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Formation of Acne: Genetic Vs. Environmental Causes

After having obtained a degree in biochemistry, Leah works for a small biotechnology company and enjoys writing about science.

Despite common myths pointing to hygiene or diet as the culprit behind chronic acne, genetic inheritance is the primary cause of this condition.

Despite common myths pointing to hygiene or diet as the culprit behind chronic acne, genetic inheritance is the primary cause of this condition.

The Bacteria that Causes Acne

The bacterium Propionibacterium acnes is the culprit behind acne breakouts, and the concentration of this bacteria in the hair follicle determines whether acne will form within that follicle. There are many different strains of P. acnes, and each strain varies in how severe the inflammation and scarring will be in a breakout. P. acnes bacteria cause many different types of infections, including skin, dental, and failed hip replacement contamination (Ajay Bhatia, Ph.D., et.al, 2004).

Pathway for Pimple Creation

Breakouts occur primarily on the face, upper arms, and back of those who struggle with the condition. The bacterium grows best in anaerobic conditions (without oxygen) and is not contagious, since it resides on the skin of nearly every human. An active infection is not caused until four major events occur:

1) Hormone induced increase in oily secretions (sebum)

2) Too much keratin produced in the hair follicle

3) Blockage of the hair follicle

4) Overgrowth of bacteria within the obstructed hair follicle, causing inflammation.

Excess sebum causes errors in the process of formation of keratin in the skin, which forms the hair shaft. When the keratinization process goes awry, the bacteria gets trapped within the follicle. The oxygen deprived environment leads to a rapid increase in the number of germs, which creates a microscopic infection pocket known as a microcomedone. As the trapped bacteria continue to increase, two types of lesions may form. The first is an open comedone, which is more commonly known as a blackhead. Blackheads do not typically cause scarring and are less likely to become inflammatory. Closed comedones, known as whiteheads, are the most likely to result in cystic acne. When the contents of the whitehead are ruptured into the under-layers of the skin (rather than externally), the body responds to the infection with an inflammatory response and a cyst forms.

Acne is formed as excess sebum is produced and trapped. Bacteria multiplies in the oxygen-deprived environment and inflammation occurs as the immune system is triggered to respond to the infection.

Acne is formed as excess sebum is produced and trapped. Bacteria multiplies in the oxygen-deprived environment and inflammation occurs as the immune system is triggered to respond to the infection.

Is Acne Genetic?

Some people appear to have a natural immunity to the bacteria and never form acne at all, even in adolescence. 50% of people who have acne after the adolescent period have a first-degree relative with the same condition. While there are some environmental influences for the formation of this skin condition, the evidence from recent studies demonstrates the overwhelming majority of acne cases are inherited.

People who have androgen receptor inactivity do not ever develop acne. Genes that increase androgen receptor activity are known to cause acne, along with other genes which may increase inflammation, reduce cell-turnover rates, and increase the amount of androgens in the body.

Many human genes influence the prevalence and severity of acne formation (Melnik, B.C., 2013, pp. 109-130). Mutations in these genes increase the ability of androgens to bind, increase the baseline level of androgens, decrease cell-turnover and death rates, and increase inflammation.

Human Genes Influencing Acne Severity

GeneMutationCorrelationEffect of Genetic Mutation

MUC1 1q21 polymorphism

Large increase in tandem repeats

Severe acne

Gene responsible for the suppression of the sebaceous gland function and development. Produces the protein Mucin 1 glycoprotein.

FGFR2 10q26

In acneiform nevus, Ser252Trp mutation in isolation. In Apert Syndrome, Ser252Trp and Pro253Arg mutations.

Increased acne

Increased functionality of the fibroblast growth factor receptor 2 protein. Increases the rate of activation of P13K/Akt signaling. The P13/Akt signal increases cell growth and reduces the rate of normal cell death.

Androgen Receptor Gene (AR) Xq11-q12

Reduced number of CAG repeats and/or GGN repeat polymorphisms.

