• Acne is a disease of the pilosebaceous unit in which sebaceous glands become enlarged and increase their production of sebum.
• Increased sebaceous gland activity is necessary for acne to develop.

• Age
  • Prevalent in a large proportion of adolescents and young adults
  • May be seen as late as the 3rd and 4th decades
• Sex
  • Found in up to:
    
    • 78% of premenarchal girls
    • 100% of adolescent boys

• Hormones
  • Androgenic stimulation of sebaceous glands increases sebum production.
• Follicular obstruction
  • Keratinous impaction develops in the pilosebaceous canal, causing outlet obstruction.
  • Sebaceous and keratinous debris accumulate behind the obstruction.
• Proliferation of the anaerobic bacterium Propionibacterium acnes:
  • Contributes to the rupture of the dilated pilosebaceous unit
  • Results in extravasation of pilosebaceous contents into the surrounding dermis and inflammatory acne lesions

• Adolescent age
• Increased level of circulating androgens
• Skin that is rich in sebaceous glands

• Noninflamed open and closed comedones
  
  • Obstruction of pilosebaceous canal causes:
    • Open comedones (blackheads)
    • Closed comedones (whiteheads)
  • Closed comedones (whiteheads) appear as dome-shaped, flesh-colored papules that are often overlooked (Figure 1).
  • Acne in prepubertal children is predominantly noninflammatory and easily overlooked.
• Inflammatory papules and pustules
  • Rare in young children and suggests a possible hyperandrogenic condition
  • Possible hyperandrogenic conditions include:
    
    • Congenital adrenal hyperplasia
    • Rare androgen-secreting tumor
  • Examine for precocious puberty in both sexes and virilization in girls.
• Cystic acne in severe cases
  • Nodules > 5 mm in diameter
  • True cysts (compressible nodules under normal-appearing skin)
  • Can result in permanent acne scars
• Lesions appear most frequently on the face.
  • They also often appear on the chest and back.
  • Lower portions of the trunk, buttocks, thighs are involved less frequently.
  • Distal extremities are always spared.

Flat warts

• See Figure 2.
• Small, flesh-colored
• Sharp, right-angled edge and finely roughened surface
• Variable in size
• Closed comedones are smooth, dome-shaped, and uniformly small.

Milia

• Small epidermal inclusion cysts
• Also confused with inflammatory pustules, especially in infants with neonatal acne

Adenoma sebaceum

• Pink papules that are occasionally confused with acne lesions
• Lesions are actually angiofibromas.
  • They are a dermal manifestation of tuberous sclerosis.
• Adenoma sebaceum lesions should be suspected if they are:
  
  • Clustered primarily in the center of the face
  • Persistent
  • Resistant to acne therapy

Acne rosacea

• See Figure 3.

• An acneiform eruption that can be distinguished from acne by:
  • Background blush of erythema and telangiectasia
  • Absence of comedones
• Most often found in middle-aged adults

Steroid acne

• Can be induced by systemic or topical steroids
• Lacking in comedones
• Involutes slowly and spontaneously after discontinuation of steroids
• Acne from systemic steroids usually is:
  
  • Made up of numerous small, uniform-sized papules and pustules
  • Found on the upper trunk
  • Lacking in comedones

Gram-negative folliculitis

• Caused by gram-negative organisms in patients being treated for acne with systemic antibiotics
• Should be suspected in patients whose disease flares up during therapy
  • Especially when flare-up produces numerous pustules

Acne conglobata

• Unusually severe acne variant caused by:
  • Sudden deterioration of existing active acne
  • Recurrence of acne that has been quiet for many years
  • Most common in 18- to 30-year-old men
    
    • Lesions consist of:
      
      • Comedones
      • Cysts with foul-smelling seropurulent material
      • Burrowing and interconnecting abscesses, leaving irregular and disfiguring scars
    • Has been associated with systemic diseases, such as:
      
      • Hidradenitis suppurativa
      • Pyoderma gangrenosum
      • Renal amyloidosis
      • Musculoskeletal syndrome
    • The mainstay of treatment is isotretinoin.

Acne fulminans

• A rare and severe form of acne
  • Usually occurs in men
  • Characterized by:
    
    • Sudden onset of painful acne nodules
    • Rarely by ulcerative lesions
    • Systemic symptoms include fever; leukocytosis; polyarthritis; splenomegaly; erythema nodosum; and lytic bone lesions in long bones, clavicle, and sternum.
• Treatment involves a combination of systemic corticosteroids initially, followed by isotretinoin.
• Prognosis is good, although residual scarring and disfigurement may persist.

