Alison Layton

New insights into the management of acne: an update from the Global Alliance to Improve Outcomes in Acne group.

The Global Alliance to Improve Outcomes in Acne published recommendations for the management of acne as a supplement to the Journal of the American Academy of Dermatology in 2003. The recommendations incorporated evidence-based strategies when possible and the collective clinical experience of the group when evidence was lacking. This update reviews new information about acne pathophysiology and treatment-such as lasers and light therapy-and relevant topics where published data were sparse in 2003 but are now available including combination therapy, revision of acne scarring, and maintenance therapy. The update also includes a new way of looking at acne as a chronic disease, a discussion of the changing role of antibiotics in acne management as a result of concerns about microbial resistance, and factors that affect adherence to acne treatments. Summary statements and recommendations are provided throughout the update along with an indication of the level of evidence that currently supports each finding. As in the original supplement, the authors have based recommendations on published evidence as much as possible.

European Evidence‐based (S3) Guidelines for the Treatment of Acne

Subcommittee Members: Dr. Alexander Nast, Berlin (Germany) Dr. Cristina Oprica, Stockholm (Sweden) Prof. Dr. Brigitte Dreno, Nantes (France) Mrs. Stefanie Rosumeck, Berlin (Germany) Dr. Vincenzo Bettoli, Ferrara (Italy) Prof. Dr. Berthold Rzany, Berlin (Germany) Prof. Dr. Klaus Degitz, Munich (Germany) Dr. Adel Sammain, Berlin (Germany) Mr. Ricardo Erdmann, Berlin (Germany) Dr. Thierry Simonart, Brussels (Belgium) Prof. Dr. Andrew Finlay, Cardiff (United Kingdom) Dr. Niels Kren Veien, Aalborg (Denmark) Prof. Dr. Ruta Ganceviciene, Vilnius (Lithuania) Dr. Maja Vurnek fivkovi , Zagreb (Croatia) Dr. Alison Layton, Harrogate (United Kingdom) Prof. Dr. Christos Zouboulis, Dessau (Germany) Dr. Jose Luis Lopez Estebaranz, Madrid (Spain) Prof. Dr. Falk Ochsendorf, Frankfurt (Germany) Prof. Dr. med. Harald Gollnick, Magdeburg (Germany)

The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies

The use of epidermal growth factor receptor (EGFR) inhibitors for the treatment of solid tumours is increasing. However, the tolerability profile for EGFR‐inhibitors, such as the monoclonal antibody cetuximab and the tyrosine kinase inhibitor erlotinib, is characterised by a unique group of skin reactions dominated by an acneiform eruption, xerosis, eczema and changes in the hair and nails. The possibility that this skin toxicity correlates with anti‐tumour activity offers the potential to titrate dosing on a case‐by‐case basis. These skin effects may constitute a significant obstacle to treatment compliance. Accordingly, there is a need for consistent, multi‐disciplinary management strategies that will allow patients to receive the recommended dosages of such targeted therapies. The eruption responds well to some acne therapies and xerosis can be controlled by standard emollients. Here we present an overview of the treatment options for skin reactions that are available today, and evaluate some of the ways in which the treatment of such EGFR‐inhibitor‐related skin reactions may be improved in the future. Evidence‐based studies are needed to determine the best way to manage these effects.

Persistent acne in women : implications for the patient and for therapy.