Increased acne

Increased androgen receptor activity on the X chromosome.

Cytochrome P450 CYP1A1 15q22-24

m-1 alleles overexpressed

Increased acne

Increases the rate of degradation of retinoids in the body. May affect the modification of oil producing cells in the skin.

CYP21A2 polymorphisms

Several different mutations

Increased acne

Synthesis of the hormone cortisol. Increased androgen production.

CYP11A1 Polymorphisms

Several different mutations

Increased acne

Synthesis of the hormone cortisol. Increased androgen production.

TNFα 6p21.3

Polymorphism

Increased acne and inflammation

Tumor necrosis factor: responsible for programmed cell death

CYP21A2 6p21.3

Several different mutations

Increased acne

Causes a deficiency of the Steroid 21-hydroxylase protein, which causes congenital adrenal hyperplasia.

HSD3B2 1p13.1

Several different mutations

Increased acne

Causes a deficiency in 3β hydroxysteroid dehydrogenase II, which causes congenital adrenal hyperplasia.

CYP11B1 8q21

Loss of function mutation

Increased acne

Causes a deficiency in the protein Steroid 11-β-hydroxylase, which causes congenital adrenal hyperplasia.

Interleukin-1A 2q14

A single Nucleotide change from Guanine to Thymine on the Interleukin-1A gene (+4845(G> T))

Increases severity of inflammatory acne

Produces the protein Interleukin-1α, which activates an increase in lymphocytes, induces fever, and increases fibroblasts. Mutation increases inflammatory response to acne.

TNFα -308 minor A allele

A single nucleotide change

Higher occurrence in female acne

Tumor necrosis factor: responsible for programmed cell death

Bacteria Types and Genes Influencing Acne Severity

There are several major types of the P. Acnes bacteria found in humans. Types I and II are found in people who have clear skin and in people who have skin with breakouts. Types IV and V are found in a much higher concentration of people who have acne than those who do not suffer from the condition. In Type III, the bacteria increase the activity of several different pro-inflammatory proteins and promotes the breakdown of the cellular matrix in the skin. This leads to the highest severity of inflammatory acne. Propionibacterium Avidum, however, only upregulates the action of two genes involving the breakdown of cellular matrix and cell proliferation, and causes less severe acne (Jasson F., et. al., 2013, pp. 587-592).

Increased Protein Production Induced by P. Acnes

One of the most inflammatory proteins produced by the bacteria responsible for skin eruptions is Christie-Atkins-Munch-Peterson protein (CAMP). This toxin induces a number of responses in the human body, which triggers the inflammatory response responsible for the formation of comedones and cysts. The toxins produced induce a cellular response in the human skin cells by increasing the production of certain proteins that cause inflammation and a breakdown of tissue.

Protein IncreasedFull NamePurpose

PAR-2

Protein Activated Receptor – 2, also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-coupled receptor 11 (GPR11) .

Modulates inflammatory response, senses enzymes that break down proteins produced during infection, modulates obesity and metabolism.

TNF-alpha

Tumor Necrosis Factor-alpha, also known as cachexin or cachectin

Involved in systemic inflammation, induces fever, induces normal cell death, stops viruses from reproducing.

MMP-13

Matrix metallopeptidase 13, also known as Collagenase 3.

Breakdown of collagen, enzymes, and glycoproteins that surround and support cells (extracellular matrix)

Highly refined sugar intake increases inflammation, so those with a genetic predisposition to acne may see an increase in breakouts if they consume a diet with a high glycemic index.

Highly refined sugar intake increases inflammation, so those with a genetic predisposition to acne may see an increase in breakouts if they consume a diet with a high glycemic index.

Environmental Factors Influencing Breakouts

While acne is largely influenced by genetics, some environmental factors influence the severity and frequency of breakouts.

