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The lecture has been given on May 15th, 2011 by Dr. Mohammad Yousif.
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Acne &Rosacea
• Stem cells reside in the
bulge region.
• Differentiate into
epidermis, HF, hair,
sebaceous gland &
duct.
Sebaceous gland morphogenesis
What is the function of the sebaceous
gland?
• To produce sebum.
• It covers the skin surface, possibly as a
protectant.
• Sebum may also have antifungal properties.
Acne vulgaris - Sebum composition
Triglycerides
FFAs
Wax esters
Squalene
Cholesterol
esters
Cholesterol
57
0
25
15
2
1
Isolated gl. (%)
65
0
0
0
15
20
Epidermal lipids (%)
42
15
25
15
2
1
Skin surface (%)
• The primary defect in acne conglobata,
the most severe expression of acne
vulgaris, is an alteration of
keratinization within the sebaceous
follicle & the leakage of retained sweat
into tissue surrounding plugged eccrine
ducts.
4 main pathologic features of
acne
Acne
P. acnes
Inflammation
Sebum androgen
Follicular keratinization
Androgens
(DHT)Follicular
hyperkeratinization
P acnes
multiplication
Inflammation &
immune response
sebum production
What is a comedo?
• A comedo is a folliculocentric collection of sebum &
keratin.
• Comedonal acne characteristically consists of both
open (blackheads) & closed comedones (white-
heads).
• When the contents of a closed comedo are exposed
to air, a chemical reaction occurs, imparting the
black color of an open comedo.
Androgens
Alteration of the follicular milieu
Colonization with P. acnes
Inflammation
Sebocyte Keratinocyte
Seborrhea Follicular desquamation
Scarring• 30% of patients have significant scarring.
• Nonscarring patients.
Holland et al. BJD 150: 72-81, 2004.
• Scarring patients
Early inflammatory response, nonspecific. CD4+, langerhans cells with HLA-DR.
Late inflammatory response, specific with memory T-cells.
CD4+, Langerhans cells. Macrophages, vascular adhesion molecules, blood
vessels.
Scarring in acneScarring in acne
Genetically prone to scarring.Genetically prone to scarring.
Whose acne has been present Whose acne has been present for a long time, for a long time, even even with moderate type.with moderate type.
With severe deep inflammatory acne.With severe deep inflammatory acne.
With severe exacerbation (flare-up) with isotretinoin With severe exacerbation (flare-up) with isotretinoin therapy.therapy.
More likely to occur in patients:More likely to occur in patients:
Designing an Acne
Treatment Plan
Mild acneUsually topical only unless!!
Mainly comedones Mainly inflammatory
• Retinoic a. 0.05%
“Retin-A®”
• AA 20%
“Skinoren®”
• Adapalene
“Differen®”
• AHAs/esters
“Sebium AKN®”
• Bpo “Panoxyl®”
• Antibiotics
• AA 20% “Skinoren®”
• Adapalene
“Differen®”
• Zinc gluconate
“Sebium AKN®”
Mixed
• Bpo + erythro
“Benzamycin®”
• Retinoids (T) +
Antibiotics (T)
• Skinoren®
• Sebium AKN®
Irritation
Moderate acne
Systemic treatment
Oral antibiotics
Appropriate
topical treatment+
? Oral isotretinoin
Severe acneand Resistant cases
Oral isotretinoin
Drugs used in the treatment of acne
Retinoic acid 0.05% Isotretinoin 0.05% Adapalene Azelaic acid
Predominantly anticomedonal
Adapalene Topical antibiotics
Predominantly antiinflammatory
Topical antibiotics
Predominantly antimicrobial
Erythromycin Clindamycin Tetracycline Erythromycin + Zinc
Azelaic acidBenzoyl peroxideBenzamycin
(Bp + erythromycin)
I) Topical
Drugs used in the treatment of acne
Tetracycline Minocycline Erythromycin Co-trimoxazole Trimethoprim
Antibiotics
Retinoids “Isotretinoin”
Steroids “Prednisolone”
Hormonal regimens Estrogen +
prednisolone Ethinyl estradiol +
cyproterone acetate Spironolactone
II) Oral
Acne vulgaris - Treatment
a) Predominantly non-inflammatory lesions: Retinoic acid 0.05% Azelaic acid 20% Adapalene Comedone extractor
I) Mild acne: usually requires topical therapy only.
b) Predominantly inflammatory lesions: Benzoyl peroxide Topical antibiotics: clindamycin, erythromycinor
erythromycin + Zn acetate 1.2% Azelaic acid 20% Adapalene
Acne vulgaris - Treatment
Systemic therapy as oral antibiotics or
cyproterone acetate should be given in
conjunction with appropriate topical therapy.
