Current problems in dermatology最新文献

{"title":"Clinical Trial and Registry Data.","authors":"Melinda Gooderham,&nbsp;Kim Papp","doi":"10.1159/000478074","DOIUrl":"https://doi.org/10.1159/000478074","url":null,"abstract":"<p><p>Physicians rely on safety and efficacy data from pivotal trials to guide treatment decisions and manage patients. Even with robust clinical trial data, there remain questions regarding rare safety events and generalizability. Registries complement clinical trials. By evaluating effectiveness and safety in broad patient populations and often providing longer term or larger numbers of patients or both compared to clinical trials, registries consolidate and may extend the safety observations derived from pivotal trials. Our review of phase 3 clinical trial data, long-term extension studies and biologics registries shows biologics to be a safe option for short- and long-term use. Tumor necrosis factor (TNF)-, interleukin (IL)-12/23- and IL-17-antagonists yield similar safety profiles regarding infections, malignancy and major adverse cardiovascular events. The known risk of tuberculosis activation with TNF agonists appears to be readily handled by screening. Mild to moderate candida infections and potential exacerbation or de novo onset of inflammatory bowel disease are associated with IL-17 blockade.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"53 ","pages":"15-27"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000478074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35547057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipids in the Skin and pH.","authors":"Johannes Wohlrab,&nbsp;Alexandra Gebert,&nbsp;Reinhard H H Neubert","doi":"10.1159/000489519","DOIUrl":"https://doi.org/10.1159/000489519","url":null,"abstract":"<p><p>The pH value is identified as an essential determinant for the lipid synthesis in the stratum corneum (SC). The activity of the enzymes that catalyse the transformation of lipid precursors into ceramides, free fatty acids or cholesterol highly depends on pH value. Additionally, there are substantial indications for pH conditions to have a direct effect on the molecular structure of the membranes and their properties. Knowledge about the sigmoidal pH gradient within the corneal layer also provides understanding of the pathological processes in a dysfunctional barrier. Shifting the pH environment from acidic into alkaline does not only inhibit the regenerating metabolic pathways but also activates enzymes that accelerate desquamation of the SC.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"54 ","pages":"64-70"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000489519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36414903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relation of pH and Skin Cleansing.","authors":"Jürgen Blaak,&nbsp;Peter Staib","doi":"10.1159/000489527","DOIUrl":"https://doi.org/10.1159/000489527","url":null,"abstract":"<p><p>Several epidermal barrier functions, like skin barrier regeneration and antimicrobial response, are related to the acidic nature of the skin surface pH (ss-pH). However, the epidermal acidification is known to be fragile and it is commonly accepted that cosmetic products, especially soaps and skin cleansing products, can induce significant changes in ss-pH. As a consequence, epidermal barrier function and skin microflora are affected negatively. ss-pH even increases after a single washing procedure or after rinsing the skin with water alone. The skin pH recovery needs time up to several hours before it can reach the physiological level. For cosmetic-relevant skin conditions, skin disorders and specific consumer groups, maintaining of the acidic ss-pH is beneficial for epidermal physiology and cutaneous microflora. In this context, cleansing and skin care products with a pH level of 4.0-5.0 may be helpful. In addition, combining the acidic product pH level with the ideal mix of surfactants, thereby enhancing product compatibility and minimizing skin irritation and intolerance, is a major challenge for the future. Beyond innovative cleansing technology, further multifaceted cosmetic research is a prerequisite to get deeper knowledge on the interrelation of product pH level, surfactant composition and corneobiology.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"54 ","pages":"132-142"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000489527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36417817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Acid Mantle: A Myth or an Essential Part of Skin Health?","authors":"Christian Surber,&nbsp;Philippe Humbert,&nbsp;Christoph Abels,&nbsp;Howard Maibach","doi":"10.1159/000489512","DOIUrl":"https://doi.org/10.1159/000489512","url":null,"abstract":"<p><p>Ninety years ago - in 1928, the term acid mantle was coined by the physicians Heinrich Schade and Alfred Marchionini in Kiel, Germany. A decade later Marchionini and several coworkers published 5 scientific communications in the Klinische Wochenschrift on \"Der Säuremantel der Haut und Bakterienabwehr\" (acid mantle and defense against bacteria). They described experimental detail, documented age- and body site as well as skin disease-dependent skin pH shifts, and discussed the significance of the pH and bacterial growth on the skin. In their fourth and fifth communication, they made the first connection between the altered quantitative and qualitative bacterial growth in pathologically modified skin and the shifted skin pH and attributed it partly to the gap in the acid mantle (pathologische Lücke des Säuremantels). They also investigated the pH of several topical dermatologic preparations and concluded that their benefit can at least partly be attributed to their acid character and recommended the systematic investigation of acid treatments in dermatology. At that time, the physiologic role of the acid skin surface was thought to be a protective mechanism against invading organisms. Hence, it seemed reasonable to allocate protection to an easy and conceivable term such as \"mantle.