Nuts and Bolts of Acne Treatment Options Theresa Coyner, MSN, ANP-BC, DCNP Randall Dermatology West Lafayette, IN

Transcription

1 Nuts and Bolts of Acne Treatment Options Theresa Coyner, MSN, ANP-BC, DCNP Randall Dermatology West Lafayette, IN Objectives Discuss the pathogenesis of acne. Identify the actions of various acne treatment options. Determine appropriate acne treatment options for selected case studies. Acne Pathogenesis Old Model Increased sebum production leading to Plugging of follicle creating microcomedone leading to Inflammatory response leading to Increase in Propiones Acne bacteria and neutrophils 1

2 New Model of Acne Pathogenesis Inflammatory cascade starts early in the pre-clinical phase Early components of T-helper lymphocytes and macrophages creates a follicular inflammatory infiltrate Concurrent formation of microcomedone Increased sebum production driven by androgens Shedding of follicular corneocytes creating plugging Follicular proliferation of Propiones acne bacteria Late increase of neutrophils. Types of Acne Lesions Comedone open and closed Inflammatory Papules Inflammatory Pustules Nodular Cystic 2

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4 Neonatal Acne Classification Birth to age 6 weeks. Small erythematous papules and pustules, no comedones located on face, neck, scalp and upper torso. Most cases due to colonization of Pitysporum. Neonatal Cephalic Pustulosis Infantile Acne Classification 6 weeks to 1 year of life. Males > female. Inflammatory lesions and comedones. Facial location. Generally due to androgen levels. 4

5 Mid Childhood Acne Classification Ages 1 to 7 years. Very Rare Generally due to underlying endocrine disorder. Evaluation includes: Ht/Wt chart Serum testosterone, FSH, LH, and DHEAS Referral to Endocrinology Pre-Adolescent Acne Classification Ages 7 to 12 years. Comedones initially on forehead followed by inflammatory lesions. Gradually may include the nose and remainder of face. Conchal bowls of ears may be involved. Assess for physical signs of adenarche. Precocious Puberty Criteria Pubic hair prior to age 8 in girls and age 9 for boys Often considered benign. May be first sign of androgen excess May be predictor of insulin resistance May be predictor of PCOS 5

6 Adolescent Acne Classification Age 12 to 18 years of age. 95% of adolescents will have a degree of acne. Comedones, inflammatory, nodular, cystic lesions. Involves face, neck, chest, back, and arms. Resolution of inflammatory lesion may leave persistent erythematous and/or hyperpigmented macules. Scarring is common including divots, dells, and hypertrophic lesions. Adult Acne Classification May be the first time acne appears. Lesions include deep inflammatory and cystic. Pattern is the U shape affecting chin, mandibular area and the neck. Pregnancy Drug Risk Categories- X Contraindicated in pregnancy. D Positive evidence of risk to human fetus. Benefits may outweigh risks of the medication. C Risk can t be ruled out - human studies lacking. Animal studies may or may not show risks. Potential benefits may justify risks. B No risk to human fetus, despite possible animal risks. OR no risk in animal studies and human studies have not been performed. A Controlled studies demonstrate no human fetus harm. 6

7 Treatment Strategies Non-prescription Prescription Topical retinoids Topical antibiotics Oral antibiotics Hormones Isotretinoin Benzoyl Peroxide Actions Diminished cohesion of epithelial cells. May prevent or eradicate antibiotic resistance. Antibacterial actions. NO bacteria resistance. Preparations 2.5% to 10% Creams, gels, lotions, washes, and foams. Pregnancy Cat -B Salicyclic Acid Actions promotes desquamation by dissolving the intercellular cement that binds cells to the stratum corneum. Types washes, scrubs, pads. Indications comedonal acne Side effects dryness and erythema Pregnancy Cat C 7

8 Sulfur Actions keratolytic may reduce obstruction of the comedone. Types creams, soaps, and washes Side effects possibly odor, dryness Individuals with sulfa allergies may not tolerate. May be combined with resorcinol. Pregnancy Cat C Retinol Actions natural form of Vitamin A. Precursor of tretinoin. Some effects on follicular epithelization. Increases turnover of skin cells. Types creams, component of many washes and cosmetic preparations. Side effects erythema, drying, peeling. Special considerations Oxidizes rapidly and is inactivated by ultraviolet light. Question Which cosmecutical company first manufactured retinol? 8

