Acne Vulgaris

BY: Maica Galvez-Vergara M.D.

ACNE VULGARIS
Greek (acme in the sense of a skin
eruption) in the writings of Atius Amidenus. Used by itself, the term "acne" refers to the presence of pustules and papules.

Chronic inflammatory disease of the

pilosebaceous unit.

Frequency 85-100% of people at some time during their lives. Mortality/Morbidity can cause physical pain and psychosocial suffering can lead to scarring A severe inflammatory variant of acne, acne fulminans, can be associated with fever, arthritis, and other systemic symptoms.

Sex males > females during adolescence. women > men during adulthood. Age first few weeks and months of life when a newborn is still under the influence of maternal hormones and when the androgen-producing portion of the adrenal gland is disproportionately large. This neonatal acne resolves spontaneously. Adolescent acne usually begins prior to the onset of puberty, when the adrenal gland begins to produce and release more androgen hormone. 10-17y.o. female 14-19y.o. male Acne is not limited to adolescence. 12% of women and 5% of men at age 25 years have acne. By age 45 years, 5% of both men and women.

History
Local symptoms may include pain or tenderness. Acne may have a psychological impact on any

patient, regardless of the severity or the grade of the disease. Systemic symptoms are most often absent in acne vulgaris. Severe acne with associated systemic signs and symptoms is referred to as acne fulminans.

Predisposing Factors:
genetic factors Menstual cycles , puberty-androgen external cause: emotional stress, occlusion and pressure

on the face. cosmetic agents and hair pomades may worsen acne. Medications: steroids, lithium, some antiepileptics, and iodides. Diet : high glycaemic index, dairy products Congenital adrenal hyperplasia, polycystic ovary syndrome, and other endocrine disorders with excess androgens may trigger the development of acne vulgaris.

Physical
characterized by comedones, papules, pustules,
and nodules in a sebaceous distribution. > affects the areas of skin with the densest population of sebaceous follicles; face, the upper part of the chest, and the back. A comedone is a whitehead (closed comedone) or a blackhead (open comedone) without any clinical signs of inflammation. Papules and pustules are raised bumps with obvious inflammation.

Pathophysiology

Multifactorial

Four key factors

are

responsible for the development of an acne lesion.

follicular epidermal hyperproliferation

with subsequent plugging of the follicle excess sebum the presence and activity of

Propionibacterium acnes,

inflammation

Follicular epidermal hyperproliferation

first recognized event in the development of acne. Androgen hormones - initial trigger. Comedones, the clinical lesion that results from follicular

plugging, begin to appear around adrenarche in persons with acne. the degree of comedonal acne in prepubertal girls correlates with circulating levels of the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S). androgen hormone receptors are present in the portion of the follicle where the comedone forms; individuals with malfunctioning androgen receptors do not develop acne.

 Earliest changes in the hair follicle occur when

the follicular canal becomes blocked with abnormally keratinized desquamating cells. This plug starts above the opening of the sebaceous gland into the follicular canal and causes gradual expansion of cells and sebum within the canal. The plug becomes visible at the skin surface as a white papule ("whitehead," or closed comedo). If the opening of the follicular canal dilates, this plug protrudes from the canal and turns a dark color ("blackhead," or open comedo).

EXCESS SEBUM PRODUCTION

changes in lipid composition have been

implicated in the development of acne vulgaris. Persons with acne frequently have excess sebum production and oily skin. excess sebum may dilute the normal epidermal lipids and result in a change in the relative concentrations of the various lipids. Diminished concentrations of linoleic acid have been demonstrated in individuals with acne and, interestingly, these levels normalize after successful treatment with isotretinoin. relative decrease in linoleic acid may be what initiates comedone formation.

P. acnes
microaerophilic organism Much of the inflammation that eventually occurs arises
from the action of enzymes produced by the bacteria. These enzymes hydrolyze sebum into free fatty acids, which stimulate the inflammatory process. P acnes stimulates inflammation by producing proinflammatory mediators that diffuse through the follicle wall. Recent studies have shown that P acnes activates the toll-like receptor 2 on monocytes and neutrophils.2 Activation of the toll-like receptor 2 then leads to the production of multiple proinflammatory cytokines, including IL-12, IL-8, and tumor necrosis factor. Hypersensitivity to P acnes may also explain why some individuals develop inflammatory acne vulgaris while others do not

INFLAMMATION
Chemotactic factors are released by this

reaction, attracting neutrophils. As the follicular wall becomes inflamed, an erythematous papule appears at the skin surface. With increased sebum production, obstruction and bacterial colonization, the follicular unit ruptures, spilling its contents into the dermis. The inflow of neutrophils causes the formation of pustules. Continuation of severe inflammation leads to formation of nodules and subsequent cysts

Histologic Findings
Microcomedo is characterized
by a dilated follicle with a plug of loosely arranged keratin. With progression of the disease, the follicular opening becomes dilated, and an open comedo results. Black color is the oxidised keratin. The follicular wall thins and it may rupture. Inflammation and bacteria may be evident, with or without follicular rupture. Follicular rupture is accompanied by a foreign body reaction. Dense inflammation into and throughout the dermis may be associated with fibrosis and scarring.

