Exactly How Does Acne Form Now That Scientists Believe It Is Primarily Inflammatory?
The Immune System Stimulates Inflammation in the Hair Follicle/Pore Right From the Start
The Essential Information
Even though acne is such a common disease, we still don't know precisely how it forms. This makes treating acne a challenge, but also makes studying acne endlessly interesting as new discoveries come to light. One such recent discovery is the central role that inflammation plays in acne development. From what scientists are uncovering, inflammation is involved in every phase of acne development, right from the start.
This article with go in-depth into how acne forms, with an emphasis on inflammation. If you want to read a more straightforward and simple article outlining what is acne, click here.
In brief: Traditionally, researchers believed that acne was caused by androgens, which are male hormones that are present in both males and females. The view was that increased androgens led to more skin oil production and clogged pores. Inside these clogged pores, skin oil would build up, and acne bacteria would thrive on the trapped skin oil, causing inflammation in the skin and acne lesions. Recent research, however, has found that inflammation is present right from the start. Because of this new knowledge, researchers now classify acne as a chronic inflammatory disease, and not just a hormonal and bacterial affliction.
Feeling geeky yet? If so, read through the entire article and then bore your friends with all the details ;-)
In the past, scientists thought that inflammation was one of the last steps in acne development. Here's an abbreviated version of how they used to think it went:
- First, it was thought, elevated androgen (male hormone) levels caused skin oil (sebum) to be overproduced and skin cells (keratinocytes) to also be overproduced. The combination of these two things clogged pores.
- Inside these clogged pores sebum got trapped. Acne bacteria (C. acnes), which lives on skin oil, overgrew in the trapped skin oil, and this caused inflammation in the skin and what we know as acne lesions.
However, new research has come to light in the past few years that shows us that inflammation is actually present right from the start. We can break down acne formation into four main steps now that we know inflammation is there from the start.
Step 1: Triggering of Inflammation
Although scientists see inflammation in the skin right from the start, they still don't know exactly what triggers it. But as science normally goes, they have put forth a hypothesis that may explain the initial inflammation that results in acne. Once we have a hypothesis, this leads to research to either prove it or disprove it, so we'll see in the future whether this pans out, but here is the hypothesis of what might trigger this initial inflammation they see in the skin.
The hypothesis: The main type of skin cell in our skin (called keratinocytes) constantly produce inflammatory molecules at low levels that act as a "surveillance system" to detect bacteria or other stimuli that would require an immediate immune response. When triggered by something, this surveillance system will then increase its production of inflammatory molecules and cause inflammation. This inflammation can then lead to changes in the tiny hair follicles that cover our skin (pores), which we will see in the following steps below.
In support of this hypothesis, researchers have found that skin cells in all people do in fact regularly release an inflammatory molecule called interleukin-1 (IL-1) at low levels.1-4,5
So what factor(s) might trigger inflammation in some pores and not in others? Suspects include acne bacteria (C. acnes), changes in skin oil (sebum) composition, and stress. But other factors, or a combination of factors, may be at play.
Step 2: Hair Follicle Changes
Once inflammation is present in a hair follicle, it begins to stimulate an overproduction of the sticky skin protein, keratin. Scientists also see changes in sebum composition at this point. The overproduction of keratin and different composition of sebum may then stimulate even more inflammatory molecules, such as IL-1, and the formation of a clogged pore.4-6
Step 3: Formation of a Comedone
The clogged pore traps sebum and excess keratin, which begins to build up. This provides the perfect breeding ground for C. acnes bacteria. Scientists have determined that C. acnes can lead to increased production of the inflammatory molecule, IL-1. The increase in IL-1 then leads to additional stimulation of keratin production. This further clogs the pore, and as sebum and keratin continues to build up inside the pore, a comedone (whitehead or blackhead) is formed.7-10
Note: C. acnes is found in most, but not all, acne lesions, so it can't be the only factor that leads to the increased production of IL-1.
