Acne in adult women is becoming more common and has a significant negative impact  on their quality of life. The causes of acne in adult women are different and a therapeutic approach must be holistic and individualised. Propionibacterium acnes (P. acnes) antibiotic resistance is a topic of increasing frequency and establishing a regimen should be made in order to minimise the resistance of P. acnes.

Acne vulgaris is one of the leading causes for visits to a dermatologist¹, and because the age of onset can be as early as 8 or 9 years of age and a substantial portion of patients also experience this condition in adulthood, addressing acne comorbidities and quality of life (QOL) is very important^2, 3.

The impact of the acne is deep and goes beyond the skin; respectively, patients with acne have a higher rate of unemployment than matched controls⁴ and at least $3 billion per year is lost in the direct and indirect costs of treatment and loss of productivity⁵.

Epidemiology, myths, and perceptions

Women may develop acne for the first time, or redevelop acne, in their mid-to-late 20s⁶ and acne that develops after 25 years of age is defined as adult female acne^7, 8. Acne frequently continues into adulthood, especially in women, and the mean age of patients who visit the dermatologist to seek treatment is approximately 24 years⁹. Acne is not related to obesity^10, 11 but there is a connection through the westernisation of diets¹² — diets rich in high glycaemic index (HGI) foods such as pasta, flour, bread and sugar.

The common perceptions about the causes of acne, especially in adults, relate acne to implications of stress, diet, skin hygiene and cosmetics, infection, exercise¹³, and sunlight^14, 15.

It is a very common perception (but false perception) that acne is a consequence of being dirty¹⁶ and poor levels of hygiene lead to the development or exacerbation of acne vulgaris^13, 17.

Impact on quality of life

Acne on the face is very visible and cannot be covered by clothes; therefore, it is understandable that Sulzberger et al came to the conclusion that: ‘There is no single disease which causes more psychic trauma, more maladjustment between parents and children, more general insecurity and feelings of inferiority and greater sums of psychic suffering than does acne vulgaris’.¹⁸

Acne is not a self-limiting cosmetic disorder¹⁹, and impact at a social, psychological, and emotional level is similar to asthma, arthritis, epilepsy, and diabetes²⁰ — serious diseases with a high negative impact on overall health.

The presence of acne in adult women increases the risk of anxiety, depression, and suicidal ideation²¹ and has a negative effect on work or eductional performance.

It is more than likely that the media’s portrayal of flawless skin as an ideal is the leading cause of psychological morbidity in females²².

Causes and trigger factors

Acne pathogenesis is connected with excess sebum production by the sebaceous glands, follicular occlusion, hyperproliferation of Propionibacterium acnes (P. acnes), and inflammation²³.

Genetic factors play an important role, so acne occurs earlier and is more severe in those with a positive family history^{24, 25}.

P. acnes was first implicated in acne pathogenesis in 1896²⁶ and individuals with active acne had higher densities of P. acnes when compared to normal controls²⁷. It was also discovered that antibiotic resistance was associated with treatment failure^28–30.

Androgens, such as dihydrotestosterone (DHT) and dehydroepiandrosterone sulphate (DHEAS)^31, 32,  as well as oestrogen, growth hormones, insulin, insulin growth factor‑1 (IGF-1), corticotropin-releasing hormone (CRF), adrenocorticotropic hormone (ACTH), melanocortins, and glucocorticoids are all strongly connected with acne and sebaceous secretion.

The skin produces hormones de novo from cholesterol^{33, 34} and have all of the necessary enzymes required for the conversion from cholesterol to steroids.

IGF-1 is correlated with acne³⁵ and women with acne present higher levels of IGF-1 compared with women without acne^36–38.

IGF-1 stimulate adrenal androgen synthesis and inhibit the production of hepatic sex hormone-binding globulin (SHBG) with the increase of free androgen³⁹, and may mediate some of the effects of androgens, growth hormone, and glucocorticoids⁴⁰.

Milk consumption is linked to acne because milk is an insulinotropic nutrient and has a high insulinaemic index⁴¹ which would increase serum insulin and IGF-1 levels^42–45. Human and bovine IGF-1 share the same amino acid sequences⁴⁶ and both are able to bind to the human IGF receptor^{47, 48}. A study in 1949 reported an association between frequent milk consumption and acne severity⁴⁹ and it is possible that upregulation of insulin secretion and the long lasting increase in serum IGF-1 levels^50, 51 could be the culprits for acne development.

