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
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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
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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
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Type of acne
Severity
Age
Location
Patient preference
• Evaluate patient
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Current medications, allergies
Menstrual history
Tanning habits, hobbies
Expectations, myths, fears
Scarring
Pregnancy
Treatment
• Approach should be multi-therapy, not monotherapy
• Topicals
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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)
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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%
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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
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2.
Pruritus
Eczema
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Typical Morphology and age-specific pattern
Chronic or relapsing history
Important Features
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Early age at onset
Atopy
Personal and/or family history
IgE reactivity
Xerosis
Associated Features
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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
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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