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Special Therapeutic Options and Substances in the Treatment of Atopic Eczema
Abstract
The introduction of glucocorticosteroids in dermatology was the greatest progress for eczema patients in the second half of the twentieth century. For atopic dermatitis, mostly mild to moderate strength steroids are adequate. The application of topical glucocorticosteroids in the correct vehicle should be timely limited and ended via a “tandem therapy.” Proactive strategies with once or twice weekly applications of the effective substance have proven helpful. The most important side effects of topical glucocorticosteroids include skin atrophy and the common manifestation of perioral rosacea-like dermatitis which occurs especially in young women after topical corticosteroids.
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Photodermatologische Verfahren sind von zentraler Bedeutung in der heutigen Dermatologie. Dieses Handbuch ist ein praxisbezogener Leitfaden durch die moderne dermatologische Phototherapie und Photodiagnostik. Es finden sich ausführliche Darstellungen bewährter und neuester photo(chemo)therapeutsicher und photodiagnostischer Verfahren. Im Vordergrund steht die zu behandelnde Hauterkrankung. Das praxisorientierte Lehrbuch richtet sich gleichermaßen an den in der Weiterbildung befindlichen Arzt wie an den erfahrenen, in der Klinik oder in der Praxis tätigen Dermatologen. So finden sich Informationen zum gegenwärtigen Wissensstand klinisch bedeutsamer photobiologischer Prozesse neben ausführlichen Darstellungen praxisrelevanter Themen, z.B. technische Hinweise zur praktischen Durchführung, Abrechnungsdetails im Zeitalter des Gesundheitsstrukturgesetzes, Maßnahmen zur Qualitätssicherung etc. Die langjährige Erfahrung der Herausgeber und Autoren in Klinik, Forschung und Lehre hat aus der Fülle der dargebotenen Informationen ein von fachlicher und didaktischer Kompetenz geprägtes Handbuch zum Thema entstehen lassen.
A lot of unconventional methods are offered to allergic patients in Germany. Only few can be considered as serious complementary methods to be used in addition to classic methods: acupuncture, balneotherapy, breathing techniques, clima therapy, relaxation techniques, some forms of dietetics, phytotherapy, physiotherapy, psychotherapy.
Patients with atopic dermatitis (AD) tend to have greatly elevated levels of serum immunoglobulin E (IgE). However, the role of IgE in the pathogenesis of AD is debated. This investigator-initiated open-label pilot study evaluates an anti-IgE-treatment approach by combining extracorporeal immunoadsorption and anti-IgE antibody omalizumab in 10 patients with severe, therapy-refractory AD. IgE levels decreased after immunoadsorption and decreased continuously in all patients during anti-IgE therapy. The reverse trend was observed during follow-up without treatment. In parallel with these observations, an improvement in AD was observed during the treatment period, with aggravation during follow-up. Further research is needed, based on the principle of reducing IgE levels in order to improve clinical symptoms, using a combination anti-IgE treatment approach, adjusted according to IgE levels.
Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs.
A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear).
Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity.
Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children.
Copyright © 2015 by the American Academy of Pediatrics.
Peanut-induced anaphylaxis is an IgE-mediated condition that is estimated to affect 1.5 million people and cause 50 to 100 deaths per year in the United States. TNX-901 is a humanized IgG1 monoclonal antibody against IgE that recognizes and masks an epitope in the CH3 region of IgE responsible for binding to the high-affinity Fc(epsilon) receptor on mast cells and basophils.
We conducted a double-blind, randomized, dose-ranging trial in 84 patients with a history of immediate hypersensitivity to peanut. Hypersensitivity was confirmed and the threshold dose of encapsulated peanut flour established by a double-blind, placebo-controlled oral food challenge at screening. Patients were randomly assigned in a 3:1 ratio to receive either TNX-901 (150, 300, or 450 mg) or placebo subcutaneously every four weeks for four doses. The patients underwent a final oral food challenge within two to four weeks after the fourth dose.
From a mean base-line threshold of sensitivity of 178 to 436 mg of peanut flour in the various groups, the mean increases in the oral-food-challenge threshold were 710 mg in the placebo group, 913 mg in the group given 150 mg of TNX-901, 1650 mg in the group given 300 mg of TNX-901, and 2627 mg in the group given 450 mg of TNX-901 (P<0.001 for the comparison of the 450-mg dose with placebo, and P for trend with increasing dose <0.001). TNX-901 was well tolerated.
A 450-mg dose of TNX-901 significantly and substantially increased the threshold of sensitivity to peanut on oral food challenge from a level equal to approximately half a peanut (178 mg) to one equal to almost nine peanuts (2805 mg), an effect that should translate into protection against most unintended ingestions of peanuts.
