Review Acne Pathogenesis Clinical Evaluation Treatment Guidelines

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Tiffany Herd, MD Pediatric Dermatology Fellow Baylor College of Medicine/Texas Children's Hospital Review Acne Pathogenesis Clinical Evaluation Treatment Guidelines Psychosocial Impact of Acne Acne is the most common skin condition in the U.S. 50 million people in the U.S. affected 85% of teenagers experience acne 1 The impact of acne may be equivalent to asthma or epilepsy 2 Acne patients experience functioning and emotional effects similar to patients with psoriasis, vitiligo, atopic dermatitis and urticaria 3 1 Zaenglein AL et. Al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016 2 Thomas, D.R. Journal of Cutaneous Medicine and Surgery. 2004 3 Nguyen CM et al. The psychosocial impact of acne, vitiligo, and psoriasis: a review. Clin Cosmet Investig Dermatol. 2016

Acne negatively impacts self esteem and is associated with poor body image 1 Acne is related to decreased willingness to engage socially and poor academic performance 1 Increased rates of suicidal ideation and attempts 2 More likely to be unemployed 3 The severity of acne may not correlate with the severity of emotional impact 1 Nguyen CM et al. The psychosocial impact of acne, vitiligo, and psoriasis: a review. Clin Cosmet Investig Dermatol. 2016 2 Picardi A et al. Clin Dermatol, 2013 3 Bhate K, et al. Br J Dermatol, 2013 PATHOGENESIS 1. Abnormal follicular keratinization (hyperproliferation and shedding results in the microcomedo) 4. Ongoing inflammation leading to nodule/cyst formation and potential scarring 2. Propionibacterium acnes proliferation 3. Increased sebum production from androgenic stimuli PATHOGENESIS Leakage of sebum into the dermis and proinflammatory mediators secreted by P. acnes leads to ongoing INFLAMMATION Krakowski AC et al. Practical Considerations in Acne Treatment and the Clinical Impact of Topical Combination Therapy. Pediatric Dermatology, 2008

James WD. Acne. New Engl J Med. 2005 James WD. Acne. New Engl J Med. 2005 Onset Severity (good, average or bad day?) Menstrual History Treatments (duration) Menstrual history Family history (genetic influence on sebum production, etc) Signs of Hyperandrogenism Morphology Location Scarring?

CASE 1 - MILD COMEDONAL ACNE ACNE MANAGEMENT Abnormal desquamation of KCs Salicylic acid Topical retinoids Sebum production Sal acid; BPO Topical retinoids Hormonal Rx Bacterial colonization Sal acid; BPO Topical antibiotics Oral antibiotics Inflammation Sal acid; BPO Topical antibiotics Topical retinoids Oral antibiotics

Thiboutot et al. Practical Management of Acne for Clinicians. J Am Acad Derm. 2017 THE BASICS OF ACNE SKIN CARE Gentle face cleansing with a mild cleanser, slight evidence to support washing twice a day 1 Avoid squeezing/picking acneiform lesions Non-comedogenic facial moisturizer with sunscreen at least daily (QAM) Select non-comedogenic (non-acnegenic, oil-free) cosmetic products (QPM) Treatment takes weeks to months Don t spot treat 1 Choi JM. A Single-Blinded, Randomized, Controlled Clinical Trial Evaluating the Effect of Face Washing on Acne Vulgaris. Pediatr Derm. 2006 Gentle Cleansers Purpose Gentle Cleansing Bar/Wash Neutrogena Fresh Foaming Cleanser Cetaphil Antibacterial Soap Vanicream Gentle Facial Cleanser Facial moisturizers for daytime Cetaphil UVA/UVB Defense Facial Moisturizer (SPF 50) Neutrogena Healthy Defense (SPF 30 or 45) Neutrogenia Oil-Free Moisture (SPF 15) For nighttime may use similar products/brand without sunscreen Benzoyl Peroxide Washes Panoxyl Acne Foaming Wash (4% or 10% BPO) Neutrogena Clear Pore Cleanser Mask Oxy Rapid Treatment Face Wash Salicylic acid washes (targets abnormal keratinization) Neutrogena Oil-free Acne Wash Make-up Oil-free Non-comedogenic Neutrogena, Clinique

Gels, creams, lotions, solutions, pads, and washes Up to 2% Bar soaps, washes, gels, lotions, creams, pads 2.5% to 10% Combination: Clindamycin, Erythromycin, or adapalene

Types: natural vs. synthetic Benefits Side effects Skin peeling, erythema, dryness, burning, and itching Minimize side effects with a daily non-comedogenic moisturizer (apply after topical retinoid) Apply at night and not in the morning Use 3 times weekly if necessary BPO inactivates topical tretinoin

