OBJECTIVES. Update on Acne Management for the Primary Care Provider. Conflict of Interest. Case. Acne vulgaris/cystica

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1 OBJECTIVES Update on Acne Management for the Primary Care Provider Elaine T. Kaye, MD Define the pathophysiology of acne and its different clinical morphologies. Discuss differential diagnosis of acne vulgaris and related conditions. Review both traditional and newer acne approaches in optimizing management. Conflict of Interest No relevant disclosures Case A 15 year old boy presents with a three year history of oily skin and pimples which have been treated with various OTC preparations. More recently, large "whiteheads" and tender nodules are noted on the face, chest and back. The patient is currently on lithium for bipolar disease and is an asthmatic sometimes requiring prednisone. Acne vulgaris/cystica Diagnosis: Acne vulgaris/acne cystica Exacerbating factors Medications (e.g. lithium, steroids) Emotional stress

2 Differential diagnosis: Staphylococcal Folliculitis/Furunculosis Pseudofolliculitis Rosacea/perioral dermatitis ACNE: New Directions for an Old Problem Caveat: Hold on to what is tried and true Acne vulgaris Most common in adolescence but can persist into adulthood, 85% in ages psychosocial effects vastly underestimated Impact on quality of life- anxiety, depression, interference with social relationships and activities, Loney, J Health Psychol 2008 Diagnosis: Acne vulgaris/ Acne cystica Etiology: Abnormal sloughing of the hair follicle Excess sebum (androgenic influence) P. acnes-lipase creates fatty acids Acne Morphology Open/Closed comedones Inflammatory papules Pustules Cysts Scars (pitted,papular) Classification of acne severity Grade I: Mild- comedones, no scarring Grade II-III: Moderate-papules, pustules,mild to moderate scarring GradeIV: papules,pustules, cystic nodules, moderate to severe scarring

3 Effective Management of Acne Acne-Dispelling the Myths (only 1 is true) Acne is caused by dirt; blackheads are black from dirt Vigorous facial scrubbing helps clear acne Fatty, high caloric Foods (chocolate, French fries) cause acne Stress can cause acne Sunlight dries up pimples and clears acne Makeup cannot be worn by acne patients The old-fashioned treatments do not work; There s nothing new to try Acne-Dispelling the Myths Acne is caused by dirt; blackheads are black from dirt Vigorous facial scrubbing helps clear acne Food (chocolate, French fries) cause acne- Role of dairy products unclear (?IGF-1; Adembamowo et al, JAAD 06/08) Stress can cause acne TRUE Sunlight dries up pimples and clears acne Makeup cannot be worn by acne patients The old-fashioned treatments do not work; There s nothing new to try- Therapeutic role for optimism! Treatment: Basic Tenets avoid overzealous cleansing, manipulation use non-comedogenic products in make-up, sunscreens Motivate with hope and educationrationale for Rxs, need for patience LISTEN to your patient to optimize regimen Aim for ADHERENCE (compliance) Overview of Acne Therapy Grade I (mild): topical retinoids,bpo/ topical antibiotic Grade II-III (moderate): topical retinoids, BPO, topical antibiotic or oral antibiotic, hormonal therapy Grade IV (severe): topical retinoids,oral antibiotics, hormonal therapy or isotretinoin Topical Treatment Retinoids/ Analogs (comedolytic)- may be worse before betterdryness, increased papules, 6-8 week wait, acclimate skin, support with moisturizer, sunscreen Tretinoin, Adapalene, Tazarotene Topical antibacterial agents (tx of inflammatory lesions) Other

4 Tretinoin Available as cream, gel, time-release microspheres Comedolytic action by normalizing follicular keratinization Photosensitivity, irritation can occur Contraindicated in pregnancy as are all retinoids Tretinoin Precautions Photosensitivity, irritation can occur, peeling esp. with waxing Contraindicated in pregnancy as are all retinoids Anti oxidant can interact with benzoyl peroxide, oxidant Ramp up SLOWLY Adapalene Gel more effective than cream Two strengths: 0.1%, 0.3% Naphothoic acid derivative, retinoid analog Decreases comedones and inflammatory lesions Unlikely to irritate skin significantly Tazarotene Acetylinic retinoid for psoriasis, acne Well suited for deep-seated comedones More irritating than counterparts- Cream preferred over gel Aim for 0.1% (can start at.05%) Apply over moisturizer if sensitive Contraindicated in sun, pregnancy (black box warning) Azelaic acid 15-20% Helpful for comedones and inflammatory lesions Not effective monotherapy, use in combination Mild bleaching effect Benzoyl Peroxide Gel, wash with concentations of 2.5, 4, 5, 6, 8,10% Kills nearly 100% P. acnes, mildly comedolytic Oxidizes retinoids (except stable microsphere formulations) Vehicle, concentration is key! Warn patients of bleaching effect

5 Topical Antibiotics Erythromycin 2% Clindamycin 1%-multiple vehicles, possibly contraindicted in patients with IBD Above two equally effective as antiinflammatories; resistance occurs Topical Antibiotics Combination benzoyl peroxide/ erythro/ clinda synergistic; no p. acnes resistance Sodium sulfacetamide10% lotion is cosmetically elegant; some have 5% sulfur Recent topical Rx additions Combination adapalene/benzoyl peroxide 2.5% (qd) Combination tretinoin/clindamycin cream (qd) Dapsone cream- novel acne medication Recent topical Rx additions- Dapsone gel Novel acne medication- oral dapsone used for dermatitis herpetiformis Active against inflammatory lesions Tested in individuals age 12 and up G6PD testing is NOT indicated for topical form Mechanism thought to be via antineutrophilic action Systemic Therapy Oral antibiotics Oral contraceptives Oral retinoids Oral antibiotics- Criteria to treat Lack of response to topicals Large, hard-to-reach areas-topicals impractical Cystic component, scarring

