Vincenzo Bettoli

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)

Diagnostic delay in hidradenitis suppurativa is a global problem.

DEAR EDITOR, Hidradenitis suppurativa (HS) is clinically defined with recognized diagnostic criteria and recognizable physical characteristics. Untreated, the disease causes significant morbidity. The prevalence varies between 0 0003% and 4% depending on the study population. Estimates from insurance databases suggest a prevalence of < 0 1%. This variation strongly suggests a significant selection bias or misclassification, and it may be speculated that not all patients present for care. This is reinforced by clinical experience and published evidence indicating a significant delay in diagnosis. This study explores the delay in diagnosis for patients with HS on an international level. The study (survey) was conducted in 2013. Observational data were collected during routine visits or extracted from case records. Because of the simple and obvious symptomatology of recurrent painful lesions present in restricted welldefined areas of the body, patients’ self-reported history was considered valid regarding onset of symptoms. Consecutive patients with HS and psoriasis were included from each participating centre during a period of 4 months or less. The data were anonymized by removing any names, addresses and social security numbers, and included age, sex, age at disease onset, age at diagnosis, delay in diagnosis, time from onset of symptoms to first physician contact, age at first medical contact, number of physicians seen prior to the diagnosis, family history and disease severity. If the diagnosis was made by a primary care physician or by a specialist other than a dermatologist prior to seeing a dermatologist, this was recorded as the date of the diagnosis. Individual centres were responsible for and obtained any locally required permissions and signed informed consent forms, for example ethics committee approval, in accordance with national registry and data protection rules. Patients diagnosed with HS or psoriasis (and confirmed by the investigator) were included. The primary outcome was quantification of the delay in diagnosis. Additionally, documentation was made of both the delay in visiting a physician (and so gaining access to specialist treatment) and the relative delay in diagnosis of HS compared with psoriasis with/without a family history. The severity of HS was determined by Hurley’s staging criteria: stage I, mild; stage II, moderate and stage III, severe. In patients with psoriasis, severity was evaluated by the Psoriasis Area and Severity Index: score < 7, mild; 7–12, moderate and > 12, severe. The t-test, Wilcoxon rank sum test and v-test were used where appropriate. Univariate and multivariate logistic regression analyses were used to identify factors predictive of significant diagnostic delay. Diagnostic delay > 2 years was defined as significant. Diagnosis, sex, age of onset, family history and disease severity were selected as potentially important

Antibiotic stewardship in dermatology: limiting antibiotic use in acne

Background/ObjectivesWidespread use of antibiotics in all areas of medicine has led to significant problems with antimicrobial resistance, which have begun to compromise the usefulness of antibiotics. Antibiotics have long been a keystone of acne therapy. There is a large population of patients with acne and antibiotic therapy is often used for long durations; thus, acne therapy results in extensive antibiotic exposure. This article discusses the role of antibiotic therapy in acne from the perspective of how clinicians can best preserve the utility of these important drugs while providing efficacious and safe therapy for acne patients.MethodsReview of literature augmented by expert opinion when literature was sparse.ResultsAntibiotic monotherapy (topical or oral) is not recommended due to the availability of clinically superior regimens. Systemic antibiotics are important for managing moderate to severe acne and should be used for a limited duration of time (3–4 months). Topical antibiotics should be paired with benzoyl peroxide to limit potential for resistance. Information gained in recent years about the pathophysiology of acne has shed light on the role of Propionibacterium acnes as well as other key pathogenic pathways such as inflammation.ConclusionsThe improved understanding of acne pathogenic mechanisms can and should be applied to develop modern therapeutic approaches that are efficacious and mesh with current public health concerns.

Oral clindamycin and rifampicin in the treatment of hidradenitis suppurativa‐acne inversa: a prospective study on 23 patients