The diagnosis of acne vulgaris is a clinical diagnosis .

Different Types of Acne Grading

Leeds acne grading technique: Counts and
categorises lesions into inflammatory and non-inflammatory (ranges from 0-10.0). Cook's acne grading scale: Uses photographs to grade severity from 0 to 8 (0 being the least severe and 8 being the most severe). Pillsbury scale: Simply classifies the severity of the acne from 1 (least severe) to 4 (most severe).

Cook grading scale

Severity of acne 0 Grade description Need not be perfect 3 small comedones, or papules if they are scattered. Very few pustules, 3 dozen papules or comedones no big or prominent lesions; hardly visible from 2.5m Bet. 2 and 6 red lesions and inflammation are present to a significant degree. Worthy of treatment. Numerous comedones nut no inflammatory lesions, numerous pustules, lesions usaully recognized at 2.5m some pustules may be quite large 1-2cm Conglobata, sinus or cystic type or highly inflammatory acne covering most of the face yellow pustules extend to neck and chin.

2 4 6 8

GOALS OF TREATMENT
normalising shedding into the pore to
prevent blockage killing P. acnes anti-inflammatory effects hormonal manipulation

CLASSIFICATION OF ACNE FOR PURPOSE OF TREATMENT

MildComedonal (non-inflammatory)

acne:

closed comedones

open comedones

(whiteheads), a mass of desquamated cells plugs the follicular canal above the opening of the sebaceous gland. Sebum accumulates within the follicular canal and results in a white papule visible at the skin surface.
(blackheads), when the opening of the follicular canal dilates, the plug protrudes from the canal and turns a dark color.

TREATMENT
TOPICAL MEDICATIONS: > benzoyl peroxide > azelaic acid > salicylic acid > topical retinoids

Mild papulo-pustular > 15 papules > 20 comedones(inflammatory) acne

The follicular wall
ruptures, releasing sebum, cells and bacteria into the surrounding tissue, causing inflammation and redness. Mild inflammatory acne is characterized by inflammatory papules and comedones.

TREATMENT
> benzoyl peroxide > topical retinoids > topical antibiotics
You may do Intralesional injection with steroid on the nodules. Dilution 1:3 kanolone:nss

Moderate inflammatory acne:

20-100 comedones 15-50 inflammatory

lesions or, total lesion count 30-125

TREATMENT
>benzoyl peroxide >topical retinoids combined with oral antibiotics (tetracyclines). > Isotretinoin is an option. IL injections

MODERATELY SEVERE ACNE

>5 cysts Total comedo count
>100 Total inflammatory count >50

Severe Nodulocystic acne

characterized by
comedones, inflammatory lesions, and large nodules greater than 5 mm in diameter. Scarring is often evident

TREATMENT
ORAL ANTIBIOTICS
ORAL ISOTRETINOIN COMBINE WITH TOPICALS HORMONE TREATMENTS (for women)

ACNE CONGLOBATA
Comedones Extensive tissue inflammation results in the formation of nodules, inflammatory lesions Large nodules greater than 5 mm in diameter. Cysts or abscesses Scarring is often evident.

SYSTEMIC THERAPHY
ORAL ANIBIOTICS
- action against P. acnes - anti-inflammatory effects 1st line. Tetracycline 500mg BD Doxycycline 100mg BD Erythromycin 500mg BD

2nd line Antibiotics

Minocycline 100mg OD Co-timoxazole 2 tabs BD
Newest Antibiotic: Lymecycline ( tetralysal ) 300mg OD x 7 to 14 days. Oral supplements praventins, colostrums, F2F , etc.

Systemic Treatment
Oral Isotretinoin
- 13 cis-retinoic acid - 0.5mg 1 mg/kg/d for 4 weeks inc. as tolerated till cumulative dose of 120mg150mg. ( to prevent relapse) Ave length of course: 4 8 months MOA: dec. sebum production dec. comedogenesis dec. inflammation

Baseline laboratory examination

o cholesterol and triglyceride o hepatic transaminases, o CBC count o Pregnancy tests
laboratory examinations should be
repeated monthly during treatment.

