THE INFLAMMATORY RESPONSE
The inflammatory response is defined as a complex series of interactions between fragments of damaged cells, surrounding tissues, circulating blood cells, and specific antibodies; it is typical of infection.¹

The onset of inflammation is multi-faceted and complex. Toll-like receptors within epidermal cells keep a close watch for invading bacteria and viruses, resulting in communication with the innate immune system that activates to eliminate them. Signs of inflammation are redness, swelling, heat, and pain, with an inability for normal cells to function correctly. Inflammation occurs only in vascular tissues.² The purpose of the inflammatory response is to mobilize the body’s defenses against infection.³ The biological signs of inflammation are due to a deluge of plasma from blood vessels into affected tissue along with the passage of leukocytes (white blood cells) into the site of injury.⁴ There is an increase of vascular permeability that allows for immune cells to enter through the walls of blood vessels to the damaged area. A cascade of responses and activation of blood plasma enzymatic systems fight off the infection.⁵ A wound healing response is determined through the degree of damage or infection. The presence of numerous mediators, such as fibroblasts, macrophages, mast cells, monocytes, lymphocytes, and others, stimulate systemic responses to the inflammatory process that can include fever and even lower blood pressure or, in severe allergy reactions, anaphylaxis shock.

CYTOKINES
Cytokines influence the inflammatory response. Cytokines (or lymphokines) are a special family of molecules that are primarily secreted from immune cells called leukocytes.⁶ Cytokine activity occurs in steps and, thus, it interacts with a cell receptor and activates or stimulates the receptor to produce an end result.⁷ Cytokines orchestrate, coordinate, and support the body’s ability to fight off pathogens, repair damage, and restore and maintain cellular health.⁸ They also make up groups of compounds called interleukins. Many cytokines are called growth factors and are chemicals that stimulate cells to divide and grow. There is an entire orchestration of events including cellular stress during inflammation. The inflammatory response is complex and requires in-depth study.

REVIEW OF THE PATHOGENESIS OF ACNE
A simple definition of acne is that it is a disease of the sebaceous follicle. It is caused by an inflammation of the oil glands that varies in severity depending upon how much obstruction exists within the follicle.⁹ Acne primarily affects the face, back, and chest.

The challenge of acne emerges during a period in life when the first recipients of this outbreak are normally growing teenagers. It is difficult enough being this age without having acne interrupt some of the most important years of growing up. There are many complex factors involving acne that will be discussed in this article.

In western culture, the journey from pre-adolescent to teenager into adulthood unveils numerous hormone changes that strongly affect the pilosebaceous unit (the hair follicle). The appearance of pimples, whiteheads, blackheads, or inflamed cysts accompanies the active life of 79% to 95% of teenagers.¹⁰ It begins around age 11 in girls and a little later in boys.¹¹ After the age of 25, some degree of facial acne may continue in 40% to 54% of men and women. Facial acne persists into middle age in 12% of women and 3% of men.¹² For women, hormonal fluctuations that occur prior to menstruation also become evident in slight breakouts. Additionally, sebaceous gland hyperplasia may develop on elderly skin that appears as isolated nodules of yellowish color found on the front and cheeks of men with very oily skin.¹³

The structure and function of the pilosebaceous unit (the hair follicle) demonstrates a very active apparatus residing within the dermis and epidermis. There are two kinds of follicles: a hair follicle and a sebaceous follicle, both having sebaceous glands attached. There may be microscopic hair in the follicle called rudimentary hair. When acne develops, the hair usually coils up and gets lost in the rest of the debris, never getting to the surface.

Sebum inside the follicle plays an important role in the building of the acid mantle. The environment within the follicle normally contains anaerobic bacteria (growing without oxygen). Bacteria feed off the triglycerides produced by the sebaceous glands leaving fatty acid by-products.

The stratum corneum curves into the top of the follicle where the opening serves as an exit and entrance to the pilosebaceous duct.