II) Moderate to severe acne
Isotretinoin
III) Severe acne
Treatment of acne• Sebum production
Hormonal therapy
isotretinoin
• P. acnes
Antibiotics
Benzoyl peroxide
Isotretinoin
• Follicular hyperkeratinization
Topical retinoids
Isotretinoin
• Inflammation
Antibiotics
Benzoyl peroxide
Hormonal therapy
Isotretinoin
Suppression
• Bpo
• Antibiotics (T)
• Retinoids (T)
• Sebium AKN (T)
• Azelaic a. (T)
• Tetracycline (S)
• Isotretinoin
Sebum
-
-
-
?
-
-
+++
Comedones
-
++
+
+
-
++
P. acnes
++
++
-
+
++
++
+
Inflam.
+
+
?
+
+
+
++
Acne vulgaris
Tetracyclines (1 gm daily) better on an empty
stomach. It is contraindicated in pregnancy,
hepatic & renal impairement.
Erythromycin (1 gm daily) especially in women
who might become pregnant.
II) Systemic treatment
Antibiotics
Systemic treatment - Antibiotics
(Cont’d)
Clindamycin (Dalacine C®): 150 mg, 3 times
daily. Risk of colitis.
Doxycycline (Vibramycin®): 100 mg daily.
Trimethoprim - sulfamethoxazole (Septrin®):
400-600 mg/day.
Systemic treatment - Antibiotics
(Cont’d)
Minocycline (Minocin®): 100 mg daily.
Side effects: Blue-black pigmentation & metallic taste.
Hypersensitivity syndrome reactions (including pulmonary
eosinophilia) & serum sickness-like reactions occur within
3 ms of treatment & are characterized by fever, malaise &
arthralgia.
Minocycline-induced systemic lupus erythematosus and
hepatitis had been reported.
Principles of antibiotic therapy
• Limit duration of systemic agents
Leyden JJ. J Eur Acad dermatol Venereol, 15: 51-55, 2001.
Velicer et al. JAMA, 29 (7): 827-35, 2004.
Antibiotic resistance.
Anti-inflammatory action of retinoids.
Breast cancer risk?
• Use BP and BP/antibiotic combinations to minimize
emergence of resistant strains.
Acne type
Mild acne
“Comedones”
Initial therapy Maintenance
Mild-to-moderate
acne (papular /
pustular)
Moderate-to-severe
acne (severe
nodulocystic)
T Adapalene or T retinoid or
Bpo / T antibiotics
T Adapalene + T / oral
antibiotic or + Bpo antibiotic or
?? oral isotretinoin
Oral isotretinoin or
Cyproterone acetate
T adapalene
(Differin®)
Failure
Failure
3 ms
Success
After 3 ms
success
Success
Initial therapy MaintenanceAcne type
Oral isotretinoinor
Hormonal therapy – womenModified from: Leyden, J Am Acad Dermatol, 2003
T. Retinoid + T./oral antibioticor T. retinoid + BPO … antibiotic
or fluid active (sebium AKN) BPOor ?? Oral isotretinoin
Failure3 ms
Failure
Mild acne“comedones”
Mild-to-moderate acne
(papular/pustular)
Moderate-to-severe acne (severe nodulocystic)
Success
T. Retinoid orT. Retinoid + BPO/T. antibiotics
After 3 ms success
T. Retinoid &/or BPOor
Fluidactive (sebium AKN)
Success
Isotretinoin
Therapeutic effects
• Reverses comedone
formation.
• Reduces sebum levels
• Reduces P. acnes
• Reduces inflammation
• Remission & cure possible
Side effects
Teratogenicity
Layton AM. Am J Dermatol Treat 4: S2-S5, 1993.
• Psychiatric
• ….
Only isotretinoin
• Miniaturizes sebaceous glands.
• Reduces sebaceous gland output.
• Reverses retention hyperkeratosis.
Isotretinoin - Side effectsIsotretinoin - Side effects
1.1. Teratogenic:Teratogenic: pregnancy is completely pregnancy is completely
contraindicated during & for 1 month after contraindicated during & for 1 month after
therapy.therapy.
Two contraceptive methods should be used Two contraceptive methods should be used
• Effective contraception must be in use for at
least 1 ms & a negative serum pregnancy test
or a negative urine pregnancy test with a
sensitivity of at least 50 mU/ml must be
obtained within 1 wk prior to beginning
therapy.
• Contact lens use may also have to be
discontinued during therapy because of
discomfort or blepharoconjunctivitis.
What is SAPHO syndrome?
• Synovitis, Acne, Pustulosis, Hyperostosis, &
Osteitis.