Diet:

There is an old myth that chocolate causes pimples to form, but a study performed with chocolate and a placebo containing no cocoa dispels that old assumption. Sugar, however, may cause an increase in inflammatory acne for those who are already prone to developing the skin condition (Mahmood, S.N. & Bowe W.P., 2014, pp. 428-435). Foods high in sugar cause a spike in hormone levels in the blood, and these hormones stimulate the production of oil. Avoiding food with a high glycemic index is a good plan for those who suffer from frequent breakouts.

Hygiene:

There is a myth that “dirty skin” causes acne. This is absolutely untrue, as the microcomedones form under the top layers of skin. Topical dirt does not cause breakouts in any way. Washing your face to clear away the oil naturally produced should not be done more than twice per day, as excessive washing will only increase the amount of sebum produced and may inflame or otherwise irritate your skin.

Treatments for Acne

The most effective treatments for acne currently include retinoids, topical creams such as benzoyl peroxide to clear pores, and topical antibiotics. Hormonal therapies are often useful to help control female post-adolescent acne problems. In the future, a vaccine therapy may be available to prevent the occurrence of acne completely.

How Does Vitamin A Reduce Acne?

Retinoids work by helping the skin to shed (peel) at a faster rate, preventing oily secretions from getting trapped with dead skin cells. This process is called desquamation, and many people with high sebum production will have the dead skin cells get trapped and not shed appropriately. Retinoid creams also block many of the inflammatory pathways triggered by cytokines in the skin (Leyden, J., Stein-Gold, L., & Weiss, J., 2017, pp. 293-304).

There are several different creams that may be applied to the skin: Tretinoin, Adapalene, and Tazarotene are common formulations that help chronic acne sufferers.

While many retinoid treatment options are by prescription only, Differin is a brand name for Adapalene and may be purchased over-the-counter. The author of this article has used this medication with great success.

For extremely severe acne, isotretinoin (13-cis-retinoic acid) may be taken systemically as an oral medication. This treatment is typically reserved for cases that are unresponsive to more traditional therapy, and patients must be monitored closely for side effects. This is the most effective treatment for inflammatory acne, and works by attacking all of the major pathways for the formation of microcomedones. This medication reduces the amount of sebum produced, is anti-inflammatory, and reduces the concentrations of P. acnes on the skin surface and within skin pores.

How Does Benzoyl Peroxide Work?

Benzoyl peroxide functions in two ways: as an oxidant and as an anti-inflammatory agent. Since the P. acnes bacterium is anaerobic, the introduction of oxygen into skin pores kills the germ responsible for breakouts. Reducing inflammation prevents small lesions from becoming cystic, which reduces the scarring potential. This topical treatment is often used in conjunction with a topical retinoid cream to treat resistant cases.

Salicylic acid may be incorporated into facial wash or into a cream. This treatment is effective for mild outbreaks.

Salicylic acid may be incorporated into facial wash or into a cream. This treatment is effective for mild outbreaks.

How Does Salicylic Acid Work?

The main ingredient in aspirin, salicylic acid increases the rate of skin cell turnover, which helps prevent sebum from getting trapped. Used topically, this medication works well for milder cases of acne. For more severe cases, a retinoid cream will be more effective at preventing breakouts.

How Do Birth Control Pills Work?

Low dose birth control pills work by regulating the hormonal cycle in women, preventing the swing in androgens that occur on a monthly cycle. Hormonal control for acne is often useful for women who struggle with post-pubertal acne that is not responding well to other medications.

How Do Probiotics Work?

Probiotics help to keep a healthy balance of bacteria in the skin, preventing the over-proliferation of the bacteria that causes breakouts. The beneficial microbiome created by consuming probiotics improve the skin barrier and reduce skin inflammation. Strains of beneficial bacteria include Lactococcus species HY449 and Streptococcus Salivarius. Both of these bacteria produce a bacteriocin-like inhibitory substance (BLIS) that prevents the growth of harmful bacteria, including P. Acnes and S. Aureus. When the probiotics are applied as a topical cream, they increase the amount of ceramides produced in the skin. This helps the skin retain natural moisture in addition to providing a natural antimicrobial property via the action of specific ceramide sphingolipids , such as phytosphingosine (Kober, M. & Bowe, W.,2015, pp. 85-89).

