What Causes Acne and Potential Forms of Treatment
What causes Acne?
The process of acnegenesis (acne formation) is rather discrete and is associated with comedogenesis, i.e., the process through which pores become clogged / inflamed (for example, by the formation of blackheads). Acnegenesis can be characterised by the inflammation of the follicular tissues covering the face (and all the remaining body surface) - epithelial tissues - whose functions are varied (protection, secretion, absorption, excretion, filtration, diffusion, and sensory reception). Such inflammation usually leads to the formation of pustules and papules (commonly known as pimples). Before proceeding with further theorisation regarding acne, we recommend the visualisation of Tech Insider video  describing what can be found inside a pimple.
Acne: How do Acne Pimples form?
The nature of acne lesions varies from case to case. Three main factors that can be identified as acne causes have, however, been determined by researchers. These ought to be carefully considered in conjunction with other elements such as hormonal activity and heredity.
- Sebaceous Gland Hyperactivity
Sebum (i.e., the oily, waxy substance provenient from the sebaceous glands) is continuously secreted to the surface of the skin through hair follicle pores. The excretion of this substance (mainly composed of lipids) happens through the sebaceous glands (located all over the human body) and is controlled by one's hormonal system. Even though the sebaceous glands can be fond in all the areas of our body, they are larger and more abundant in certain body parts, one of them being the face.
During puberty, the sebaceous glands' activity increases substantially. This is due to the androgens (male sex hormones) becoming more numerous and active, which invariably triggers sebum production. As the production of sebum is rather speedy at this stage, the tissues responsible for secretion (epithelium) are not able to keep up with it. This will most likely lead to the hair follicle becoming blocked by sebum, which will subsequently have inflammation as a result. The hormonal system continues to play a vital (if not the main) role in terms of acne throughout adulthood. In the case of men, the gland activity (namely secretion) is influenced by testosterone. For women, the expressive increase of the luteinising hormone (the one responsible for the menstrual cycle) experienced immediately after ovulation triggers the acceleration of sebaceous glands' activity.
Due to the higher sebum secretion right before (2 to 7 days) menstruation, acne breakouts are likely to happen. Women suffering from polycystic ovary syndrome (PCOS) usually suffer from severe acne as well. This is because of the excessive presence of androgens in their organism. Acne patients often present larger sebaceous glands than the people who do not suffer from conditions of such nature. Moreover, they comparatively tend to exhibit a higher level of sebum production (a key factor for acnegenesis).
Nevertheless, at this point, there seem to be no traceable differences when comparing acne sufferers' sebum composition to the remaining population's. Specialists have detected, though, the existence of an inverse relation between sebum secretion and linoleic acid concentration (i.e., the lower the presence of linoleic acid, the higher the secretion of sebum). This has led researchers to infer that acne patients present a deficiency of linoleic acid - a fatty acid which is essential to foster the barrier function of the epithelium. Besides weakening this barrier, such deficiency may also result in hyperkeratosis (the thickening of the skin's outer layer). Both these factors will certainly contribute to acne aggravation.
- Changes in Follicular Keratinisation
During the process of keratinisation (the migration of keratinocyte cells from the basal layer towards the surface of the skin - as a consequence of these cells' maturation, they become filled with keratin), the maturation of keratinocytes takes place and, subsequently, their exfoliation into the follicle occurs. This is where the formation of comedones (small, flesh-coloured acne spots) begins. In the case of acne sufferers, keratinocytes stick together and usually block the pore (follicle). If the pore is open, a blackhead will be originated (open comedone); if, on the other hand, the pore is closed, a whitehead will be created (closed comedone).
The bacteria mainly responsible for acne manifestations are scientifically called Propionibacterium acnes and they find clogged pores a rather appealing nutritional source (they tend, therefore, to concentrate around blocked pores). The presence of such bacteria is usually recognised by the immune system, which produces a response whose visual translation is often redness, pus, and inflammation (or, in other words, the formation of pimples).
- The Influence of Bacteria
Propionibacterium acnes has unequivocally been identified as the cause of acne. Several studies corroborated that these bacteria are invariably present in teenagers suffering from acne. On the other hand, traces of P. acnes have not been identified in adolescents without acne. This is, however, different in the case of adults, who may carry these bacteria regardless of being acne sufferers or not. Both the accumulation of sebum caused by excessive lipid secretion and hyperkeratosis (i.e., the thickening of the outer layer of the skin) contribute to the increase of the incidence of bacteria on the skin. In spite of the scenario described above, it is important to highlight that bacteria are not deemed by specialists as being the most direct cause of acne breakouts.