9 Alpha-hydroxy Acids Actions reduces adherence of cells in the stratum corneum. Reduces follicular obstruction. Types Washes, creams, and components of many cosmetics. Percentage is usually a 10%. Side effects may include dryness, erythema and peeling. Tea Tree Oil Actions antimicrobial actions. Essential oil of an Australian tree - alternifolia. Study indicated it was superior than vehicle alone and was comparable to 5% Benzoyl Peroxide in effectiveness. Onset of action slower than BP. Reference: Bowe, W.P. & Shalita, A.R. (2008). Effective overthe-counter acne treatments. Seminars in Cutaneous Medicine and Surgery. 27: Light Treatments Actions- Reduce the inflammatory effect. Types Red and Blue Light Treatments range from 5 minutes to 20 minutes Side Effects erythema Considerations Frequent treatments may be needed, costly and difficult to get insurance coverage. 9

10 Laser Treatments Actions heat can reduce bacteria in the follicle. Some remodeling of collagen can occur. Types usually the 500nm spectrum will be effective. This will help with persistent acne lesions and reduce erythema. Others may actually cause new growth of skin cells helping to reduce divoting. Side Effects transient swelling, erythema and peeling. Considerations Expensive, discomfort level, and difficult to get insurance coverage. Prescriptive Medications Topical retinoids Topical antibiotics and anti-inflammatory agents. Oral antibiotics Hormones Oral isotretinoin. Retinoids Actions regulate gene transcription. Normalize follicular epithelium desquamation. Decrease microcomedone formation. Promotes clearance of microcomedones. Anti-inflammatory actions Side effects erythema, drying, peeling. Special considerations most are degraded by ultraviolet light SHOULD BE CONSIDERED FIRST LINE Treatment 10

11 Adapalene Strengths 0.1% in cream, gel and lotion, 0.3% in gel Penetrates follicular opening within 5 minutes. Pregnancy Category C Special considerations: Approved for use in children age 9 and above Only topical retinoid that is NOT degraded by ultraviolet light. Tretinoin First topical retinoid developed. Vitamin A derivative. Preparations: 0.025%, 0.05%, and 0.1% cream 0.01%, 0.025% gel 0.05% solution 0.04%, 0.1% micro gel formulation Topical absorption slight but Vitamin A in excessive quantities is tetratogenic Avoid in pregnancy. Pregnancy Category - C Tazarotene Only topical retinoid that has no generic. Formulations: 0.05%, 0.1% cream 0.05%, 0.1% gel More potential irritation but highly effective Pregnancy Category X Females of child bearing capacity should have initial negative pregnancy test prior to use of medication. Highly effective birth control method utilized during treatment. 11

12 Clinical Pearls Adequate patient instruction mandatory prior to starting topical retinoids. Potential irritation can be avoided by: Limiting the amount of topical to less than a pea sized amount. Start use with every other night use. Consider use of a moisturizer over the retinoid. Topical Antibiotics Clindamycin Erythromycin Sulfacetamide Azelaic Acid Dapsone Clindamycin Phosphate 1% Actions reversibly binds to 50s subunit of ribosomal RNA subunit. Inhibits protein synthesis. Formulations: lotion, gel, solution Pregnancy Category B Indications inflammatory lesions Side effects itching, burning, stinging, dryness, and erythema. Oral form associated with colitis. Rare in the topical form. 12

13 Erythromycin Actions reversibly binds to 50s subunit of ribosomal RNA. Inhibition of protein synthesis. Formulations gel, pads, solution in 2% and 3% Pregnancy Category B Oral form has high degree of P. acnes resistance. Side Effects scaling, tenderness, burning, itching, and general irritation. Azelaic Acid Actions disruption of mitochondrial DNA synthesis. Also inhibits division and differentiation of keratinocytes. Demonstrates bacteriostatic and bactericidal actions against P. acnes. Formulations -20% cream, 15% gel Pregnancy Category B Side Effects itching, burning, scaling Special Considerations decreases the hypermelanosis caused by post-inflammatory hyperpigmentation. Dapsone Actions categorized as a sulfone Inhibition of dihydropteroate synthetase and nucleic acid synthesis. Interferes with neutrophil activity. Formulation: 5% gel Pregnancy Category C Side effects transient dryness, erythema, rash Generally can be used by individual with sulfa allergy No requirement for G6PD screening for topical. 13