\" Today, \"acid mantle\" as a term is still a very suitable metaphor to illustrate the protective quality of the \"acid\" in the skin and the term has become part of colloquial speech. In the meantime, our understanding of the skin pH has broadened, and we know that the acid character and its gradual change within the skin also help to orchestrate epidermal differentiation and corneocyte shedding. For many more biochemical processes within the skin, the compartmental pH is crucial, for example, in pigmentation, ion homeostasis, epidermal (stem) cell behavior, and so on. The often existing difference between the H+ concentration of extra- and intracellular as well as subcellular compartments establishes an ionic, electric, and/or osmotic driving force; hence, H+ concentration per se acts as an extra-, intra,- and subcellular signaling modality affecting and controlling many cellular functions. One may even consider pH a universal signal and effector. It is therefore also no surprise that skin pH shifts have been observed in various skin pathologies. More recently, in carefully controlled trials (acne, atopic dermatitis, incontinence-associated dermatitis, aged skin), the benefits of targeted skin acidification have become evident and the use of topical preparations with reduced pH may be recommended. The currently prevailing formulation concepts for direct acidification are based on a reduced pH of the hydrophilic product phase in combination with a buffer with a sufficiently high buffering capacity within the vehicle.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"54 ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000489512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36412674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse Reactions of Antibody-Therapy for Primary Cutaneous Lymphomas: Rituximab, Brentuximab Vedotin, Alemtuzumab, and Mogamulizumab.","authors":"I Saulite,&nbsp;E Guenova,&nbsp;W Hoetzenecker","doi":"10.1159/000478079","DOIUrl":"https://doi.org/10.1159/000478079","url":null,"abstract":"<p><p>Treatment of advanced PCLs is limited and rarely reaches complete remission despite aggressive treatment modalities, such as polychemotherapy with various adverse effects. However, several monoclonal antibodies drug agents in patients with advanced primary cutaneous lymphomas demonstrate promising efficacy and manageable safety profiles. The monoclonal antibodies drug agents have favourable tolerability compared with multi-agent cytotoxic chemotherapy. However, adverse effects manifest with a broad clinical spectrum, hence the markers of targeted therapies are not limited to tumour cells but found on tumour cells and also on benign T and/or B cells. Moreover, the safety profile and direct causal association of drug and adverse effects should be interpreted with caution because many of the patients in clinical studies have received multiple treatments. Here, we focus on the safety profile of mAbs therapies that have recently been approved or are currently under preclinical or clinical investigation for CBCLs (rituximab) and CTCLs (brentuximab, mogamulizumab, and alemtuzumab). Further studies to define clinical safety profile in the patient cohort with cutaneous lymphomas are needed.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"53 ","pages":"70-81"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000478079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35547009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH in Atopic Dermatitis.","authors":"Simon G Danby,&nbsp;Michael J Cork","doi":"10.1159/000489523","DOIUrl":"https://doi.org/10.1159/000489523","url":null,"abstract":"<p><p>Atopic dermatitis (synonym atopic eczema, AD) is a chronic inflammatory skin disorder essentially characterised by a red \"itchy\" skin rash. The condition is prevalent around the world, affecting 15-30% of children and 2-10% of adults [Odhiambo et al.: J Allergy Clin Immunol 2009;124:1251-1258.e23]. The pathophysiological mechanisms underpinning AD are complex, broadly involving skin barrier dysfunction, an altered immune response (affecting both the adaptive and innate immune systems) and an unfavourable environment (external stressors) [Werfel et al.: J Allergy Clin Immunol 2016;138:336-349]. Intriguingly at the centre of this maelstrom of events, linking them together, is a very basic skin property - skin pH. Skin pH is a central regulator of skin barrier homeostasis and an important innate defence mechanism. Moreover, recent evidence suggests that elevated pH can also drive altered immune responses placing it squarely in the centre of AD pathogenesis, but just how important is skin pH to the development of AD? In this chapter, the current evidence entangling skin pH in AD pathogenesis is reviewed.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"54 ","pages":"95-107"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000489523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36417879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse Reactions to Biologics in Psoriasis.","authors":"Stephen J Lockwood,&nbsp;Lisette M Prens,&nbsp;Alexa B Kimball","doi":"10.1159/000478072","DOIUrl":"https://doi.org/10.1159/000478072","url":null,"abstract":"<p><p>Psoriasis is a chronic autoimmune disease which affects millions of people worldwide. Not only can psoriasis itself be debilitating and significantly reduce an individual's quality of life, but it is also a risk factor for other systemic disorders, such as metabolic syndrome, cardiovascular disease, and malignancy. Tremendous strides were made in the treatment of psoriasis during the mid-to-late-20th century, including the emergence of topical corticosteroids and vitamin D analogs, methotrexate, systemic retinoids, and phototherapy. However, it was not until 2004 with the advent of systemic biologic agents, which precisely target components of the immune system involved in the pathophysiological process of psoriasis, that the primary treatment benchmark increased from 50% improvement in the Psoriasis Area and Severity Index (PASI 50) to PASI 75, PASI 90, and even PASI 100, or complete resolution of cutaneous disease. Today, many patients receiving biologic therapy routinely experience greater than 75% or 90% reduction in cutaneous disease burden and a significant improvement in overall quality of life. These biologic agents are generally well-tolerated and safe but, like any medication, have associated adverse effects, some of which are predictable based on the effects of immune modulation, animal model studies, and human populations with known cytokine deficiencies. Going forward, it will be important to carefully monitor the safety profiles of these agents in both clinical trials and post-marketing surveillance registries to ensure long-term safety. It is reassuring that large safety registries are consistent in demonstrating an improved safety profile with newer and emerging biologic therapies.