The use of oral antibiotics and probiotics as a combination therapy show promising results for the treatment of inflammatory acne. Several commercial preparations are now available for topical application, and ingestible probiotics have been available over-the-counter for a considerable period of time. Probiotics are an easy, low cost treatment option for those struggling with acne.

How Does Tetracycline Work?

This antibiotic works primarily by killing the bacteria in and on the skin. This treatment was the first topical cream therapy approved for the treatment of acne. Unfortunately, many formulations do not penetrate well into the skin, reducing the efficacy. New formulations such as Imex (tetracycline hydrochloride 3%) have been compounded to increase the penetration of the skin and are shown to be effective at reducing the rate of skin lesions.

Effective Acne Medication: A Poll

Is There a Vaccine for Acne?

There is not currently a vaccine for acne, but several companies are working on creating an immunization. One promising pathway is to immunize people against the CAMP toxin produced by the P. acnes bacteria. Current trials have been successful in mice and in human skin tissues taken from acne biopsies, but true human trials haven’t been attempted yet.

Sources

Ajay Bhatia, Ph.D., Jean-Francoise Maisonneuve, Ph.D., & David H. Persing, M.D., Ph.D. (2004). Propionibacterium Acnes and Chronic Diseases. The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary.

Melnik, Bodo C. (2013). Sebum, Skin Type, and pH, Chapter 14, pp. 109-130.

Jasson F., Nagy I., Knol A.C., Zuliani T., Khammari A., Dréno B. (2013). Different strains of Propionibacterium acnes modulate differently the cutaneous innate immunity. Journal of Experimental Dermatology, Volume 9, pp. 587-592.

Mahmood, S.N. & Bowe W.P. (2014). Diet and Acne Update: carbohydrates emerge as the main culprit. Journal of Drugs in Dermatology, Volume 4, pp. 428-435.

Leyden, J., Stein-Gold, L., & Weiss, J. (2017). Why Topical Retinoids Are Mainstay of Therapy for Acne. Dermatologic Therapy, Volume 7 (3), pp. 293-304.

Kober, M. & Bowe, W. (2015). The effect of probiotics on immune regulation, acne, and photoaging. International Journal of Women’s Dermatology, Volume 1(2), pp. 85-89.

© 2018 Leah Lefler

Comments

Leah Lefler (author) from Western New York on January 13, 2019:

I also have issues with adult acne, and use Adapalene (a retinoid cream) to help. Restricting the amount of refined sugar and using non-irritating soap helps, too.

Some populations never have issues with acne, and the genetic predisposition for the condition can make treatment more difficult. I hope your cysts clear up with some dietary modifications in addition to your current Benzoyl Peroxide routine!

Glenn Stok from Long Island, NY on January 12, 2019:

I’m so glad I found this article of yours Leah. I recently had a problem with cysts on my back. My dermatologist prescribed a Benzoyl Peroxide wash and that has had slow results.

You mentioned the issue with too much sugar. Reading that had alerted me to the fact that I’ve been eating more sugary deserts lately. Maybe that’s what brought on the problem all of a sudden at my age. I'm going to eliminate those deserts, now that I know the effects of it.

The part about Probiotics was interesting too. I didn’t know that this can be helpful for this condition too. Thanks for a very thorough and educational article.

Liz Westwood from UK on November 21, 2018:

Thanks for your helpful reply, Leah.

Leah Lefler (author) from Western New York on November 20, 2018:

The tetracycline used to treat acne is typically prescribed as a topical cream, Liz, so it is not ingested. Unfortunately, however, even the topical application has led to resistant strains of P. acnes. This treatment modality is one of the oldest and has fallen out of favor as retinoids are the favored topical treatment, along with benzoyl peroxide.

Liz Westwood from UK on November 20, 2018:

This is a thorough and very detailed article. How does the use of tetracycline work when doctors are becoming increasingly reluctant to prescribe antibiotics.

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