Side effects
Teratogenicity Dry mucous membrane and skin Hyperlipidaemia Raised liver enzymes HA and benign intracranial hypertension Arthralgia. Myalgia Depression

Contraindications
Pregnancy considered at high risk for abnormal
healing and development of excessive granulation tissue following procedures. dermabrasion or laser resurfacing delayed for up to a year after completion of therapy tattoos, piercings, leg waxing, and other epilation procedures.

DIFFERENTIAL DIAGNOSIS

ACNE ROSACEA

OLDER AGE FEMALES > MALES CENTRAL FACE ERYTHEMA WITH PROMINENT TELENGIECTASIAS, PAPULES, PUSTULES, EDEMA. NO COMEDONES, CYST OR SCARRING

GRAM NEGATIVE FOLLICULITIS

MAY COMPLICATE LONG TERM ACNE
TREATMENTS. SUDDEN ERUPTIONS OF SMALL FOLLICULAR PUSTULES OR AS DEVELOPMENT OF NODULOCYSTIC LESIONS. TX: AMOXICILLIN AND CO-TRIMOXAZOLE

PITYSPORUM FOLLICULITIS
Pitysporum yeast. Erythematous
monomorphic follicular pustules and papules Sites of predilection: trunks and shoulders. Usually pruritic. TX: Ketoconazole 200mg x 10 days. anti fungal creams and

PERIORAL DERMATITIS
PAPULES AND

PAPULOPUSTULES FROM PROLONGED THERAPHY OF STEROIDS. FLOURINATED PRODUCTS

BENZOYL PEROXIDE
keratolytic bactericidal strong oxidizer (essentially a mild bleach) and thus does
not appear to generate bacterial resistance. causes dryness, local irritation and redness. A sensible regimen may include the daily use of low-concentration (2.5%) benzoyl peroxide preparations, combined with suitable non-comedogenic moisturisers to help avoid overdrying the skin. Care must be taken when using benzoyl peroxide, as it can very easily bleach any fabric or hair it comes in contact with. Prescription-strength benzoyl peroxide preparations do not necessarily differ with regard to the maximum concentration of the active ingredient (10%), but the drug is made available dissolved in a vehicle that more deeply penetrates the pores of the skin.

TOPICAL ANTIBIOTICS
Erythromycin: SANSACNE. DUAC Clindamycin Tetracycline
While topical use of antibiotics is equally as
effective as oral use, this method avoids possible side effects including upset stomach and drug interactions .

Topical retinoids
for normalization of the follicle cell lifecycle helps prevent the hyperkeratinization of cells that can
create a blockage. tretinoin (brand name Retin-A) adapalene (brand name Differin) epiduo ( adapalene and benzoyl peroxide ) tazarotene (brand name Tazorac) related to vitamin A, generally have much milder side effects. Retinol, a form of vitamin A, has similar but milder effects and is used in many over-the-counter moisturizers and other topical products. Topical retinoids often cause an initial flare up of acne and facial flushing.

OTHER TOPICALS
AZELAIC ACIDS- antibacterial and
antiproliferative activity

GLYCOLIC ACID: AHAS: keratolytics SALICYLIC ACIDS : keratolytics

FOOD SUPPLEMENTS
PRAVENTIN (lactoferrin preparations)
F2F : 100 mg 2 x a day for 2 months then once daily dosing thereafter. Generic brands....

Hormonal treatments
antiandrogen, Cyproterone, in combination with
an oestrogen is particularly effective at reducing androgenic hormone levels. Diane-35 cyproterone acetate 2mg, ethinylestradiol .035mcg. ALTHEA- ciproterone acetate 2mg, ethinyl estradiol 35 mcg Progestin drospirenone is now available with fewer side effects than Diane 35 / Dianette. Both can be used where blood tests show abnormally high levels of androgens, but are effective even when this is not the case. Along with this, treatment with low dose spironolactone can have anti-androgenetic properties, especially in patients with polycystic ovarian syndrome.