14 Sodium Sulfacetamide Actions inhibits dihydropteroate synthetase. Formulations: 10% lotion, washes. Often combined with 5% sulfur Pregnancy Category C Side effects dryness and transient pruritus Topical Combination Products Advantages: simplifies the regimen, may decrease bacteria resistance, may facilitate the topical absorption into the epidermis and follicle. Formulations: Erythromycin 3% & BP 5% gel Clindamycin Phosphate 1.2% & BP 2.5% gel Clindamycin Phosphate 1.2% & BP 5% gel Clindamycin Phosphate 1.2% & Tretinoin 0.025% Adapalene 0.1% % BP 2.5% gel Oral Antibiotics Indications: Lack of therapeutic response to topicals. Widespread acne. Nodular-cystic acne. Special Considerations: Should NOT be monotherapy Antibacterial resistance can be common. Therapy should be limited to less than 6 months. 14

15 Tetracycline Actions Dosage Adverse Reactions Bacteriostatic Inhibit bacterial protein synthesis by binding to the 30s subunit of bacterial ribosome. Anti-inflammatory properties Inhibit production of neutrophils 60% excreted by urine, remainder in bile/feces mg every 6 to24 hours Must not be taken with food or milk. Pregnancy Cat D GI upset, esophagitis, photosensitivity, tooth discoloration Doxycycline Actions Dosage Adverse Effects Bacteriostatic Inhibitbacterial protein synthesis by binding to the 30s subunit of bacterial ribosome. Anti-inflammatory Inhibits production of neutrophils 60% excreted in urine, the remainder in bile/feces 50 to 200mg daily Pregnancy Cat D GI upset, esophagitis, photosensitivity including photo-onycholysis Tooth discoloration Pseudotumor cerebri is rare. Minocycline Actions Dosage Adverse Effects Bacteriostatic Inhibitbacterial protein synthesis by binding to the 30s subunit of bacterial ribosome. Anti-inflammatory Inhibits production of neutrophils 60% excretion in the urine with remainder in bile/feces mg every 12 to 24 hours Extended release mg daily Dosed at 1mg/kg/day Pregnancy Cat D Less photosensitivity and less GI upset than Doxycycline and Tetracycline. Dizziness, tooth discoloration. Cutaneous and mucosal discoloration. Pseudotumor cerebri is rare Drug hypersensitivity syndrome Serum sickness type syndrome and lupus like syndrome. 15

16 Erythromycin Actions Dosage Adverse Effects Bacteriostatic and Bacteriocidal Bindsto 50s ribosomal subunit Inhibits protein synthesis Metabolized by liver Excretion mainly through the liver small amount in urine 30 to 50 mg/kg per day divided every6 to 8 hours Pregnancy Cat B GI upset,diarrhea, hepatic dysfunction Prolongation of QT interval Many drug-drug interactions May have over 50% resistance to P.acnes Azithromycin Actions Dosage Adverse Effects Bacteriostatic and Bactericidal Binds to 50s ribosomal subunit Inhibits protein synthesis Metabolized in liver Excretion through bile but small amount through the urine Variable regimens Pulsed dosing for 3 to 4 consecutive days every 10 to 30 days. Alternative 250mg MWF Routine use for acne is not recommended Pregnancy Cat B GI upset, diarrhea Hepatiticdysfunction is rare Prolongation of QT interval Drug/drug interactions less than Erythromycin Amoxicillin Actions Dosage Adverse Effects Bactericidal Inhibitscell wall mucopeptide synthesis Metabolized by the liver Excreted by kidneys 500 mg 2 to 3 times daily Routine use for acne is not recommended. Pregnancy Cat B GI symptoms Vaginal candidiasis Hypersensitivity reactions 16

