Acne vulgaris, disease of our modernity
With prevalence of about eighty percent in our young population, acne vulgaris is considered one of the most common disease of our era. Increased serum level of testosterone and its metabolites at onset of adulthood precipitates certain changes in sebaceous structures, among them sebaceous glands hypertrophy and a significant elevation of sebum synthesis and release. These alterations in enviroment of sebaceous follicles causes proliferation and hyperkeratosis of follicular epithelium. Acne vulgaris is defined by hypercornification of sebaceous follicles which characterizes closed comedones or open comdeones which as is later explained in this article demonstrate subclinical inflammation. Consequent colonization by propionibacterium acnes and staphylococcus exaggerates inflammatory response and leads to a full blown disease with considerable emotional impact on its patient population.
Acne is always inflammatory
The first studies to evaluate role of inflammation
in pathogenesis of acne and initiationg mechanism by which inflammation is formed performed in group of patients presented with acne who had not previously received any form of treatment. In these experiments infiltration of CD4 lymphocytes were demonstrated. Even though preceding research was indicative of inflammation as a secondary event caused by Propionibacterium acnes following follicular hyperkeratinization. However, more recent research suggest enhancement of interleukin-1 dynamism in intact sebaceous follicles taken from areas of the skin not affect by any acne lesion. This is a paradigm shift in way acne vulgaris has been long viewed as primarily hyperkeratosis disease while the proof of these studies is robustly proposing acne as a constitutionally inflammatory skin disease. This novel insight has two implications of paramount importance, one is the unaffected areas of the skin should be considered in treatment and second the treatment should be aimed to targeting inflammation as a major pathogenic factor with substantial atrocity.
How sebum changes causes acne
signifies a very important role in the pathogenesis of acne. Multiple lines of studies demonstrated a link between sebum production and development of acne. The connection may be referenced to the insight that acne frequently initiates when sebaceous glands secretions start a surge in adolescence. Even though sometimes cases of acne vulgaris have been observed in new borns due to hormonal changes which might concurrently occur. On the other hand acne seems to be fully treated when the axis of sebum production is under control. Among drugs which reduce and suppress sebum production are retinoids which is a first line in treatment of acne according to the guidelines. Detailed mechanisms underlying sebum control and its effectiveness in treament of acne are not fully elucidated despite our understating of sebum implication in comedonal acne. Animal studies of a quarter century ago indicates comedogenicity of sebum, attributed to free fatty acids. More recent research confirms these observations and conferred a mechanism which is reproducible. Also previous research proposes that sebum production may be controlled by suppression of linoleic acid in surface skin lipids, which may lead to deficiency of essential fatty acids
at the level of keratinocytes and sebaceous follicles and increased epithelial keratinization. This observation is further validated by correction of level of linoleic acid when epithelial cells are exposed to retinoic acid. Another aspect of this scenario is that level of linoleic acid in sebum is directly affected by sebocytes production of this acid rather than its production by an individual sebaceous gland, these two indexes are proportional in normal individuals. In contrast, for adolescents sebum synthesis of individual sebocytes increases before any observable change in sebum secretion, which may result in low levels of essential fatty acids and development of acne without any systemic changes in level of linoleic acid.
Squalene, protective or damaging?
Squalene, a major constituent of sebum, has been well recognized for its protective effect against oxidative stress and free radicals skin damage, which may also be induced by smoking. However, this precious molecule which confers the skin anti aging advantages in older adults, once oxidized may induce comedogenesis, which is cause of significant concern especially in adolescence.
The central aim of acne treatment
is to curb and manage present lesions, prevent acne scars and shorten the duration of the disease to lessen burden of the disease and its consequences. These goals should be discussed with the patients as patient understanding and cooperation plays a significant role especially about the remissions, periods in which patient may be acne free. Another aspect of patient education relies on the fact that treatment should be continued for at least eight weeks for an effective to be seen as many patients tend to discontinue their treatment in first two weeks, not observing expected relief.
Far more crucial to the treatment of acne is tailoring of treatment to each individual as comorbidities and use of medications often exist. More importantly, severity of the disease and patients preferences are two major determinant of management protocol for each patient. Tendency and preference of patients in using systemic versus topical
and plant based treatments or laser treatments, or acupuncture
may be considered and openly discussed. Most recent studies suggest approaches which target all aspects involved in acne pathogenesis rather than treatments which aim to one single aspect of acne vulgaris, one recent example is Olumacostat Glasaretil
. In further management of acne, patient response to various treatments must be registered and improvement in terms of patients satisfaction may be consulted in each visit.