Milk induces an increase in IGF-1 levels, especially skimmed milk intake, which causes a break-out and/or worsening of acne^53, 54. It also contains oestrogen, progesterone, androgen precursors, and 5α-reductase-dependent steroids, which are implicated in comedogenesis⁵⁴.

The studies of Adebamowo^{52, 53, 55} are the first to provide direct clinical evidence on the association between milk/dairy consumption and acne.

Yoghurt consumption was not correlated with acne vulgaris occurrence and is consistent with the findings of a number of studies^{52, 53, 55} and lactoferrin-enriched fermented milk decreases acne severity owing to the anti-inflammatory effects of lactoferrin and its ability to suppress microbial growth^56–58.

An intake of polyunsaturated fatty acids (omega-6 and omega-3) modulates the skin’s inflammatory response⁵⁹ and omega-3 fatty acids may decrease acne by decreasing insulin⁶⁰ and IGF-1 concentrations⁶¹, and increasing IGFBP-3 concentrations⁶².

Chocolate is rich in biologically active compounds (caffeine, theobromine and serotonin), which increases secretion of insulin and its peripheral resistance^63, 64. Chocolate has an effect on the pathophysiological processes involved in the development of acne lesions, especially related to carbohydrate metabolism, and certain individuals eating chocolate may present with the development or worsening of acne lesions.

Some cosmetics can contain comedogenic agents that block follicular structures and induce comedonal disease on the cheeks of females, such as isopropyl myristate. However, because the majority of cosmetic products are now noncomedogenic, cosmetics are  an uncommon cause^65–68.

Stress is a major factor in acne development^69–71, involved both as a trigger factor and exacerbating factor. Stress induces both neuroendocrine changes that are involved in the appearance of acne lesions and can lead to trauma of the lesions, as well as use of empirical treatments that cause worsening or development of acne lesions.

Smoking is associated with skin diseases, inclusively skin cancer⁷² and practitioners see in daily practice an impairment of wound healing in smokers, mainly by vasoconstriction⁷³. Smoking has a lot of adverse effects on the skin, owing to the effect on skin microcirculation, as well as keratinocytes, collagen, and elastin synthesis.

Smoking is strongly linked to acne, with the severity of acne following a linear correlation with the number of cigarettes smoked. The prevalence of acne in smokers is higher compared with non-smokers⁷⁴. Smoking is associated with development of wrinkles, atrophy, grey appearance or red complexion, and is commonly defined as ‘smoker’s face’⁷⁵.

Smoking is a major factor in non-inflammatory type post-adolescent female acne^76, 77, probably owing to an increase of sebum production induced by the nicotine and the reduced level of vitamin E in the sebum. Additionally, some compounds found in cigarette smoke, including nicotine, have a hyperkeratinising  effect^76–78.

Differences between acne in adults and adolescents

We have two major subtypes of adult female acne, one is  ‘persistent acne’ (which is a continuation or a relapse from adolescence) and the other is ‘late-onset acne’ (presents for the first time after 25 years)^{8, 79}.

Adult female acne may be very refractory to treatment and older skin may be more predisposed to irritation with certain topical treatments⁸⁰. Women over the age of 25 years have higher rates of treatment failure; Goulden et al found that 82% fail multiple courses of systemic antibiotics, and 32% relapse after isotretinoin⁸¹.

Severity

The severity of acne depends on lesion size, density, type, and distribution, and acne can be evaluated not only from objective disease activity (based on measurement of visible signs) but also from impact on QOL.

Prognostic factors of disease severity include acne family history, early onset of comedonal acne, persistent or late-onset disease, hyperseborrhoea and androgenic triggers and psychological sequelae^82–85.

Treatment and management

The main principles in managing adult female acne are enhancing the care of patients (including psychological care), lessening of serious conditions and scarring, raising of adherence, and prevention of antibiotic resistance.

The choice of treatment is connected with the resistance of female adult acne to various therapies and the specific characteristic of the skin, which can be more predisposed to irritation⁸⁶. Severity and duration of the acne, previous treatments, the predisposition to scarring and hyperpigmentation, and the areas affected by acne are all factors which have specific effects on the choice of therapy^{87, 88}.

The rates of adherence to treatments are higher in adult females, compared with males and teenagers⁸⁹. However, the response to the treatment may be very slow and practitioners must explain the importance of time to reach any significant clinical results^88, 90. A simple and specific way to improve adherence is to use fixed-dose combinations⁹¹.

