Download Pathogenesis of Acne

Acne Vulgaris
and
Rosacea
Dr. Lyn Guenther
University of Western Ontario
Objectives
State the incidence of acne
• Discuss the psychosocial impact of acne &
scarring
• Discuss the pathophysiology of acne
• Differentiate acne vulgaris from rosacea
• Elicit a history and perform a relevant
examination
• Give an approach to acne and rosacea
treatment from mild to severe
•
Acne vulgaris
Incidence: 95%
• Scarring
•
- In 95% seeing a dermatologist for the first
time
- Increased with:
Squeezing
• Inflammatory lesions
• Longer disease duration
•
Psychological Scarring
•
QOL studies:
- Social, psychological & emotional deficits
comparable to:
• Asthma
Epilepsy
• Diabetes Mellitus
• Back Pain
• Arthritis
•
Pilosebaceous Unit
Sebaceous Gland
• Sebum
• Follicle
• Arrector Pili Muscle
•
900 glands/cm2 on face, back, chest
<100 glands/cm2 on rest of body
Pathogenesis of Acne
Abnormal Keratinization (genes)
• Androgens cause increased sebum
production
• Propionibacterium acnes
• Inflammation
•
Acne Vulgaris
Pathophysiology
Microcomedones
Accumulation of Sebum
Closed/Open Comedones(non-inflammatory acne)
Proliferation of P. acnes
Infiltration of neutrophils
Ruptured comedones
Papules, Pustules, Cysts (inflammatory acne)
Acne vulgaris - History
Age of onset
• Family history of acne
• Location and severity of lesions
• Scarring
• Psychosocial impact
• Menses/Contraceptive use
• Moisturizer and foundation
• Medications & Drug Allergies
• Current and Past treatment
including response and A/E’s
•
Physical Examination:
Scarring and Pigmentary Changes
Scarring: depressed / ice pick / saucer / keloid
Excoriations
Hyper / hypo-pigmentation
Lesion Morphology
Non-inflammatory
Comedonal
Inflammatory
Papules / pustules
Nodules / cysts
Acne Lesions
Comedones
Papules & Pustules
Cysts
Acne vulgaris - Why treat?
Improve appearance
• Minimize scarring
• Eliminate discomfort of inflammatory
lesions
• Reduce psychological consequences
•
Acne vulgaris - Dispel myths
•
Acne is NOT caused by:
- Chocolate
- Fried or fatty food
- Too much or too little sex
- Dirt
- Wrong kind of soap
•
Not contagious
Acne vulgaris - Aggravating
Factors
Stress
• Lack of sleep
• Tight headbands/helmets
• Grease-filled environments
• Heavy makeup while exercising
• Premenstrual in some
•
Acne vulgaris - Cleansing
Wash BID
• Lukewarm water
• Mild cleanser
• No abrasives
• No scrubbing
• Don’t squeeze
•
Acne vulgaris
Moisturizers and Foundation
Non-comedogenic
• Non-acnegenic
•
Treatment Guidelines
Non-scarring
acne
* Comedones: Retinoid
* Tretinoin cream .01-.05% daily or
* Tazarotene cream/gel or
* Differin cream/gel
* Papules/Pustules
* Topical antibiotic B.I.D.
* Benzoyl peroxide 5% daily
* Antibiotic/benzoyl peroxide
* Oral antibiotics
* Hormonal agents for women
desiring oral contraception
ANTIBIOTIC
Tetracyclines
Tetracycline
DOSE
500 mg B.I.D.
Minocycline
100 mg/day
Doxycycline
100 mg/day
Erythromycin
500 mg B.I.D.
Trimethoprim
100 - 200 mg/day
NOTES
*Avoid in pregnancy or
children < 8 years
*Take on empty stomach
*G.I. irritation
*May be taken with food
*Dizziness may develop
at higher dos es
*Pigmentary changes
*May be taken with food
*Phototoxicity a potential
problem
*Safe in pregnancy and
for children
*May caus e G.I. Ups et
*Useful in those resistant
to other antibiotics
Hormonal Therapies for Acne
Diane-35® cyproterone acetate/ ethinyl estradiol
Ortho -Tricyclen® norgestimate/ ethinyl estradiol
Alesse® levonorgestral/ ethinyl estradiol
Yasmin ® drospirenone-ethinyl estradiol
Treatment Guidelines
Severe or
Scarring acne
Isotretinoin:
* 0.5mg/kg/day for the first 2-4 weeks
* 1 mg/kg /day for the next 4-5
months to a total cumulative dose of
120-150 mg/kg
* 80% have long-term drug free remission
* 20% require a second course
* patients unable to take isotretinoin should
be given topical therapy combined with
systemic antibiotics or hormonal agents
Isotretinoin
Sebaceous follicles
Decreases sebum
production within 2 weeks
• Corrects follicular
hyperkeratinization
• Decreases growth of P.