Acne is traditionally regarded as a skin disorder of the teenage years. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. One recent community-based UK study estimated the prevalence of facial acne in adult women aged between 26 and 44 years to be 14%. It is not clear whether there is a true increase in acne in this age group or whether these patients are less tolerant of their acne and/or better informed of available therapies and so seek advice. The reasons for persistent acne are not fully understood. External factors such as use of certain cosmetics, ingestion of drugs, and endocrine abnormalities should all be considered when managing these patients. Post-adolescent acne in females can be divided into ‘persistent acne’, which represents a continuation of acne from adolescence into adult life, and ‘late-onset’ acne, which describes significant acne occurring sometimes for the first time after the age of 25 years. The clinical picture of each of these forms of acne in adult females can differ slightly from conventional adolescent disease. The course of each form is more indolent. Because of these variations, the approach to investigation and management of these cases may have subtle differences when compared with that for teenage disease. Acne treatment should aim to reduce sebum, comedogenesis, propionibacteria population, and inflammation. Treatment selection will depend on the acne grade and site as well as the patient‘s preference and ability to comply with therapy. Maintenance therapy plays an important role in managing this group of patients. As the response to treatment is inevitably slow, patients must be encouraged to adhere to the chosen treatment regimen.This article reviews the literature on persistent acne in women in terms of clinical presentation and possible etiologic factors, and outlines principles of therapy related to managing these cases.

Is antibiotic resistance in cutaneous propionibacteria clinically relevant? : implications of resistance for acne patients and prescribers.

AbstractIt is well recognized that some patients with acne do not respond adequately to antibiotic therapy. It is important to distinguish antibiotic recalcitrant acne which we would suggest represents acne that shows a diminished response to treatment irrespective of the cause as opposed to ‘antibiotic-resistant acne’ which is acne that is less responsive to treatment as a direct consequence of skin colonization with resistant propionibacteria. Here we show that antibiotic-resistant acne is not just a theoretical possibility but a real phenomenon that could have important consequences for patients and prescribers. The relationship between skin colonization by antibiotic-resistant propionibacteria and treatment outcomes is a complex one that is explained at the follicular level by physiological differences affecting local drug concentrations. A systematic review of the literature on antibiotic-resistant propionibacteria revealed methodological shortcomings in studies of their prevalence and a paucity of evidence on their clinical significance. Despite the elucidation of resistance mechanisms in cutaneous propionibacteria, our continuing inability to distinguish between strains of Propionibacterium acnes means that we still do not fully understand how resistance spreads, although person-to-person transfer is most likely. Finally, we present a decision tree for acne management in an era of prudent antimicrobial prescribing that provides an alternative to existing treatment algorithms by placing topical retinoids and not antibiotics at the cornerstone of acne management.

Large-scale worldwide observational study of adherence with acne therapy

Acne is a common chronic disease that typically requires prolonged treatment. Several small studies conducted over the past few years suggest that adherence to acne medications is often poor. In addition, data regarding the factors that positively or negatively impact adherence in patients with acne are sparse. This study utilized a simple, validated questionnaire (ECOB, Elaboration d’un outil d’evaluation de l’observance des traitements medicamenteux) to assess the risk of poor adherence in a large worldwide cohort of acne patients (n = 3339) from three major geographic regions [the Americas (n = 952), Europe (n = 1196), and Asia (n = 1191). In addition, information about patient and treatment characteristics was collected to identify factors that correlated with adherence. Overall, there was a poor adherence rate of 50% in this study; this varied by region, with significantly worse adherence in Europe versus Asia and America (poor adherence rates of 58%, 48%, and 43%, respectively, P < 0.0001). To provide insight into factors that affect medication‐taking behavior in acne, adherence was analyzed by the type of treatment (a combination of topical and systemic, topical only, oral isotretinoin). Among patients taking a combination of both systemic and topical therapy, 60% (n = 944) of patients had poor adherence to at least one treatment as defined in the study protocol. In this group, there was a higher proportion of patients who had poor adherence to systemic treatment versus topical treatment (54% vs. 44%, respectively). Among patients treated with topical therapy only, poor adherence occurred in 40% (n = 356) of cases. A total of 46% (n = 325) of patients using oral isotretinoin therapy had poor adherence. Multivariate analysis showed that poor adherence was independently correlated with young age (most strongly with <15 years but also in the age group from 15 to 25 years), the occurrence of side effects, lack of improvement as evaluated by dermatologist, previous systemic therapy, lack of knowledge about acne treatment, consultation with a primary care physician, and lack of patient satisfaction with treatment. Factors that had a positive effect on adherence were more severe acne, use of cosmetics (moisturizers, cleansers), use of either topical therapy alone or isotretinoin, good clinical improvement as evaluated by the dermatologist, patient satisfaction with therapy, and knowledge of acne treatment.

