A novel approach to treatment of Acne Vulgaris


Chronic inflammatory disease of pilosebaceous complex which involves hypersecretion of sebaceous glands, hyperkeratosis and bacterial colonization of this complex, acne vulgaris has been subject of multitude of studies for its broad impact and psychosomatic burden. The four etiologic factors, inflammation, hyperkeratosis, sebaceous hyperactivity and colonized pilosebaceous complex, are in a continuous dialogue and persistent interactions to one another which poses a challenge to gain a leverage in understanding the initial culprit [1].

The objective of this study is to explore failure of acne treatment plans that target mainly one etiological factor known in pathogensis of acne. Moreover, overworked sebaceous glands, increased in sebum production and change in composition of sebum is simply disregarded in most treatment protocols [2]. This study is to suggest that any therapeutic plan that fails to address one of etiological entities may not effectively and /or entirely treat either comedones or acne.

Electron microscopy of a comedo, which is more amenable to acne treatment

Electron microscopy of a comedo, best amenable to acne treatment

Therapeutic considerations and how to approach

There is no single best mode for management of all lesions . Treatment is determined by many factors, including the type of lesions present, duration of disease, past and present response to treatment, tendency for scarring and development of acne spots and more importantly severity of disease. Knowing the symptoms and treating acne vulgaris early and adequately are the keys to a successful management. Acne is a chronic disease and poor adherence to treatment is a major contributor to unresponsiveness [3].

Comorbidities and current use of medications especially oral contraceptives, corticosteroids and topical antibiotics may affect management . Psychological factors may have great impact on therapeutic plans [4]. Also adult patient’s overall hygiene, facial care, hair grooming, mechanical manipulation of lesions and use of cosmetics must be considered. There are two important points that acne patients should be aware of. First, six to eight weeks of acne treatment is required before improvement is noted [5]. Change of the regimen or addition of a new agent should be withheld during this period. Second, body lesions including back, chest, shoulder lesions respond more slowly to topical applications than do those on the face.

A rational approach to treat acne could be to selectively target the therapy to factors involved in development of acne and its underlying mechanisms [6]. This approach provides a guideline for prevention and medically intervene acne. First, prevention of comedones (whiteheads and blackheads). Second, sebum production reduction and control of sebaceous glands hyperactivity [7]. Third, inhibition of hormonal culprit, typically hyperandrogenism, topically or systemically [8]. Preventing rupture of comedones. Fourth, resolution of inflammation concurrent with treating acne [9]. Fifth, preventing and correcting acne scars. Treating these sequels of acne could become even more cumbersome.

Acne in development, inflammatory factors to address in treatment

Acne in development, inflammatory factors to address in treatment

Acne treatment based on severity

Some authors suggest addition of one agent, topical or systemic, at a time and implementation of the regimen for at least eight weeks before any change or addition of another agent could be made [5]. It is important to note that moderate to severe acne must be consulted with a physician in particularly to diagnose variants of acne vulgaris of more severe cystic form such as acne conglobata with more weighty psychosomatic impact.

According to guidelines, acne management would be based on severity of acne lesions. Mild, moderate and severe acne are to be treated with different management protocols. Mild form (grade I) is treated with topical retinoid with or without benzoyl peroxide. Topical clindamycin or erythromycin could be added if no adequate response withing eight weeks. For moderate acne (grade II-III) oral antibiotics can be started.

Hormone therapy, oral contraceptive or progesterone preparations, for females are added in more severe forms. Warranting systemic modalities, cysts treatment is either isotretinoin or combination of what is indicated for mild to moderate forms. Here you can find more information on maintenance treatment and its algorithm based on acne grade. Evidently, isotretinoin and antibiotic therapy is not included in acne maintenance treatment, which targets comedogenesis, for their potential side effects and toxicity. Maintenance treatment is necessary to prevent development of microcomedones.

NON pharmacological approach:

Acne skin care, commonly overlooked by physicians, may work by itself in mild to moderate acne without implementing any pharmacological regimen. Among the benefits of any non-pharmacologic regimen, less antibiotic resistance, a more nature-conscious choice, much less side effects including contact dermatitis and skin irritations could be counted. Change in composition of sebum, type of fatty acids, squalene increase and skin’s mantle call for a skin care which respects this alteration and address this frequently-discounted fragment of acne pathology [10]. Alteration in skin’s microbiome and the equilibrium between the two main skin’s commensals, C. acnes and S. epidermidis, has been purported to breed inflammation by modifying skin surface’s lipids and its manipulation hold sufficient promise to deserve an opportunity in treatment armamentarium of acne vulgaris.

