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Acne Vulgaris Updates on Approach to Treatment Frank Morocco D.O. December 8, 2012 Acne Vulgaris • Most common skin disease presenting to primary care physicans. • Chronic disease for some patients • Don’t underestimate the social and psychological effect of acne on patients • Acne is not necessarily a rite of passage Pathophysiology • Four primary pathogenic factors which interact in complex manner – – – – Sebum production by the sebaceous gland P. acnes follicular colonization Alteration in the keratinization process Release of inflammatory mediators into the skin • Other factors – Androgens, stress, occupational exposure, underlying metabolic abnormalities • Treatment should target these pathogenic factors . Thiboutot D, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group J Am Acad Dermatol 2009;60:S1-50. Clinical Features • Non-inflammatory Lesions – Open comedones (blackheads) – Closed comedones (whiteheads) • Inflammatory Lesions – Pustules/papules – Nodules – Cysts • Help determine treatment modalities Primary Lesions Variants of Acne • • • • • • • • • • • • Acne cosmetica Acne excoriee Senile comedones Milia Acne mechanica Gram-negative acne Steroid-induced acne Occupational acne Favre-Racouchot syndrome Solid facial edema Neonatal acne Drug-induced acne Treatment • Choice of treatment depends on – – – – – Type of acne Severity Age Location Patient preference • Evaluate patient – – – – – – Current medications, allergies Menstrual history Tanning habits, hobbies Expectations, myths, fears Scarring Pregnancy Treatment • Approach should be multi-therapy, not monotherapy • Topicals – – – – – Antibiotics Retinoids Benzoyl peroxide Combination therapies Other therapies • Oral therapy – Antibiotics – Isotretinoin • Adjunctive therapy – Hormonal/anti-androgen therapy – Chemical peels – Scar treatment . Thiboutot D, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group J Am Acad Dermatol 2009;60:S1-50. Treatment Approach Non-inflammatory Acne Mild Inflammatory Acne Moderate-Severe Inflammatory Acne Topical Therapies Oral antibiotics Retinoids Antibiotics Salacylic Acid BPO +/- Washes Adjunctive Therapies Adjunctive Therapies OCPs, chemical peels, anti-androgens Tetracyclines Failure of oral antibiotics Severe or Scarring Isotretinoin Pregnant Azelaic Acid (Cat B) Clindamycin Lotion (Cat B) Treatment Approach • Early, appropriate treatment is best to minimize potential for acne scars • Combination of a topical retinoid and antimicrobial agent remains the preferred approach for almost all patients with acne – Attacks 3 of the 4 major pathogenic factors of acne: abnormal desquamation, P. acnes colonization, and inflammation – Retinoids are anticomedogenic, comedolytic, and have some anti-inflammatory effects – BPO is antimicrobial with some keratolytic effects and antibiotics have anti-inflammatory and antimicrobial effects . Thiboutot D, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group J Am Acad Dermatol 2009;60:S1-50. Treatment Approach • Topical retinoids should be first-line agents in acne maintenance therapy • Avoid contributing to antibiotic resistance . Thiboutot D, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group J Am Acad Dermatol 2009;60:S1-50. Benzoyl Peroxide • Mechanism of action1 – Bactericidal for P. acnes – Inhibits triglyceride hydrolysis – Decreases inflammation of acne lesions • Advantages – No resistance demonstrated to date1 – When used in combination with a topical antibiotic can help to prevent resistance2 – Activity is enhanced when combined with other topicals (i.e. clindamycin)1,2 • Formulations – OTC & prescription – Washes, gels, lotion, solution 1. Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. 