• Diagnosis is rarely difficult.
• Comedonal lesions may require closer inspection to avoid confusion with:
  
  • Warts
  • Milia
  • Adenoma sebaceum
  • Acne variants

• In cases of possible hyperandrogenic condition, screening blood studies should include serum levels of:
  
  • Testosterone
  • Dehydroepiandrosterone sulfate
  • 17-hydroxyprogesterone
• In possible gram-negative folliculitis
  • Bacterial culture with antibiotic sensitivity studies

• Acne is important to the patient seeking help and should be managed seriously.
  
  • Some young people appear to be more affected psychologically than others, but no one is comfortable with acne.
• Four methods of treatment have proved effective.
  
  • Topical comedolytic agents
  • Topical and systemic antibiotics
  • Systemic hormonal therapy
  • Systemic retinoids
• The most traditional and effective treatment regimen is a combination of comedolytics and antibiotics.

Comedolytics

• Retinoids
  
  • Topical retinoids help disimpact the keratinous plug in the follicular canal.
  • Topical comedolytics are available in a variety of preparations; the preparation strength reflects its irritancy and probably also its efficacy.
    • Tretinoin
      • Preparation strength depends on concentration of the drug and nature of the vehicle in which it is contained.
      • Cream in 0.025% (mildest), 0.05% (mild), 0.1% (moderate)
      • Gel in 0.01% (mild), 0.025% (moderate), 0.05% (strongest)
      • Solution in 0.05% (strongest)
    • Adapalene
    • Tazarotene
    • Benzoyl peroxide
    • Salicylic acid
    • Azelaic acid
    • Sodium sulfacetamide
  • Most helpful in treating superficial acne lesions, including comedones and superficial papules and pustules
  • Also reduce inflammatory lesions and enhance penetration of other medications
  • Consensus is that in most cases, topical retinoids (alone or in combination) should be used as first-line therapy for mild-to-moderate inflammatory acne in addition to comedonal acne.
  • Preferred agent for maintenance therapy
• In combination with another topical agent
  • Apply the retinoid at bedtime and the other agent each morning.
  • Adapalene
    
    • Gel in 0.1% and 0.3% and cream in a concentration of 0.1%.
  • Tazarotene
    
    • Gel and cream; each is available in concentrations of 0.05% and 0.1%.
  • Benzoyl peroxide
    
    • Gel in concentrations of 2.5%, 5%, and 10%
  • Salicylic acid
    
    • Large variety of preparations and concentrations
  • Sodium sulfacetamide
    
    • Lotion in 10% concentration
  • Patients are initially prescribed in the mildest preparations; potency is increased if necessary.
• Side effects
  
  • Skin irritation is the most common.
  • ~1% of patients develop true allergic contact dermatitis to benzoyl peroxide.
    • Requires permanent discontinuation of this agent
  • Benzoyl peroxide can bleach clothing and linens.
  • Topical retinoids may make the skin more susceptible to the effects of sunlight.
    • Patients should avoid excessive exposure to the sun and use oil-free sunscreens.

Antibiotics

• Indicated for patients who have inflammatory acne lesions
• Topical agents
  
  • Erythromycin
  • Clindamycin
  • Combinations of benzoyl peroxide and erythromycin or clindamycin are often prescribed before oral antibiotics.
    
    • Benzamycin® gel (5% benzoyl peroxide and 3% erythromycin) twice daily
    • Benzaclin® gel (5% benzoyl peroxide and 1% clindamycin phosphate) twice daily
• For inflammatory lesions extensive enough to make topical therapy impractical (i.e., involving the neck, shoulders, and upper trunk) or unresponsive to a topical regimen, systemic antibiotics are warranted.
  
  • Tetracycline is the drug of choice.
    
    • Proven efficacy, relative low cost, and low incidence of side effects, even over a long period
    • Should be taken on an empty stomach (on awakening or on retiring)
    • The initial dose is 500 mg orally twice daily; the dose is decreased to 500 mg once daily after sustained response is achieved.
  • Tetracycline and other drugs in the same class (i.e., doxycycline and minocycline) should not be used in patients under 8 years because of dental staining.
  • Erythromycin may be used as an alternative if patient does not respond to tetracycline.
  • Doxycycline and minocycline may also be substituted.
    • Doxycycline is more likely to cause photosensitivity.
    • Minocycline is very expensive.
• Resistance to P. acnes may affect as many as 25% of patients taking antibiotics.
  • Preventive measures should be taken.
    