ACNE MANAGEMENT Abnormal desquamation of KCs Salicylic acid Topical retinoids Sebum production Sal acid; BPO Topical retinoids Hormonal Rx Bacterial colonization Sal acid; BPO Topical antibiotics Oral antibiotics Inflammation Sal acid; BPO Topical antibiotics Topical retinoids Oral antibiotics

Doxycycline Minocycline Erythromycin (47% resistance) Azithromycin Trimethoprim-sulfamethoxazole Limit therapy to 3 to 6 months

James WD. Acne. New Engl J Med. 2005 HORMONAL ACNE: EVALUATION Endocrine work-up is rarely indicated Strength of Recommendation A/Level I Evidence Reserved for Females w/ recalcitrant acne Females w/ demonstration of hyperandrogenism Acanthosis and Hirsutism are the most reliable markers of PCOS 1 Mid-childhood acne Bone age Total/free testosterone DHEA-S Sex hormone-binding globulin 17-hydroxyprogesterone LH/FSH Total and free Testosterone 1 Schmidt TH et al. Cutaneous Findings and Systemic Associations in Women with Polycystic Ovarian Syndrome. JAMA Dermatol. 2016 1 Layton AM et al. Oral Spironolactone for Acne Vulgaris in Adult Female Patients. Am J Clin Dermatol. 2017 Combined Oral Contraceptives Oral Spironolactone 5 alpha reductase and sex hormone globulin 25 mg daily (up to 100-200 daily) Can be combined with OCP (augmented benefit?)? Increased risk of breast cancer No need to check K in healthy patients 1

ACNE MANAGEMENT Abnormal desquamation of KCs Salicylic acid Topical retinoids Bacterial colonization Sal acid; BPO Topical/oral antibiotics Sebum production Sal acid; BPO Topical retinoids Hormonal Rx Inflammation Sal acid; BPO Topical/oral antibiotics Topical retinoids

Oral isotretinoin should be first-line therapy for very severe acne Weight-based dosing starting at 0.1 mg/kg/day Goal dose of 120mg-150mg/kg = average 6 months therapy Some studies suggest higher cumulative doses to 225 mg/kg (should proceed until full clearance of acne) Ipledge Side effects Lab monitoring Ages 1-7* Concern for underlying hyperandrogenism Full history and physical examination including assessment of height growth velocity Precocious puberty Cushing syndrome Late-onset congenital adrenal hyperplasia Adrenal or gonadal secreting tumor Consider bone age, DHEA-S, FSH, LH, prolactin, 17-OHP, cortisol, endocrine involvement

Bree AF et al. Acne Vulgaris in Preadolescent Children: Recommendations for Evaluation. Pediatr Dermatol. 2014 A. Fried foods B. Polycystic ovarian syndrome C. Chocolate D. Stress E. Hypothyroidism A. Fried foods B. Polycystic ovarian syndrome C. Chocolate D. Stress E. Hypothyroidism

A high-glycemic-index/-load diet was positively associated with acne vulgaris 1 A positive association exists between intake of skim milk and acne2 1 Cerman 2 LaRosa AA et al. Dietary glycemic factors, insulin resistance, and adiponectin levels in acne vulgaris. J Am Acad Dermatol 2016 CL et al. Consumption of dairy in teenagers with and without acne. J Am Acad Dermatol 2016 Some evidence that topical tea polyphenols may decrease sebum production (anti-inflammatory and anti-microbial properties)1 Topical antioxidants and niacinamide may have sebostatic effects 2 Salicylic acid and alpha-hydroxyl acids, linoleic acids target abnormal keratinization 2 Zinc salts may have anti-inflammatory effects and may have a role in acne therapy (limited data) 2 1 Saric S et al. Green Tea and Other Tea Polyphenols: Effects on Sebum Production and Acne Vulgaris. Antioxidants 2016. 2Araviiskaia E et al. The role of topical dermocosmetics in acne vulgaris. JEADV 2016.

Acne Guidelines Early and effective treatment is important to minimize potential risk for acne scarring Abnormal follicular keratinization has an early role in acne pathogenesis Retinoids essential role in acne therapy For the majority of patients a topical retinoid plus BPO is first line therapy Avoid topical or systemic antibiotics as a monotherapy Benzoyl peroxide concentrates within the sebaceous follicle and works through free-radical mediated degradation of bacterial proteins thus decreasing antibiotic resistance and increasing efficacy when used with topical/systemic antibiotics Most patients with acne should receive maintenance therapy with a topical retinoid with or without BPO Consistent use of medications for 8-12 weeks is necessary before efficacy can be determined