2. Thiboutot D, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad Dermatol 2009;60:S1-50. Retinoids • Most important class of drugs used to treat acne • Topical form of vitamin A • Mechanism of Action1 – Normalize follicular keratinization – Act on the microcomedone • Proper instruction on application is essential to compliance – Gradual application with small amount of drug – “Training for a marathon” 1. Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. Retinoids • “Least Irritating” (most tolerable) – Adapalene gel (Differin® 0.1%, 0.3%) – May be appropriate starting point for ethnic and/or sensitive skin • “Moderately Irritating” – Tretinoin (cream, gel) • • • • Tretinoin 0.01%, 0.05%, 0.025% Retin-A Micro® 0.1%, 0.04% Atralin™ Gel 0.05% Renova® 0.02%, 0.05% • “Most Irritating” (least tolerable) – Tazarotene (Tazorac®/Avage® 0.05%, 0.01%) Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. Topical Antibiotics • Erythromycin – Akne-mycin® 2% gel, Erygel ® 2% gel, – Resistance of some P. acnes strains – Usage fallen out of favor • Clindamycin phosphate 1% – – – – Generic, Cleocin T® (lotion, gel, solution), Evoclin® foam Antibiotic-associated colitis very unlikely Work best in combination with BPO Good choice for pregnant women (Pregnancy Category B) • Azelaic acid – Finacea™ – Bacteristatic/bactericidal against P. acnes – Good choice for pregnant women (Pregnancy Category B) Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. Topical Antibiotics • Sodium sulfacetamide/sulfur (10%/5%)1 – Klaron® lotion, Plexion® line, Rosac® line, Clenia® – Keratolytic effects, antibacterial for P. acnes – Used most commonly for rosacea • Metronidazole1 – Benefit for acne debatable – Metronidazole lotion (generic), Metrogel 1%® • Dapsone gel 5% (Aczone®)2 – Approved for moderate to severe acne – BID dosing – May cause a temporary yellow or orange discoloration of skin and facial hair if used along with BPO – Low risk of hemolytic anemia in G6PD deficient patients 1. Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. 2. Aczone® prescribing information. January 2009. Combination Therapies • Clindamycin/Benzoyl peroxide – Clindamycin phosphate 1%/benzoyl peroxide 5% (Benzaclin®Gel) – Clindamycin phosphate 1%/benzoyl peroxide 5% (Duac®Gel) – Clindamycin phosphate 1.2% /benzoyl peroxide 2.5% (Acanya™ Gel) • Erythromycin/Benzoyl peroxide – Erythromycin 3%/benzoyl peroxide 5% (Benzamycin®) • Retinoid/Benzoyl peroxide – Adapalene 0.1%/benzoyl peroxide 2.5% (Epiduo™ Gel) • Retinoid/Clindamycin – Tretinoin 0.025%/Clindamycin phosphate 1.2% (Ziana® Gel) Thiboutot D, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad Dermatol 2009;60:S1-50. Oral Antibiotics • Therapeutic role in acne – Reduction of P. acnes – Anti-inflammatory activity • Dosing – Start high then taper down after control is achieved – Use PRN during flares – Do not use as monotherapy Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. Oral Antibiotics • Antibiotic Choice – Tetracylcine Class (minocycline, doxycycline, tetracycline) • Solodyn® (minocycline HCl), Minocin ® (minocycline) • Doryx® (doxycycline hyclate), Adoxa® (doxycycline monohydrate) – Erythromycin (Ery-tab®) – Trimethoprim/sulfamethoxazole – Amoxicillin • Anti-inflammatory antibiotics/no antimicrobial activity – Doxycycline 20 mg (Periostat®) – Doxycycline 40 mg (Oracea®) Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. How to Prevent Resistance • Combine a topical retinoid plus an antimicrobial • Limit the use of antibiotics to short periods and discontinue when there is no further improvement or the improvement is only slight • Co-prescribe a BPO-containing product or use as washout • Oral and topical antibiotics should not be used as monotherapy Thiboutot D, et al. New insights into the management of acne: An update from the Global Alliance