Treatment
Topical therapy Salicylic acid (Keralyt) Tretinoin (Retin-A)

Comedonal
X X

Inflammatory

Nodulocystic

Azelaic acid (Azelex)

Benzoyl peroxide Adapalene (Differin) Tazarotene (Tazorac) Antibiotics Systemic therapy Oral contraceptives Erythromycin Tetracycline Doxycycline (Vibramycin) Minocycline (Minocin) Isotretinoin (Accutane)

X
X X X X*

X
X X X X

X X X X

X X X X X X

Adverse reaction
Dyspepsia Vaginal yeast infection Photosensitivity Possible interference with oral contraceptives Tooth discoloration in children younger than 13 years or in developing fetuses Propionibacterium acnes antibiotic resistance Hyperpigmentation in scars Pseudotumor cerebri Vestibular toxicity

Doxycycline

Tetracycline
X X X X

(Vibramycin)
X X X X

Minocycline
X X X* X

Erythromycin
X X X

X X X X X

Lupus-like reaction2
Single-organ dysfunction2 Hypersensitivity reaction2 Serum sicknesslike reaction||2
X X X X X X

X
X X X

Other treatment options:

Phototheraphy- blue and red light. Laser treatment Acne surgery Cortisone treatment: IL injections. Peeling

Phototherapy
'Blue' and red light visible light has been successfully employed to treat acne (phototherapy) - in particular intense violet light (405-420nm) generated by purposebuilt fluorescent lighting, dichroic bulbs, LEDs or lasers. Used twice weekly, this has been shown to reduce the number of acne lesions by about 64%; and is even more effective when applied daily. The mechanism appears to be that a porphyrin (Coproporphyrin III) produced within P. acnes generates free radicals when irradiated by 420nm and shorter wavelengths of light.

Particularly when applied over several days, these free radicals ultimately kill the bacteria. Since porphyrins are not otherwise present in skin, and no UV light is employed, it appears to be safe, and has been licensed by the U.S. FDA. The treatment apparently works even better if used with red visible light (660 nanometer) resulting in a 76% reduction of lesions after 3 months of daily treatment for 80% of the patients; and overall clearance was similar or better than benzoyl peroxide. Unlike most of the other treatments few if any negative side effects are typically experienced, and the development of bacterial resistance to the treatment seems very unlikely.

Laser treatment
Laser surgery has been in use for some time to
reduce the scars left behind by acne, but research has been done on lasers for prevention of acne formation itself. The laser is used to produce one of the following effects: to burn away the follicle sac from which the hair grows to burn away the sebaceous gland which produces the oil to induce formation of oxygen in the bacteria, killing them Since lasers and intense pulsed light sources cause thermal damage to the skin, there are concerns that laser or intense pulsed light treatments for acne will induce hyperpigmented macules (spots) or cause long-term dryness of the skin.

Future treatments
A vaccine against inflammatory acne has been tested
successfully in mice, but it is not certain that it would work similarly in humans. A 2007 microbiology article reporting the first genome sequencing of a Propionibacterium acnes bacteriophage (PA6) said this "should greatly enhance the development of a potential bacteriophage therapy to treat acne and therefore overcome the significant problems associated with longterm antibiotic therapy and bacterial resistance."

Failure of treatment:
Two clinical entities must be considered: antibiotic resistance folliculitis related to overgrowth of gram-negative Enterobacteriaceae, Staphylococci or Malassezia yeasts. Aerobic and anaerobic cultures and sensitivity determinations should be used to decide on appropriate antibiotics. Gram-negative folliculitis is frequently treated with ampicillin, less commonly with trimethoprimsulfamethoxazole (Bactrim, Septra) and, occasionally, with isotretinoin. The addition of topical benzoyl peroxide, a broad-spectrum antimicrobial agent, may also be beneficial in many patients who have folliculitis related to either bacteria or yeast.

Side Effects of acne

Emotional Distress : Inferiority Complex Pigmentations Acne scars
and a classic sign of acne scarring. Box car scars - Angular scars that usually occur on the temple and cheeks, and can be either superficial or deep, these are similar to chickenpox scars. Rolling scars - Scars that give the skin a wave-like appearance. Hypertrophic scars - Thickened, or keloid scars.
Ice pick scars - Deep pits, that are the most common

Algorithm for Treatment of Acne Vulgaris

Ist Visit: Medicines; option to do peels. 2nd Visit: Acne Facial every 2 weeks for

the next 6 to 8 weeks. Improvement: every 3 weeks till resolution of acne. Maintenance: monthly.

Take home medicines:

Soap Toner AM meds PM meds Moisturizers - optional Sunblocks

Example of RX:
AM Regimen

1.SOAP 2.TONER 3.B. PEROXIDE 4.M. CREAM

(OPTIONAL) 5.SUNBLOCK

PM Regimen

1.SOAP 2.TONER 3.RETINOIDS 4.M. CREAM

(OPTIONAL)

Thank you!