Current problems in dermatology最新文献

The industry offers a vast armamentarium of skin care products (SCP) to cleanse the skin; to reduce/eliminate unpleasant skin symptoms; to restore, reinforce, fortify and protect undamaged, vulnerable or damaged skin; and to provide a pleasant skin and body feel. Skin care products are readily available and their promotions with a variety of tall claims are omnipresent. This text discusses the various interpretations of skin care, the diversity of its comprehensions and the various groups of receivers and their needs for skin care. Skin care is part of our daily routines, the information on the effects of SCP is omnipresent and the purchase of SCP seems straightforward. However, the true essence of SCP remains concealed to many. This is mainly due to that fact that the "physico-chemical anatomy," the nomenclature and the regulatory classification of SCP as well as the role and the significance of active and inactive ingredients within these products are not well understood. This text addresses the different views, interpretations and comprehensions. The final part highlights the current challenges with SCP and gives an outlook on how to improve our mutual understanding of SCP.

With increasing use of immunotherapies such as anti-cytotoxic T cell lymphocyte antigen-4 and anti-programmed cell death 1 antibodies, various skin toxicities have emerged. Severity of skin toxicities varies from mild lichenoid reaction to severe toxic epidermal necrolysis. Appropriate diagnosis and management of these skin toxicities are essential for optimal patient care and to avoid unnecessary cessation of anti-cancer therapies. This review summarises a wide range of cutaneous manifestations associated with immunotherapy usage in patients with metastatic melanoma.

The management of oncology patients has changed significantly over recent years, with the development of new targeted anticancer therapies. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents; their intensity can be dose-limiting or lead to the discontinuation of therapy. Tyrosine kinase inhibitors can cause maculopapular rash and hand-foot reaction, whereas papulopustular rash, paronychia, regulatory changes in hair, and dryness are caused by epidermal growth factor receptor inhibitors. SMO inhibitors, vismodegib and sonidegib, may result in muscle spasms and alopecia.

Paradoxical reactions during treatment with a biologic agent can be defined as the appearance or exacerbation of a pathological condition that usually responds to this class of drug while treating a patient for another condition, which usually remains under control (even though there may be a change in morphology or phenotype). Paradoxical reactions were initially described as isolated case reports or case series in patients treated with anti-tumor necrosis factor (TNF) α agents, first in inflammatory rheumatic diseases, later in psoriasis and inflammatory bowel disease. Paradoxical reactions have subsequently been reported with other biological drugs or classes (e.g., tocilizumab), even though in some cases insufficient efficacy or phenotype switch may be difficult to differentiate from true paradoxical reactions. This chapter will deal with the most frequently reported variants of paradoxical reactions: palmoplantar pustular and psoriasiform reactions, psoriatic arthritis, hidradenitis, inflammatory bowel disease, uveitis, pyoderma gangrenosum, granulomatous reactions, and vasculitis. The underlying pathomechanism in these complex diseases with involvement of multiple immunological pathways is most likely a cytokine imbalance, and substitution of the anti-TNFα agent by an alternative anti-p40 or anti-IL-17A biologic may be extremely helpful. Paradoxical reactions can cause serious handicap, and early recognition and treatment of these drug class effects is of paramount importance, especially when the primary disease is relatively devoid of therapeutic alternatives and its reactivation may have catastrophic consequences. Close surveillance of patients treated with newly available biologic drugs is necessary to detect and describe new paradoxical reactions.

Skin barrier repair therapies often involve the use of medicated and non-medicated topical preparations. To measure the effect of topical preparations, clinical (scoring systems, for example, Score of Atopic Dermatitis, Dermatology Quality of Life Index) and biophysical procedures (e.g., trans-epidermal water loss, skin hydration) are widely used. However, the results of these procedures describe the condition of the barrier indirectly. A direct assessment of skin barrier integrity is primarily possible by electron-microscopic examination, visualization and morphometric analysis of the lipid lamellae in the intercellular space of the stratum corneum (SC) and by quantitatively characterizing the composition of key SC lipids. Recently, the combination of a non-invasive lipid barrier visualization (Lipbarvis®) technique (SC sampling and morphometric analysis) and SC lipid composition analysis (chromatographic analysis) has been proposed to directly characterize the skin barrier integrity. Initial experience demonstrates that morphometric analysis of the lipid lamellae organization in the intercellular space of the SC as well as the characterization of the composition of key SC lipids may serve as surrogate marker to study the influence of topical non-medicated preparations including pH-lowered preparations.