Background: Cyclosporin A (CsA) has been shown to be highly effective in the therapy of atopic dermatitis (AD). However, little information exists on the treatment of AD patients with Sandimmun Neoral® (Neoral), a microemulsion of CsA with improved pharmacokinetic properties in comparison to Sandimmun®. Objective: We have compared the efficacy and tolerability of Sandimmun and Neoral. Methods: In a randomised, monocentric, double-blind, cross-over pilot study (n = 14), each formulation was administered for 8 weeks, followed by switching to the other treatment group for another 8 weeks. Results: After 2 weeks of therapy, the improvement under Neoral therapy was significantly higher than with Sandimmun (disease activity p = 0.047; extent of disease p = 0.016). In contrast, after 8 weeks of therapy, both formulations yielded similar improvement in the patients’ condition. Conclusion: While both formulations are effective and well tolerated in the treatment of severe AD, Neoral may have a faster onset of action and higher initial efficacy, which makes it an adequate replacement for Sandimmun.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Case: An otherwise healthy 55-year-old man reports that he has been itchy all over for 6 months. The itch interferes with falling asleep and wakes him repeatedly during the night. Initially, there was no rash, but during the past 4 months, itchy nodules and plaques have developed on his back, arms, and legs. Treatment with sedating and nonsedating oral antihistamines and topical glucocorticoids has had no effect. How would you evaluate and manage this case?
Topical application of coal tar is one of the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte-mediated skin disease associated with loss-of-function mutations in the skin barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, the molecular mechanism of coal tar therapy is unknown. Using organotypic skin models with primary keratinocytes from AD patients and controls, we found that coal tar activated the aryl hydrocarbon receptor (AHR), resulting in induction of epidermal differentiation. AHR knockdown by siRNA completely abrogated this effect. Coal tar restored filaggrin expression in FLG-haploinsufficient keratinocytes to wild-type levels, and counteracted Th2 cytokine-mediated downregulation of skin barrier proteins. In AD patients, coal tar completely restored expression of major skin barrier proteins, including filaggrin. Using organotypic skin models stimulated with Th2 cytokines IL-4 and IL-13, we found coal tar to diminish spongiosis, apoptosis, and CCL26 expression, all AD hallmarks. Coal tar interfered with Th2 cytokine signaling via dephosphorylation of STAT6, most likely due to AHR-regulated activation of the NRF2 antioxidative stress pathway. The therapeutic effect of AHR activation herein described opens a new avenue to reconsider AHR as a pharmacological target and could lead to the development of mechanism-based drugs for AD.
Atopic dermatitis leads to, and can be triggered by, stress. Psychological interventions have been shown to have positive effects on skin status, itch and scratching behaviour. However, it has not been analysed whether stress management leads to a change in physiological stress level and psychophysiological stress reaction under acute stress in this patient group. In this study 28 patients with atopic dermatitis were randomized to an experimental group (cognitive behavioural stress management) or a control group. The endocrine stress level and skin status were measured before and after the stress management programme. A public-speaking paradigm was used to induce acute stress. The study revealed that the experimental group had a tentatively reduced cortisol awakening response after the stress management programme. In addition, the experimental group remained calmer and showed lower salivary cortisol levels under acute stress. Thus, stress management might be a useful addition to standard treatment in patients with atopic dermatitis.
Dieses Buch, erarbeitet von erfahrenen Dermatologen, Kinderärzten, Psychologen und Ökotrophologen und konzipiert für den praktisch tätigen Arzt, gibt Antwort in allen Fragen im Zusammenhang mit der Behandlung und Betreuung von "Neurodermitis-Kindern". Zahlreiche Farbabbildungen zeigen die große klinische Vielfalt der atopischen Dermatitis und ihrer Differentialdiagnosen. Alle Behandlungsmöglichkeiten werden ausführlich erläutert, Provokationsfaktoren, psychosomatische Aspekte und Möglichkeiten der Prävention werden beschrieben. Im Anhang, Buchempfehlungen für Kinder und Erwachsene, Internetadressen, Selbsthilfegruppen und Adressen von Kliniken die sich auf die Behandlung von Kindern mit Neurodermitis spezialisiert haben sowie ein in der Klinik entwickelter Patientenfragebogen.
In a randomised placebo controlled double blind study, 50 adult patients with mild to moderate atopic dermatitis were treated with borage oil (verum) or palm oil (placebo) for 12 weeks. Besides the drug under investigation only nonspecific topical ointments and creams were allowed to use. The ADASI (Atopic Dermatitis Area Severity Index)-score was measured daily. The ADASI itself is defined by the severity of eczema and the intensity of pruritus and allows an estimation of the intraindividual efficacy of the drug. In addition, the essential fatty acids and the IgE in the sera were measured. 18 patients of the verum-group and 14 patients of the placebo-group finished the study. After 12 weeks of therapy with daily 2 x 1,000 mg borage oil (Glandol®) or daily 2 x 1,000 mg palm oil (placebo), inside the verum-group, in 14 of 18 (78%) of the patients, the ADASI-score increased significantly, inside the placebo-group, in 6 of 14 (43%) of the patients (p < 0.05). Parallel to the improvement of the atopic dermatitis in the verum-group, the dihomo-gammalinolenic acid in serum increased significantly (p < 0.05). There was also an increase for gammalinolenic acid and arachidonic acid. There was no significant change in the total amount of serum IgE before and after therapy. In the present study borage oil showed good effects on the course of mild to moderate atopic dermatitis.