to Improve Outcomes in Acne Group. J Am Acad Dermatol 2009;60:S1-50. Hormonal Therapy • FDA-approved OCPs for acne – Ortho Tri-Cyclen® – Estrostep® – Yaz® • Anti-androgens – Spironolactone • Doses range between 50-200mg • Not FDA-approved for acne • Monitor side effects: menstrual irregularities, hyperkalemia Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. Isotretinoin • Approved for the treatment of severe recalcitrant nodular acne in 1982 • Member of the Vitamin A family • Effects on acne – Normalizes the keratinization process – Reduces sebocytes and secretions – Reduces inflammation – Reduction in numbers of P. acnes Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. Isotretinoin • Pre-medication counseling – Side Effects – Contraception – Compliance/duration of treatment – Laboratory monitoring – iPledge registration • Dosing 1-2 mg/kg/day – Goal 120-150 mg/kg over course of treatment Wolverton SE. editor Comprehensive Dermatologic Drug Therapy 2nd Ed. Philadelphia: Saunders Elsevier; 2007. Case Studies Case One • 15-year-old male • Non-inflammatory & inflammatory acne – Face only – Open/closed comedones – Papules • Treatment Plan? Treatment Approach Non-inflammatory Acne Mild Inflammatory Acne Moderate-Severe Inflammatory Acne Topical Therapies Oral antibiotics Retinoids Antibiotics Salacylic Acid BPO +/- Washes Adjunctive Therapies Adjunctive Therapies OCPs, chemical peels, anti-androgens Tetracyclines Failure of oral antibiotics Severe or Scarring Isotretinoin Pregnant Azelaic Acid (Cat B) Clindamycin Lotion (Cat B) Case Two • 17-year-old-female • Inflammatory acne – Regular menstrual cycles (-flares) – Face, chest, back involved – Pustules, papules – Open & closed comedones • Treatment plan? Treatment Approach Non-inflammatory Acne Mild Inflammatory Acne Moderate-Severe Inflammatory Acne Topical Therapies Oral antibiotics Retinoids Antibiotics Salacylic Acid BPO +/- Washes Adjunctive Therapies Adjunctive Therapies OCPs, chemical peels, anti-androgens Tetracyclines Failure of oral antibiotics Severe or Scarring Isotretinoin Pregnant Azelaic Acid (Cat B) Clindamycin Lotion (Cat B) Case Three • 22-year-old female • Mild-moderate inflammatory acne – Regular menstrual cycles (+ flares) – Face involved – Chest, back spared – Nodular lesions along jawline – Comedones • Treatment plan? Treatment Approach Non-inflammatory Acne Mild Inflammatory Acne Moderate-Severe Inflammatory Acne Topical Therapies Oral antibiotics Retinoids Antibiotics Salacylic Acid BPO +/- Washes Adjunctive Therapies Adjunctive Therapies OCPs, chemical peels, anti-androgens Tetracyclines Failure of oral antibiotics Severe or Scarring Isotretinoin Pregnant Azelaic Acid (Cat B) Clindamycin Lotion (Cat B) Atopic Dermatitis and Eczema Atopic Dermatitis • “The itch that rashes” • Hereditary skin manifestation; family history of eczema, asthma, and hay fever – >50% of children with one atopic parents and 79% of children with both atopic parents develop allergic symptoms before 2yo • Ddx: seb derm, contact derm, scabies, and psoriasis Atopic Dermatitis • 3 Stages – Infantile (2mos-2yrs): • Risks: African and Asian races, males, greater gestational age at birth, Fam HX • 60% of atopic pts present 2mos-1yo. Disappear by 2yo. • Usually begins as papular or exudative erythema and scaling of the cheeks, may extend to scalp, neck, forehead, wrists, extensor extremities. Plaques become lichenified. • Become secondarily infected. • Worsening after immunization or infection. • Remission in summer (UV and humidity), relapse in winter (wool and dryness). • Role of food allergy is contraversial; may be milk, eggs, peanuts, tree nuts, grains, fish, and soy. Some association with cow’s milk. Atopic Dermatitis • 3 Stages – Childhood (2-10yrs): • Lichenified, indurated plaques on