On the other hand, burgeoning evidence hypothesizes that the microbiome dysbiosis may be modulated by non-microbial factors such as diet, hormones or skin type. Achievements of nutriceutical interventions aimed at restoring normal skin surface lipid composition and homeostasis are feasible therapeutic goals [11] [12]. Multitude of studies suggest a direct relationship between high glycemic index foods and acne vulgaris, demonstrating diets devoid of western refined foods ameliorate non-inflammatory and inflammatory acne.

In parallel to these studies, dairy have been found to be acneogenic due to their insulinotropic effects by enhancing IGF-1 or insulin itself. On the other hand, randomized controlled studies cast doubt on precedent works which gainsaid any association between diet and dietary habits with acne severity by revealing an increase in level of anti inflammatory fatty acids with consumption of mixed probiotics.

Topical Treatment:

Among therapeutic approach to mild forms of acne such as comedones (whiteheads and blackheads), small pustules and scattered papules are over the counter treatment products with desquamating agents such as benzoyl peroxide, among leading over-the-counter drugs it could be counted. Its antibacterial efficacy is noteworthy in rapid destruction of Propionibacterium acnes. This suppressive impact is much faster compare with that of antibiotics as it acts through generation of free oxygen radicals that destroy bacterial proteins [13]. In contrast to antibiotics, resident organisms do not become resistant to this agent.

This anti acne agent also demonstrates mild anti-inflammatory activity [14]. Its comedolytic property is comparatively slight in contrast to other topical agents used for treatment of acne. Benzoyl peroxide reduces sebum secretion by 22.5%.after 2 months use [15]. Contact allergy is quite rare with it. Skin irritation is considerable. Synergistic effect this agent has been shown with antibiotics such as erythromycin and clindamycin in topical preparations [16] [17]. On the other hand, cytotoxicity and reactive oxygen species, ROS, associated with use of this modality warrants concurrent utilization of antioxidants in any evidence based skin care regimen which targets bacterial colonization axis as primary culprit in acne vulgaris.

Among comedolytic treatment agents salicylic acid [18], which could be used as alternative or adjunct to benzoyl peroxide, is considerably being used. This combination therapy has been associated with favorable outcomes among modalities for moderate acne forms. Salicylic acid comedolytic activity justifies its therapeutic value in acne. Keratolytic activity of this BHA causes peeling and removal of top layer of the skin. This can result in preventing the follicles from getting plugged. Salicylic acid is also moderately potent in destructing Porpionibacterium acnes and shows moderate antibacterial efficacy.

pH control is another means to treat acne as proprionibacterium acne alters skin’s pH and its modification may have a role in acne treatment. Application of alpha hydroxy acids may resolve the comedones and prevent more severe acne such as cysts. Use of hydroxy acids,AHA’s, alone is not indicated for acne. However, a positive effect through control of sebum production and ductal hypercornification is likely. Peels of alpha and beta hydroxy acids have been shown of efficacy in control of oily skin [19]. Azelaic acid in 10-20% preparation have been used with promising results, however, some studies have been found benzoyl peroxide superior to azelaic acid in treatment of acne vulgaris. Topical azelaic acid was also found effective to control rosacea by barring ROS production and quenching inflammation.

Antioxidants are another category amid long term goals for acne therapy. Superoxide and other free radicals production appear to be involved in aggravation of acne vulgaris. Proprionibacterium acne may be accounted for superoxide’s radicals generation. Among antioxidants alpha lipoic acid, bioflavanoids and sea buckthorn have been subject of some studies and suggested by them in management. Oxidative stress exists in patients with acne vulgaris and play a role in etiopathogenesis and/or progression of the disease. The addition of modalities with antioxidative effects seems to be valuable in the control of acne vulgaris [20]. Certain antioxidants are well- known for their inhibitory effect on androgens. Genistein is non-steroidal inhibitor of 3-beta-hydroxysteriod dehyrodrogenase, zinc, gamma-linolenic, alizarin and curcumin are non-steroidal inhibitors of 5-alpha-reductase [21].

Sodium ascorbyl phosphate lotion demonstrated statistically significant improvement when compared to vehicle in all of the parameters measured. The adverse event frequency and cutaneous tolerability profile for sodium ascorbyl phosphate lotion were similar to vehicle [22]. Mangensium ascorbyl phosphate serum has also been associated with favorable outcomes in patients with acne through perpetual delivery of vitamin C and its inhibitory impact on lipid peroxidation.

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