acnes
• Decreases inflammation
•
Pre-Accutane On Accutane
Isotretinoin
Contraindication:
Absolute:
Pregnancy (see Pregnancy Prevention
Program™)
•
Relative:
• History of pre-morbid depression
• History of hypertriglyceridemia/
hypercholesterolemia
• Pre-existing liver disease
Accutane use and pregnancy
•
Isotretinoin is a potent teratogen
- >25% risk of fetal malformation.
Reported pregnancy rate on
Accutane<1%
•
- Average age: 26 years.
•
Reasons for these pregnancies:
- abstinence unsuccessful
- use of ineffective method of contraception
- contraceptive used inconsistently
- unexpected sexual activity
- failure of contraceptive method
Pregnancy Prevention
Program™
Two negative pregnancy tests required
before starting Accutane
•
- Initial visit & day 2-3 of next period
•
Two effective forms of birth control
- one primary and one secondary
•
Begin therapy on 2nd or 3rd day of next
menses
Pregnancy Prevention
Program™
•
One month prescription only
•
Monthly pregnancy testing
•
Monthly contraceptive counseling
•
Initial Consent form
•
Patient Information booklet
Effective Forms of
Contraception
Primary
•
Tubal ligation
•
Partner’s vasectomy
•
Birth control pills
•
Injectable/implanted
hormones
•
IUD
Secondary
•
Diaphragms with
spermicide
•
Latex condoms
with
spermicide
•
Cervical caps with
spermicide
Isotretinoin Adverse Events
Cheilitis 96%
• Dermatitis 55%
• Dry nose 51%
• Eye irritation 11%
• Joint pain 13%
• Depression rare
• Elevated TG (25%) & cholesterol (7%)
• Elevated liver enzymes (15%)
•
Isotretinoin and Psychiatric Events
Depression
Isotretinoin
Use
Suicide/attempt
10-13 per
1-1.7 per
100,000 patients 100,000 patients
(1982-2000)
20 per
20,000 per
USA General
100,000 patients 100,000 patients
Pop’n
(CDC 1980-92)
Isotretinoin
Mucutaneous adverse events:
• Chapstick
• Lubricants
Lab monitoring:
• CBC, liver function and fasting lipids
• Pregnancy test
Case studies
Case 1
Washes with apricot
scrub
• Has tried numerous
other cleansers
• Has stopped eating
chocolate
• No other treatment
•
•
Case 2
Won’t socialize
• Regular menses
• Not sexually active
• No prior treatment
•
Case 3
Oily skin
• Seborrheic
dermatitis
• Plucks facial hair
• Irregular menses
• Proactive-No help
•
Case 4
Acne lesions hurt
• Tetracycline 500 mg
BID for 6 months, then
• Minocycline 100 mg BID
for 8 months
• Differin gel x14 months
•
Rosacea
~10% of Canadians affected
• Women: Men=2:1, but men
more prone to rhinophyma
• Celtic descent
•
- Uncommon in Africans & Asians
•
Onset usually after age 30
- Peak: 4th to 7th decade
- Rarely in children
Konshik PC et al. Dermatol Clin 1992;10(3):533-47
Rosacea Pathophysiology
Genetic
• Abnormalities of cutaneous vasculature
•
- Dysregulation of thermal mechanisms
•
Dermal matrix degeneration
- Poor connective tissue support for cutaneous
vessels
•
Infectious organisms
- Demodex
- Helicobacter pylori
Excess of canthelicidins and protease stratum
corneum tryptic enzyme (STCE) in facial skin
•
Yamaski K et al. Nat Med 2007;13:975-80
Rosacea Pathophysiology
•
Murine model:
- Injection of cathelicidins found in rosacea or addition of
SCTE → skin inflammation
- Deletion of the serine protease inhibitor gene Spink5 →
protease activity → skin inflammation
- TCN + Minocycline indirectly inhibit serine proteases
and work even in the face of bacterial resistance
Hypothesis: Increase in local antimicrobial peptide
expression may change the normal skin microflora in
rosacea
Yamaski K et al. Nat Med 2007;13:975-80
Rosacea affects QOL
•
Recent Canadian Survey (n=1271):
- Social life affected in 36%
•
16% of all respondents declined a social
invitation due to rosacea symptoms
Lower self esteem
• Affects professional interactions
•
Rosacea: Skin changes
•
Symmetric over convexities of
central face
- nose, cheeks, chin, central
forehead
Occ. on neck, scalp, chest
• Very rarely on back and limbs
•
Rosacea: Skin changes
•
Primary features:
- Flushing:
Usually lasts > 10 minutes
• Sparing of periocular skin
• Often assoc. with burning, stinging
•
- Persistent Erythema
- Telangiectasia
- Papules, pustules (follicular and nonfollicular)
……..NO
COMEDONES
Rosacea: Skin changes
•
Secondary features:
- Burning or stinging
- Lowered threshold for irritation from topical substances
- Plaques
- Dry appearance
- Edema (e.g. periorbital, glabellar, malar)
• Acute, chronic recurrent, chronic persistent
• Pitting or non-pitting
- Ocular
- Peripheral location (neck, chest, scalp, ears, back)
Subtypes of Rosacea
1.
