[Acne]. / Akne.

Acne vulgaris is one of the most frequent dermatological diseases with a lifetime prevalence of about 85%. The clinical spectrum shows a great variety. Key factors of pathogenesis are increased sebum production, hyperkeratinization of the follicular infundibulum, inflammatory processes, and a dysbiosis of the skin microbiome. In addition to endogenous factors (e.g., disturbances of the androgen metabolism) or other hormonal changes, exogenous factors (e.g., diet, mechanical irritation or the use of inappropriate cosmetics) can also play an important role. The clinical spectrum is broad, extending from neonatal Acne (A.) to adult A., from comedonal A. to fulminant A., from cosmetic A. to A. excoriée (skin picking disorder). The psychological effects of acne can be profound and can cause a severe reduction in quality of life. Therefore, in addition to an effective therapy with regular medical check-ups and good adherence, it is always necessary to consider psychological aspects.

Biologic Therapy for Hidradenitis Suppurativa Plus Conglobate Acne Associated with SAPHO Syndrome: A Case Report.

is missing (Short Communication).

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

Verantwortlicher Umgang mit Antibiotika: Notwendigkeit der Antibiotikareduktion in der Aknetherapie.

Der übermäßige oder unkritische weltweite Einsatz von Antibiotika in der Medizin hat die Ausbreitung von Antibiotikaresistenzen beschleunigt. In einigen Bereichen sind viele Antibiotika bei bakteriellen Infektionen, die zuvor noch gut auf antibakterielle Wirkstoffe reagierten, mittlerweile wirkungslos geworden. Dermatologen/Venerologen setzten orale und topische Antibiotika bei der Behandlung von Acne vulgaris routinemäßig ein, obwohl Akne weder eine infektiöse Erkrankung ist noch alleine durch das Propionibacterium getriggert wird. Vielmehr ist sie eine komplexe, chronische entzündliche Hauterkrankung, die durch verschiedene pathogenetische Faktoren wie follikuläre Hyperkeratose, erhöhter Sebumproduktion, bakterielle Proliferation und Entzündung zustande kommt. Folglich sollte eine erfolgreiche Therapie auf die Bekämpfung verschiedener pathogenetischer Faktoren und nicht nur auf die von Propionibacterium acnes abzielen. Daher wurden topische Retinoide und Benzoylperoxid als Mittel der ersten Wahl definiert. Monotherapien mit lokalen Antibiotika sollten insgesamt vermieden werden. Systemische Antibiotika der Tetrazyklin-Gruppe haben bei bestimmen Krankheitsstadien ihren Sinn, ihre Wirkung könnte aber eher auf der antientzündlichen als auf der antibiotischen Reaktion beruhen. Gesundheitsbehörden ermahnen alle Gesundheitsdienstleister, den Einsatz von Antibiotika einzuschränken. Das Nutzen-Risiko-Verhältnis muss bei der Entscheidung für oder gegen eine antibiotische Therapie bei einem einzelnen Patienten immer auch in Bezug auf das öffentliche Interesse am Erhalt der Wirksamkeit von Antibiotika abgewogen werden. Im Folgenden werden das aktuelle Krankheitskonzept zu Acne vulgaris und die sich daraus ableitenden Konsequenzen für den Einsatz von Antibiotika vorgestellt.

Efficacy of adapalene/benzoyl peroxide combination in moderate inflammatory acne and its impact on patient adherence.

BACKGROUND AND OBJECTIVES: Adapalene 0.1 %/benzoyl peroxide (BPO) 2.5 % (Epiduo®) is the first, fixed-dose topical combination gel developed for the once-daily treatment of acne. The objective of this observational study was to assess efficacy and patient adherence under daily clinical practice conditions in a large population of young adults and adolescents (12 to 20 years) with moderate inflammatory acne. PATIENTS AND METHODS: A total of 2 780 patients receiving adapalene-BPO were evaluated in this multicenter, open-label, prospective non-interventional observational study. Observation time per patient was approximately 12 weeks. Assessment parameters included changes in acne severity, treatment success, safety, and therapeutic adherence. RESULTS: After 12 weeks, the majority of patients (91.5 %) showed improvement of acne under adapalene-BPO treatment, with an initial therapeutic response noted after a median time of 14 days. Overall, 21.8 % of participants displayed complete resolution of visible acne lesions. Treatment adherence was assessed as good in 63.2 % of patients. The majority of individuals (69.5 %) experienced no or only mild local skin irritations. No serious adverse drug reactions (ADR) were reported during the course of the study. CONCLUSIONS: Adapalene-BPO is effective and safe in the treatment of moderate inflammatory acne. The fixed-dose combination and easy application simplifies the therapeutic regimen, leading to good treatment adherence in the majority of patients.

Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation.

