Dermatology 5th year, 4th lecture (Dr. Mohammad Yousif)

transcript

Acne &Rosacea

• Stem cells reside in the

bulge region.

• Differentiate into

epidermis, HF, hair,

sebaceous gland &

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

Wax esters

Squalene

Cholesterol

esters

Cholesterol

Isolated gl. (%)

Epidermal lipids (%)

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

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®”

• 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

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

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?

• 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).

• 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

• 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

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

• 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

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.

Ocular involvement.

Lymphoedema.

Complications

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.

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

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.

Dermatology 5th year, 4th lecture (Dr. Mohammad Yousif)

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