Guidelines for optimal use of isotretinoin in acne.

Isotretinoin is most effective for patients with acne who fail to respond to other forms of treatment; virtually all patients respond to isotretinoin, 0.5 to 1.0 mg/kg/day. As many as 61% of patients are cured after one course, but 39% require further isotretinoin (16%) or oral antibiotics (23%). The relapse rate can be reduced by the administration of the higher dose of 1 mg/kg/day (thus achieving a significant cumulative dose of > 120 mg/kg), especially to young patients and men with truncal acne and more severe disease. About 85% require a 4-month course, but 15% require longer treatment, with some up to 10 months. There are several reasons for a slow response to treatment, including the presence of macrocomedones, ovarian dysfunction, and as-yet unknown factors. Macrocomedones can be treated with light cautery, ovarian dysfunction with hormonal therapies, and in those persons who have no obvious explanation for slow response, persistence with isotretinoin alone is required. Repeat courses of isotretinoin can also be given. Six years ago most patients treated with isotretinoin had severe acne (60%), but today most patients (60%) have therapy-resistant moderate acne. Isotretinoin is a consideration in such patients to reduce the physical and psychological effects of acne, particularly because there is no simple method to treat acne scars.

Optimal Management of Acne to Prevent Scarring and Psychological Sequelae

Acne vulgaris is one of the most common inflammatory dermatoses and is seen in both the hospital setting and in general practice. Multiple factors are involved in the pathophysiology of acne, including: an alteration in the pattern of keratinization within the pilosebaceous follicles resulting in comedone formation; an increase in sebum production which is influenced by androgens; the proliferation of Propionibacterium acnes; and the production of perifollicular inflammation. Genetic and hormonal factors may also contribute to acne. Better understanding of the pathophysiology of the disease has led to the development of novel therapies which are directed at one or more of the implicated etiologic factors.Systemic antibiotics for acne have been the mainstay of treatment for many years. The main cause for concern following the use of systemic antibiotics is the emergence of antibiotic-resistant strains of P. acnes. Concomitant use of non-antibiotic therapies such as benzoyl peroxide helps to decrease the occurrence of resistance and can be effective in the treatment of resistant and nonresistant propionibacterial strains. However, no one agent is able to eradicate resistant strains completely and as resistant strains correlate to poor clinical response to therapy, prescribing strategies are required to minimize the occurrence of resistance to P. acnes.When assessing acne it is important to take an all embracing approach and to examine carefully for both the clinical and psychologic effects of the disease process. There are numerous forms of acne scarring and it is important to be aware of these as patients who are developing scarring merit early effective therapy. Some patients with acne will develop psychologic problems as a consequence of their condition. Even mild to moderate disease can be associated with significant depression and suicidal ideation and psychologic change does not necessarily correlate with disease severity. Acne scars themselves have been shown to produce significant psychopathology.When initiating treatment it is important to consider the aims of therapy. Treatment should be aimed at achieving clearance of acne, prevention of scarring and, where necessary, relief from any psychologic stress resulting from the acne. Therapy should be commenced early in the disease process in order to prevent scarring and it is important to select appropriate therapies according to the clinical signs and psychologic disability. It is also important to ensure that the patient is able to comply with therapy and clear guidelines regarding treatment, possible adverse effects and realistic expectations should be provided.

Laser and other light therapies for the treatment of acne vulgaris: systematic review

Background  Acne is common and can lead to scarring of the skin, as well as to psychological distress and reduced self‐esteem. Most topical or oral treatments for acne are inconvenient and have side‐effects. Laser and other light therapies have been reported to be convenient, safe and effective in treating acne.

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial

Summary Background Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3–9, 10–30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1–3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3–5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. Findings Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1–26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9–30·1), p=0·001. Interpretation Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. Funding NIHR Health Technology Assessment Programme.