Acne Workshop Pediatric Acne: What s Erupting? AZAAP. Marcia Hogeling, MD, FAAD, FAAP

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1 Acne Workshop Pediatric Acne: What s Erupting? AZAAP Marcia Hogeling, MD, FAAD, FAAP

2 Disclosures Advisory Board Leo Pharma & Anacor Off label use of acne medicines

3 Objectives Diagnose comedonal, inflammatory and cystic acne Understand pediatric acne treatment guidelines Analyze current acne treatment options

4 Acne Vulgaris: Basic Facts acne is caused by inflammation of pilosebaceous follicles. Typically presents ages 8-12 as the first sign of puberty peaks at ages 15-18, and resolves by age 25 Affects 90% of adolescents, affects races equally, and there is often a family history

5 Why treat acne? Substantial acne associated with Social impairment Diminished quality of life Impact on global self esteem Depression

6 Acne by Age Neonatal 0-6 weeks Infantile 0-1 year Mid-childhood 1-7 year Preadolescent 7-12 years Adolescent years or after menarche in girls

7 Diagnosis? Neonatal acne First 6 weeks Malassezia sp +/- increased sebum due to maternal hormones Aka neonatal cephalic pustulosis Tx parental reassurance or 2% ketoconazole cream may reduce fungal colonization if extensive lesions

8 Diagnosis? Infantile acne 6 weeks to 1 year of age Comedones more prominent May have pitted scars, cysts, nodules Resolves in 1-2 years

9 Infantile acne Most infantile acne is self limited, however look for signs of hormonal abnormalities No FDA approved treatments in this age group We use topical retinoids, topical antimicrobials For inflammatory lesions: oral erythromycin Rarely isotretinoin

10 Acne Guidelines: Mid childhood acne (onset 1 7 years) is unusual On physical exam look for signs of sexual precocity, virilization and /or growth abnormalities Appropriate work up or referral to endocrine for assessment of endocrinologic diseases, tumors, gonadal/ovarian pathology

11 Mid childhood acne 1-7 years Differential Diagnosis: Adrenal tumors Congenital adrenal hyperplasia Cushing syndrome Gonadal tumors Ovarian tumors PCOS Premature adrenarche True precocious puberty

12 Acne: Increasingly Early Analysis of NAMCS database ( ) revealed a decrease in the average age of children seeking treatment for acne 12 years of age no longer the low end of the normal range for acne onset NAMCS, National Ambulatory Medical Care Survey

13 Earlier Puberty: It s real! Younger age of onset of puberty in many countries: generally accepted AAP study: US girls typically displaying pubertal development about a year earlier than previously assumed Euling et al Pediatrics 2008 Biro et al Pediatrics 2010

14 Preadolescent Acne 7-12 years Common May precede other signs of puberty Work up beyond history and physical is generally unnecessary unless there are signs of androgen excess, PCOS, etc

15 Pre-adolescent acne: normal variant COMEDONES COMMON EARLY Early comedonal acne may predict later severe acne in girls Forehead, mid face Truncal much less common

16 Preadolescent acne 7-12 years Differential Diagnosis Pomade acne Angiofibromas Corticosteroid induced acne Flat warts Keratosis Pilaris Milia Molluscum Contagiosum Perioral dermatitis Syringomas

17 Adolescent Acne years Differential Diagnosis: Corticosteroid induced acne Demodex folliculitis Gram negative folliculitis Keratosis Pilaris Pityrosporum folliculitis Papular sarcoidosis

18 Acne Myth: Poor hygiene and improper cleaning causes acne Harsh cleansers Disrupt skin barrier Increase transepidermal water loss Encourage bacterial colonization Promote comedones Cause burning/stinging

19 Face washing Recs Twice a day Gentle, ph balanced cleanser Antibacterial soaps (other than benzoyl peroxide) not effective Caution with facial toners as they can be irritating and affect tolerability of acne meds

20 Acne myth: Cosmetics worsen acne Oil free, non-comedogenic makeup can: Improve quality of life Doesn t worsen severity of acne Select sunblocks and moisturizers that are non comedogenic

21 Acne Vulgaris: types of pimples There are many morphologies seen in acne including open and closed comedones, papules, pustules, and cysts Comedones are the hallmark lesion of acne vulgaris Comedonal acne is a mild form that involves comedones or whiteheads and blackheads Comedones are precursors to developing the other acne lesions Treating comedones to prevent new ones is central to treating all types of acne

22 Types of pimples Papular acne is a form with more papules and pustules that occurs in individuals with coarse/oily skin Larger cysts and nodules Permanent scarring and post inflammatory hyperpigmentation are sequelae of acne Treat acne aggressively to prevent scarring!

