Female type of adult acne: Physiological and psychological considerations and management

Transcription

1 Review Submitted: Accepted: DOI: /ddg Female type of adult acne: Physiological and psychological considerations and management Brigitte Dreno 1, Edileia Bagatin 2, Ulrike Blume-Peytavi 3, Marco Rocha 2, Harald Gollnick 4 (1) Department of Dermatology, University of Nantes, France (2) Department of Dermatology, Federal University of São Paulo UNIFESP, São Paulo, Brazil (3) Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Germany (4) Department of Dermatology and Venereology, Otto-von-Guericke Universität, Magdeburg, Germany Summary Today we see more cases of acne after adolescence, with a greater prevalence in females than males. Adult female acne has a distinct clinical presentation and is associated with a number of specific pathophysiological features and gender-specific triggers. The psychological impact of acne is generally significant and largely underestimated; stress during professional and private life, anxiety and sleep quality, in particular, have a reciprocal relationship with disease susceptibility and severity. It is essential to compare with males. Acne in females often causes greater distress in adults than in adolescents. The impact of disease may therefore be greater for female patients, triggering higher levels of psychosocial anguish and increasing the likelihood of sequelae such as skin picking and the risks of cutaneous superinfection, scarring and PIH and acne recurrence. The management of adult female acne should encompass not just medical treatment of the symptoms, but also a comprehensive, holistic approach to the patient as a whole, her individual lifestyle factors and the impact of acne on her quality of life. Future management of this disease should aim to improve patient adherence to therapy and to develop validated outcomes of treatment regarding overall skin appearance and quality of life. Introduction Acne vulgaris is a common, chronic, inflammatory dermatosis among teenagers that regresses spontaneously during late adolescence or early adulthood. The clinical presentation and pathophysiology have been reviewed previously [ 1 4 ], and may involve comedones, papules, pustules, nodules, and scarring or hyperpigmentation from resolved lesions [ 4, 5 ]. A significant number of patients experience acne after adolescence, with three distinct sub-types of disease: persistent acne (a continuation of the disease from adolescence into adulthood); relapsing acne, with regression after adolescence and recurrence in adulthood; and late-onset acne, which first presents well after puberty (commonly in the early- to mid-twenties) [ 6, 7 ]. The mean age at presentation for adult acne treatment is around 24 years, and 10 % of visits to a physician are by patients 35 to 44 years of age [ 8 ]. The incidence of adult acne in particular in ethnic groups with white skin type has increased over the past years, with a greater prevalence in women than in men at all ages after adolescence ( 20 years) [ 9 ]. The aim of this review is to outline the differences between acne in adult and adolescent females with regard to clinical characteristics, treatment, psychosocial factors and quality of life (QoL). Specific characteristics of adult female acne The clinical characteristics of adult female acne differ from those of adolescent acne [ 6 ] ; the key morphological differences are listed in Figure 1. Acne on the chin (deep-seated, long-lasting small nodules (< 0.5 cm) and cysts in the U-zone alone) appears to be specific to women; however, mixed presentations with inflammatory and non-inflammatory lesions involving 1185

2 Figure 1 Morphological differences in adolescent and adult female acne. Figure 2 Severe female acne of adult type with lesions spreading beyond the mandibular border. Note the hypertrichosis in this image, which may be related to ethnic and/or androgenic factors. multiple areas of the face are frequent [ 10, 11 ]. Localization of acne on the submandibular area is seen in only 11 % of adult females (Figure 2 ). Acne of the trunk is less common in this population [ 12 ]. Hyperseborrhea is present in about 70 % of adult females, although acne is frequently mild to moderate in these patients [ 5, 11 ]. Flare-ups before menstruation appear to be more common in older women, and are observed in about half of adult patients with acne [ 13 ]. These flares are due to increased water content of the follicular wall in the last week of the menstrual cycle, and may be more marked in patients using androgenic, progesterone-derived oral contraceptives (first and second generation) than in patients using more recent formulations [ 14 ]. Persistent, relapsing and new-onset types of adult female