Angeregt durch die steigende Anzahl der Allergiepatienten, die ungenügende therapeutische Wirkung der medikamentösen Therapie sowie Hyposensibilisierung, aber auch durch das steigende Interesse der Patienten an der Naturheilkunde, wandten wir uns der Akupunkturtherapie bei Patienten mit Rhinopathia pollinosa zu. Zur Akupunktur kamen von 1987 bis 1990 174 Patienten (95 weibliche, 79 männliche), das Durchschnittsalter lag bei 33 Jahren und die Erkrankungsdauer bei 12,5 Jahren. Nach dem Zufallsprinzip wurden 3 Patientengruppen gebildet. Die eine Patientengruppe (63 Patienten) erhielt Nadelakupunktur, die andere (73 Patienten) Laserakupunktur und die Kontrollgruppe (38 Patienten) wurde mit Placebolaserakupunktur behandelt. Die Nadelakupunktur erfolgte 3mal wöchentlich 3 Wochen lang je 20 min. Die Laserakupunktur wurde mit dem He-Ne-Laser HN 40 5mal wöchentlich 3 Wochen lang durchgeführt. Die Bestrahlungsdauer betrug 20 s pro Punkt, bei mittlerer Bestrahlung von 2,54 J/cm2.
The question whether or not homoeopathic remedies are more effective than placebos remains unresolved. Delayed-onset muscles soreness (DOMS) is a suitable model to test this hypothesis. Computerised literature searches cr ere conducted to retrieve all placebo-controlled trials on the subject. Eight such studies were identified. Most trials were burdened with serious methodological flaws. All of the randomised studies showed no significant differences between placebo and verum. It is concluded that the published evidence to date does not support the hypothesis that homoeopathic remedies used in these studies (mainly Rhus toxicodendron and Arnica montana) are more efficacious than placebo in alleviating the symptoms of DOMS.
Sublingual immunotherapy (SLIT) is currently accepted as a viable option to injection immunotherapy and is widely used in many European countries, although several issues regarding efficacy and safety still need to be resolved. A considerable amount of new data concerning clinical, immunologic and practical aspects of SLIT has been published and there have been confirmatory metaanalyses of the efficacy of SLIT in rhinitis and asthma, as well as data in children. Moreover, several postmarketing surveys have confirmed acceptable safety, including in children below the age of 5 years. Because of the good safety profile it may be possible to give SLIT without the updosing phase and, in fact, the most recent clinical trials have been performed with a steady-dosage regimen. Nevertheless, treatment with SLIT still requires a precise diagnosis, detailed patient information, and strict follow-up. Additional encouraging information is now available on patient compliance measured in both adults and children. One pharmacoeconomic study showed that in pollinosis, SLIT was more advantageous than drug treatment alone. Furthermore, as with the injection route, SLIT can prevent the onset of new sensitizations and the onset of asthma. These findings need to be confirmed by larger studies, as does the long-lasting effect after discontinuation of treatment. The mechanisms of action are only beginning to be investigated in detail and the biodistribution of sublingual allergens also requires further study. More and more new data on SLIT are rapidly appearing in the international literature that confirm the value of this treatment and show that SLIT is a viable and useful form of immunotherapy. Nevertheless, patient selection and optimal dose regimens still need to be defined unequivocally.
The objective of the study described in this paper is to assess efficacy of classical homeopathic treatment in patients with neurodermatitis. The study follows the nowadays accepted scientific research standards as well as the needs of classical homeopathy. After a baseline-phase of 4 weeks duration all patients undergo subsequently a anamnese by a homeopathic doctor who tries to select the proper remedy respecting the case and the characteristics of the patient as a whole, following the principles and guidelines of classical homeopathy. After this the patients are randomized in a placebo- and verum-group and stay in the study for 8 months. During this time they are allowed to use indifferent external ointments only. The homeopathic doctor is completely free to change remedies, dosages or potencies if required by the reaction or a new case picture of the patient. The efficacy of the therapy will be statistically shown in comparison to the scorepoints of the multiparameter-neurodermatitis-score, which was assessed in each patient at the beginning and at the end of the study. Effects of the treatment concerning the patient's ability to deal with the disease, his quality of life and other health problems besides his skin disease will be described and discussed. The design of this study is published in advance to give reviewers of the study the opportunity to verify if the study complies with the original plan. This is important because a critical discussion of this study is to be expected.
Allergy is one of the major health problems of most modern societies. Although allergic diseases are well-known for almost two hundred years, their prevalence has increased dramatically over the last decades. Allergic reactions manifest in various organs, most commonly in the skin and mucous membranes, the frontier surfaces where the contact between the individual and the environment takes place. In a very concise and practical way this book covers all aspects of allergic reactions from pathophysiology to diagnosis, therapy and prevention with a strong focus on relevant aspects for the everyday work of the practising dermatologist and allergist in the hospital or office. This book reflects the rich personal experience of a German allergist with international training and reputation, who is active in immunology and allergy research and practice for almost 30 years. In this book, not only IgE-mediated allergic reactions are covered but all other kinds of allergies such as atopic eczema, contact dermatitis, drug eruptions, anaphylaxis and food allergies are equally represented as well as psychosomatic aspects and problems of environmental intolerances. © Springer-Verlag Berlin Heidelberg 2005, All rights are reserved.
