Impact of acne on the daily life of adult patients: building a self-administered patient questionnaire.

BACKGROUND: Acne is a long-lasting disease in adolescents and adults impacting the patient's daily life. Currently, there is no specific questionnaire that assesses its impact in adult patients. AIM: To build a self-administered questionnaire assessing the impact of acne on the daily life in adult patients. METHOD: A multidisciplinary working group was created, including 3 experts in healthcare questionnaires and dermatologists specialized in acne. A questionnaire using a standardized methodology for designing self-administered patient questionnaires according to conceptual, development and validation phases was developed. A cultural and linguistic validation into US English was conducted, based on the original French version. RESULTS: A 14-item questionnaire demonstrating consistency, reproducibility and high reliability was build. The questionnaire significantly correlated with the SF-12 mental and SF-12 physical scores and CADI, indicating good external validity. CONCLUSION: The present acne burden questionnaire AI-ADL allows the practioner to assess quickly and easily the burden of acne in patients during his daily clinical practice. Moreover, its short format allows patients to express easily and quickly their feelings and to initiate a conversation between the practioner and his patient. Thus, AI-ADL may help to better understand the multidimensional nature of acne, as well as the individual impact on the acne patient's daily life and moreover, it may play a key role in the decision-making process of treatment initiation and involvement of the patient in the management of his acne.

Predictive value of FDG-PET imaging for relapse in metastatic melanoma patients treated with immunotherapy.

BACKGROUND: Anti-PD1 immunotherapy has shown a sustainable clinical activity in patients with metastatic melanoma. However, strong predictive factors of the long-term response or risk of relapse remain to be identified. OBJECTIVES: To determine whether FDG-PET imaging could be superior to CT scan in distinguishing residual tumours versus the absence of tumour in patients with a partial response (PR) or stable disease (SD) and whether a complete metabolic response (CMR) was associated with better outcomes. METHODS: Retrospective study conducted in all patients with metastatic melanoma treated with anti-PD1 immunotherapy between October 2014 and October 2017 considered to be in complete remission. The primary outcome was the occurrence of a relapse during the follow-up. CT scan and FDG-PET scan had to be performed within a maximum of 2 months of treatment discontinuation. For CT imaging, the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 were used and included progressive disease (PD), SD, PR and complete response (CR). For FDG-PET imaging, the metabolic responses were classified as progressive metabolic disease, stable metabolic disease, residual FDG avidity (RFA) and CMR. RESULTS: Twenty-six patients were in complete remission after collegial decision. Two patients had a SD on CT scan and a CMR on FDG-PET scan, and none of them relapsed. Ten patients had a PR on CT scan and a CMR on FDG-PET scan, and none of them relapsed. The mean treatment duration to achieve a complete remission was 7 months (3-23). A univariate analysis showed that a RFA assessed on the FDG-PET scan was significantly associated with a relapse (P = 0.00231). CONCLUSIONS: Most patients with a PR on the CT scan and a CMR on the FDG-PET scan should be considered with a CR. Our study showed that FDG-PET imaging could play a crucial role in predicting the long-term outcome and help to decide whether treatment should be discontinued.

Acne fulminans and Cutibacterium acnes phylotypes.

BACKGROUND: Acne fulminans (AF) is a rare and severe form of inflammatory acne. It is characterized by a sudden worsening of acne with appearance of ulceronecrotic lesions, which can be associated with systemic signs. Its pathophysiology and the best therapeutic strategy are only partially known. OBJECTIVE: Our main objectives were to describe the clinical and biological profile of AF patients and to determine whether there was a difference in Cutibacterium acnes phylotype in AF compared to acne vulgaris. The secondary objective was to assess the efficacy of different therapies. METHODS: A retrospective observational study was conducted in all patients followed for AF in our department between 2008 and 2018. Bacteriological samples were taken from each patient to analyse C. acnes phylotype distribution. The therapeutic response was assessed using the ECLA and GEA scales. RESULTS: Fifteen patients with a median age of 15 years were included (12 men, 80%). A family history of acne was found in 86.7% of patients. Nine patients (60%) had isotretinoin-induced AF. Only one patient (6.7%) showed systemic signs. The bacteriological culture was positive for C. acnes in 80% of patients. The predominant phylotype was IA1 in 60% of patients, corresponding to the predominant phylotype in acne vulgaris. Only 33.3% of patients were in remission after a first-line treatment with systemic corticosteroids, alone or in combination. Seven patients were treated with biotherapy, including five successfully with secukinumab. CONCLUSION: Our results suggest that there is no specific C. acnes phylotype associated with AF, raising the hypothesis that acute inflammation associated with AF may be more related to an abnormal cutaneous innate immunity activation. The use of preventive strategies, the impact of combined treatments and an assessment of the role of biotherapies, especially anti-IL-17, in AF treatment remain to be more investigated.