acne are frequently associated with inflammation (deep nodules), post-inflammatory pigmentation and a high frequency of scarring, with a significant negative impact on the QoL [ 15 ]. Overuse of cosmetics such as make-up and peeling techniques to address these conditions may be an issue [ 16 ]. Hyperpigmentation is more prevalent in women with dark skin or phototype IV, and may be of greater concern than for women with a lighter skin complexion [ 17, 18 ]. Adolescent acne that persists and is transformed to adult acne often involves frequent relapses [ 6 ] ; adult female acne therefore requires even more maintenance therapy for an extended period than adolescent acne (in which the numerous pubertal lesions usually respond quickly to treatment). Although no clear difference in pathogenesis between adult female acne and adolescent acne has been demonstrated, adult female acne is dominated by three main pathophysiological factors: (a) resistant strains of Propionibacterium acnes may cause chronic stimulation of the innate immune system, initiating and exacerbating inflammatory lesions [ 5 ] ; (b) levels of dihydroepiandrosterone sulfate (DHEA-S) in the upper range of normal [ 9, 19 ] stimulate IL-2 production and enhance Th1 immune function [ 20 ] ; and (c) a genetic predisposition in over half the patients (acne experienced by mother, father or siblings) [ 5, 11 ]. Increasing evidence suggests that levels of anti-müllerian hormone are elevated in adult females with acne, further supporting a state of mild endocrine dysfunction [ ]. Increased serum levels of insulin-like growth factor 1 correlate positively with female acne lesion counts, with evidence that a low-glycemic-load diet may significantly reduce acne severity and improve insulin sensitivity [ 1, 5 7 ]. Obesity and insulin resistance are relatively high with a Western diet/lifestyle, and are intrinsically linked to acne and other systemic diseases. They can therefore be positively influenced by low-glycemic-load dietary restrictions. By contrast, recent studies of carbohydrate-rich diets in eumenorrheic women did not show a clear correlation between IGF and insulin resistance or androgens [ 24 ]. Differential diagnosis of adult female acne Adult acne is rarely misdiagnosed, but some conditions have similar presentations and should be excluded, including grade 2 rosacea (flushing and inflammatory lesions), Staphylococcus aureus folliculitis, boils, syringomas, milia, acne agminata, Demodex folliculitis and Pityrosporum folliculitis. Perioral dermatitis (POD) can present with acneiform features on the cheeks and suborbital region, but usually presents 1186

3 around the mouth. Perioral dermatitis treated by topical corticosteroids can cause even more severe problems and the patient may be superinfected by Candida albicans. Skin-picking, usually associated with obsessive-compulsive disorder, may leave inflammatory lesions and scarring that mimic acne [ 25 ], and acne itself may be comorbid with conditions such as Prurigo-type of atopic dermatitis. In adult females, acne may indicate an underlying endocrine disorder such as polycystic ovary syndrome (PCOS), adrenal hyperplasia or virilizing tumors [ 5 ]. Systemic signs of hyperandrogenism might be irregular menstrual cycles, clitoral hypertrophy, hirsutism, bi-temporal or female-pattern alopecia (not diagnostic as a solitary finding), late menarche (age > 15 years), or resistant or sudden-onset acne. Clinical symptoms of other endocrine disorders may occur, such as amenorrhea, hypermenorrhea, oligomenorrhea, infertility, metabolic syndrome [ 5 ], hypothyroidism and HAIR-AN syndrome. Contraceptive measures containing an androgenic progestin and dermal contraceptive implants may cause acne among other symptoms (norgestrel, levonorgestrel, etonogestrel, DMPA); for this reason, more selective 3 rd and 4 th generation combined oral contraceptives with minimal androgenic properties may be preferred to earlier formulations [ 25, 26 ]. Psychological and dermatological interactions with acne Acne has a large impact on appearance, which is linked with self-esteem, self-consciousness, and everyday functions. The psychological impact of acne is largely underestimated, and can be greater in women than female adolescents due to a more persistent course, despite a presentation that is usually less severe. Acne has been associated with significant depression and suicidal thoughts, social dysfunction (including concerns about social interactions and public appearances) and reduced employment opportunities [ ]. Factors that influence the psychological impact of acne include perceived sexual attractiveness, relationships with family and friends, judgments of others, stigmatization, stress, and fear of scarring or disease