Epithelial cells inside the follicle are an extension of the stratum corneum. They are interspersed with melanocytes and line the entire pilosebaceous unit. At the base of follicle is the papilla that supports the various stages of the hair growth cycle. Also known as the bulge, it houses several types of stem cells that supply the follicle with new cells.

Just as cells desquamate off the stratum corneum, the same process occurs inside the follicle, where the movement of sebum washes cellular debris upward to the opening of the follicle, spilling its contents onto the surface of the skin. The hair acts as a wick inside the follicle.

HEALTH OF THE ACID MANTLE
The first line of defense for the skin is the acid mantle, which should maintain a pH between 4.5 and 6.5. Normal sebaceous lipid composition is made up of squalane, sterols, wax esters, sterol esters, and triglycerides. However, during chronic inflammation, the composition of pustules and papules, as well as comedones, contains a high level of free fatty acids and affects the pH of the mantle.

THE ROLE OF PROPIONIBACTERIUM (P.ACNES BACTERIA)
The normal role of P.acnes bacteria is to support the formation of the acid mantle. They have evolved to be both anaerobic and aero tolerant and reside at the top of the pilo sebaceous duct and on the skin surface near the exit. As sebum moves up the follicle, the triglycerides are transformed into free fatty acids. P.acnes use sebum as an energy source, ingest the triglycerides that are abundant in the sebum, and excrete specialized enzymes (lipases) required to create the free fatty acids. This action also creates the pH of 5.5 for the acid mantle.

It is important to mention that propionibacterium does not directly cause significant damage to the follicle and surrounding skin when it is functioning normally. Most of the damage caused by acne is due to an inflammatory process of the immune system.¹⁴ Whenever there is an impairment of the acid mantle, including being stripped by harsh chemicals, the P.acnes move away from their normal environment and seek the next highest source of triglycerides, the sebaceous gland interior down inside the follicle. It is here where the bacteria continue to breakdown triglycerides into free fatty acids. Unfortunately, this location is very close to the dermis, which has a pH of around 7. The acidic nature of the free fatty acids now becomes pro-inflammatory and comedogenic. Irritation soon causes pustules due to the arrival of the cells from the immune system to combat the inflammation and infection. The immune system looks at the bacteria components of the P.acnes as adversary molecules. Immune cells also release large amounts of inflammatory cytokines that induce more white blood cells to release destructive enzymes and free radicals at the infection site.¹⁵

ROSACEA
Rosacea is a common condition that affects approximately 16 million people in the United States.16 According to the National Rosacea Society, rosacea is a chronic but treatable condition that primarily affects the central face. It can typically begin after age 30 with signs of flushing and redness on the cheeks, nose, chin or forehead.¹⁷ Early symptoms may last several hours or several days. Redness may be intensified by stress, agitation, alkaloids in coffee or tea, alcohol, hot spices, or changes in environmental temperatures (hypothermia in cold winter and direct exposure to infrared radiation in sunlight).¹⁸ The effects on hyperactive blood vessels may become damaged, leading to permanent telangiectasias and inflammation in the vascular endothelium, showing erythema symptoms. Consistent redness causes the skin to become ruddier. The barrier function also becomes compromised.

There are four phenotypes of rosacea: erythematotelangiectatis rosacea (dry skin rosacea), papulo-pustular rosacea (wet or active rosacea), phymatous rosacea (thickening of skin, irregular surface nodularitys, rhinophyma), and ocular rosacea.¹⁹

People with fair skin who tend to blush easily may be at a higher risk for rosacea. It appears more often in women, but men tend to have more severe symptoms.