6 Oral antibiotics Dosage and duration are key Erythromycin mg bid, 333mg tid, consider drug interactions, consider P. acnes resistance The tetracyclines-lipophilic, photosensitizing (doxy>tetra>mino), esophageal irritation (glass of water,>1hr before bed) Oral antibiotics Tetracycline- empty stomach,500 mg bid, currently commercially unavailable Minocycline mg bid/ dizziness, blue pigm., hypersensitivity reaction among side effects (DRESS lymphoma-like syndrome) Doxycycline mg bid/ photosensitivity, esophageal irritation Link to IBD inconclusive; doxy/crohn s dz; no cause effect established (Am. J. Gastro, 2010; 105) Newer oral abx additions Availability of varying minocycline dosages to personalize regimen for patient weight Submicrobial doses of doxy-avoid resistance 40mg qd FDA approved for rosacea 20mg bid FDA approved for gingivitis Goal is to achieve anti-inflammatory effect with minimal side effects Oral Contraceptives May contain norgestimate, first FDA approved progestin for acne, norethindrone or drospirenone. Similar efficacy; Drosperinone may have increased risk for blood clots compared with other progestins Parkin et al, Jick et al BMJ 2011 Oral Contraceptives May be useful in women with high or normal androgen levels Estrogen may take 3 cycles to act Oral Isotretinoin (Accutane) Oral Isotretinoin (13-cis retinoic acid) Indicated for severe, treatmentresistant, nodulocystic acne/ shrinks sebaceous glands

7 Oral Isotretinoin (Accutane) Psychological effect (black box warning) of depression/suicide-controversial screen, warn and monitor carefully O Reilly KC, Neuropsychopharmacology study in mice Rubinow DR, JAAD reduction in sx after tx Kaymak Y, Inter J Derm no increase in depression/anxiety in tx d group Oral Isotretinoin (Accutane) Link to inflammatory bowel diseaseinconclusive, discuss with pts Reddy D, J Gastroent 2006-? Trigger in subset of pts Crockett SD, Am J Gastroent Current evidence is insufficient to confirm or refute a causal association between isotretinoin and IBD. Oral Isotretinoin (Accutane) Link to inflammatory bowel diseaseinconclusive, discuss with pts Bernstein CN, Am J Gastroent Manitoba epidem- data suggest that isotretinoin is not likely to cause chronic IBD. Etminan M et al, JAMA Dermatol., 2013 metaanalysis-2159 IBD cases- no increase in risk for IBD, including UC or CD, with use of isotretinoin Oral Isotretinoin (Accutane) Alternative explanation: Murphy CL, Amer J Gastroent. Inflammatory Bowel Disease and Acne weeks treatment; dosage 0.5-2mg/kg/day; try to achieve 120 mg/kg to reduce recurrence Teratogenic-contraceptive counseling, informed consent; careful monitoring especially in females ipledge Program F.D.A. approved restricted distribution program for isotretinoin Initiated March 1, 2006 with aim to minimize fetal exposure Computer-based risk management system with trackable links between registered prescriber, patient and pharmacy All patients, including males and women who cannot get pregnant, must register

8 Case Presentation A 16 boy presents with one month after experiencing a fever, elevated ESR, joint aches and eruptive, erosive cystic acne nodules. These signs started one week after dermatologist started him on isotretinoin. The patient was on a prednisone taper at the time of presentation. Acne Fulminans Acute febrile ulcerative acne, acne conglobata Fever, ulcerating acne, polyarthritis Can arise spontaneously or rarely with initiation of isotretinoin Treatment with systemic steroids, oral antibiotics (in this case trimethoprim sulfa) Acne sequelae..now What? Acne sequelae Post-inflammatory hyperpigmentation common The Patience Factor! Tretinoin/Glycolic acid Hydroquinones Laser therapy

9 Acne sequelae Acne scarring Tretinoin(?), fillers, dermabrasion, laser (PDL-585nm) and radiofrequency devices for pitted/crateriform scarring Intralesional steroids cautiously for papular/ keloidal scarring on back Subcision of rolling scars Future directions in acne therapy Non-ablative radiofrequency- device delivers heat to sebaceous glands/dermis Light/Laser strategies: Blue light to kill P. acnes Photodynamic therapy (PDT) combination of amino-levulinic acid (ALA) and light or pulse dye laser Other Conditions Perioral Dermatitis More common in teenagers, young women Probably variant of rosacea Erythema, scaling, papules/pustules in periorificial areas Often history of treatment with fluorinated steroids Rosacea therapy- topical metronidazole Case Presentation A 20 year old woman presents with a history of frequent pimples and boils in her axillae and groin since puberty with several painful lesions that are currently draining purulent material. On exam she has tender, draining nodules, comedones and scarring under her arms and in the anogenital area. Hidradenitis suppurativa Occlusion of the apocrine follicular units Ddx: early furunculosis, late LGV/Crohn s Superinfection with Staph, strep (or gram negative) organisms Onset in puberty, sometimes remission with age

10 Hidradenitis suppurativa Associated with acne cystica/conglobata (sebaceous follicular occlusion) Associated with inflammatory bowel disease Van Der Zee HH, Br J Derm, 2010 Hidradenitis suppurativa Treatment Local care (hygiene, topical antibacterials) Intralesional corticosteroids Oral antibiotics (similar to acne tx) Hidradenitis suppurativa Treatment Oral retinoids Anti-androgens Surgical excision Biologics (infliximab, adalimumab,anti- TNF Ab) Van Rappard DC, BJD, 2012 Kimball, Ann Intern Med, 2012 Now it s your turn!

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