The clinical experience with topical calcineurin inhibitors in the field is still rudimentary, if compared to our knowledge of topical corticosteroids. This is especially true for the long-term effects. The systemic transcutaneous absorption that occurs during the therapy of atopic dermatitis is quantitatively irrelevant. However, in the setting of permanent disruption of the skin barrier, as may be encountered in rare Genodermatoses, but as well in cases that do not respond to therapy, continued treatment my result in clinically relevant blood levels. Side effects of topical calcineurin inhibitors may be separated into two groups, i.e.local intolerance reactions, and skin infections. While the typical burning sensation of the newly treated skin is ephemeral, local alcohol intolerance, albeit less frequent, will persist throughout the treatment period. Regarding skin infections, Eczema herpeticatum seems to be the only serious complication; adequate preventive will further reduce the risk of this rare complication.
In Germany, alternative medicine is presently very popular and is supported by the federal government. When deliberating on the essence of alternative medicine we should simultaneously reflect on the intellectual and moral basis of regular medicine. To provide an epistemological demarcation of the 2 fields, the following 12 theses are advanced: (1) alternative and regular medicine are speaking different languages; (2) alternative medicine is not unconventional medicine; (3) the paradigm of regular medicine is rational thinking; (4) the paradigm of alternative medicine is irrational thinking; (5) the present popularity of alternative medicine can be explained by romanticism; (6) some concepts of alternative medicine are falsifiable and others are not; (7) alternative medicine and evidence-based medicine are mutually exclusive; (8) the placebo effect is an important factor in regular medicine and the exclusive therapeutic principle of alternative medicine; (9) regular and alternative medicine have different aims: coming of age vs faithfulness; (10) alternative medicine is not always safe; (11) alternative medicine is not economic; and (12) alternative medicine will always exist. The fact that alternative methods are presently an integral part of medicine as taught at German universities, as well as of the physician's fee schedule, represents a collective aberration of mind that hopefully will last for only a short time.
The following guideline of the "Arbeits-gruppe Nahrungsmittelallergie der DGAKI und des ADA" (Task Force on Food Allergy of the German Society for Allergology and Clinical Immunology and the Medical Association of German Allergologists) summarizes different procedures, when food allergy is suspected in atopic dermatitis (neurodermatitis, atopic eczema). The problem is clinically relevant because many patients assume allergic reactions against foods being responsible for triggering eczematous reactions or worsening eczema. It is important to identify such patients who indeed benefit from an elimination diet and to avoid unnecessary diets. Elimination diets (especially in early childhood) are associated with the risk of malnutrition and additional emotional stress for the patients. The gold standard for the diagnosis of food-dependent reactions is to perform placebo-controlled, double-blind oral food challenges because specific IgE, prick tests and anamnestic data often do not correlate with clinical reactivity. This is particularly true in the case of delayed eczematous skin reactions. The instrument of diagnostic elimination diets should be used before an oral provocation test. If multiple sensitizations against foods are discovered in a patient, an oligoallergenic diet and a subsequent stepwise supplementation of the nutrition should be performed. If a specific food is suspected of triggering food allergy, oral provocation should be performed after a diagnostic elimination diet. As eczematous skin reactions may develop slowly (i.e., within one or two days), we recommend that the skin is inspected the day after the provocation test and that a repetitive test should be performed if the patient has not reacted to a given food on the first day of oral provocation. The guideline discusses various clinical situations for patients with atopic dermatitis, allowing for differentiated diagnostic procedures.
IL-23 is associated with plaque psoriasis susceptibility and pathogenesis. BI 655066 is a fully human IgG1 mAb specific for the IL-23 p19 subunit.
This first-in-human proof-of-concept study evaluated the clinical and biological effects of BI 655066 in patients with moderate-to-severe plaque psoriasis.
We performed a single-rising-dose, multicenter, randomized, double-blind, placebo-controlled, within-dose cohort phase I trial. Patients received 0.01, 0.05, 0.25, 1, 3, or 5 mg/kg BI 655066 intravenously, 0.25 or 1 mg/kg BI 655066 subcutaneously, or matched placebo. The primary objective was safety evaluation.
Thirty-nine patients received single-dose BI 655066 intravenously (n = 18) or subcutaneously (n = 13) or placebo (n = 8). Adverse events were reported with similar frequency in the BI 655066 and placebo groups. Four serious adverse events (not considered treatment related) were reported among BI 655066-treated patients. BI 655066 was associated with clinical improvement from week 2 and maintained for up to 66 weeks after treatment. At week 12, 75%, 90%, and 100% decreases in the Psoriasis Area and Severity Index were achieved by 87%, 58%, and 16% of BI 655066-treated patients (any dose), respectively, versus none receiving placebo. BI 655066 treatment resulted in reduced expression of lesional skin genes associated with IL-23/IL-17 signaling pathways and normalization of psoriatic lesion gene expression profiles to a profile approaching that of nonlesional skin. Significant correlation between treatment-associated molecular changes and psoriasis area and severity index improvement was observed (r = 0.73, P = 2 × 10(-6)).