Causes of rosacea are inconclusive. Fortunately, researchers continue to uncover new theories prompting expanded awareness of the pathology of rosacea. Research by Uchida and Elias found that stress to skin cells caused by ultraviolet radiation, heat, or other rosacea triggers results in a cascade of events in the body in which the production of one substance leads to another. The substances include the protective antimicrobial peptide called cathelicidin (CAMP) that speeds physical repair but worsens rosacea symptoms. This finding led to further study to discover how to reduce this peptide without compromising the body’s ability to defend and repair itself.²⁰

University of California at Los Angeles professor Richard Gallo, MD, PhD, has extensively studied the molecular pathology of rosacea. He says that rosacea is “a disease of aberrant innate immune responses – a hypothesis that may explain the diverse presentation of the disease. Patients with rosacea may have a defect in innate immunity so that they are more sensitive to certain environmental triggers and that, once triggered, molecules in the innate immune system would be activated that could cause the disease.” Gallo also confirmed that these findings were applicable to other cutaneous diseases such as psoriasis and atopic dermatitis.²¹

It is clearly demonstrated that there is an immeasurable difference between acne and rosacea. As a skin care professional, it is recommended to pursue further study and refer to the citations at the end of this article. Both disorders require specialized care which typically includes medical intervention. Always perform a thorough skin analysis and carefully review the health intake form completed by the client.

References
1 Pugliese, P. M.D. Advanced Professional Skin Care. Medical Edition. (Bernville: The Topical Agent, 2005), 421.
2 Ibid, 165
3 Ibid, 176
4 Ibid, 165
5 Ibid, 165
6 Ibid, 163
7 Ibid, 162
8 Ibid, 160
9 Fernandes, Des, MD. “Acne Vulgaris: Introducing an effective treatment regimen.” Beauty Mag Online. http://www.beautymagonline.com/beauty-articles/953-acne-basics-3.
10 Cordiain, L., S. Lindeberg, M. Hurtado, K. Hill, S.B. Eaton, and J. Brand-Miller. “Acne vulgaris: a disease of Western civilization.” Archives of dermatology 138, no. 12 (2002): 1584-90.
11 Lamb, Philina. “Checkup on Health: Don’t let acne ruin those important teenage years.” UC Davis Health. http://www.ucdmc.ucdavis.edu/welcome/features/20090909_teen_acne.
12 Lautenschläger, Hans and Elke Klein. “Acne – prevention and care.” Kosmetik International 5 (2003): 27-31.
13 Barrett-Hill, Florence. Advanced Skin Analysis. Virtual Beauty Corporation, 2011.
14 “What are Propionibacterium acnes?” Science of Acne. http://thescienceofacne.com/what-is-propionobacterium-acnes.
15 Ibid, Ref. 2
16 Gallo, Richard. “The Molecular Pathology of Rosacea: An Expert Interview tithe Richard L. Gallo, MD, PhD.” https://www.rosacea.org/grants/reports-on-completed-research.
17 “All About Rosacea.” National Rosacea Society. https://www.rosacea.org/patients/all-about-rosacea.
18 Lautenschläger, Hans. “Couperosis – a field for active agent concentrates.” Kosmetische Praxis 1 (2007): 8-10.
19 “Special Report: Standard grading system for rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea.” https://www.rosacea.org/pdf/gradingsystem.pdf.
20 “All About Rosacea.” National Rosacea Society. https://www.rosacea.org/patients/all-about-rosacea.
21 Ibid, Ref. 16
22“Acne: Signs and Symptoms.” American Academy of Dermatology | Association.https://www.aad.org/public/diseases/acne-and-rosacea/acne#symptoms.
23 “Is that acne or rosacea on our skin?” American Academy of Dermatology | Association. https://www.aad.org/public/diseases/acne-and-rosacea/is-that-acne-orrosacea.

Alexandra J. Zani, licensed instructor and owner of AEsthani Skincare Institute, LLC, is an award-winning international educator, researcher, and author with a background in cell biology and medical technology. Her passion for education resulted in earning numerous advanced certifications, both in the United States and abroad. Zani holds an instructor license for aesthetics and cosmetology, is certified in oncology aesthetics and the Pastiche Method of Advanced Skin Analysis, and is a member of NCEA. She is on the education committee for the International Association of Applied Corneotherapy (IAC) and is co-founder of Intellective Aesthetics.