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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

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Acne Vulgaris Updates on Approach to Treatment Frank Morocco D.O. December 8, 2012


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acne vulgaris
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
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
Clinical Features
  • Non-inflammatory Lesions
    • Open comedones (blackheads)
    • Closed comedones (whiteheads)
  • Inflammatory Lesions
    • Pustules/papules
    • Nodules
    • Cysts
  • Help determine treatment modalities
variants of acne
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
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
treatment1
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
slide9

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 AcadDermatol2009;60:S1-50.

treatment approach
Treatment Approach

Non-inflammatory

Acne

Mild Inflammatory Acne

Moderate-Severe Inflammatory

Acne

Pregnant

Azelaic Acid (Cat B)

Clindamycin Lotion (Cat B)

Topical Therapies

Retinoids

Antibiotics

Salacylic Acid

BPO

+/- Washes

Oral antibiotics

Tetracyclines

Adjunctive Therapies

Severe or Scarring

Isotretinoin

Adjunctive Therapies

OCPs, chemical peels,

anti-androgens

Failure of oral

antibiotics

treatment approach1
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 approach2
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
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
  • AcadDermatol2009;60:S1-50.
retinoids
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.

retinoids1
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
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 antibiotics1
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
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
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 antibiotics1
Oral Antibiotics
  • Antibiotic Choice
    • Tetracylcine Class (minocycline, doxycycline, tetracycline)
      • Solodyn® (minocyclineHCl), Minocin ® (minocycline)
      • Doryx® (doxycyclinehyclate), 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
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
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
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.

isotretinoin1
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 one
Case One
  • 15-year-old male
  • Non-inflammatory & inflammatory acne
    • Face only
    • Open/closed comedones
    • Papules
  • Treatment Plan?
treatment approach3
Treatment Approach

Non-inflammatory

Acne

Mild Inflammatory Acne

Moderate-Severe Inflammatory

Acne

Pregnant

Azelaic Acid (Cat B)

Clindamycin Lotion (Cat B)

Topical Therapies

Retinoids

Antibiotics

Salacylic Acid

BPO

+/- Washes

Oral antibiotics

Tetracyclines

Adjunctive Therapies

Severe or Scarring

Isotretinoin

Adjunctive Therapies

OCPs, chemical peels,

anti-androgens

Failure of oral

antibiotics

case two
Case Two
  • 17-year-old-female
  • Inflammatory acne
    • Regular menstrual

cycles (-flares)

    • Face, chest, back involved
    • Pustules, papules
    • Open & closed

comedones

  • Treatment plan?
treatment approach4
Treatment Approach

Non-inflammatory

Acne

Mild Inflammatory Acne

Moderate-Severe Inflammatory

Acne

Pregnant

Azelaic Acid (Cat B)

Clindamycin Lotion (Cat B)

Topical Therapies

Retinoids

Antibiotics

Salacylic Acid

BPO

+/- Washes

Oral antibiotics

Tetracyclines

Adjunctive Therapies

Severe or Scarring

Isotretinoin

Adjunctive Therapies

OCPs, chemical peels,

anti-androgens

Failure of oral

antibiotics

case three
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 approach5
Treatment Approach

Non-inflammatory

Acne

Mild Inflammatory Acne

Moderate-Severe Inflammatory

Acne

Pregnant

Azelaic Acid (Cat B)

Clindamycin Lotion (Cat B)

Topical Therapies

Retinoids

Antibiotics

Salacylic Acid

BPO

+/- Washes

Oral antibiotics

Tetracyclines

Adjunctive Therapies

Severe or Scarring

Isotretinoin

Adjunctive Therapies

OCPs, chemical peels,

anti-androgens

Failure of oral

antibiotics

atopic dermatitis
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 dermatitis1
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 dermatitis2
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 dermatitis3
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
Modified Criteria for Children with Atopic Dermatitis

Essential Features

  • Pruritus
  • Eczema
    • Typical Morphology and age-specific pattern
    • Chronic or relapsing history

Important Features

  • Early age at onset
  • Atopy
  • Personal and/or family history
  • IgE reactivity
  • Xerosis

Associated Features

  • Atypical vascular responses (e.g. facial pallor, white dermatographism)
  • Keratosispilaris/ichthyosis/hyperlinear palms
  • Orbital/periorbital changes
  • Other regional findings (e.g. perioralchanges;periauricular lesions)
  • Perifollicular accentuation/lichenification/prurigo lesions
features associated with atopy
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 atopy1
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
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
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 atopy1
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
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
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
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
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
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
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 eczema1
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
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 eczema1
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
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