Specific interference with molecular mechanisms guiding tissue localization of leukocytes may be of great utility for selective immunosuppressive therapies. We have discovered and characterized efomycines, a new family of selective small-molecule inhibitors of selectin functions. Members of this family significantly inhibited leukocyte adhesion in vitro. Efomycine M, which was nontoxic and showed the most selective inhibitory effects on selectin-mediated leukocyte-endothelial adhesion in vitro, significantly diminished rolling in mouse ear venules in vivo as seen by intravital microscopy. In addition, efomycine M alleviated cutaneous inflammation in two complementary mouse models of psoriasis, one of the most common chronic inflammatory skin disorders. Molecular modeling demonstrated a spatial conformation of efomycines mimicking naturally occurring selectin ligands. Efomycine M might be efficacious in the treatment of human inflammatory disorders through a similar mechanism.

A Janus-Faced Bacterium: Host-Beneficial and -Detrimental Roles of Cutibacterium acnes.

The bacterial species Cutibacterium acnes (formerly known as Propionibacterium acnes) is tightly associated with humans. It is the dominant bacterium in sebaceous regions of the human skin, where it preferentially colonizes the pilosebaceous unit. Multiple strains of C. acnes that belong to phylogenetically distinct types can co-exist. In this review we summarize and discuss the current knowledge of C. acnes regarding bacterial properties and traits that allow host colonization and play major roles in host-bacterium interactions and also regarding the host responses that C. acnes can trigger. These responses can have beneficial or detrimental consequences for the host. In the first part of the review, we highlight and critically review disease associations of C. acnes, in particular acne vulgaris, implant-associated infections and native infections. Here, we also analyse the current evidence for a direct or indirect role of a C. acnes-related dysbiosis in disease development or progression, i.e., reduced C. acnes strain diversity and/or the predominance of a certain phylotype. In the second part of the review, we highlight historical and recent findings demonstrating beneficial aspects of colonization by C. acnes such as colonization resistance, immune system interactions, and oxidant protection, and discuss the molecular mechanisms behind these effects. This new insight led to efforts in skin microbiota manipulation, such as the use of C. acnes strains as probiotic options to treat skin disorders.

Can we define acne as a chronic disease? If so, how and when?

There is widespread misunderstanding of acne amongst both the medical and lay community, who often perceive the condition to be a simple, self-limited affliction of adolescents. Because many think that the disease "will go away on its own," they do not feel an urgency to aggressively treat acne. However, very often the reality is that acne treatment can be quite difficult. Furthermore, acne can be a devastating disease for the patient, since it manifests on visible body parts and in children near puberty, who are vulnerable both socially and psychologically. Most typically, acne is not an acute disease but rather a condition that continuously changes in its distribution and severity. Usually, acne treatment is necessary for many months and sometimes years. Despite treatment, acne may cause scarring and associated negative psychological effects. It is important for both patients and physicians to be aware that very effective treatments are available. It is also important to realize that new studies have proven the benefit of maintenance therapy with topical retinoids; these agents can minimize the potential for relapse, which is part of the natural history of acne. This article reviews the evidence suggesting that acne is a chronic disease in at least a subset of individuals. The members of the Global Alliance to Improve Outcomes in Acne believe that acne should be recognized and investigated as a chronic disease. This will change expectations of clinical trial design and treatment and will highlight gaps in the knowledge of acne epidemiology. The result should be an improvement in patient outcomes.

Anti-acne drugs in phase 1 and 2 clinical trials.

INTRODUCTION: Despite the impressive increase of knowledge on acne etiology accumulated during the last 20 years, few efforts have been overtaken to introduce new therapeutic regiments targeting the ideal treatment of acne. The increasing emergence of microbial resistance associated with antibiotics, teratogenicity, particularly associated with systemic isotretinoin, and the need for an adverse drug profile, which can be tolerated by the patient, make the need of new pathogenesis relevant anti-acne agents an emerging issue. Areas covered: A search for phase 1 and 2 acne treatment trials in the US National Institutes of Health database of clinical trials and the European Medicines Agency database with the key words 'acne' and 'treatment' was carried out, on 6 January 2017. Expert opinion: The detected trials mostly investigate topical agents that may act via sebosuppressive effects, antimicrobial properties or anti-inflammatory actions. The compounds under investigation include olumacostat glasaretil, cortexolone 17α-propionate, stearoyl-CoA desaturase 1 inhibitors, agents affecting the melanocortin system, omiganan, and minocycline. Systemic studied anti-acne drugs include finasteride, biologics, low dose anti-inflammatory antibiotics, and leukotriene B4 inhibitors.

Acne: topical treatment.

Acne vulgaris is a common skin disease, affecting about 70-80% of adolescents and young adults. It is a multifactorial disease of the pilosebaceous unit.(1) The influence of androgens at the onset of adolescence leads to an enlargement of the sebaceous gland and a rise in sebum production. Additional increased proliferation and altered differentiation of the follicular epithelium eventually blocks the pilosebaceous duct, leading to development of the microcomedo as the primary acne lesion. Concomitantly and subsequently, colonization with Propionibacterium acnes increases, followed by induction of inflammatory reactions from bacteria, ductal corneocytes, and sebaceous proinflammatory agents (Fig 1).(2-5)

Synergistic efficacy of adapalene 0.1%-benzoyl peroxide 2.5% in the treatment of 3855 acne vulgaris patients.