persistence. Stress is a significant factor in acne. The stresses of daily life can lead to excoriations and skin-picking that can cause further inflammation, scarring, hyperpigmentation and image-related anxiety, especially for women with dark skin [ 16, 17 ]. Physiological stress responses (adrenergic and cholinergic stimulation and activation of the hypothalamic-pituitary-adrenal axis) have a significant impact on cutaneous barrier function, wound healing and susceptibility to skin infection, and catecholamines increase the ability of certain bacteria to adhere to skin tissue and proliferate [ 29, 30 ]. Stress may also lead to comfort eating (particularly in women) [ 31 ] and obesity-related changes in insulin signaling, which can affect differentiation of sebocytes and their expression of Toll-like receptors [ 32 ]. Increased leptin levels also contribute to inflammation [ 33 ]. Regular exercise can aid weight control, but also causes alterations in stress hormone regulation (dependent on the amount and intensity of activity) and increases levels of adrenal hormones and testosterone [ 34 ]. The sebaceous glands play a central role in promoting acne, due to the response to stress-related hormones and neuropeptides, release of enzymes that increase hormone and cytokine production, and a contribution to the systemic milieu [ ]. Females are more likely than males to suffer from stress-related depressive disorders and anxiety, and show different effects of stress on cellular and molecular pathways [ 20, 38 ]. Women also experience gender-specific stress triggers, including menstruation-related hormonal fluctuations. Sleep has a complex relationship with maintenance of body homeostasis, and lack of sleep or poor sleep quality can exacerbate dysfunction in disease, immune imbalance and increased secretion of stress hormones [ 39 ]. Several skin diseases, including acne, show bidirectional relationships with sleep; sleep itself being affected by stress, comorbid diseases and the menstrual cycle. Women experience sleep problems more frequently than men; their sleep quality may be affected due to their greater susceptibility to anxiety and to changes in their sleep profile related to their menstrual cycle [ 39 ]. Management of adult female acne Physicians should be encouraged to take a holistic approach to managing women with acne, considering the distinctive features and circumstances of each individual. These include: extent, severity and duration of disease; response to previous treatments; predisposition to scarring and post-inflammatory hyperpigmentation (PIH), as well as patient preference, mindset and lifestyle (comprising personal relationships, sun tanning, smoking, nutrition, family planning, professional life and sporting activities) and sensitivity of the skin [ 5 7 ]. The unique features of adult female acne have led to recent guidelines that include specific therapy recommendations for these patients, in addition to those for acne in general [ 2, 4, 5, 40 ] ; Tables 1 and 2 and the sections below summarize these. Most controlled clinical studies have shown that adult acne responds similarly to general acne management, as seen and evaluated in the study results for adolescents. Management of female acne induced by significant endocrine disorders (e.g. polycystic ovarian syndrome, adrenal hyperplasia, virilizing tumors) is not discussed in this review; however, the endocrinology profile should be assessed in adult females who have acne and already show evidence of hormonal imbalance in a dermatological setting. Tests should be performed between 1187

4 Table 1 Recommendations for therapy of female adult acne, by type and severity. Only Retentional lesions/ Inflammatory acne Nodular acne comedones (less common in adult females) Mild inflammation with papules Papulopustular lesions Mild Moderate Severe First-line: - Topical retinoids First-line: - Topical retinoids - Topical azelaic acid - BPO (2.5-5%) First-line: - Topical retinoids + BPO (f.c.) - Topical antibiotics + BPO or retinoids (f.c.) - Topical retinoids + azelaic acid First-line: - Any topical regimen + systemic antibiotics, OC or spironolactone ( mg/day) First-line: - Oral isotretinoin Systemic therapy: - Oral isotretinoin - OC ± anti-androgens or isotretinoin - Spironolactone ± OC or antibiotic - Antibiotics Second line: - Topical azelaic acid (15 % gel; 20 % cream) - BPO (2.5 5 %) Second line: - Topical retinoids + azelaic acid Second line: - Topical treatments (f.c.) + oral anti-androgens or OC Second line: - Hormonal therapy + antibiotics + BPO system. Topical therapy: - Antibiotics + BPO or retinoids (f.c.) - Retinoids + BPO (f.c.) - Retinoids + azelaic acid - Dapsone (5 %) + BPO Adjunctive Therapies Without macrocomedones: - Superficial chemical peels With macrocomedones: - Mechanical cosmetic procedures - Physical extraction or electro cautery of macrocomedones - Superficial chemical peels - Superficial chemical peels - Photodynamic therapy - Intra-lesional steroid injection Modified and Based on Dreno B et al. [ 5 ] Abbr.: BPO, benzoyl peroxide; OC, oral contraceptive; f.c., fixed combinations. 1188