23 Acne evaluation Classify as comedonal, inflammatory or mixed Also general assessment of mild, moderate and severe is helpful Assess for scarring, brown pigmentary changes and erythema

24 Case 1

25 Case 1: History 18-year year-old healthy adolescent that presents with 2 years of pimples on his face. He washes his face regularly and reports that he began to note increased pubic hair at the time of onset PMH: none Allergies: none Meds: none FH: father and mother had acne as children SH: lives at home with parents and attends high school ROS: negative

26 Acne Vulgaris Classification Mild: Open comedones Mild to moderate: Open and closed comedones and some papulopustules Moderate: Pustular Acne Severe: Nodulocystic Acne

27 How would you describe the following acne patients?

28 Importance of History questions Medications: a number of meds can cause or exacerbate acne including: Lithium Phenytoin Systemic steroids Androgens Diet: a high glycemic diet may worsen acne Weight gain and supplements: if a young person is gaining wait and using supplements explore the use of anabolic steroids

29 Acne Vulgaris pathogenesis Acne Vulgaris is related to 4 factors: 1. Presence of hormones (androgens) 2. Sebaceous gland activity (increased in presence of androgens) 3. P. acnes (bacteria) in the hair follicle (it lives on the oil and breaks it down to free fatty acids which cause inflammation) 4. Plugging of the hair follicle as a result of abnormal keratinization of the upper portion

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31 Treatment of Acne Vulgaris The treatments for acne are directed at one or more of the 4 causative factors. Acne causes facial disfigurement and scarring is difficult to treat! In combining agents therapeutically, agents with activity against different pathogenic causes should be used (e.g. topical antibiotic plus tretinoin) Aggressive prevention is important

32 Pediatrics 2013;131:S

33 New Acne Guidelines published in Pediatrics Why guidelines? Possibly more acne at a younger age Different prescribing patterns between dermatologists and pediatricians/pcps Evidence-Based Recommendations for the Diagnosis and Treatment of Pediatric Acne, Pediatrics, May 2013;131 Supplement 3

34 Acne Vulgaris: Treatments There are two main classes of treatments: Antibacterials: prevents bacterial component Topical: clindamycin, benzoyl peroxide Systemic: doxycycline, minocycline Anti-comedonal affects keratinization Topical: Tretinoin [Retin-A], adapalene [Differin], benzoyl peroxide Systemic: Accutane (isotretinoin) Also hormonal treatments: certain oral contraceptives (ortho tricyclen) Washing the face DOES NOT help to prevent acne

35 Treatment of Preadolescent Acne in the US: An analysis of Nationally Represenatative Data National Ambulatory Medical Care Survey Data (NAMCS): Data were stratified according to age group and physician specialty Davis et al Pediatric Dermatology 2013

36 Leading Acne Meds in Pre-Teens: Specialty Differences Dermatologists Adapalene Benzoyl Peroxide Tretinoin Pediatricians/Primary care Minocycline Clindamycin Tretinoin

37 PRACTICE GAP: topical retinoid use Prescribed in 41% of acne visits Lower prescriptions if: Seeing pediatrician or family doctor Also male gender, Medicaid insurance

38 PRACTICE GAPS Over reliance on oral antibiotics Underuse of topical retinoids Use of oral antibiotics without benzoyl peroxide or retinoids Under appreciation of early, significant acne as a predictor of worse acne over time

39 Mild acne

40 Acne Guidelines: Mild Acne Benzoyl peroxide one of the most versatile, safe, inexpensive and effective acne treatments Can use benzoyl peroxide in the morning (either a % wash, topical cream or gel) Careful causes bleaching of towels/clothes

41 Benzoyl Peroxide Adverse Effects Dryness, erythema, peeling on initiation of treatment Start with lower concentration e.g. 2.5% Use a moisturizer Allergic contact dermatitis occurs in 1 in 500 Itching, swelling of eyes

42 Benzoyl peroxide formulations 2.5% - 10% Higher concentrations do not increase efficacy but are more irritating Back may be special site where increased concentration is beneficial Leave on vs washes Used in regimens of care for all acne types

43 Benzoyl Peroxide May minimize development of antibiotic resistant P. acnes When used with topical or oral antibiotics

44 Acne Guidelines: Mild Acne Topical retinoids and topical benzoyl peroxide are first line Increased efficacy of benzoyl peroxide if used with retinoid Apply a pea sized amount of retinoid to entire face at night (need to apply at night because sunlight inactivates)

45 Types of topical retinoids Adapalene, Tretinoin 0.025%, 0.05%, 0.1%, tazarotene Start with lower concentration of retinoid as they can be drying and irritating If irritation occurs: apply every other night, or apply a non comedogenic moisturizer overtop of the medication Or if good insurance can get single combination product with benzoyl peroxide/adapalene and apply once daily

46 Acne Guidelines: Key Point Topical retinoids (tretinoin, adapalene, tazarotene) may be used as monotherapy or in combination products for: All types and severity of acne because treating the comedone is central to treatment Children and adolescents of all ages Retinoids promote normal follicular desquamation so prevent new comedones and get rid of old ones

47 Retinoids Adapalene: Photostable Weaker Tazarotene: Less often used as first line Known to be more irritating, less tolerated

48 Safety of topical retinoids Natural endogenous retinoids are in plasma of normal healthy girls from dietary consumption (fish, carrots, sweet potatoes, red peppers) Continuous daily dosing of tretinoin 0.1%, tazarotene 0.1% and adapalene 0.1% only slightly increased mean plasma levels Serum retinoid levels more influenced by diet than topical retinoids