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"53 ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000478072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35547056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH and Microbial Infections.","authors":"Frank Rippke,&nbsp;Enzo Berardesca,&nbsp;Teresa M Weber","doi":"10.1159/000489522","DOIUrl":"https://doi.org/10.1159/000489522","url":null,"abstract":"<p><p>Maintenance of an acidic stratum corneum pH is a major component of the skin's protective system and creates a hostile environment for colonization with pathogenic microorganisms. This barrier can however be overcome on healthy and in particular on compromised skin. Mycosis, diaper/incontinence dermatitis and wound healing are examples of cases where microbial infection is promoted by the altered skin conditions or environment. Fungi have a complex system that senses ambient pH that leads to metabolic responses allowing adhesion, growth and invasion, as microbial metabolites further increase skin pH resulting in a clinically manifest infection (mycosis). Diabetic patients with a higher pH in intertriginous areas are particularly vulnerable to candidiasis. In diaper and incontinence dermatitis, the increase in skin pH and damage to the skin barrier function is triggered by the contact with urine and faeces with or without occlusion and maintained by host and microbial enzymes and metabolites. This leads to the reduction of the protective resident microflora and fungal overgrowth, mostly with Candida albicans. Skin care with slightly acidic products may help to prevent and treat this kind of dermatitis. Wound healing is a complex sequence of biologic events correlated with ambient pH, which influences the different phases of the healing process. The pH determines the appropriate activity of immune cells and key enzymes as well as biofilm formation. Chronic wounds emerging from the disruption of the healing process are characterized by a neutral to slightly alkaline pH and may benefit from wound pH monitoring and therapeutic acidification.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"54 ","pages":"87-94"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000489522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36417878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Buffering Capacity.","authors":"Ehrhardt Proksch","doi":"10.1159/000489513","DOIUrl":"https://doi.org/10.1159/000489513","url":null,"abstract":"<p><p>Each biological system possesses a widely unrecognized buffer system to maintain acid-base balance to a specific pH. Our lives are dependent on the functioning of buffer systems. A buffer system is a solution that resists a change in pH when acids or bases are added. The skin possesses a fairly high buffer capacity, which is determined by the amount of H+ or OH- ions that is needed until the pH value of a solution changes by the unit 1. Buffers contain a weak or medium strong acid (base) and the corresponding salt. Buffers that show a pKa in the range of the Stratum corneum surface pH are most important for the skin. Buffer capacity is reduced both in baby skin and in aged skin. External factors, water, and detergent may reduce the local buffer capacity because of the elution of buffer chemicals leading to increased pH and irritative contact dermatitis. Inflammatory diseases, including atopic dermatitis, psoriasis, and acne vulgaris, which show an increased pH should probably also have reduced buffer capacities. For the treatment of the skin diseases and in aged skin, emollient with a pH that is slightly more acidic than the average normal pH and an appropriate buffer capacity should be preferably used.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"54 ","pages":"11-18"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000489513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36414899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH and Acne.","authors":"Nanna Schürer","doi":"10.1159/000489525","DOIUrl":"https://doi.org/10.1159/000489525","url":null,"abstract":"<p><p>Acne is based on a complex, multifactorial pathophysiology beginning with a microcomedo. Comedogenesis involves follicular hyperproliferation and disturbed keratinization, hyperseborrhea and hyperplasia of sebaceous glands as well as disturbances in skin microbiome. Acne is treated with antibiotics, retinoids, keratolytics, hormonal and anti-inflammatory agents. Efficacy and side effects of given medications are well known. The uppermost layer of the stratum corneum is acidic. The low pH provides protection by slowing down the growth of some bacteria. Increase of skin surface pH leads to impaired barrier function, disturbances in skin microbiome and inflammation. Acne-predisposed skin is in a constant state of subclinical inflammation. Subclinical inflammation may be linked to changes in skin surface pH and disturbances of the stratum corneum, allowing microorganisms to stimulate the production of pro-inflammatory cytokines. Here, based on the current literature, the possible link between the skin surface pH, epidermal barrier function and acne is reviewed.</p>","PeriodicalId":11010,"journal":{"name":"Current problems in dermatology","volume":"54 ","pages":"115-122"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000489525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36417815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}