5 Table 2 Recommendations for therapy of female acne, regardless of type or severity. Recommendations General skin care - Gentle, non-soap cleanser (ph around 5.5) - Non-comedogenic, oil-free moisturizer - Limited use of facial treatments - Cosmetic concealers (make-up and camouflage cream) of good quality (non-comedogenic, oil-free) - Ultraviolet-blocking photoprotection (light, non-comedogenic) Post-inflammatory hyperpigmentation First line: - Topical azelaic acid (15 % gel; 20 % cream) - Topical retinoids - BPO + topical retinoids Second line: - Hydroquinone - Hydroquinone + retinoic acid + corticosteroid - Adjunctive therapies: - Non-ablative fractional photochemolysis - Superficial chemical peels Scarring Maintenance therapy Psychological support First line: - Topical retinoids Adjunctive therapies: - Cryosurgery - Dermabrasion, microneedling, chemical peels - Laser therapy - Punch excision and punch elevation/grafting of deep scars - Subcision and fillers - Azelaic acid - Topical retinoids (e.g. adapalene or tazarotene) - Empathy and understanding of the impact of disease on quality of life (personal and professional factors) - Self-perceptions of acne severity vary and can be misjudged - Assess stress and sleep patterns the mornings of the 3 rd and 5 th day after menstruation starts (i.e. free and total testosterone, DHEA-S, androstenedione, 17-alpha hydroxy-progesterone, anti-müllerian hormone, SHBG, prolactin, cortisol). Topical therapies Topical agents are usually sufficient to manage mild disease; however, for adult females (who often have a longer duration of disease), a fixed combination of topical agents or a topical agent plus a systemic treatment may be required [ 40, 41 ]. Retinoids are a first-line choice for most mild-to-moderate types of adult acne. They are comedolytic, anti-comedogenic and anti-inflammatory. They reduce hyperpigmentation and are pro-collagenic, assisting rebuilding of the papillary matrix. Third-generation agents such as adapalene 0.1 % and microcrystalline solutions of tretinoin (< 10 microns) are better tolerated than older retinoid generations and formulations [ ]. However, women should avoid retinoids, at least during the first trimester of pregnancy, due to their teratogenicity. But a representative prospective study with two cohorts of pregnant women either exposed or not exposed to topical tretinoin showed similar outcomes regarding malformations. However, the regulations are handled differently in different parts of the world. For example, some countries (such as the US) may permit administration of adapalene 0.1 % as an OTC preparation without any warnings, while others (such as Germany) still require warnings in the patient insert. Azelaic acid (20 % cream or 15 % gel) is also a firstline choice for mild-to-moderate adult acne in females; it has good efficacy and a favorable safety profile, even in pregnant women [ ] and demonstrates anti-tyrosinase activity 1189

6 (useful for PIH) and antibacterial, anti-inflammatory and anticomedogenic activity [ 52 ]. Benzoyl peroxide (BPO) has strong bactericidal properties and can be used in pregnancy, but may cause irritation and dryness of the skin [ 53, 54 ]. Topical antibiotics should not be considered for monotherapy or alongside systemic antibiotics, due to the long duration of female acne and high prevalence of bacterial resistance [ 55, 56 ] ; however, they can be combined with a retinoid or BPO. With mild inflammatory acne, topical retinoids can be combined with BPO, azelaic acid, sytenol or clindamycin phosphate in fixed formulations according to the prevalence of retentional or inflammatory lesions; with moderate disease, these agents can be prescribed alongside systemic treatments (e.g. cyclins, anti-androgens or zinc salts). However, no topical antibiotics are recommended with systemic antibiotics [ 57, 58 ]. Systemic therapies Systemic treatments are usually required for moderate to severe acne as well as for mild forms (mainly mandibular acne) associated with scarring, long duration or failure to respond to topical therapies [ 5 8, ] Combination with fixed-dose topical therapies is useful in moderate to severe disease and may be more convenient than multiple individual agents. Zinc salts may be useful for general inflammation and during pregnancy. Systemic antibiotics should not be used alone [ 40, 58 ], but may show synergistic efficacy