of conception. Nineteen percent of female patients reported exposure to PUVA at the time of conception or during pregnancy. Induced and spontaneous abortions were reported as the outcome of pregnancy more often by female than by male patients (12% vs 30%). Two congenital malformations and two stillbirths occurred, an incidence not significantly different from that expected for the general population. Although the power of our study to detect an increase in the risk of specific defects is limited, our data show no evidence to suggest that PUVA is a potent teratogen. Still, because PUVA is mutagenic, we believe it prudent for patients to avoid PUVA treatment during pregnancy whenever practical.     

Translational drug discovery and development with the use of tissue-relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy

Due to the clinical development of drugs such as secukinumab, ustekinumab and dupilumab, major changes have been achieved in the treatment of patients diagnosed with psoriasis and atopic dermatitis. In academia and the pharmaceutical industry, research is increasingly moving towards the development of bispecific antibodies and multi-specific nanobodies, as there is a compelling need for new treatment modalities for patients suffering from autoimmune or malignant disease. The purpose of this review is to discuss aspects of translational drug development with a particular emphasis on indications such as psoriasis and atopic dermatitis. The identification of biomarkers, the assessment of target organ pharmacokinetic and pharmacodynamics interactions and a wide range of in vitro, ex vivo and in vivo models should contribute to an appropriate prediction of a biological effect in the clinical setting. As human biology may not be perfectly reflected by approaches such as skin equivalents or animal models, novel approaches such as the use of human skin and dermal microperfusion assays in healthy volunteers and patients appear both reasonable and mandatory. These models may indeed generate highly translationally relevant data that have the potential to reduce the failure rate of drugs currently undergoing clinical development.