Step 4: Rupture of the comedone
Eventually, the build up of keratin, sebum, and--usually--C. acnes puts pressure on the pore wall. The pressure becomes too high and causes the wall to rupture, releasing the pore's contents into the surrounding skin. The body's immune system reacts to the contents of the pore as a "foreign invader" and reacts with much more inflammation, which leads to the production of red and sore inflammatory acne lesions, such as a pustule.
Note: Even though C. acnes is not found in all acne lesions, it is found in most of them. Scientists have found the C. acnes often contributes to the rupture by producing proteins and recruiting cells that facilitate pore wall damage. After release into the surrounding skin, C. acnes can cause additional inflammation by interacting with certain immune system cells and stimulating more production of IL-1.11,12 In other words, when C. acnes is around, it most likely contributes to the pore wall break, and after the pore wall break, also most likely contributes to the production of more inflammation.
Conclusion - Inflammation Is There All Along
Scientists have updated their hypothesis regarding steps to acne formation now that it has become apparent that inflammation is there before a pore even gets clogged. Beginning with an unknown trigger, the immune system stimulates inflammation in the pore. This initial inflammation then triggers changes in the pore that include overproduction of keratin and changes in sebum composition, which clogs a pore. These factors, usually combined with C. acnes growth, result in even more inflammation and the formation of a comedone. Eventually, the pore becomes overfilled with keratin, sebum, and--usually--C. acnes, which results in the rupture of the pore. The rupture stimulates further inflammation as the follicular contents come into contact with surrounding skin, causing red and sore inflamed acne lesions.
- Danby, F. W. Ductal hypoxia in acne: Is it the missing link between comedogenesis and inflammation? J Am Acad Dermatol 70, 948 - 949 (2014). https://www.ncbi.nlm.nih.gov/pubmed/24742839
- Cunliffe, W. J., Holland, D. B. & Jeremy, A. Comedone formation: Etiology, clinical presentation, and treatment. Clin Dermatol 22, 367 - 374 (2004). https://www.ncbi.nlm.nih.gov/pubmed/15556720
- Kircik, L. H. Advances in the understanding of the pathogenesis of inflammatory acne. J Drugs Dermatol 15, s7 - s10 (2016). https://www.ncbi.nlm.nih.gov/pubmed/26741394
- Williams, H. C., Dellavalle, R. P. & Garner, S. Acne vulgaris. Lancet 379, 361 - 372 (2012). https://www.ncbi.nlm.nih.gov/pubmed/21880356
- Tanghetti, E. A. The role of inflammation in the pathology of acne. J Clin Aesthet Dermatol 6, 27 - 35 (2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780801/
- Zouboulis, C. C., Jourdan, E. & Picardo, M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol 28, 527 - 532 (2014). https://www.ncbi.nlm.nih.gov/pubmed/24134468
- Kistowska, M. et al. IL-1β drives inflammatory responses to Propionibacterium acnes in vitro and in vivo. J Investig Dermatol 134, 677 - 685 (2014). https://www.ncbi.nlm.nih.gov/pubmed/24157462
- Li, Z. J. et al. Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes. J Investig Dermatol 134, 2747 - 2756 (2014). https://www.ncbi.nlm.nih.gov/pubmed/24820890
- Thiboutot, D. M. Inflammasome activation by Propionibacterium acnes: the story of IL-1 in acne continues to unfold. J Investig Dermatol 134, 595 - 597 (2014). https://www.ncbi.nlm.nih.gov/pubmed/24518111
- Selway, J. L. et al. Toll-Like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne. BMC Dermatol 13, 1 - 7 (2013). https://www.ncbi.nlm.nih.gov/pubmed/24011352
- Toyoda, M. & Morohashi, M. Pathogenesis of acne. Med Electron Microsc 34, 29 - 40 (2001). https://www.ncbi.nlm.nih.gov/pubmed/11479771
- Contassot, E. & French, L. E. New insights into acne pathogenesis , Propionibacterium acnes activates the inflammasome. J Investig Dermatol 134, 310 - 313 (2014). https://www.ncbi.nlm.nih.gov/pubmed/24424454