Editor Hidradenitis Suppurativa-Acne Inversa (HS-AI) is a relapsing and chronic inflammatory skin disease affecting the big folds. HS-AI is currently thought of as being an inflammatory and not an infectious disease, but sometimes various bacteria combined in polymicrobial infections can be present. Coagulasenegative staphylococcus and anaerobic bacteria are the most frequently isolated. The bacteria are suspected of playing a role in the disease process, probably through immune-mediated mechanisms of inflammation. Therapy of HS-AI is often difficult. Medical, surgical and physical therapeutical options are available. Although antibiotics are widely used to treat HS-AI limited data on their efficacy are available. To assess the efficacy and the tolerability of a 10-week combination of oral clindamycin (600 mg daily) and rifampicin (600 mg daily) in the treatment of HS-AI, 23 patients affected by severe and actively inflammatory HS-AI were enrolled in a prospective non comparative study. The ethical committee considered as not needed its official consensus to precede. No restrictions about previous treatments were established. The parameters used to evaluate the efficacy of the treatment were as follows: (i) severity of the disease, assessed with the Sartorius score before (T0) and after (T1) treatment and (ii) the number of exacerbations during the treatment period compared with those occurring in the previous three months. The authors considered as exacerbation the acute development of at least one wide inflammatory lesion. Finally, patients were asked about side-effects during treatment. Statistical analysis was performed using parametric test (t-test). Significance was accepted at P < 0.05. The main clinical-demographic data, collected in a standardized form, are summarized in Table 1. Three patients did not complete the treatment: one for personal reasons, one because of gastro-intestinal side-effects not related to Clostridium difficile colitis, and one, affected by amyotrophic lateral sclerosis, complained of a worsening of the neurological disease, probably not related to antibiotic assumption. The 20 patients who completed the 10-week therapy showed a mean Sartorius score of 132.05 (range 28.00–298.05) at T0 and 71.50 (range 19.50–183.00) at T1 corresponding to a mean reduction of 45.85% (range 5.41–81.95%). The authors considered as responders the 17 patients who achieved a Sartorius score improvement higher than 25%, corresponding to the 85% of the patients who completed the treatment. The mean number of exacerbations was 6.00 (range 1.00–20.00) at T0 and 2.40 (range 0–10.00) at T1 corresponding to a mean reduction of 60% (range 0–100%). Both Sartorius score and the number of exacerbations showed a significant reduction after treatment: P = 0.00098 for Sartorius score and P = 0.0091 for the number of exacerbations, respectively. Three out of 23 patients (13.04%) complained of side-effects, mostly nausea and vomiting: one patient stopped the therapy before the scheduled end, whereas the two remaining completed the 10-week treatment. The efficacy and tolerability of this combination treatment in HS-AI has previously been assessed in three retrospective studies. The present one is the first prospective study and the results are in agreement with those reported in literature (Table 2). The reason why this antibiotic combination is effective is not fully understood yet. This study has some limitations. The patients were not randomized vs. placebo or other treatments. This decision was made for ethical reasons and because, in the authors’ experience, this treatment is the best option in severe HS-AI in terms of efficacy, tolerability, quick onset of action and cost. No data about long-term follow-up and recurrences are given because a maintenance treatment with oral zinc was prescribed, according to the desire of the patients to do as much as possible to maintain the results they had obtained.

European evidence-based (S3) guideline for the treatment of acne - update 2016 - short version.

European evidence-based (S3) guideline for the treatment of acne – update 2016 – short version A. Nast,* B. Dr eno, V. Bettoli, Z. Bukvic Mokos, K. Degitz, C. Dressler, A.Y. Finlay, M. Haedersdal, J. Lambert, A. Layton, H.B. Lomholt, J.L. L opez-Estebaranz, F. Ochsendorf, C. Oprica, S. Rosumeck, T. Simonart, R.N. Werner, H. Gollnick Division of Evidence-Based Medicine, Klinik f€ ur Dermatologie, Charit e Universit€atsmedizin Berlin, Berlin, Germany Department of Dermatocancerolgy, Nantes University Hospital, Hôtel-Dieu, Nantes, France 3 Department of Clinical and Experimental Medicine, Section of Dermatology, University of Ferrara, Ferrara, Italy Department of Dermatology, School of Medicine University of Zagreb, Zagreb, Croatia 5 Private practice, Munich, Germany Department of Dermatology and Wound Healing, Cardiff University School of Medicine, Cardiff, UK Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark University Hospital of Antwerp, University of Antwerp, Antwerp, Belgium Department of Dermatology, Harrogate and District Foundation Trust, Harrogate, North Yorkshire, UK Aarhus Universitet, Aarhus, Denmark Dermatology Department, Alcorcon University Hospital Foundation, Alcorc on, Madrid, Spain Department of Dermatology and Venereology, University of Frankfurt, Frankfurt, Germany Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge and Diagnostiskt Centrum Hud, Stockholm, Sweden Private practice, Anderlecht, Belgium Department of Dermatology and Venereology, University of Magdeburg, Magdeburg, Germany *Correspondence: A. Nast. E-mail: alexander.nast@charite.de

