Dermatologists are faced with an increasing number of acne patients, especially adult women, who are looking for treatment options. Interest in complementary and alternative medicine treatments (CAMs) is on the rise as more and more dermatology patients seek complementary and alternative medicine (CAM) practitioners. For those who wish to substitute medications, CAM treatment can be used as monotherapy. More commonly, CAM treatment is used in combination with conventional medications or as maintenance therapy. As a result, they can speed up healing time, reduce medication time, or alleviate the adverse side effects of acne medications, including skin irritation, antibiotic resistance, and antibiotic-induced gastrointestinal discomfort. Despite the growing interest in alternative treatment options, the current acne care guidelines for AAD do not recommend the use of herbal and alternative treatments due to limited data on the safety and efficacy of herbal and alternative treatments. Therefore, there is a need to address a research gap on how CAM treatment treats acne in a more holistic way.
Although the intact pathophysiology is still developing, the development of acne is often seen as the result of four causative factors that occur locally in the sebaceous gland unit (PSU): follicular hyperkeratosis, excessive sebum secretion, acnes bacillus acnes (C. acnes) colonization, and local immune responses. Therefore, current treatments have targeted these mechanisms. Acne removers, antimicrobials, hormonal therapies, including combined oral contraceptives (COCs) and antiandrogens, are designed to prevent hair follicle clogging, reduce sebum production, eliminate pathogenic microorganisms, and/or prevent locally associated inflammation.
Although these are the established mechanisms of acne development, recent research has shown that there are other factors that drive or exacerbate acne in our patients. These factors influence the pathogenesis of acne by affecting the microenvironment of the patient as a whole, not just the sebaceous gland unit (PSU). Endocrine changes, diet, lifestyle, stress, and other system-wide factors are now being considered when treating acne patients. These factors provide us with additional therapeutic targets that may be amenable to the treatment of CAM therapies.
Endocrine changes
Almost all acne has an underlying hormonal component, and it is agreed that androgens are the main factor. The onset of acne is associated with an increase in androgen production in both sexes during puberty. Polycystic ovary syndrome (PCOS) is a condition that affects about 6-12% of women of childbearing age in the United States and is closely related to acne. Dermatologists often diagnose polycystic ovary syndrome because these patients exhibit skin symptoms of hyperandrogenism. More commonly, adult women often complain of so-called "hormonal acne" that occurs around the time of menstruation. These outbreaks are due to increased progesterone and sebum secretion during the luteal phase of the menstrual cycle. Therefore, managing hormone fluctuations is a critical part of addressing acne in adult female patients. Anti-androgens and COCs are often prescribed to female acne sufferers to target hormonal fluctuations, but the limitation of these drugs is that they cannot be used in women who are trying to conceive or who are currently pregnant.
Lifestyle considerations
Lifestyle should also be considered when treating acne, especially adult women. Busy schedules, stressful work and family obligations can be beyond the reach of adult women. Stress is known to be associated with acne flare-ups and is now considered a systemic driver of acne. Stress in acne creates a vicious cycle for adult female patients, where stress leads to acne and acne flare-ups lead to more stress. Stress often affects skin health and can aggravate inflammatory conditions like psoriasis and eczema. Studies have shown that there is a correlation between average stress severity and acne grade as well as impaired wound healing, which may hinder the resolution of acne lesions. At the systemic level, stress drives hormonal fluctuations through the hypothalamic-pituitary-adrenal axis (HPA), along with the release of corticotropin-releasing hormone (CRH) and an increase in circulating cortisol. CRH stimulates the sebaceous glands, steroid production, and keratinocytes to produce cytokines, leading to acne inflammation. At the site of the lesion, peripheral nerves have been observed to release substance P, a neuropeptide that accumulates locally around the sebaceous glands. Substance P stimulates mast cell proliferation, degranulation, and the release of pro-inflammatory cytokines. In conclusion, physiological responses to stress are both systemic and local drivers of acne-related inflammation.
diet
Diet and metabolism of macronutrients, vitamins, and minerals can affect skin health. A standard Western diet, high in carbohydrates and low in nutrients, is thought to be the main cause of acne. High glycemic index diets affect multiple pathways, leading to immune activation and increased inflammation of PSU. Glycemic load, blood glucose levels, insulin, and insulin-like growth factor (IGF-1) are associated with increased PSU sebum secretion, hyperkeratosis, cutaneous endocrine responses, and systemic immune activation. As a result, diet is now considered to be an important factor in the cause of acne.