The inflammation that takes place in the context of this condition is most likely due to 'free fatty acids that result from the breakdown of triglycerides (a type of blood fat) in the sebum' . Extracellular enzymes, proteases (the enzymes that break down proteins) and hyaluronidases (the enzymes that break down hyaluronic acid) may also contribute to inflammation. The Toll-like receptors (TLRs) have also become an object of interest for researchers focusing on how acne develops. TLRs can be defined as a type of proteins pivotal to the innate immune system. Studies have hypothesised that the acne bacteria can instigate TLR immune response, which will manifest in the form of acne inflammation.
Many variants of the acne condition can be identified. Furthermore, there is a wide set of other dermatologic issues that even though unrelated to acne, can mimic its symptoms and, therefore, lead to potentially inaccurate diagnoses.
a) The fundamental acne lesion
The basic acne lesion is called microcomedone and can be described as an expanded hair follicle full of P. acnes and sebum. As mentioned above, the comedone may assume one out of two possible forms: the open comedone (the one that opens to the surface of the skin, forming a blackhead), and the closed comedone (which stays beneath the skin in the form of a whitehead). Besides these, acne condition has other manifestations such as: papules (pink, tender, non-pustular bumps - they are normally small and inflamed); pustules (pustular lesions which are inflamed and usually small - they are tender and have a red base). These two lesions are superficial. There are two other ones - nodules and cysts - whose location is deeper in the dermis. Cysts can be distinguished from nodules due to the fact that they live deeper in the skin. Nodules present as spherical and rather large, and may often be painful. Cysts are inflamed pustular, usually painful lesions that may frequently cause scarring.
b) Conditions often misdiagnosed as acne
As Baumann & Keri (2009)  suggest, the main focus of most acne treatment protocols is not so much tackling existing, present lesions but, instead, preventing the occurrence of future eruptions / breakouts. As the key aim of these treatments is prevention, it normally takes time (8 weeks at least) for their efficacy to become visible. It is paramount to bear in mind that, for existing acne lesions, only salicylic acid, benzoyl peroxide and steroids have shown evidence of effectiveness in terms of potential forms of treatment. Although steroids are part of this short list, they are normally advised against as they can have a reverse effect on the skin and lead to steroid acne. There are 5 main principles which have been deemed by specialists as effective in terms of their contribution for acne treatment:
1. Normalising Keratinisation / Exfoliation
Preventing keratinocytes from sticking together is the first step towards successful acne control. Retinoids are particularly effective in this regard, as they help to reduce the internal factors that make the cells become sticky, and to decrease one's transglutaminase (the enzyme whose main function is to bond the keratinocytes' cell membrane proteins). Tretinoin (a type of retinoid) has been highlighted by researchers for its ability to eliminate existing comedones and to actively prevent the formation of new ones. For Baumann & Keri (2009) , tretinoin should be used as a preferred therapy for acne, as it adequately and effectively increases the follicle's receptiveness to the penetration of antibiotics. Isotretinoin (an oral retinoid) is recommended especially for the treatment of cystic acne - a condition which tends to show a certain degree of resistance to other therapies. This type of retinoid is unprecedented in terms of normalising keratinisation and reducing sebaceous gland activity. A substantial decrease in the production of sebum has been verified within 2 weeks of the application of this therapy .
2. Reducing / Eliminating P. Acnes Bacteria
Antibiotics as well as benzoyl peroxide attack bacteria and, therefore, contribute to decrease the incidence of inflammatory extracellular elements induced by P. Acnes. Clindamycin and erythromycin are considered the two most effective antibiotics in terms of acne treatment - so much that they are the most commonly used. Besides being highly antibacterial , they present exponential anti-inflammatory features by lowering the amount of the inflammatory free fatty acids that arise as a result of bacterial digestion of surface lipids [idem]. It is, however, important to take into account that there is a fairly high percentage of P. Acnes strains - carried by around 60% of acne patients - that are resistant to the action of antibiotics. According to Baumann & Kerri (2009), trials undertaken over time have suggested that the topical application of erythromycin is more likely to loose its efficacy, when compared to clindamycin, in patients carrying bacteria that show resistance to antibiotics . The standard therapy for acne when it comes to antibiotics is still very much mainly based on the prescription of oral antibiotics. Nevertheless, newer, lower-dose antibiotics [idem] are arising and starting to be regarded as a sound approach to fight bacterial resistance. These lower doses of antibiotics act fundamentally as anti-inflammatories (not so much as antimicrobials). Benzoyl peroxide generates reactive oxygen species in the follicle. This process will kill bacteria. One of the potential disadvantages of using benzoyl peroxide is that it causes the formation of free radicals, which may instigate an accelerated aging of the skin. It is useful to know that, when benzoyl peroxide and tretinoin are applied simultaneously, there is a high chance that the former will denature and reduce the efficacy of the latter.