• The acne associated with this syndrome is most
often acne conglobata – with highly
inflammatory comedones, nodules, abscesses,
& draining sinuses located primarily on the
trunk, which often heal with significant scarring.
Is there a difference between neonatal
acne & infantile acne?
Yes
• Neonatal acne occurs in up to 20% of newborns; it
usually develops during weeks 2-4 of life.
• It is more common in males, is relatively mild, &
regresses spontaneously in most infants by age 6 ms.
• It is thought to be due to maternal androgens & is not
associated with significant scarring or an increased
incidence of acne in later life.
Is there a difference between neonatal acne & infantile acne? (Cont’d)
• Infantile acne usually begins between the
third & sixth months of life & may persist to
age 5 & rarely longer.
• It is uncommon & occurs more often in
males. It can be severe, with nodules, cysts &
significant residual scarring.
Is there a difference between neonatal acne & infantile acne? (Cont’d)
• Endocrine abnormalities & virilizing
tumors can be associated.
• Some studies show an increased
incidence of severe acne in later life.
How does steroid acne differ from
acne vulgaris?
• Steroid acne has a sudden onset, the lesions are
monomorphic (all lesions at the same stage of
development), & comedones are absent.
• It occurs primarily on the upper trunk, less
frequently on the face, & clears when the drug is
withdrawn.
What is Favre-Racouchot syndrome?
• This describes the development of multiple
open comedones located on the inferolateral
aspect of the orbital rim in elderly patients.
• It is associated with marked solar elastosis of
the surrounding skin.
Regulation of sebaceous glands
• Retinoids.
• Androgens / estrogens.
• Melanocortins.
• Corticotrophin releasing hormone.
• Insulin-like growth factors / growth hormone.
• Peroxisome proliferator activated receptors
(PPARs).
IGF-1
• Insulin at high levels can interact with IGF-1
receptor.
• IGF-1 promotes expression of enzymes
responsible for androgen biosynthesis &
conversion.
Sebum production
• Increased sebum production in acne.
• Micro-organisms hydrolyze triglycerides into free fatty
acids.
Squalene, wax & triglycerides.
Promote bacterial clumping & colonization.
Increase inflammation.
Comedogenic.
Kligman et al. Arch Dermatol. 102: 267-75, 1970.
Seb. gl. / sebum
• Sebum comp. is unique to man
• TGs FFAs (comedogenic)
• linoleic a. conc.
• Sebum related to acne and acne severity
Lipase
Could acne be related to
a change in skin lipid
composition irrespective
of the rate of sebum
excretion
?
Squalene
“sebum”
Oxidated squalene
Hyperproliferation Sebum fluidity
Microcomedo
Oxidation
Propionibacterium acnes
• Colonizes sebaceous follicles.
• Lipases break down sebaceous lipids into free
fatty acids.
• Produces enzymes leading to rupture of
comedone walls.
• Activate toll-like receptors.
Microcomedo
• Precursor lesion of
acne
• Formation is inhibited
by topical retinoids
Acne Excoriée
• Sertroline (Zoloft) 25 mg to 50 mg
• Takes weeks to have full impact
• Patients do not seem to consciously admit that
it helped
• Some feel paroxetine (Paxil) more effective
• Olanzapine (Zyprexa) 2.5 – 5.0 mg hs
… and consider the possibility the patient is
excoriating because of demodecideosis
Crotamiton or Pyrethrin
Acne Excoriée
Acne Excoriée
Use topicals!
… even if you don’t think they help
… it gives the patient some way to touch the face
without guilt – and without picking
Diet & acne
• Examined two non-westernized cultures &
found no acne.
• Hypothesis that the non-westernized diet, low
in high-glycemic load carbohydrates,
contributed to the absence of acne.
Cordain et al., Arch Dermatol., 2002; 138: 1584-90.
Does chocolate cause acne?
• No….
• But, insulin & insulin-like growth factor-1
both stimulate the sebaceous gland &
androgen production & insulin-like growth
factor promotes keratinocyte proliferation.
Diet – hypothesis!
• A diet that encourages a high insulin
response chronically could promote acne by
resulting in hyperinsulinemia and increased
levels of IGF-1.
• Hyperinsulinemic states as seen in some women
with PCOD are associated with acne vulgaris.
• Medications that decrease insulin resistance
also improve acne in some PCOD patients.
Diet in acne
Diet in acne
• Skim milk was most highly associated with the
prevalence of acne.
• Other dairy products associated with acne
included instant breakfast drinks, sherbet,
cream cheese & cottage cheese.
Adebamowo et al.
Diet in acne
• Sode, french fries, chocolate candy, and
pizza were not significantly associated with
acne.