combined with topical therapies (except topical antibiotics). Adding BPO aids prevention of bacterial resistance, while retinoids can target most pathogenic factors more effectively than anti-microbial therapy alone. Doxycycline and lymecycline are preferred choices (once-daily formulations with few food interactions and good patient adherence). These can be combined with BPO, retinoid or azelaic acid, but tetracyclines and retinoids need to be avoided during pregnancy. Erythromycin is associated with greater bacterial resistance than other antibiotics, but is the first choice for pregnant women [ 60 ]. Hormonal therapies, including anti-androgens and 3 rd /4 th generation OCs, primarily reduce excess sebum production and should be combined with other classes of agent (e.g. azelaic acid, retinoids and new BPO formulations). Hormonal therapies are usually highly effective, and are useful for patients with severe seborrhea, flare-ups before menstruation, endocrine abnormalities, persistent inflammation recalcitrant to treatment, late-onset acne, androgenic alopecia and where OC is required [ 61, 62 ]. Androgen receptor blockers such as cyproterone acetate can be used as monotherapy. Oral contraceptives used in combination with ethinylestradiol include cyproterone acetate (CPA), chlormadinone acetate (CMA), and drospirenone. Metformin can be used off-label to decrease insulin resistance [ 5 8, 63 ]. Spironolactone as low-dose monotherapy ( mg/day) or combined with topical therapy can be used for acne resistant to standard treatment (a 3 rd /4 th generation OC may be added for menstrual irregularity); however, its use in acne is currently off-label in Europe and the US (where clinical trials are ongoing) and should be avoided in pregnancy. Adrenal androgen inhibitors (low-dose glucocorticoids, e.g. prednisone) are recommended for acute flares and short-term treatment of severe acne or androgenic disorders (e.g. congenital adrenal hyperplasia) [ 5 ]. Isotretinoin is a highly effective oral treatment, specifically indicated for use after failure of other therapies; however, in women it may be used as first-line treatment for severe nodular cystic acne or second-line treatment for severe acne unresponsive to topical/oral combination therapy [ 61, 62, 64, 65 ]. Isotretinoin is associated with significant dose-related side effects and is contraindicated in pregnancy. Combining isotretinoin with OCs when contraception is required offers synergistic effects, and concomitant use of oral antihistamine (off label) reduces the degree of side effects. Isotretinoin is more often associated with relapses when an androgen excess is present. Adjunctive therapies Light therapy including lasers, blue/blue-red light, intense pulsed light, pulsed dye lasers and photodynamic therapy (with or without photosensitizing agents) may be effective, but further evidence-based comparative and long-term studies are required [ 2, 40 ]. Photodynamic therapy appears to provide improvements in some cases of deep inflammatory lesions, and some types of laser are useful in the treatment of scarring [ 66, 67 ]. Chemical peels (e.g. glycolic acid, salicylic acid, Jessner s solution) show adjunctive efficacy in mild to moderate disease [ 68, 69 ], but further data are needed. Mechanical procedures (e.g. comedone extraction, cautery, hyfrecation, microdermabrasion, microneedling) may be useful to reduce non-inflammatory lesions [ 69 ], improve atrophic scars [ 70 ], and in combination with chemical peels [ 71 ]. Intralesional corticosteroids are effective for rapid treatment of deep inflammatory nodules [ 72 ]. Maintenance therapy The pathophysiology of adult female acne is not yet fully explored, but persistence and relapse are a typical course. Therefore, treatment duration and appropriate long-term patient support should be management considerations. Maintenance therapy is required to minimize the risk of relapse after acute treatment and where recurrences are frequent [ 5, 40, 73 ]. Specific guidance on maintenance therapy for adult females is currently lacking; however, this gap is addressed in detail by a practical algorithm for acne (see later). Topical 1190