Vitamins and minerals have long been recognized for their role in skin health, as deficiencies in these nutrients can lead to diseases characterized by skin findings. Low levels of vitamins A, D, and folic acid were observed in patients with acne, suggesting that vitamin levels are related to epithelial health. Zinc, selenium, and vitamin D have all been found to be associated with acne and/or disease severity. In conclusion, we know that nutritional status affects acne and should be part of the discussion when managing people with acne with a system-wide approach.
pressure
Acne sufferers are known to be under systemic and skin oxidative stress. Reactive oxygen species (ROS) can be produced by environmental exposures or as a byproduct of mitochondrial energy production. Studies have shown that patients with acne have increased biomarkers of oxidative stress cycles, such as thiobarbituric acid reactive substances (TBARS) and malondialdehyde (MDA), and decreased vitamins and enzymatic antioxidants. In PSU, ROS accumulation leads to oxidation of sebaceous lipids such as squalene. Acne colonization can also lead to neutrophil infiltration, which further produces ROS. Therefore, oxidative stress may be an early factor driving the acne process.
The role of the microbiome in the pathogenesis of acne is constantly evolving. It is now known that acne itself is not caused by the excessive proliferation of the Acnes bacillus, but by the dysbiosis caused by the loss of the diversity of the types of the Acnes bacillus. This dysbiosis triggers the activation of the innate immune system, releasing inflammatory mediators that lead to PSU inflammation. In addition, Staphylococcus epidermidis controls the growth of bacilli acnes and reduces inflammation caused by Clostridium acnes. Acne also inhibits the growth of Staphylococcus epidermidis by maintaining an acidic environment in PSU. On a broader scale, the role of bacteria in the pathogenesis of acne extends beyond the skin. Patients with acne had a lower gut microbiome diversity compared to healthy controls. Dysbiosis of the gut microbiota disrupts the intestinal barrier, triggers immune activation, and leads to the release of inflammatory mediators, including lipopolysaccharide endotoxins, into the systemic circulation. This systemic inflammatory response may play a role in triggering or exacerbating acne.
Other system-wide factors
The combined action of these systemic drivers of acne leads to an abnormal or excessive immune response that leads to acne. Oxidative stress, microbial dysregulation, emotional stress, and other factors discussed here are associated with immune system activation and increased release of inflammatory mediators such as IL-1, IL-6, TNF, and substance P. The local immune response to PSU includes resident macrophages, mast cells, and other immune cells. Acnes triggers immune responses through a variety of pathways, including interaction with Toll-like receptors, activation of inflammasomes, induction of matrix metalloproteinase production, and stimulation of antimicrobial peptide activity. Neutrophil recruitment to the site of inflammation leads to damage to the sebaceous glands and epithelium. This chain of events can lead to inflammation, erythema, pain, and acne sequelae.
We currently have a number of tools for treating acne, although most of them are for PSU-level acne. A growing body of evidence suggests that many acne are caused by other factors, such as diet, lifestyle, environmental exposures, endocrine disorders, and other systemic metabolic processes that lead to a systemic inflammatory response. Therefore, it makes sense to use nutritional interventions, supplements, and lifestyle changes to target these factors as part of a more comprehensive strategy for adults with acne. By using a more holistic approach, dermatologists can help patients achieve clearer skin, improving skin health and overall well-being.
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