BI 655066 was well tolerated and associated with rapid, substantial, and durable clinical improvement in patients with moderate-to-severe psoriasis, supporting a central role for IL-23 in psoriasis pathogenesis.
Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Background: Specific immunotherapy (SIT) is the only causative method of treatment in the case of IgE-mediated allergic disease. There is extensive literature on the use of SIT in the management of respiratory allergies and insect venom hypersensitivity, but there is a paucity of published data concerning its use as a therapeutic approach in atopic dermatitis (AD). Objective: A double-blind placebo-controlled trial was conducted over a period of 12 months in order to evaluate the efficacy of SIT in the management of atopic dermatitis attributable to house dust mites or grass pollens. Methods: A total of 20 patients (5 - 40 years old) with AD and monovalent sensitization to airborne allergens (house dust mites or grass pollens) were enrolled in the study. SIT was performed using aluminum hydroxide-adsorbed allergen preparations administered by subcutaneous injection. Clinical efficacy of the treatment was assessed using the clinical score W-AZS index. Serum concentration of total IgE and allergen-specific IgE were measured, as were various immunological parameters including ECP, SIL-2R, IFN-y, IL-4, IL-5 and IL-10. Results: The mean value of W-AZS index in the SIT group before treatment was 87.6 ± 15.8 patients, and this decreased to 38.8 ± 34.4 patients after 12 months of therapy (p < 0.01). In the placebo group, the mean W-AZS index before treatment was 86.3 ± 15.7 patients and after 12 months of therapy it increased to 111.9 ± 41.7 patients. Comparative statistical analysis indicated a significant difference between the 2 groups in favor of patients treated with the active allergy vaccines (p < 0.01). Serum levels of specific IgE in the SIT group showed a tendency to decrease, whilst those in the placebo group tended to increase. Serum concentrations of selected immunological parameters including ECP, SIL-2R, IFN-y, IL-4, IL-5 and IL-10 were monitored before and after treatment, but did not show significant differences. Conclusion: Allergen-specific immunotherapy appeared to be an effective method of treatment for atopic dermatitis as judged by significant improvement in clinical index in cases with well-documented IgE-mediated allergic disease.
The care of patients with chronic pruritus as a symptom of a wide variety of underlying diseases continues to confront dermatologists with diagnostic and therapeutic challenges. However, a structured history and a physical examination may already substantially help in narrowing down the number of potential differential diagnoses. Apart form reducing the intensity of pruritus, identification and appropriate treatment of the underlying disease are important needs of patients. If these goals doesn't lead to improvement of itch, current guidelines provide a number of topical and systemic therapies for symptomatic treatment. Various skin lesions (for example, xerosis caused by irritant substances, secondary scratch lesions) prompt patients to consult a dermatologist, but most cases require an interdisciplinary therapeutic approach to identify potential internal medicine, neurologic, or psychosomatic aspects. Although great strides have been made in basic research, specific therapies are still rare, and a precise knowledge of the legal framework for the implementation of guidelines (for example, off‐label use) is essential.
This CME article gives an overview of the causes of and treatment options for chronic pruritus and discusses both advances in basic research as well as progress in clinical knowledge.
Atopic dermatitis (AD) is a distressing dermatological disease which is highly prevalent during infancy, can persist into later life and requires long-term management with anti-inflammatory compounds. The introduction of the topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, more than 10 years ago was a major breakthrough for the topical anti-inflammatory treatment of AD. Pimecrolimus 1% is approved for second-line use in children (≥2 years old) and adults with mild-to-moderate AD. The age restriction was emphasised in a boxed warning added by the FDA in January 2006, which also highlights the lack of long-term safety data and the theoretical risk of skin malignancy and lymphoma. Since then, pimecrolimus has been extensively investigated in short- and long-term studies including over 4000 infants (<2 years old). These studies showed that pimecrolimus effectively treats AD in infants, with sustained improvement with long-term intermittent use. Unlike topical corticosteroids, long-term TCI use does not carry the risks of skin atrophy, impaired epidermal barrier function or enhanced percutaneous absorption, and so is suitable for AD treatment especially in sensitive skin areas. Most importantly, the studies of pimecrolimus in infants provided no evidence for systemic immunosuppression, and a comprehensive body of evidence from clinical studies, post-marketing surveillance and epidemiological investigations does not support potential safety concerns. In conclusion, the authors consider that the labelling restrictions regarding the use of pimecrolimus in infants are no longer justified and recommend that the validity of the boxed warning for TCIs should be reconsidered.This article is protected by copyright. All rights reserved.
Introduction:
Atopic eczema (AE) is a chronic relapsing inflammatory skin condition and one of the most common, potentially debilitating diseases with increasing incidence.