7 retinoids (e.g. adapalene or tazarotene) and azelaic acid are good candidates for maintenance therapy. The effect of adapalene has been shown to persist after cessation of active treatment [ 73 ], and azelaic acid has demonstrated non-inferiority to adapalene, with a favorable safety profile for maintenance therapy of adult female acne [ 74 ]. Skin care Patients may benefit from support and advice on general skin care, including products to use and integration with topical medication [ 27, 75 ]. All adult female acne patients should use a gentle, non-soap cleanser with a ph close to 5.5, and a non-comedogenic, oil-free moisturizer. Women may be particularly inclined to use cosmetic products and processes to improve the appearance of their skin, including facial treatments (at spas and commercial private clinics), and to use make-up and camouflage creams; however, cosmetic over-treatment is counterproductive. Any cosmetic products for covering lesions, scarring or PIH should be non-comedogenic and oil-free. Sun exposure (in particular the use of artificial sunbeds) may trigger or worsen acne and produce comedones [ 76 ], together with risks of ultraviolet damage and promote skin cancer. Photoprotection is recommended in the labels of several acne medications (e.g. topical retinoids, oral tetracyclines and BPO). Ultraviolet-blocking sunscreen is advisable for many women, especially those living in countries with intense sunlight and those susceptible to hyperpigmentation. Sun protection products should not be comedogenic or emollient; they should be photoprotective emulsions with good tolerability that are easy to rinse off [ 76, 77 ]. Appropriate cosmetics should provide three-fold benefits [ 77 ]. They should improve self-esteem and QoL; be compatible with prescribed medications and reduce the number of stress-related aggravating factors or skin-picking episodes if possible; and should also contribute to photoprotection. Psychological support The psychological impact of acne may not be fully appreciated by relatives and healthcare professionals, and the degree of distress varies between patients [ ]. Psychological evaluation is generally only undertaken in secondary care or if the psychological effect of acne is regarded as particularly severe. This can be misleading, because perception of severity can differ considerably between patients and healthcare professionals. The empathy of a healthcare professional affects patient outcome, and establishing trust is key. Clinicians should be non-judgmental and demonstrate an understanding of the patient s feelings, the impact of acne on their personal and professional life, and their self-perception of acne severity (which may not correspond to the clinical evaluation). Given that women are more prone to stress-related disorders and anxiety than men, it is especially important to evaluate and address the perceived QoL and psychological state of women with acne. A number of tools are available to assess QoL, although there is little consistency between them and many are not validated [ 11, 17, 18 ]. A patient s QoL should improve as acne severity and appearance improves. A number of clinical and observational studies have shown the benefits of treatment efficacy on QoL, with improvements related to the initial impact of disease [ 81, 82 ]. Prior to acne improvement, the use of good quality make-up can assist with improving a patient s confidence in her appearance. Future directions Improvements in patient adherence In 2003, the World Health Organization noted that Increasing the effectiveness of adherence interventions may have a far greater impact on the health of the population than any improvement in specific medical treatments. [ 7, 83 ]. Adherence to acne therapy, especially systemic treatments, can be low. Adult female patients may be difficult to motivate and maintain on treatment (especially outside of clinical studies) due to greater duration and psychological impact of acne, stress-related issues and low expectations of further treatment efficacy (often feeling that they have tried everything but nothing works). A new acne treatment algorithm may help adult female patients to adhere better and longer to treatment [ 84 ]. The patient-physician relationship has a significant impact on adherence to medication and thus outcome. Response to acne treatment can be slow; patients should be made aware of the time that is probably required for clinical improvement. Potential side-effects should be proactively explained, so that patients can fully exercise their choice of optimal therapy. Outcome of recent studies It can be challenging to recruit and retain adult female acne patients in clinical trials; in future, fewer study participants may be required since the microcomedone count is now an acknowledged surrogate marker of efficacy, and can improve inter-center reproducibility. However, this measure requires clear definition in updates to treatment guidelines before it is fully adopted. The authors have observed that nurse-led telephone follow-up and support at key time points can improve patient adherence to treatment and retention in trials (unpublished). Clinical observations suggest that acne treatment can improve overall skin appearance (smoothness, scaliness, elasticity, color) while reducing comedones, papules and pustules. 1191