Practitioners must have a holistic approach, respectively integrate the diet, sun exposure, use of specific cosmetics with local and general treatment. Laser surgery can also be beneficial for both active acne and sequelae post inflammation.

Regarding sun exposure, some patients may experience a worsening of acne after exposure to sunlight⁹². In these cases, it is very important for the management of photosensitivity caused by some medical treatments of acne, such as tetracycline^93–95  and isotretinoin^{96, 97}. Cycline or retinoid drugs (commonly used to treat acne) are associated with photosensitivity reactions, so patients with acne must adopt active photoprotective behaviour (avoiding exposure to sun during the hottest parts of the day, correct and consistent use of sunscreen creams, using certified protective sunglasses, and appropriate clothing to reduce skin surface exposed to the sun).

Many patients with acne have a strong (and false) belief about cleanliness^98–100 and this results in not only the misguided use of a lot of washing products but also a delay before seeking a medical consultation⁹⁹. However, the truth is very different, face-washing exacerbates acne¹⁰¹, and can increase skin irritation adverse effects of topical therapy, and isotretinoin treatment^102–104.

Advice on the use of cosmetics, moisturisers, sunscreens, and hair gels may be appropriate⁶⁷, and should be a part of acne management in adult acne.

Studies have demonstrated that acne improves when patients with polycystic ovary syndrome (PCOS) are treated with medications that improve insulin metabolism such as metformin, tolbutamide, pioglitazone, and acarbose^{105, 106}.

Polycystic ovarian syndrome is a condition with a lot of features, including insulin resistance, hyperinsulinaemia, hyperandrogenism, and acne¹⁰⁷. These patients typically maintain elevated serum concentrations of androgens, IGF-1, and lower concentrations of SHBG^108–111.

Falsetti et al agree with the fact that acne is an important feature in PCOS patients, who are also frequently obese, hyperinsulinaemic, insulin resistant, and hyperandrogenic¹⁰⁸. Insulin resistance generally precedes and gives rise to endocrine characteristics of PCOS (elevated androgen and IGF-I concentrations and low SHBG)¹¹².

It was in 1956 when one of the first observations about the fact that treatments for PCOS with oral hypoglycaemic agents, not only improve insulin sensitivity and restore fertility but improve acne as well¹¹³.

Metformin treatment in patients with PCOS will decrease serum IGF-1¹¹⁴, fasting insulin, DHEAS, and testosterone^{114, 115}. Insulin is a stimulator of hepatic IGF-1 secretion¹¹⁶ and by reducing the insulin level, metformin will reduce elevated serum IGF-1 levels, therefore, decreasing the level of acne.

Metformin¹¹⁷ not only improves insulin metabolism but results in a depression of adrenocorticotropic hormone-stimulated androgen production in women with PCOS. Both of these physiological changes would be therapeutic for acne patients, supporting the positive effects of metformin in acne.

The basic principles of diet in a patient with acne refers to the prohibition of consumption of milk or milk-derived and high glycemic index foods. The regime is designed  to minimise the effects of food on various pathways involved in the development of acne lesions.

Conclusions

Acne is a polymorphic disease with non-inflammatory and inflammatory aspects and nowadays is considered to be a chronic disease¹¹⁸. Before any treatment, practitioners must inform and educate their patients and the myths surrounding acne should be discussed.

It is a lot of little actions which will have a big impact on acne evolution and it is essential to discuss the time required to see a positive effect (acne wil not be cured overnight). Practitioners should also emphasise the importance of: not over-washing the face (too frequently and too aggressively), not picking and popping the pimples because there is a very high risk of multiplying the lesions and developing scars,  changing the diet, and using topical products in the ways which were prescribed (quantity and frequency).

Adult female acne is different from adolescent acne and two factors are involved, hormones and innate immunity.

The public health issue in acne is frequency, cost, impact on QOL, antibiotic resistance of P. acnes, and associated morbidity. Practitioners have the opportunity to reduce antibiotic resistance for both P. acnes and other bacteria. Also, by reducing mTORC1 activation through diet manipulation, practitioners have the opportunity to prevent serious diseases like diabetes type 2, obesity, neurodegenerative diseases, and cancer.

Acne treatment is not only an acute intervention, but also maintenance therapy¹¹⁹ and practitioners have to address individual needs of a specific patient and the treatment should consider a lot of factors. One of the more important is the duration of disease, because acne that persists for longer periods is more likely to lead to scarring¹²⁰, both physical and psychological.