17 Cephalosporin Actions Dosage Adverse Effects Bactericidal Inhibits cell wall mucopeptide synthesis Excreted by kidneys 500 mgtwo times daily Routine use in acne is not recommended Pregnancy Cat B GI upset Vaginal candidiasis Hypersensitivity reactions Trimethoprim- Sulfamethoxazole Actions Dosage Adverse Effects Inhibits production of tetrahydrofolic acid Interferes with bacterial nucleic acid and protein synthesis Metabolized by liver Excreted in urine Singleor double strength given every 12 to 24 hours Reserved for refractory cases Pregnancy Cat C Photosensitivity Urticaria Bone marrow suppression Drug hypersensitivity syndrome including Stevens Johnson and TENS Hormonal Treatments Hormones modulate amount and availability and actions of Androgens Usually predictable flares around menses Inflammatory and nodulocystic lesions Mechanisms increased androgen levels leads to increased adrenal DHEAS, testosterone, and dihydrotestosterone Dihydrotestosterone binds androgen receptors on sebaceous glands and increases the activity of the gland. 17

18 Spironolactone Actions Dosage Adverse Effects Binds androgen receptors Blocks testosterone and DHT OFF-label use for acne Ranges from 25 to 200mg daily Can be used as monotherapy or combined even with OC s Pregnancy Cat D Breast tenderness Irregular menses Diuretic effects Avoid with concomitant use of lithium Avoid in kidney disease and concomitant use of other diuretics' Potential risk of elevated potassium levels Risk of hypospadias if taken during pregnancy Oral Hormones Decrease free testosterone and inhibits activity in the follicular sebaceous unit Usually contain 20 to 50 mcg or ethinylestradiol and a few may contain mestranol Progesterone agents include: Norgesterol - more androgenic properties Levonogesterol more androgenic properties Desogesterol Norethindrone Norgestimate Drospirenome 3mg dose equivalent to 25mg spironolactone Hormones Oral Preparations Monophasic Triphasic Oral Patches Vaginal devices DepoProvera and Implanon contain more adrogenic properties 18

19 Question How many combined oral contraceptives have FDA indications for acne? A. None B. 2 C. 3 D. 10 E. All Absolute Contraindications Pregnancy Undiagnosed vaginal bleeding History of clotting disorder Relative Contraindications Migraine headaches Strong family history of embolic events Menses less than 1 year Age older than 35 Smoking 19

20 Side Effects Desirable Lighter menses Decrease cramping Decreased risk of uterine and ovarian cancer Undesirable May cause menstrual irregularities Breast tenderness Fluid retention Nausea Weight gain generally not more than 2 pounds Headaches Increased risk of thromboembolic events Medication Interactions Decreased Effectiveness Rifampin Griseofulvin Barbiturates St. John s Wort Oral contraceptive with antibiotics Concern with the 2 nd pass with liver No evidence that concomitant use with oral antibiotics interferes with effectiveness Patient Instructions Take at the same time daily If pill is missed take as soon as possible May take up to 2 pills per day for 2 days to catch up When pills are missed the effectiveness for pregnancy prevention is severely limited Take at night with crackers if nausea occurs 20

21 Isotretinoin Vitamin A derivative Sensitized in 1955 Originally studied for disorders of keratinization Late 1970 s confirmed to be effective for acne Approved in 1982 for acne treatments Actions Acts at the retinoid receptor Inhibits sebaceous gland function Reduces sebum production Metabolized by the liver Excreted in urine and feces Terminal elimination can take up to 30 days Dosage 0.5mg to 2mg/kg daily Therapy usually 5 to 7 months Preparations 10mg 20mg 25mg 30mg 35mg 40mg 21

22 Expected Side Effects Mucosal drying Skin Lips Mucous Membranes Potential Adverse Effects Night blindness occurs in 20% patients Mood disturbances Hair loss Pseudotumor cereberi rare Birth Defects if becoming pregnant on therapy Early miscarriage Cardiac problems Cranio-facial disorders Increase in liver enzymes Paronychia Musculoskeletal Pain Possible early onset of Crohns or Ulcerative Colitis I Pledge Program Providers must be enrolled in Ipledge program Attest every 1 year All patients must be enrolled and sign consent forms Female patient must be on 2 highly effective birth control methods All patient must sign consent form Patients must be enrolled in Ipledge 22