8 Given that skin appearance affects patient-perceived efficacy and QoL, and scientific evidence is lacking for these subjective outcomes, future studies should include epidermal barrier and function parameters. The Dermatology Life Quality Index (DLQI), is a widely used QoL measure in dermatological diseases, including psoriasis, atopic dermatitis and acne [ 85, 86 ] ; however, the utility of the DLQI for adult female acne has not been formally evaluated. Future clinical trials could include measures of patient QoL (including psychological factors), such as the Acne-Qol, which is validated in many languages. This will help to improve real-world patient management, especially for women requiring long-term dermatological therapy. Conclusions Adult female acne is a distinct part of the acne disease spectrum. It is associated with a specific balance of pathophysiological factors, and has a different clinical pattern and disease course from classical acne. The psychological impact of acne can be significant, varying between individuals, but may have a particular impact on women due to their greater susceptibility to stress and gender-specific triggers for it. Stress has a reciprocal pathophysiological link to acne susceptibility and severity, and should be actively managed as part of a comprehensive, holistic treatment plan. The therapy plan that is chosen should aim not only to improve the clinical symptoms of disease, but also to reduce psychological distress and improve the quality of life, including appropriate use of selected cosmetics to raise self-esteem. Financial support In part editorial assistance in the drafting of this manuscript was provided by Claire Price of Lucid UK, and this assistance was funded by Bayer Consumer Care. Conflict of interest Prof. Brigitte Dréno has participated in acne-relevant clinical and experimental studies, symposia and advisory boards for Galderma, Intendis, Meda, Merz, Pierre Fabre, La Roche Posay, and Bioderma. Prof. Edileia Bagatin, Prof. Ulrike Blume-Peytavi and Dr. Marco Rocha have participated as a speaker, consultant and advisory board member for Bayer Consumer Care. Prof. Harald Gollnick has participated in acne-relevant clinical and experimental studies, symposia and advisory boards for Bayer, Galderma, Stiefel/GSK, Intendis, Meda, Merz, Hoffmann-LaRoche, Novartis, Schering, Pierre Fabre, IMTM, and Vichy. Correspondence to Harald P.M. Gollnick, MD, PhD Professor (emeritus) Dept. Dermatology & Venereology Otto-von-Guericke University Magdeburg/Germany harald.gollnick@med.ovgu.de References 1 Gollnick HP. From new findings in acne pathogenesis to new approaches in treatment. J Eur Acad Dermatol Venereol 2015 ; 29 ( Suppl 5 ): Nast A, Dreno B, Bettoli V et al. European evidence-based (S3) guidelines for the treatment of acne-update J Eur Acad Dermatol Venereol 2016 ; 30 : Rocha MA, Costa CS, Bagatin E. Acne vulgaris: an inflammatory disease even before the onset of clinical lesions. Inflamm Allergy Drug Targets 2014 ; 13 ( 3 ): Thiboutot DM, Dréno B, Abanmi A et al. Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol 2018 ; 78 S. S1 S23. 5 Dreno B, Layton A, Zouboulis CC et al. Adult female acne: a new paradigm. J Eur Acad Dermatol Venereol 2013 ; 27 ( 9 ): Holzmann R, Shakery K. Postadolescent acne in females. Skin Pharmacol Physiol 2014 ; 27 ( Suppl. 1 ): Williams C, Layton AM. Persistent acne in women: implications for the patient and for therapy. Am J Clin Dermatol 2006 ; 7 ( 5 ): McConnell RC, Fleischer AB, Jr., Williford PM, Feldman SR. Most topical tretinoin treatment is for acne vulgaris through the age of 44 years: an analysis of the National Ambulatory Medical Care Survey, J Am Acad Dermatol 1998 ; 38 ( 2 Pt 1 ): Collier CN, Harper JC, Cafardi JA et al. The prevalence of acne in adults 20 years and older. J Am Acad Dermatol 2008 ; 58 ( 1 ): Dreno B. Treatment of adult female acne: a new challenge. J Eur Acad Dermatol Venereol 2015 ; 29 ( Suppl 5 ): Dréno B, Thiboutot D, Layton AM et al. Large-scale international study enhances understanding of an emerging acne population: adult females. J Eur Acad Dermatol Venereol 2015 ; 29 ( 6 ): Tanghetti EA, Kawata AK, Daniels SR et al. Understanding the burden of adult female acne. J Clin Aesthet Dermatol 2014 ; 7 ( 2 ): Stoll S, Shalita AR, Webster GF et al. The effect of the menstrual cycle on acne. J Am Acad Dermatol 2001 ; 45 ( 6 ): Salvaggio HL, Zaenglein AL. Examining the use of oral contraceptives in the management of acne. Int J Womens Health 2010 ; 2 : Pagliarello C, Di Pietro C, Tabolli S. A comprehensive health impact assessment and determinants of quality of life, health and psychological status in acne patients. G Ital Dermatol Venereol 2015 ; 150 ( 3 ):

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