Autoimmune bullous diseases are a heterogeneous group of blistering diseases affecting the skin and/or mucous membrane. Systemic corticosteroids, which are often associated with immunosuppressants, are the main treatment option for these diseases. The 2 main biologics used in the treatment of autoimmune bullous diseases are rituximab, especially in pemphigus and mucous membrane pemphigoid, and omalizumab in bullous pemphigoid. Rituximab is a promising therapeutic option in pemphigus and mucous membrane pemphigoid. Its tolerance is rather good, although rare but potentially severe side effects can occur. Omalizumab has not been robustly evaluated in the treatment of bullous pemphigoid. Some case reports suggest that this drug might be of interest in a few patients with recalcitrant BP and high immunoglobulin E serum levels. Interestingly, this drug is generally well tolerated.

There is increasing use of cytokine inhibitors (including biologics) in the treatment of psoriasis as their efficacy and safety have been demonstrated. Cytokines are important signaling molecules evolved to coordinate a response to infectious threat. In this study, we review available trial, registry and cohort study data pertaining to the immunosuppressive effects of these medications when used to treat psoriasis. The risk of infection associated with these medications is small. Special considerations include the use of these agents in the setting of granulomatous infections, viral hepatitis, human immunodeficiency virus infection, fungal infection and in the perioperative state.

Virtually all therapeutic proteins (biologics) elicit an immune response with the consequent production of anti-drug antibodies (ADA). The majority of ADA to therapeutic monoclonal antibodies (mAbs) are directed against the antigen-binding site of the therapeutic mAb, and hence are neutralizing. This nature of the ADA response explains why fully human antibodies can still be highly immunogenic. The detection of ADA is technically challenging and all assays have limitations, namely a limited capacity in detecting ADA in the presence of a drug due to immune complex (IC) formation, which may underestimate the ADA incidence. Refined assays, able to disrupt drug-ADA ICs, have revealed the presence of ADA in a higher proportion of patients. The great heterogeneity among ADA assays prevents a direct comparison of immunogenicity between different molecules and across studies. The formation of drug-ADA ICs can significantly alter pharmacokinetics and directly reduce drug efficacy if the ADA titer (i.e., concentration) is sufficiently high and persistent. In patients with low ADA titer, free drug concentrations may remain high enough to be effective, while in patients developing high ADA titer a substantial part of the drug will be neutralized and clinical non-response is likely to occur. ADA can also increase the risk of adverse events, namely hypersensitivity reactions. Several studies have revealed the presence of ADA before a clinically overt adverse reaction, highlighting their predictive value. Algorithms integrating therapeutic drug monitoring and immunogenicity information in the current clinical evaluation of patients receiving biologics are today available to guide therapeutic decisions in clinical practice, helping us to design safer and more cost-effective therapeutic strategies.

The pH is an important physicochemical factor that plays a significant role in various metabolic, molecular and cell-regulating processes. In the epidermis, the pH affects the barrier function on different levels. In many dermatoses that come along with an impaired barrier, shifts in the pH can be observed, and this is a problem that definitely needs to be addressed by finding appropriate galenic formulas when prescribing barrier protective basic care. With this in mind, 66 cosmetic preparations have been chosen following German market analysis. These preparations have been investigated regarding phase relation of the emulsion, absolute pH value and buffer capacity. The results show that only 23 preparations have an appropriate pH of ≤5.5 and only 3 preparations show a buffer capacity of ≥1.0. This outcome demonstrates the fact that the significance of pH and buffer capacity as quality criteria for barrier-protective preparations is still highly underrated from the view point of manufacturers and users.

The visibility of a skin condition or dermatosis led to the reasonable assumption that the direct application of a therapeutic remedy to the target tissue holds many advantages. Through centuries, the nomenclature of topical preparations has proliferated and finally been moulded into the compulsory nomenclature of official compendia. In everyday life, many terms have been added and have complicated understanding and communication among and between healthcare professionals and laypersons. A large proportion of marketed topical preparations contain significant amounts of volatile vehicle ingredients that evaporate once they are applied onto the skin, that is, the vehicle format as well as the sum of vehicle ingredients in the primary container are different from the vehicle format and the sum of vehicle ingredients on the skin. This phenomenon and the potential consequences have so far been often ignored by many healthcare professionals and laypersons. To gain a better understanding, this phenomenon has been coined as the metamorphosis of the vehicle. The metamorphosis of the vehicle describes the vehicle (a) in the primary container (primary formulation), (b) during and immediately after application onto the skin (secondary formulation) and (c) after all volatile vehicle ingredients have evaporated from the vehicle on top of the skin (tertiary or residual formulation). The secondary and tertiary formulations may offer increased delivery of cosmetic or pharmaceutical actives. This is achieved by (a) an intended post-application creation of supersaturation of actives in the secondary and tertiary formulations or by (b) physico-chemical triggers such as pH.