Areas covered:
The complex etiology of AE with multiple systemic and local immunologic and inflammatory responses and interactions between susceptibility genes and environmental factors leading to defects in skin barrier function and eczematous skin lesions is presented. Knowledge of pathogenesis is important for understanding the more innovative treatment approaches discussed.
Expert opinion:
Basic therapy consists of hydrating topical treatment and avoidance of specific and unspecific provocation factors. For acute eczematous skin lesions, anti-inflammatory treatment consists mainly of topical glucocorticoids and topical calcineurin inhibitors. Microbial colonization and superinfection may induce skin exacerbation, which can be treated by either topical or systemic antimicrobial treatment. Systemic anti-inflammatory therapy is limited to severe cases and consists of systemic steroids, cyclosporine A or mycophenolate mofetil. Novel anti-inflammatory concepts that go beyond corticosteroids are in the early phases of development. There are targeted therapeutic approaches, such as cytokine and chemokine modulators, and it remains to be investigated how effective they will be and what side effects they may carry. Existing treatment modalities such as barrier repair therapy, topical immunosuppressive agents, antiseptic treatment as well as systemic treatment options are discussed.
Background
Current data from daily practice show that vitamin D3 analogues, corticosteroids and their fixed combination products are used heterogeneously for topical long-term treatment of psoriasis.AimTo evaluate scientific evidence about topical long-term therapy with vitamin D3 analogues, corticosteroids and their two-compound-products in psoriasis vulgaris and scalp psoriasis and to develop daily practice recommendations.Methods
Systematic literature review via PubMed® and Embase® and informal expert consensus.ResultsThe search strategy identified 21 relevant clinical trials. Best evidence regarding topical long term treatment was available for the two-compound-formulation containing calcipotriene and betamethasone. In a comparative trial in psoriasis vulgaris the two-compound-formulation showed superior tolerability and cost effectiveness compared to monotherapy. In scalp psoriasis the two-compound-gel was superior compared to calcipotriene monotherapy. Standardized and simplified treatment application modes resulted in a better clinical outcome comparing to on-demand therapies.Daily practice recommendationsPatients should be proactively involved in the choice of treatment, formulation and mode of application. Besides long-term treatment with the two-compound-formulation other treatment regimens including calcipotriene monotherapy can also be considered. Due to a favorable risk-benefit ratio in maintenance trials and due to better cost-effectiveness the application of two-compound-products once or twice a week after initial therapy is recommended.
Objective:
Asthma is a common chronic disease with various phenotypes and therapeutic responses. Unlike other diseases, current anti-inflammatory treatment with corticosteroids does not include any reference to biological measures which may vary among different asthma phenotypes. Morbidity from uncontrolled asthma suggests a need for specific targeted treatment approaches such as biologic medications. In half of asthmatics, chronic airway inflammation may be driven by T helper (Th)-2 cells, which release pro-inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13, contributing to eosinophil inflammation and IgE production. Earlier studies of cytokine-targeted biologic therapy on non-phenotyped asthma patients were generally not clinically effective.
Methods:
Literature published from 1958-2013 was identified through PubMed using the search terms which included asthma and therapy. A total of 32 studies were reviewed covering both pediatric and adult asthmatics and included double-blind randomized placebo-controlled trials testing efficacy of biologic agents to treat asthma.
Results:
More recent approaches to personalized medicine with expression profiling studies, genetic analysis and clinical biomarkers of Th2 inflammation have allowed identification of asthma phenotypes including a Th2 "high" phenotype. Studies targeting IgE, IL-5, IL-13 and the IL4 receptor alpha chain have shown some efficacy in phenotyped patients. For those without evidence of Th2 inflammation, no specific therapies have been identified.
Conclusions:
In recent years, the identification of Type-2 cytokine "high" asthma in numerous studies has predicted the clinical response to the Th2 associated therapies. It is not yet clear whether all Type 2 high asthma will respond similarly to IL-4, 5 and 13 approaches.
Cytokines have been proposed as histamine-independent itch mediators. To investigate this hypothesis, single doses of interleukin-2 (IL-2, 10 MU/mL) and tumour necrosis factor alpha (TNF-alpha, 10 micrograms/mL) were delivered to the epidermis of 10 healthy volunteers with a controlled skin-prick model; 1% histamine and solvent controls were included in a double-blind, randomized crossover design. Itch ratings (computerized visual analogue scale) were obtained every 20 s for 15 min and cutaneous reactions (weal, flare and temperature) were measured. Reactions were also recorded after 2, 24 and 48 h. The mean itch ratings were: histamine 35.5, IL-2 3.3 (both P < 0.01 compared with control), TNF-alpha 1.6 and solvent control 1.75 (not significant). Weal and flare occurred only with histamine. In two volunteers, an inflammatory papule with transient pruritus developed 12-18 h after applying IL-2. In conclusion, IL-2 showed a rapid, low pruritogenic effect, which may be followed by an inflammatory response. TNF-alpha induced no itching in this setting. Skin-prick testing with appropriate doses of potential pruritogens provides a safe and sensitive model for further chemoreceptor studies.