the antecubital and popliteal fossae, flexor wrists, eyelids, face, and around the neck. • Itching → scratching → secondary changes → itch • If >50% BSA, associated with growth retardation Atopic Dermatitis Adult: • Pruritus with heat or stress • Localized, erythematous, scaly, papular, exudative, or lichenified plaques. Prurigo-like paps are common. • Hyperpitmentation in dark skin with hypopitmentated healed excoriated lesions • Often antecubital and popliteal fossae, neck, forehead, and eyes. • Older adults: chronic hand dermatitis (women after first child), worse with frequent wet exposure. r/o contact allergy. • Usually improves with time, uncommon after middle life • New-onset in adulthood: HIV can be a trigger Modified Criteria for Children with Atopic Dermatitis Essential Features 1. 2. Pruritus Eczema • • Typical Morphology and age-specific pattern Chronic or relapsing history Important Features 1. 2. 3. 4. 5. Early age at onset Atopy Personal and/or family history IgE reactivity Xerosis Associated Features 1. 2. 3. 4. 5. Atypical vascular responses (e.g. facial pallor, white dermatographism) Keratosis pilaris/ichthyosis/hyperlinear palms Orbital/periorbital changes Other regional findings (e.g. perioral changes;periauricular lesions) Perifollicular accentuation/lichenification/prurigo lesions Features Associated with Atopy • Dennie-Morgan fold: linear transverse fold just below the lower eyelid • Prominent nasal crease • “Normal” skin is subclinically inflamed, dry, scaly • Pityriasis alba: hypopigmentation with sclight scale on cheeks, upper arms, trunk in young children. Responsive to emollients and topical steroids • Keratosis pilaris: horny follicular lesions of outer aspects of upper arms, legs, cheeks, and buttocks; refractory to treatment • Dirty neck appearance due to hyperkeratosis and hyperpigmentation Features Associated with Atopy • • • • Perioral, perinasal, and periorbital pallor White dermatographism Increased susceptibility of cataracts Increased susceptibility of infection; – Patients heavily colonized with Staph. Treatment of lesional skin reduces colonization even w/o ABX • Chronic suppressive ABX therapy may stabilize disease: Cephs, Bactrim, clinda, doxy – Eczema herpeticum: generalized herpes simplex, sudden vesicular, pustular, crusted or eroded lesions. Become secondarily infected. – Eczema vaccinatum: widespread vaccinia infxn – Extensive flat wart or molluscum; poor tolerance to Tx Atopy: Pathogenesis • Immunologic defects are the main component – Th2 activation with IL-4, 5, 10, and 13. Elevated IgE and eosinophilia; impaired antiviral activity. • Defects in barrier function with increased transepidermal water loss, correlating with disease severity. Increased TEWL in winter and in stress. • Environmental factors: increased with increased hygeine and higher socioeconomic status. May have allergens to dust mites, grass pollens Management of Atopy • Infants and children: – Avoid hot baths, alkaline soaps, vigorous rubbing and scrubbing. – Short, once-a-day, tepid baths followed by a barrier cream using soak and smear; ointment bases are preferred. – Immediate change of wet or soiled diapers. – Nighttime sedating antihistamines for itch – Dietary restriction for a specific known antigen Management of Atopy • Adults – Avoid temperature extremes – Hydrate dry skin especially in winter – Avoid overbathing and hot water – Avoid wool – Biofeedback techniques for emotional stress Topicals for Atopy • Topical corticosteroids are the mainstay – 1-2.5% hydrocortisone in infants. Monitor growth in infants and young children. – Mid-potency (TAC) in older children and adults except on the face – 1-2x a day is enough to saturate receptors; more provides only emollient effect – Occlusion increases penetration and receptor