Cutibacterium acnes phylotypes diversity loss: a trigger for skin inflammatory process.

BACKGROUND: Acne has long been understood as a multifactorial chronic inflammatory disease of the pilosebaceous follicle, where Cutibacterium acnes (subdivided into six main phylotypes) is a crucial factor. In parallel, the loss of microbial diversity among the skin commensal communities has recently been shown as often accompanied by inflammatory skin disorders. OBJECTIVE: This study investigated the association of C. acnes phylotype diversity loss and the impact on Innate Immune System (IIS) activation. METHODS: The IIS response of skin after incubation with phylotypes IA1, II or III individually and with the combination of IA1 + II + III phylotypes, was studied in an in vitro skin explant system. The inflammatory response was monitored by immunohistochemistry and ELISA assays, targeting a selection of Innate Immune Markers (IIMs) (IL-6, IL-8, IL-10, IL-17, TGF-ß). RESULTS: IIMs were significantly upregulated in skin when being incubated with phylotype IA1 alone compared with the combination IA1 + II + III. In parallel, ELISA assays confirmed these results in supernatants for IL-17, IL-8 and IL-10. CONCLUSION: We identify the loss of C. acnes phylotype diversity as a trigger for IIS activation, leading to cutaneous inflammation. These innovative data underline the possibility to set up new approaches to treat acne. Indeed, maintaining the balance between the different phylotypes of C. acnes may be an interesting target for the development of drugs.

Evolution and duration of nodules in severe nodular acne on the back: results from a four-week non-interventional, prospective study.

BACKGROUND: Severe nodular acne is characterized by inflammatory nodules and scarring. Their natural evolution and duration are insufficiently investigated. AIM: To investigate the evolution and duration of untreated acne nodules. METHODOLOGY: Four-week, single-centre, non-interventional, prospective study in subjects with severe nodular acne on the back. Nodule evolution and duration was assessed using standardized photographs taken twice weekly. RESULTS: Data from 23 subjects were evaluable. Mean age was 25.1 ± 4.9 years, 87% were males, and mean acne duration was 9.7 ± 6.7 years. At baseline, the overall total nodule count was 132 (mean number: 5.7 ± 3.0 nodules/subject). Among others, the following two main pathways were observed: nodules evolving directly into atrophic scars (31.8%) and nodules evolving towards papules into atrophic scars (37.9%). After 4 weeks, 77.3% of baseline nodules had evolved into atrophic scars. After baseline visit, a total of 247 new nodules (3.1 ± 2.2 nodules/week/subject) with a mean duration of 4.9 ± 2.6 days were observed. The mean duration of new nodules was significantly longer in subjects (n = 16) with ≥6 new nodules compared to subjects (n = 7) with <6 new nodules (5.2 ± 1.4 vs. 3.6 ± 0.8 days; P = 0.008)). There was no correlation between the number of new nodules and acne duration or with the number of baseline nodules. CONCLUSION: This study documents the natural nodule evolution and duration over 4 weeks and showed in 23 patients the scarring potential of untreated severe nodular acne of the back.

Taxonomy and phylogeny of Cutibacterium (formerly Propionibacterium) acnes in inflammatory skin diseases.

Since its discovery, Propionibacterium acnes has undergone various name changes, and has been known since 2016, as Cutibacterium acnes. Herein we set out the history and rational of these taxonomic changes together with a description of a new genus, Cutibacterium, which includes five species within the cutaneous ecosystem. Modern microbiological techniques allow finer distinction between species and subspecies while also enabling the identification of separate subtypes within the population of Cutibacterium acnes. Phylogeny and molecular typing techniques thus provide a better understanding of the subtypes involved in certain inflammatory skin diseases, including acne, folliculitis and progressive macular hypomelanosis.

