Emerging pathogenesis of Acne and the role of Dermal Clinician’s in the management of Acne

Acne vulgaris is the most common inflammatory dermatological disease which disturbs the pilosebaceous unit. Acne is distinguished by non-inflammatory lesions in the form of comedones; or inflammatory lesions in the manifestation of papules, pustules, nodules and cysts. However widespread acne may be globally, the comprehensive pathogenesis of acne is complex, multifactorial and still unidentified. Formerly, it has been proposed the progression of acne is due to four factors; the production of additional sebum, the interference of keratinisation within the infundibulum of the hair follicle, the colonisation of the pilosebaceous duct by Propionibacterium acnes and the discharge of inflammatory mediators into the skin. Yet, emerging and continuing research encompassing the pathogenesis of the chronic inflammatory disorder is still advancing.


Propionibacterium acnes (P. acnes)


For an extended time, it has been thought P. acnes, fostered on the skin of most humans, donates considerably to the pathogenesis of acne, though, it has been conjectured that not all who harbour P. acnes suffer from acne, as P. acnes, located within the pilosebaceous unit bestows in both acne sufferers and healthy individuals. Henceforth, evidence and research is continuously emergent surrounding the role of P. acnes in acne advancement, with one study implicating that certain P. acnes strains may be linked to healthy individuals, whilst other P. acnes strains may be closely related to acne sufferers. Studies have also inferred that P. acnes may be significant in the adaptive immune response of acne. In biopsy tests of inflammatory acne lesions Interleukin 17 (IL-17) cells were discovered in perifollicular infiltrates and resultant of P. acnes being an inducer of IL-17 and IFN-y from CD4 T-cells a consensus was drawn that acne may possibly be a T-helper type 17 (Th17) mediated condition, where Th17 cells could possibly contribute to either the homeostasis or the pathogenesis of acne vulgaris. Considering these findings, it is imperative to note that the P. acnes strain and its correlation to the development of acne is controversial and not yet wholly understood or recognised.


Inflammation


A noteworthy expanse of histological, immunological and clinical research indicates inflammation is significant in all stages of the acne lesion, including the instigation, propagation and resolution. Recent findings indicate inflammation and follicular epithelial hyperproliferation are present in the microcomedo, prior to the the comedo formation, which tests the categorisation of non-inflammatory and inflammatory acne lesions and the consensus that inflammation is only extant in the delayed phases of acne vulgaris lesions. Research has also demonstrated that uninvolved skin from acne patients contains raised levels of CD3+ and CD4+ T-cells in the perifollicular and the papillary dermis in accumulation with amplified macrophage activity, similarly to that of papular lesions. Additionally, in the regression period of acne lesions an excessive level of T-cells, macrophages and leukocyte antigens are found to be existing, suggesting that delayed hypersensitivity reactions are significant in the inflammation of acne.


Hormones


An upsurge in androgen levels inspires sebum production via the binding of receptors on sebaceous glands and pilosebaceous ducts, and research has exhibited that acne prone skins have higher levels of androgen receptors and increased testosterone and 5a-dihydrotestosterone activity. This discovery further supports the proposed correlation between acne development and those possessing high levels of androgens, which is seen in puberty, Polycystic Ovarian Syndrome and Congenital Adrenal Hyperplasia, whilst conversely, those with deficient androgens are said to not develop acne. Interestingly, endocrine interrupting chemicals which are widely used in industrial, pharmaceutical and personal care products, have the potential to inhibit synthesis of natural hormones, and studies suggest contact with these chemicals can result in raised androgen levels and henceforth are also capable of promoting the progression of acne.



Sebum composition


Emerging evidence also indicates that it is not the amount of sebum secreted rather the alterations in the components and composition of sebum lipids which correlates with the occurrence and the development of inflammation and acne. Sebum is composed of a mixture of non-polar and polar lipids consisting of triglycerides and free fatty acids (57.5%), wax esters (26%), squalene (12%) and cholesterol and cholesterol esters (4.5%) and research has indicated that certain molecules found within the composition of sebum are cytotoxic and irritant and therefore provoke reactive follicular hyperkeratosis and the formation of comedones. This concept is further supported by the mechanism of antiacne compounds which have the ability to reduce acne lesions through inhibition of proinflammatory lipids.


Diet and Environmental Factors


Exposome factors involving nutrition, medication, occupational aspects, pollutants, climatic, psychosocial and lifestyle influences are also said to contribute to the development of acne due to their capabilities to interact and generate a chronic inflammatory response within the pilosebaceous unit and therefore affect the skins natural barrier and microorganisms. In conjunction with the Exposome factors, examinations have also hypothesised that the Western Diet of hyperglycaemic carbohydrates and dairy proteins are fundamental contributors in the progression of acne due to their ability to upregulate the insulin-like growth factor (IGF-1) and alter the composition of sebum. It is also interestingly noteworthy that acne is absent in populations which consume less insulinotropic Palaeolithic diets which could be due to the lower insulin-like growth factor (IGF-1).


Interprofessional practice and the role of Dermal Clinician’s in the management of Acne


Research affirms that acne necessitates systemic treatments in the form of Oral Antibiotics (Benzoyl Peroxide Antibiotics, Clindamycin and Crythromycin), Oral Hormone Antiandrogens and Oral Retinoids (Isotretinoin). Though, due to the collective cases of antibiotic resistance and the major adverse effects of these medications, such as Xerosis and skin irritations, an increased demand for alternative therapies in the management of acne has become apparent. As Dermal Clinicians there are a number of ways we can work interprofessionally to aid in the support, treatment and management of acne sufferers, some of these involve;

  • Photodynamic Therapy, which can destruct sebocytes and reduce inflammation via the application of 5-aminolevulinic acid and the use of Red Light.

  • Non-Ablative Radiofrequency which can be used to denature bacteria and diminish sebaceous glands through heating of the dermis and subcutaneous tissue via the use of radio waves.

  • Fractional Radiofrequency, which entails the use of microneedles to target the mid dermis and reduce inflammation of acne lesions.

  • Laser, which can reduce sebaceous gland activity and inflammation through Thermal coagulation of the sebaceous glands and the associated hair follicles.

  • IPL, which can treat inflammatory lesions and cause destruction of the sebaceous glands by targeting the blood cells using heat and energy generation. In addition, through selectively targeting the chromophores melanin and water, IPL devices can also be used to treat post inflammatory pigmentation and atrophic scarring linked with acne.

  • LED can photoactivate endogenous porphyrins in P. acnes.

  • Chemical Peeling Preparations can be used for antibacterial, anti-inflammatory, keratolytic and comedolytic effects, these are achieved through the manipulation and creation of a controlled and managed injury to the skin, which promotes regeneration of the epidermal layer of the dermal tissues.


It is vital to note, depending on the severity of the acne, these modalities and alternative treatments alone may not achieve complete resolution of the condition. Therefore, it is recommended for best clinical outcomes that Dermal Clinicians work interprofessionally alongside other medical specialists and in some cases, treatment and management can be undertaken in conjunction with the administration of topical or systemic medications.



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