saturation – Must be strong enough to control pruritus and remove inflammation • Regular emollients: petrolatum, hydrophilic creams with ceremides • Anti-Staph therapy for acute flares • Topical calcineurin inhibitors Systemics for Atopy • Antihistamines for sedation: hydroxyzine, diphenhydramine, or clopheniramine. – The nonsedating antihistamines do not relieve pruritus • Short courses of anti-Staph ABX, topical mupirocin for nasal carriage • Systemic steroids only for acute exacerbations, in short courses of 3 weeks or less • Cyclosporin is usefule but expensive; symptoms recur on stopping meds • Immunosuppressives and antiproliferatives (Immuran, Cellcept, MTX) can be effective for unresponsive dz • Phototherapy: PUVA, UVA, narrow-band UVB, or Goeckerman with tar may be helpful Atopy: Treating the Acute Flare • Treat triggers and the precipitant of the flare • Short course of systemic steroids • 3-4 days of home hospitalization: – Bedrest and isolation of stressors with large doses of antihistamine at bedtime – Daily tub soaks followed by topical steroid ointment under wet pajamas and a sauna suit Eczema • Broad range of conditions beginning as spongiotic progressing to lichenified • Acute: red edematous plaque with small grouped vesicles • Subacute: erythematous plaques with scale or crusting • Chronic: dry scale and lichenification Regional Eczemas • Ear: external canal most frequently affected. Earlobe = nickel allergy. – Gentle lavage to remove scale and cerumen. Topical steroids if not infected. • Eyelid: may be related to volitle chemicals, or transfer of allergen from hands. – Allergic contact affects upper lids, atopic affects both • Breast/Nipple: Painful fissuring can occur, esp in nursing mothers. If >3 mos BX to r/o Paget’s Hand Eczema • Most commonly in atopic patients • Complete H&P and patch testing to distinguish from atopic/allergic/irritant/psoriasis • Allergens: glyceryl monothioglycolate, ammonium persulfate, isothiazolinones, formaldehyde, paraben, Compositae plants, nickel, dyes (p-phenylenediamine) Hand Eczema • Most commonly in atopic patients • Acute Vesiculobullous Hand Eczema (Pompholyx, Dyshidrosis): idiopathic, patients have hyperhydrosis. Severe sudden pruritic vesicular outbreak, can coalesce to bullae. “Tapioca pudding”. Spontaneously resolve over weeks. • Chronic Vesiculobullous: hyperkeratotis, scaling, fissured • Hyperkeratotic Hand Dermatitis: hyperkeratotic, fissure-prone erythematous areas of middle or proximal palm and volar fingers. R/o psoriasis. Treatments for Hand Eczema • Vinyl gloves during wet work, or rubber if there is no allergy. White cotton gloves under vinyl may be effective. • Protective clothing during gardening/hobbies/chemical exposure • Glycerin and dimethicone barrier products • Moisturizing protective cream/ointments after hand washing and at night. White petrolatum restores barrier function. Treatments for Hand Eczema • Systemic steroids results in dramatic improvement but relapse is common • Topical calcineurin inhibitors, tar soaks, phototherapy, PUVA can be effective • Oral MTX, azathioprine, cellcept may be helpful • Superpotent and potent topical steroids are first-line pharmacotherapy and efficacy is enhanced by occlusion. Use should not exceed 2-3 weeks, then tapered to weekend-only with weaker topicals on weekdays Diaper Dermatitis • Irritant: erythematous dermatitis limited to exposed surfaces, folds are unaffected. Can become ulcerated (Jacquet erosive diaper dermatitis) papular, or nodular (granuloma gluteale infantum) • Skin wetness encourages frictional irritation and bacterial/Candidal growth • Protection of skin with superabsorbant gel diapers, frequent changing, Zn oxide paste, mixture of Nystatin ointment and 1% hydrocortisone ointment after each diaper change