Expression of Three Adipokines (Adiponectin, Leptin and Resistin) in Normal Canine Skin: a Pilot Study.

Adipokines are biologically active cytokines that are mainly produced in adipose tissue. There is evidence, in man and mice, that some adipokines may be secreted in other tissues including the vascular endothelium, epithelia and sebaceous glands. Moreover, modified serum levels of adipokines have been detected in people with acne vulgaris or psoriasis; it is suspected that adipokines could contribute to local and systemic inflammatory conditions. We aimed to evaluate the expression of three adipokines (i.e. leptin, adiponectin and resistin) in normal canine skin. Formalin-fixed, paraffin wax-embedded punch biopsy samples were obtained from the sparsely-haired skin of the caudal ventral abdomen of a single clinically healthy dog with no history of skin disease. Immunohistochemistry was applied, using rabbit polyclonal primary antibodies specific for leptin, adiponectin and resistin. Adipokines were not expressed in normal canine dermis or hypodermis. In contrast, they were detected in the keratinocytes of all epidermal layers and hair follicle segments, sebocytes, apocrine gland cells and in the vascular endothelium. This is the first report on the expression of adipokines in normal canine skin, a first step in studying their role in the skin physiology and inflammatory skin diseases of dogs.

Characterisation of Cutibacterium acnes phylotypes in acne and in vivo exploratory evaluation of Myrtacine®.

OBJECTIVE: Our main objective was to compare Cutibacterium acnes (C. acnes) skin colonisation in patients with mild to moderate acne versus healthy controls and secondly, to evaluate a Myrtacine® -based cream on C. acnes total population and antibioresistant Cutibacteria in patients with acne. METHODS: In 60 acne patients (Global Acne Severity Scale, GEA grades 2-3), of mean age 20 [15-30] years and in 24 age- and sex- matched healthy controls, forehead strips samplings were performed for microbiological analysis of comedones by colony forming unit (CFU) counts of global C. acnes and erythromycin (EryR) or clindamycin-resistant (ClnR) populations of Cutibacterium and determination of phylotypes by MALTI-TOF. Clinical evaluations of acne patients (GEA, lesion count, porphyrin fluorescence) were performed at baseline and after 56 days of twice-daily application of a Myrtacine® -based cream. RESULTS: We first showed (i) high and similar levels of C. acnes colonisation in superficial pilosebaceous follicles and detection of EryR and ClnR strains in both acne and control groups; (ii) different repartition of phylotypes in acne patients versus healthy control, with a predominance of phylotype IA in acne patients and a link between phylotype IA and erythromycin resistance. Besides, after treatment with the Myrtacine® -based cream in acne patients, there was no change in C. acnes total load, but a significant decrease of EryR Cutibacteria, reduced porphyrin production by C. acnes, a decrease in acne severity (GEA), associated with reduced retentional and inflammatory lesions. CONCLUSION: Cutibacterium acnes colonisation was not significantly different in acne versus control groups. Phylotype IA was predominant in acne patient and in EryR C. acnes. A Myrtacine® -based cream significantly reduced the level of EryR Cutibacteria in vivo and improved acne lesions.

Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: a brief look at the latest updates.

While the commensal bacterium Propionibacterium acnes (P. acnes) is involved in the maintenance of a healthy skin, it can also act as an opportunistic pathogen in acne vulgaris. The latest findings on P. acnes shed light on the critical role of a tight equilibrium between members of its phylotypes and within the skin microbiota in the development of this skin disease. Indeed, contrary to what was previously thought, proliferation of P. acnes is not the trigger of acne as patients with acne do not harbour more P. acnes in follicles than normal individuals. Instead, the loss of the skin microbial diversity together with the activation of the innate immunity might lead to this chronic inflammatory condition. This review provides results of the most recent biochemical and genomic investigations that led to the new taxonomic classification of P. acnes renamed Cutibacterium acnes (C. acnes), and to the better characterisation of its phylogenetic cluster groups. Moreover, the latest data on the role of C. acnes and its different phylotypes in acne are presented, providing an overview of the factors that could participate in the virulence and in the antimicrobial resistance of acne-associated strains. Overall, this emerging key information offers new perspectives in the treatment of acne, with future innovative strategies focusing on C. acnes biofilms and/or on its acne-associated phylotypes.