49 Topical retinoids and pregnancy Study of 215 females accidentally exposed to topical tretinoin during 1 st trimester 430 age matched controls No difference in developmental anomalies Jick et al. First trimester topical tretinoin and congenital disorders Lancet 1993

50 Antibiotics Acne is not an infection Antibiotics decrease P acnes colonization of the skin and follicles Inhibit bacterial protein synthesis Decrease inflammation via inhibition of bacterial pro inflammatory mediators Decrease neutrophil chemotaxis

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52 Acne Guidelines: Key Point Topical antibiotics (clindamycin, erythromycin) are not recommended as monotherapy Slow to work and increase bacterial resistance with monotherapy Topical benzoyl peroxide should be added Due to P. acnes resistance

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54 Moderate to severe inflammatory acne Consider derm referral Oral antibiotics appropriate at any age for moderate to severe acne Second generation tetracyclines (doxycycline, minocycline) usually preferred Under age 8: erythromycin (less effective due to p.acnes resistance), azithromycin, trimethoprim/sulfamethoxazole : risk of hypersensitivity, SJS, TEN!

55 Oral Doxycycline Adverse effects: Photosensitivity pill esophagitis, GI upset Pseudotumor cerebri (rare) Counter measures: Sun protection Drink large glass of water, remain upright for 1 hour after ingestion, take with food Dosage of 100 mg qd or bid

56 Oral Minocycline Adverse effects Drug hypersensitivity syndrome Steven Johnson syndrome Lupus like syndrome Hyperpigmentation (scars, sclera, oral mucosa) Hepatitis Vestibular toxicity Pseudotumor

57 Systemic antibiotics Some evidence that long term antibiotics cause increase in resistant coagulase negative staph Possible increased risk of URI while on antibiotics

58 How we manage moderate acne at PCH Doxycycline 100 mg qd bid (usually 3-6 months) Topical retinoid & benzoyl peroxide Within 1-2 months of the inflammatory acne improving: discontinue or taper Continue with topicals If need retreatment, use the same antibiotic that was previously effective

59 Acne Consensus Guidelines Oral antibiotics are appropriate for moderate to severe acne of any age Don t use doxy or mino <8 years Educate patient on side effects and monitor for adverse events

60 Hormonal therapy for Girls Suppresses ovarian androgen production Blocks effects of androgens on sebaceous glands Certain oral contraceptives spironolactone

61 Combination Oral Contraceptives 3 are FDA approved for moderate acne Ortho tri cyclen (15 years) Estrostep (15 years) Yaz (14 years) Generally start them 1 year after onset of menses

62 Spironolactone Synthetic steroidal androgen receptor blocker FDA approved as a diuretic for a variety of conditions Less studied in pediatric patients Add on top of oral contraceptive Irregular periods if taken alone Pregnancy category X (feminization of male fetal rats)

63 Acne Guidelines: Hormonal therapy Combined oral contraceptives may be useful as second line therapy in regimens of care in pubertal females with moderate to severe acne Tobacco use and family history of thrombotic events should be assessed

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65 Oral Isotretinoin Targets all of the factors involved in acne with typically excellent results Starting dose of 0.5 mg/kg/day for 4 weeks Then increase to full 1 mg/kg/day Usually a 6 month course Severe, refractory, scarring acne

66 Isotretinoin Severe scarring and/or refractory acne in adolescents and may be utilized in younger patients Extensive counselling about teratogenicity, avoidance of pregnancy, and careful monitoring of potential side effects and toxicities Ipledge system

67 Isotretinoin side effects Most common: Dry, chapped lips and skin Dry eyes Myalgias Nose bleeds Increased triglycerides Changes in liver enzymes We do fasting serum lipids and liver function tests at baseline and monitor periodically

68 Isotretinoin: teratogenicity In 2007, FDA mandated a computerized risk management program called Ipledge Registers all patients, physicians, pharmacies and manufacturers Monthly monitoring of pregnancy status in females Girls need to be on two forms of birth control

69 Isotretinoin: other side effects Skeletal issues Inflammatory bowel disease controversy May be an association affecting a small subset of patients, epidemiology studies have not shown link Confounders: age, previous antibiotics, IBD&acne link Mood changes Anecdotal evidence (case series) Large epidemiologic studies do not support a causative association Acne severity itself is a predictor of mental health issues and suicidal ideation

70 Guidelines for Acne Vulgaris Treatments Comedonal: topical retinoids, benzoyl peroxide Pustular/papular: Oral antibiotics PLUS adequate topical therapy; hormonal therapy Cystic: Oral Antibiotics; Isotretinoin

71 Discuss expectations Teens are impatient! Explain acne may worsen or irritation may happen initially with gradual improvement Review face washing practices and how to use topical medications properly acne handout or in your end of visit summary Usually see improvement by 8 weeks We usually have a 3 month follow up to assess response to treatment and ask about adherence

72 Pediatric Acne Update Recognize early acne, pathologic acne, and scarring acne Aggressive, but responsible therapy should be initiated

73 Thank you