Adebamowo et al.
Diet in acne
Hypothesis
Adebamowo et al.
• Hormonal content of milk may be responsible
for the association with acne.
• Milk contains estrogens, progesterones, and
androgen hormones as well as glucocorticoids
and IGF-1.
Conclusions
• Milk intake may influence comedogenesis through: Steroid hormones: androgens, 5-reduced steroids,
other steroid hormones.
IGF-1 pathway.
Whey proteins & -lactalbumin -lactalbumin is a potential transport protein for
sex steroids & has androgenic effect on fed rats
-lactalbumin undergoes pressure induced
conformational change with functional alteration
Treatment of acne• Sebum production
Hormonal therapy
Sebum correction
isotretinoin
• P. acnes
Antibiotics
Benzoyl peroxide
Isotretinoin
• Follicular hyperkeratinization
Topical retinoids
Topical tazarotene
(receptor selective)
Isotretinoin
• Inflammation
Antibiotics
Benzoyl peroxide
Hormonal therapy
Isotretinoin
Rosacea (Acne Rosacea)
It is a chronic, vascular inflammatory
disorder, usually limited to the center of face
and characterized by persistent erythema,
telangiectasia, papules and pustules.
Age: more between 30-50 years.
Sex: females are affected more.
Rosacea (Acne Rosacea)
Ocular involvement.
Lymphoedema.
Complications
Rosacea (Acne Rosacea)
It affects mainly the center of the face.
It begins as a transient erythema with edema and
telangiectasia. In most patients there are papules
which are asymptomatic (in contrast with AV), and
less frequently pustules but comedones and
scarring are absent.
Rhinophyma.
Clinically
• The earliest sign of rosacea are facial
telangiectases & persistent erythema of the
central face &, less often, the neck & upper
chest.
• Most patients ultimately develop inflammatory
follicular papules & pustules.
• Comedones, if present, aren’t a 1ry manifestation
of rosacea but a result of other factors such as
sun exposure (Favre-Racouchot disease).
• In a small proportion of patients, inflammation
progresses, producing large nodules, edema &
tissue hyperplasia.
• A rare persistent nonpitting edema of the central
face & forehead, similar to that reported in acne
patients, has also been reported.
• Another variant, granulomatous rosacea, is
characterized by multiple brown-red infiltrative
papules & nodules.
• Biopsy reveals noncaseating granulomas.
Rosacea (Acne Rosacea)
GIT disturbances. Reaction to the follicular mite, Demodex
follilculorum. Climatic (sun). Vasomotor instability. Psychic factors. Role of helicobacter pylori. Rosacea has been reported as a manifestation of
HIV infection.
Etiology and exacerbating factors
Rosacea (Acne Rosacea)
Avoid extremes of heat & cold, excessive sunlight,
spices, hot liquids & alcohols.
Treatment
I) Systemic treatment
Tetracyclines: 250 mg 3 times daily.
Metronidazole (Flagyl®) 200 mg twice daily.
Isotretinoin (Accutane®).
Rosacea - Treatment (Cont’d)
II) Topically Bland emollient
Anti-acne agents
Topical metronidazole 0.75% gel
(Metrogel®)
III)Plastic surgery for rhinophyma
Perioral dermatitis
Persistent erythematous eruption of tiny
papules and pustules around the mouth,
nose and may be eyes. A clear zone is
often seen around the vermilion border of
the lips.
Perioral dermatitis
It may be due to prolonged therapy with
fluorinated steroids. However, sunlight, oral
contraceptive pills and fluorinated tooth
paste may play a role. Many patients are
heavy users of cleansers, moisturizers and
make-up.
Etiology
Perioral dermatitis
Avoid strong topical steroids.
Topically: hydrocortisone or non-fluorinated
steroids.
Tetracyclines (1 g/day).
Treatment
What is perioral dermatitis?
• This common distinctive acneiform skin
eruption occurs mainly in women aged 15-25
yrs, but also occurs in children.
• Perioral dermatitis is characterized by erythema,
scaling & follicular papules that occur around
the mouth, nose & less frequently, the eyes.
What is perioral dermatitis? (Cont’d)
• The etiology is unknown, but many patients
have used mid- or high-potency steroids
inappropriately. In one study, 20% of children
with perioral dermatitis have a family history
of rosacea.
What is perioral dermatitis? (Cont’d)
• The treatment includes the cessation of all topical
corticosteroids & an 8-10 wk course of a
tetracycline antibiotic.
• Tetracycline & derivatives should not be used in
children under 8 yrs of age. Oral erythromycin &
topical clindamycin are effective substitutes.
• Recurrences are rare.