Atrophic scar formation in patients with acne involves long-acting immune responses with plasma cells and alteration of sebaceous glands.

BACKGROUND: Possible outcomes of acne lesions are atrophic scars, which may cause serious psychological distress. Current treatments for postacne scarring often require invasive procedures. Pathophysiological studies on acne scarring have only investigated the first week of papule life. OBJECTIVES: To study the pathophysiology of atrophic scar formation to identify molecular and cellular pathways that can lead to new therapies for the prevention of acne scarring. METHODS: Large-scale gene expression profiling and immunohistochemistry analysis were performed on uninvolved skin and papules in both scar-prone (SP) and non-scar-prone (NSP) patients with acne, at different time points. RESULTS: Gene expression and immunohistochemistry analyses showed a very similar immune response in 48-h-old papules in SP and NSP populations, characterized by elevated numbers of T cells, neutrophils and macrophages. However, the immune response only persisted in SP patients in 3-week-old papules, and was characterized by an important B-cell infiltrate. Transient downmodulation of sebaceous gland markers related to lipid metabolism was observed in 48-h-old papules in NSP patients, followed by normalization after 3 weeks. In contrast, in SP patients a drastic reduction of these markers persisted in 3-week-old papules, suggesting an irreversible destruction of sebaceous gland structures after inflammatory remodelling in SP patients with acne. CONCLUSIONS: Long-lived acne papules are characterized by a B-cell infiltrate. A relationship exists between the duration and severity of inflammation and the alteration of sebaceous gland structures, leading to atrophic scar formation in acne.

Cutibacterium acnes molecular typing: time to standardize the method.

BACKGROUND: The Gram-positive, anaerobic/aerotolerant bacterium Cutibacterium acnes is a commensal of healthy human skin; it is subdivided into six main phylogenetic groups or phylotypes: IA1, IA2, IB, IC, II and III. To decipher how far specific subgroups of C. acnes are involved in disease physiopathology, different molecular typing methods have been developed to identify these subgroups: i.e. phylotypes, clonal complexes, and types defined by single-locus sequence typing (SLST). However, as several molecular typing methods have been developed over the last decade, it has become a difficult task to compare the results from one article to another. AIMS: Based on the scientific literature, the aim of this narrative review is to propose a standardized method to perform molecular typing of C. acnes, according to the degree of resolution needed (phylotypes, clonal complexes, or SLST types). CONTENT: We discuss the existing different typing methods from a critical point of view, emphasizing their advantages and drawbacks, and we identify the most frequently used methods. We propose a consensus algorithm according to the needed phylogeny resolution level. We first propose to use multiplex PCR for phylotype identification, MLST9 for clonal complex determination, and SLST for phylogeny investigation including numerous isolates. IMPLICATIONS: There is an obvious need to create a consensus about molecular typing methods for C. acnes. This standardization will facilitate the comparison of results between one article and another, and also the interpretation of clinical data.

TOXICAN: a guide for grading dermatological adverse events of cancer treatments.

PURPOSE: The dermatological toxicity of cancer treatments is frequent and sometimes debilitating. Its reference classification, the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), is sometimes difficult to use and does not include yet the newest toxicities. Our objective was to create a guide, TOXICAN, based on the CTCAE, which is easy to use in everyday practice and which facilitates the recognition and grading of these dermatological toxicities. METHODS: This guide was developed by a working group ("GESTIM") comprising oncodermatologists, allergists, pathologists, and researchers from Nantes University Hospital. It was based on the dermatological toxicities found in the CTCAE and adapted to daily practice. These toxicities were grouped into categories and associated with photographs of typical cases to aid recognition. A simplified grading scale derived from the CTCAE was also created. This booklet was validated by means of user evaluation, and then the Delphi consensus method. RESULTS: We selected 32 dermatological toxicities, including 12 created by our group, sorted into 7 categories: skin rash, dry skin/pruritus, hyperkeratotic papules, palmoplantar changes, hair and nail changes, mucosal changes, and others. Our simplified grading scale only differed from the CTCAE for one item, urticaria. Three items were modified after evaluation by the user group and 11 after application of the Delphi method. CONCLUSION: The objective of our practical guide is to facilitate the use of the CTCAE for recognizing and grading dermatological toxicity of cancer treatments in order to provide optimal guidance for therapeutic adaptations. Its impact on clinical practice remains to be evaluated.