2.
3.
4.
Erythematotelangiectatic
Papulopustular
Phymatous
Ocular
Phymatous Variant
Men
• Erythematous, irregularly swollen, bulbous,
dilated pores, telangiectasia
•
- Rhinophyma (nose)
- Metophyma (forehead)
- Gnathophyma (chin)
- Blepharophyma (eyelids)
- Otophyma (ears)
Aloi F et al. JAAD 2000;42:468-72
Rosacea-Ocular
•
50% of patients
•
6th-7th decade (later than skin)
• Women=Men
• Onset with skin:2
- 53% skin first
- 20% eyes first
- 27% together
•
Strong correlation with flushing3
1. Barankin B, Guenther L. Can Fam Physician. 2002;48:721-4.
2. Borrie P. Br J Ophthalmol 1953:65:458.
3. Wilkin JK. Int J Dermatol 1983;22:393-400.
Rosacea-Ocular
Dry, gritty eyes, itching, burning, tearing, blurry
vision, photophobia
• Blepharitis (93%), conjunctival hyperemia (86%),
conjunctivitis, keratitis, superficial punctate
keratopathy (41%), keratoconjunctivitis sicca (up to 40%)
corneal vascularization ulceration and perforation,
iritis (20%), chalazion (22%)
• ~ 60% of patients with chalasion have rosacea
•
Barankin B, Guenther L. Can Fam Physician. 2002;48:721-4.
Rosacea Triggers
•
Food:
- Hot food
- Spicy food
- Tomatoes
- Chocolate
- Yogurt, sour cream,cheese
Alcohol
• Hot and cold temperatures
• Wind
• Exercise
• Stress
•
Rosacea Triggers
•
Drugs:1
- Corticosteroids
- Amiodarone
•
Rosacea + multiple chalazia2
- Epidermal growth factor receptor inhibitors
- High dose vitamin B6 and B12
1.
2.
Crawford GH et al. JAAD 2004;51:327-41
Reifler DM et al. Am J Ophthalmol 1987;103:594-5
Rosacea Treatment
Avoid triggers
• Flushing:
•
- Clonidine 0.05 mg OD→BID
- Green moisturizers
•
Telangiectasia
- Vascular lasers
(e.g. pulsed dye, KTP, 532 and
810 light-emitting diode (LED),
Alexandrite, Nd-TAG, IPL
alone or with PDT)
Rosacea Treatment: Topical
Mild cleansers
• Sunscreen: titanium dioxide & zinc oxide well tolerated
• Topical
•
- Metronidazole
- Azelaic acid 15% (Finacea)
- Sodium sulfacetamide 10%/sulfur 5%
- Clindamycin
- Dapsone
- Pimecrolimus/Tacrolimus
- +/- BP, VAA (phymatous rosacea; may irritate)
•
Eye:
- Warm soaks, dilute baby shampoo
- Topical steroids (ophthalmologist)
- Artificial tears:
Rosacea Treatment: Oral
•
Oral antibiotics (skin + eye)
- Tetracyclines:
Tetracycline
• Minocycline
• Doxycycline
•
- Others:
Erythromycin
• Clarithromycin
• Azithrmycin
• Metronidazole
• Dapsone
•
Isotretinoin (skin including
phymas + eye)
•
Rosacea Treatment: Rhynophyma
Medical: Isotretinoin
• Surgical:
•
- Ablative lasers
- Shave excision
- Cryosurgery
- Electrosurgical loops to
shave off excessive
tissue, then fine tune with
dermabrasion
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