The adapalene-benzoyl peroxide (adapalene-BPO) combination gel is efficacious and safe in the treatment of acne vulgaris. We aimed in this pooled analysis to determine whether the adapalene-BPO combination demonstrates synergistic efficacy. Data were pooled and analyzed from three double-blind controlled studies, in which patients were randomized to receive adapalene-BPO, adapalene, BPO or vehicle once daily for 12 weeks. Efficacy assessments included percent reduction in lesion counts and Investigator's Global Assessment (IGA) success. Benefit of each treatment relative to vehicle was calculated by subtracting the vehicle result from the efficacy result. Synergy was defined as the benefit of the combination greater than the sum of benefits of adapalene and BPO monotherapies. Adapalene-BPO was significantly more efficacious than its monotherapies in decreasing lesion counts as early as week 1 and throughout the study (p < 0.05). Synergy in total lesion count reduction was observed up to week 8, contributing 48.7% of the benefit of adapalene-BPO relative to vehicle in decreasing total lesions at week 1. Synergy of the combination in IGA success was observed at weeks 1, 4, 8 and 12. In conclusion, the fixed-dose adapalene-BPO combination gel provides synergistic and significantly greater efficacy than its monotherapies in the treatment of acne vulgaris.

Inhibitors of dipeptidyl peptidase IV-like activity mediate antifibrotic effects in normal and keloid-derived skin fibroblasts.

Suppression of collagen and matrix synthesis and inhibition of the fibrogenic cytokine transforming growth factor-beta(1) (TGF-beta(1)) is a major therapeutic goal in the treatment of fibrosis and keloids. Inhibitors of dipeptidyl peptidase IV (DP IV)-like activity affect cell growth and cytokine production and are currently under investigation for the treatment of metabolic, autoimmune and inflammatory diseases. We show here that the inhibitors of DP IV-like activity, Lys[Z(NO(2))]-thiazolidide and Lys[Z(NO(2))]-pyrrolidide, suppress proliferation in human skin fibroblasts and keloid-derived skin fibroblasts in vitro. They significantly decrease TGF-beta(1) expression and secretion of procollagen type I C-terminal peptide in supernatants of both cell types. Furthermore, they abrogate the TGF-beta(1)-induced stimulation of collagen synthesis, matrix deposition, and TGF-beta(1) and fibronectin expression. Both inhibitors lead to dephosphorylation of mitogen-activated protein kinases pp38 and pERK1/2, which are activated upon TGF-beta1 stimulation and have been implicated in fibrogenesis. In a mouse model of dermal fibrosis, induced by repetitive intracutaneous injections of TGF-beta(1), the profibrotic effect of TGF-beta(1) detected by dermal thickening, collagen I, and alpha-smooth muscle actin expression, is significantly suppressed in the presence of inhibitors. Inhibition of DP IV-like enzymatic activity may therefore represent a promising therapeutic approach for the treatment of fibrotic skin disorders and keloids.

Topical treatment in acne: current status and future aspects.

During the last 20 years, the number of topical and systemic drugs for the treatment of acne vulgaris has been enriched. Topical drugs on the one hand have been newly discovered or further developments of already available agents such as in the group of retinoids or galenic formulation have improved efficacy or local tolerance. Topical retinoids are a mainstay in acne treatment since 1962. All-trans retinoic acid was the first and is still in use. Its irritative potential has led to the new galenics, i.e. incorporation in microsponges and in propolyomers, which increased the tolerability significantly. The isomer of tretinoin, isotretinoin, has the same clinical efficacy, but also a lower irritancy. A real breakthrough was adapalene, a retinoid-like agent, with a different retinoid receptor-binding profile, but in addition to the same clinical efficacy on inflammatory and non-inflammatory acne lesions compared to tretinoin, a better tolerability and, therefore, compliance. Unfortunately, over the past years topical retinoids have been less used in inflammatory acne than they should be, taking the the mechanisms of action into account. Topical antimicrobials, in particular topical antibiotics, should be used less often than in the past and only for short periods to avoid the development of resistances. It seems better to combine those agents with topical retinoids, with BPO or with azelaic acid to enhance the efficacy and slow down the development of resistance. BPO is still the gold standard for papular-pustular acne of mild-to-moderate type in concentrations of 2-5%. Azelaic acid is an alternative with efficacy on the comedo and is antibacterial without development of resistances. Finally, the physical removal by electrocautery or CO(2) laser of multiple densely packed closed comedones, macrocomedones and microcysts is necessary to enhance the efficacy of topical comedolytic agents and to speed up the therapeutic results. Photodynamic therapy has not yet been proven efficacious in controlled studies. Blue and red light can probably be used in association with local agents but enhancement of the irritative potential of topical and systemic agents has to be considered.