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.

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.

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.