23 Female Patients of Childbearing Capacity Must have initial negative pregnancy test Repeat pregnancy test within 30 to 90 days Must fill prescription within 7 day window Pregnancy test should be within the first 5 days of menses If script is not filled within the first 7 days must have another pregnancy test Laboratory Monitoring Complete blood count Liver enzymes Lipid panel Pregnancy test either urine or serum Non-acceptable Birth Control Methods for IPledge Female condoms Progesterone only pills IUD with Progesterone Natural family planning Fertility Awareness methods Lactation Withdrawal Cervical Shield 23

24 Women of Non-Childbearing Potential Hysterectomy Laboratory Verified Menopause Ipledge Acceptable Birth Control Methods Primary Form Tubal Sterilization Partner Vasectomy Intrauterine Device Hormones including oral contraceptives, Patches, Injection, Implants, and Vaginal Ring Secondary Forms Barrier forms: Diaphragms Cervical Cap Male latex condoms Vaginal Sponge that contains spermicide Patient Assessment Types of lesion Scarring or potential for scarring is high Patient motivation Are they able to handle complex regimen? Skin type oily, dry, or combination Family history of acne Work or if student active in sports? Past experience with treatments Type of insurance 24

25 Patient Adherence Highly motivated patients more likely to adhere to treatment regimen Keep regimen simple Cost of medications Realistic expectations no therapy works quickly Quick follow-up appointment Anticipatory Guidance as to expected side effects and therapeutic actions of the medications Listening and addressing patient concerns Putting It All Together Mild Acne comedonal Topical retinoid Topical benzoyl peroxide Moderate Acne comedones/inflammatory lesions Topical Retinoid Topical benzoyl peroxide Topical antibiotic Possibly oral antibiotic Hormonal treatment Putting It All Together Severe Acne-comedones, inflammatory lesions, nodulocystic lesions, scarring Topical retinoid Topical antibiotics Oral antibiotics Hormones Isotretinoin 25

26 Case Study 1 13 year old male. Both parents had severe acne in their teens. Active in baseball Likes to be outdoors. Face became very red and dry with OTC benzoyl peroxide. Does not interact much with provider. Skin appears dry. Lesions are open and closed comedonesin the T-zone a few lesions in the conchal bowls of the ears, isolated erythematous papules, and no lesions on the arms, back, or chest. Case Study 2 17 year old female Acne flares with menses, regular menses Has tried topical benzoyl peroxide stating that it worked initially but has stopped Wears make-up to cover her acne Does not work outside of school Involved in dance Father had acne in his teens Combination skin oily in T zone dry elsewhere Lesions include closed comedoneson the forehead, erythematous papules with one cystic area on the left cheek about 8mm in size, erythematous papules located on the upper chest, upper back and posterior shoulders. Case Study 3 32 year old female with 3 children, does not plan on additional children Birth control method is DMPA Very distressed about her acne. States the acne started about 2 years ago after the birth of her last child. Denies any acne in teens. Denies any other medications States she has tried everything OTC and nothing works. Skin is dry uses a daily moisturizer Wears make-up daily to cover the acne Lesions appear to be in tender, firm erythematous papules located in the mandibular area of the face, neck, and upper chest. 26

27 Case Study 4 17 year old male Has had acne for 4 years but recently worsened in the past year. Works as a stocker in a grocery store but plans to lifeguard and work as a summer camp counselor at the end of the school year. Tried topical tretinoin and doxycycline about 2 years ago with modest improvement. Lesions include open/closed comedoneson the face, erythematous papules, nodules and cystic areas on the cheeks, neck, upper chest, posterior shoulders, and upper portion of the back. There is some evidence of mild scarring. References Habif, T Clinical Dermatology 5 th Ed. Mosby, St. Louis. Kircik, L.H The role of benzoyl peroxide in the new treatment paradigm for acne. Journal of Drugs in Dermatology. 12(6): s Radkey, K. & Tucker, R Dapsonein the management of acne vulgaris. Journal of Drugs in Dermatology. 15(6): Mancini, A. J., Eichenfield, L.F. & Del Rosso, J. Q. Acne In Review Guide. Educational Testing and Assessment Systems. Wolverton, S.E Comprehensive Dermatologic Drug Therapy. 3 rd Ed. Saunders. 27