Products to consider for this step : topical antibiotics (clindamycin, erythromycin); benzoyl peroxide; azelaic acid; sodium sulfacetamide; sulfur; oral antibiotics; light therapy.
3. Removing the material that clogs the pores
For this step, BHA (salicylic acid) and AHAs (alpha hydroxy acids) such as lactic and glycolic acids help to unclog the pores as they loosen the keratinocytes. Baumann & Kerri (2009) suggest that salicylic acid is deemed as more effective in decreasing the amount of comedones, when compared to AHAs. In the case of more severe acne lesions, procedures such as comedone extraction and/or acne surgery may also often be considered.
Products to consider for this step : retinoids; salicylic acid; AHAs (lactic acid and glycolic acid); azelaic acid.
4. Attacking the inflammatory response
Salicylic acid is, once again, an important element to this step, due to its anti-inflammatory features. The use of steroid injections or corticosteroids (especially potent topical corticosteroids)  is ill-advised in most cases, due to the fact that they may cause steroid atrophy and/or steroid acne. However, intralesional and oral corticosteroids may be considered for the treatment of the scarring caused by cystic acne. In-office BHA treatments also deserve to be highlighted in this context as they may have a pivotal role in reducing acne inflammation.
5. Decreasing the level of sebum
The main goal of this step is to decrease sebaceous gland activity. The application of topical and oral retinoids may be powerful in this regard. For women, the usage of oral contraceptives has also been indicated as an effective way of promoting hormonal stabilisation, in order to decrease the incidence of sebaceous secretions.
Products to consider for this step : oral contraceptives; retinoids.
Acne and moisturisation
Baumann & Keri (2009) have analysed a study conducted by Swinyer in 1980  in which the treatment of acne patients living in normal / humid countries was compared with the one applied to patients living in dry areas. This comparison allowed Swinyer to conclude that skin dryness is an important factor to consider, as it contributes to perpetuate the acne cycle and, thus, to decelerate its treatment. Studies were also conducted so as to examine what the most adequate way to clean acne patients' skin is [idem]. In this context, after 3 months of analysis, an emollient facial wash performed better in terms of acne treatment (namely reducing the incidence of papules and open comedones) than pure soap and benzoyl peroxide wash. Acne sufferers tend to experience an urge to frequently clean their skin. It is, therefore, necessary to ensure that the products used for such cleanse are not abrasive and contain noncomedogenic agents. It is also paramount to hydrate while cleansing through the usage of emollient facial cleansers. This is very much likely to positively impact the acne patient's treatment regimen.
In order to prevent acne, it is important to establish a skincare routine that touches, as much as possible, each of the five steps explained above. Baumann & Kerri (2009) outlined the following regimen, as an example :
1) Wash the skin with a salicylic acid cleanser (mild - 2%).
2) Apply a topical antibiotic solution / azelaic acid.
3) Apply sunscreen (SPF 45, if possible), with moisturising cream / lotion.
1) Wash the skin with the same salicylic acid product you used in the morning (c.f. step 1).
2) Apply topical retinoid.
Note: there may be slight changes / variations / additions depending on the physician following each patient's case and depending on each person's skin features.
Acne is the result of an intricate interplay of hormonal, hereditary and, in some cases, exogenous (exterior) factors . When a change in the inner area of the hair follicle occurs (i.e., when a set of cells clump together), the usual passage of sebum is inhibited and the follicle becomes blocked. At this point, the acne bacteria (P. Acnes) start to spread and inflammation takes place. Acne treatment can be approached from several perspectives and approaches, and needs to be tailored to each patient's specificities. There is, however, a set of principles which have been scientifically legitimised and deemed as effective in terms of acne treatment. Prevention and / or early treatment are pivotal for the successful treatment of acne.
 Baumann, L & Keri, J. (2009) 'Acne (Type 1 Sensitive Skin)' In L. Baumann, S. Saghari & E. Weisberg (Eds.) Cosmetic Dermatology: Principles and Practice (pp. 121-127). US: McGraw-Hill Companies.
 Tech Insider (2018) What's Inside a Pimple?. [Video]. YouTube. https://www.youtube.com/watch?v=UDBzqZp7slM&t=1s&ab_channel=TechInsider