Die Abhängigkeit des atopischen Ekzems von meteorologischen Bedingungen wurde mit Hilfe von Fragebogen zur Juckreizstärke, Wetterempfinden sowie meteorologischen Messungen bei insgesamt 2106 Patienten mit atopischem Ekzem in Davos, Schweizer Hochgebirge, untersucht. Die Beobachtungsperiode betrug 7 Jahre. Es konnten hochsignifikante Korrelationen zwischen der Pruritusstärke und der Ausprägung meteorologischer Einzelparameter, insbesondere eine negative Beziehung zwischen der Stärke des Pruritus und der Höhe der Lufttemperatur, des Luftdampfdrucks und der Sonnenscheindauer ermittelt werden, darüber hinaus erhöhte subjektive Empfindlichkeitsraten der Patienten für Luftfeuchtigkeit und Lufttrockenheit. Damit wurden erstmals Daten erhoben, die die besondere Relevanz der atmosphärischen Umwelt für die Symptomausprägung beim atopischen Ekzem belegen. Die Ergebnisse lassen vor allem darauf schließen, dass ein mittlerer thermisch-hygrischer Bereich, bei dem sich der Wärmeübergang an der Hautoberfläche und der epidermale Wassergehalt die Balance halten, therapeutisch günstige Einflüsse besitzt. Die eingeschränkte klimatische Toleranz ist Folge der gestörten kutanen Barriere beim atopischen Ekzem.
Aim To compare the clinical efficacy of a cream combination containing 2% fusidic acid and 1% hydrocortisone acetate in the treatment of patients with mild to moderate atopic dermatitis.Subject Atopic dermatitis and efficacy of antibacterial and antiinflammatory topical therapy.Methods Randomized, double blind, prospective, parallel group trials.Results Study I, involving 186 patients, compared the combination 2% fusidic acid and 1% hydrocortisone acetate with 1% hydrocortisone cream. Analysis was performed on patients who had pathogens at entry and on the total patient population. Study II, involving 68 patients, compared the combination 2% fusidic acid and 1% hydrocortisone acetate with 2% fusidic acid cream. Analysis was the same as in study I.Results of study I in patients with pathogens at baseline showed a significant difference in favour of the combination (P = 0.04) in terms of the primary efficacy criterion which was a combination of clinical and bacteriological efficacy measures. When all patients in the study were analyzed there was no significant difference between the two groups. The combination was significantly more effective in removing pathogens than 1% hydrocortisone cream (P < 0.0001).Results of study II in all patients showed that the combination was significantly better than 2% fusidic acid cream (P = 0.04) in terms of the primary efficacy criterion. Both preparations were highly successful in eradicating pathogens.Pooled analysis of studies I and II showed a difference with respect to the primary efficacy criterion among the 3 preparations in the order Fucidin 2% plus HC 1% cream > HC 1% cream > Fucidin 2% cream in all patients and in those with pathogens (P = 0.007 for all patients and P = 0.01 for those with pathogens). Similarly, regarding the reduction in sign/symptom score a significant difference among the 3 preparations existed (P = 0.009 for all patients and P = 0.01 for those with pathogens). Adverse events with the combination were minimal.Conclusion 2% fusidic acid and 1% hydrocortisone acetate cream is an effective therapy in patients with mild to moderate degrees of atopic dermatitis.
Exposure to ultraviolet radiation can lead to suppression of many adaptive immune responses, both to antigens encountered within a short period of the irradiation (primary) and to antigens previously encountered (memory). The pathways involved are complex and not completely elucidated. This brief review summarizes the information available currently regarding the multiple steps involved, with the aim of providing a general overview of the main aspects of photoimmunosuppression and its clinical consequences.
Summary Background Long-term safety evaluations of biologics are needed to inform patient management decisions.
Objectives To evaluate the safety of ustekinumab in patients with moderate-to-severe psoriasis treated for up to 5 years.
Methods Safety data were pooled from four studies of ustekinumab for psoriasis. Rates of adverse events (AEs), serious AEs (SAEs) and AEs of interest [infections, nonmelanoma skin cancers (NMSCs), other malignancies and major adverse cardiovascular events (MACE)] per 100 patient-years (PY) of follow-up were analysed by ustekinumab dose (45 or 90 mg) and by year of follow-up (years 1–5) to evaluate the dose response and impact of cumulative exposure. Observed rates of overall mortality and other malignancies were compared with those expected in the general U.S. population.
Results Analyses included 3117 patients (8998 PY) who received one or more doses of ustekinumab, with 1482 patients treated for ≥ 4 years (including 838 patients ≥ 5 years). At year 5, event rates (45 mg, 90 mg, respectively) for overall AEs (242·6, 225·3), SAEs (7·0, 7·2), serious infections (0·98, 1·19), NMSCs (0·64, 0·44), other malignancies (0·59, 0·61) and MACE (0·56, 0·36) were comparable between dose groups. Year-to-year variability was observed, but no increasing trend was evident. Rates of overall mortality and other malignancies were comparable with those expected in the general U.S. population.