Understanding innate immunity and inflammation in acne: implications for management

Acne has long been understood to have a complex physiological basis involving several main factors: hormonally‐stimulated sebum production, abnormal keratinization of the pilosebaceous duct, and an inflammatory immune response to Propionibacterium acnes. Recent studies at the molecular and cellular level have begun clarifying how all of these factors interact, and the role of the innate immune system is better appreciated. Inflammation has been demonstrated in all acne lesions ‐ the preclinical microcomedo, comedones, inflammatory lesions, ‘post‐inflammatory’ erythema or hyperpigmentation, and scarring. Inflammation localized to the pilosebaceous unit can be considered the defining feature of acne and should be addressed via multiple therapeutic pathways. Clinicians tend to think oral antibiotics should be used to ‘calm’ inflammatory acne, but there is good evidence showing that topical retinoids also have anti‐inflammatory properties as a class effect. For best therapeutic outcomes, most patients with acne should be treated first line with a topical retinoid plus an antimicrobial agent, as has been demonstrated in thousands of patients involved in clinical trials and recommended by the Global Alliance to Improve Outcomes in Acne for more than a decade. Moving away from reliance on antibiotic therapy for acne is particularly important in an era of worsening antimicrobial resistance and worldwide calls to reduce antibiotic use. Improved understanding about the role of P. acnes and the innate immune system in acne should help clinicians in designing efficacious treatment strategies.

Management of severe acne

Acne is the most common skin disease, affecting up to 95% of adolescents. Severe episodes of acne can cause considerable physical and psychological scarring, and overexpression of transforming growth factor‐β can lead to formation of hypertrophic scars and keloids. The severity of acne in adolescence is associated with a positive history of severe acne in first‐degree relatives, especially the mother. In most cases acne is a chronic disease, and it is often a component of systemic diseases or syndromes. All forms of severe acne require systemic treatment. The available options include oral antibiotics, hormonal antiandrogens for female patients and oral isotretinoin, as well as other combination treatments. Oral isotretinoin is the only drug available that affects all four pathogenic factors of acne. However, due to possible serious side‐effects, a European directive states that oral isotretinoin should be used only as a second‐line therapy in cases of severe, nodular and conglobate acne. The pharmaceutical quality of generic isotretinoin products and the obtainability of isotretinoin through e‐pharmacies without prescription raise new therapeutic problems. New anti‐inflammatory compounds, such as the 5‐lipoxygenase inhibitor zileuton, may replace systemic antibiotics in the future, especially under the scope of antibiotic resistance prevention. This review looks into the various options and latest approaches, and factors to consider, when combating severe acne.

Retinoids in the chemoprevention of non-melanoma skin cancers: why, when and how

Introduction: The chemoprevention refers to the use of various types of chemical agents for preventing carcinogenic progression. Systemic retinoids are the most studied chemopreventive agents due to their capacity to regulate cell proliferation and their demonstrated efficacy in several clinical studies. Objectives: The aim of the authors was to give precise indications regarding the use of the systemic retinoid in the chemoprevention of non-melanoma skin cancer (NMSC). Methods: The authors reviewed the literature found through a search to MEDLINE (from 2001 to December 2011). Results: Both acitretin and isotretinoin are effective for the prevention of NMSC. Isotretinoin is preferred in xeroderma pigmentosum and nevoid basal cell carcinoma syndrome, whereas acitretin is more used in transplant recipients, psoriasis and severe sun damage. Conclusion: Despite numerous studies of the literature concerning retinoids in chemoprevention of NMSC, precise details of the type of retinoid to use, dosage and the duration of this preventive treatment and how to manage side effects in the case of long-lasting treatment are still not uniform and comparable. Moreover, neither guidelines nor approval by Food and Drug Administration exist to regulate the use of retinoids in chemoprevention.

Low-cumulative dose isotretinoin treatment in mild-to-moderate acne: efficacy in achieving stable remission

Background  Aimed at the reduction of post‐treatment relapse of severe acne, the cumulative dose of oral isotretinoin should be ≥120 mg/kg. However, data on the appropriate oral isotretinoin treatment regimen in mild and moderate acne are lacking.