Conclusions No dose-related or cumulative toxicity was observed with increasing duration of ustekinumab exposure for up to 5 years. Rates of AEs reported in ustekinumab psoriasis trials are generally comparable with those reported for other biologics approved for the treatment of moderate-to-severe psoriasis.
44 children (aged 5–15 yrs) with atopic eczema took part in a controlled trial in which they were treated with hypnotherapy or encouraged to use a biofeedback device based on galvanic skin resistance (as relaxation techniques) to control their symptoms. A 3rd group discussed the problems of having eczema without being given specific suggestions to help reduce the symptoms. Complete data were available for 31 Ss. The total amount of body surface affected by eczema was not altered in any of the groups. 20 wks after entry to the trial, Ss in the 2 relaxation groups showed a significant reduction in the severity of surface damage and lichenification compared with the control group. Girls in the hypnotherapy group showed greater improvement than the girls in other groups and showed greater improvement than the boys in the hypnotherapy group. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The effect of a new non-steroid anti-inflammatory substance (bufexamac) in a special constituent was compared with that of 0.1% triamcinolone acetonide, 1% hydrocortisone cream, and placebo during a double-blind multicentre trial. The clinical effect of these four creams was studied in 193 patients receiving treatment for the following skin disorders: atopic dermatitis, allergic contact dermatitis, and non-allergic contact dermatitis, as well as dermatitis seborrheica. After 2 and 4 weeks’ treatment, when 193 and 157 patients, respectively, were re-examined, the effect of triamcinolone acetonide and hydrocortisone cream was significantly better, than that obtained with bufexamac in the cream basis employed. On the other hand, no statistically significant difference in effect between bufexamac and placebo cream was observed.
ZusammenfassungHintergrund: Zur Wirksamkeit der Homöopathie bei atopischem Ekzem (atopische Dermatitis, Neurodermitis constitutionalis atopica) liegen zwar eine Reihe von Kasuistiken, aber keine kontrollierten Therapiestudien vor. Methoden: Monozentrische, randomisierte Doppelblindstudie, in der individuell verordnete homöopathische Arzneien mit Placebo verglichen wurden. Eingeschlossen wurden junge Erwachsene im Alter von 18–35 Jahren mit atopischem Ekzem. Nach einer unbehandelten Eingangsperiode von 4 Wochen wurden alle Patienten 32 Wochen lang behandelt und beobachtet. Als Begleitmedikation waren nur indifferente Salben zugelassen. Hauptzielkriterium war der Multiparameter-Score (MP-Score) von Costa und Saurat. Ergebnisse: Von 744 gescreenten Patienten wurden 24 randomisiert und analysiert (10 Verum, 14 Placebo). Beide Gruppen waren zu Therapiebeginn vergleichbar, die Verumgruppe war allerdings signifikant schwerer erkrankt (p = 0,034, t-Test). 10 Patienten (5 je Gruppe) brachen die Studie vorzeitig ab, vor allem wegen Nicht-Wirksamkeit der Therapie und notwendiger Begleitbehandlungen. In beiden Gruppen fiel der MP-Score deutlich: in der Verumgruppe von 54,5 ±11,0 auf 40,7 ±12,5, in der Placebogruppe von 45,9 ±7,6 auf 32,7 ±21,8, was in einem leichten, nicht signifikanten Gruppenunterschied von 5,6 Punkten zugunsten der Placebogruppe mündete (CI: –9,0 bis 20,2; p = 0,46; ANCOVA). In den sekundären Zielparametern (Lebensqualität, Krankheitsverarbeitung, allgemeine Einschätzung des Therapieerfolgs) ergaben sich ebenfalls keine signifikanten Gruppenunterschiede (jeweils p > 0,15). Schlussfolgerungen: Individualisierte homöopathische Arzneien hatten in dieser Studie zum atopischen Ekzem keinen über Placebo hinausgehenden Effekt. Die Generalisierbarkeit der Ergebnisse ist aufgrund der geringen Fallzahlen und des hohen Prozentsatzes nicht eingeschlossener Patienten eingeschränkt.
The usual psychoneurotic symptoms are ascribed to neuromuscular hypertension, which can be reduced by voluntary practice in muscular relaxation. The author's technique for progressive muscular relaxation, general and differential, is given; it depends upon learning to recognize muscle tenseness and to relax the sensation away. The author's experiments indicating reduction of reflexes, and of mental activity when relaxed are given. There are extensive references to and quotations from the literature of neuro-physiology, tending to justify the author's views. Case reports include spastic esophagus, mucous colitis, insomnia, compulsion neurosis, phobia, and neurasthenia as amenable to the method. Reference is also had to its use in manic states. A chapter differentiates this method from suggestion and allied methods, and argues for its superiority over them. There is brief reference to Freudian analysis which the author regards as more time consuming, less fundamental, and less satisfactory in securing lasting effects than is progressive relaxation. Bibliography of 33 pages. (PsycINFO Database Record (c) 2012 APA, all rights reserved)