    • Limit the use of oral antibiotics to shorter periods.
    • Combining topical comedolytics (especially topical retinoids) with topical antibiotics.
    • Avoid the use of oral antibiotics as maintenance therapy.

Systemic retinoids

• Isotretinoin
  
  • Reduces follicular keratinization, sebum production, and intrafollicular bacterial counts, resulting in a dramatic improvement in acne
  • Therapeutic effect usually takes several months and often persists long after the course of therapy is discontinued.
  • Historically, 6-month courses have been used, but recently some practitioners focus more on total dose given instead of duration.
    
    • Target is 100 to 150 mg/kg total dose.
  • Side effects are common.
    
    • Almost all patients experience mucocutaneous reactions (cheilitis, conjunctivitis, and dry mucous membranes of the mouth and nose).
    • Extracutaneous complications also occur, including:
      
      • Elevation of plasma lipid levels
      • Asymptomatic vertebral hyperostoses
      • Depression and pseudotumor cerebri (rarely)
    • Female patients must exercise strict birth control while taking this drug.
      
      • Exposure to isotretinoin in pregnancy has been associated with a 25-fold increased risk of major fetal malformations.
      • The U.S. Food and Drug Administration requires that all patients being prescribed isotretinoin be enrolled in a national registry.
  • Isotretinoin is recommended only for:
    
    • Patients with severe cystic and/or scarring acne (or both)
    • A minority of patients who have severe noncystic acne and have not responded to topical comedolytics and oral antibiotics

Hormonal therapy

• An excellent option for women with moderate to severe acne if:
  
  • Oral contraception is desired.
  • An alternative to repeated courses of isotretinoin is preferred.
  • Certain endocrine disorders are present.
• All combination contraceptives reduce free testosterone and have a positive effect on acne.
  • No single preparation is demonstrably superior.
• Contraceptives containing only progestins should be avoided because intrinsic androgenic activity may aggravate acne.

Patient compliance

• Patient compliance is the single most important aspect of successful acne treatment.
• To maximize compliance:
  • Take time at the initial visit to explain use, anticipated effects, and side effects of each medication.
    
    • Printed instructions are good reinforcement.
  • Medications are taken twice daily.
    
    • Link to an established daily routine, such as brushing the teeth.
  • The concept that the treatment will take time to be effective needs to be emphasized.
  • The most common patient questions, often unasked, pertain to diet, cleanliness, cosmetics, and picking at the lesions.

Diet

• Some evidence indicates that the usual American diet may have adverse effects on acne; however, specific foods have not been implicated.
• For most people, a sensible diet is all that is suggested.

Cleanliness

• A primary question from parents
  
  • The notion that acne is a function of poor hygiene should be dispelled.
• In general, cleaning agents for acne need not be recommended.
  
  • Most irritate the skin, unnecessarily compounding irritation caused by topical comedolytics.
• A mild soap-free cleanser is often suggested.

Cosmetics

• Cosmetics have been implicated as possibly contributing to the acne process.
• It is preferable to avoid using them.
• If used, they should be water based and applied sparingly.

Picking

• Much of skin damage in acne patients is self-inflicted.
• Picking, probing, and squeezing cause tissue damage and sometimes produce scars.
• For some patients, picking may become so obsessive that excoriations are the only lesions seen.

• Patients unresponsive to oral antibiotics and topical comedolytics
• Patients with cystic or scarring acne
• Young girls with acne or girls with acne and irregular menses
• Patients with acne fulminans
  
  • Abrupt onset of cystic acne, fever, arthralgias

• The first scheduled return visit should be at 2 to 3 months after the start of therapy.
  • Improvement usually occurs within this period.
  • At this visit, the acne regimen can be adjusted as necessary.
    
    • For example, comedolytics and antibiotics can be increased (or reduced) depending on the initial response.
• Continued improvement is to be expected with continuation of therapy.
  
  • For many, the dose of systemic antibiotics can be reduced gradually and eliminated after 6 to 12 months.
  • Most patients require prolonged maintenance therapy (often over years) with topical agents.
  • Some require continued topical antibiotic therapy.

• The major complications are the psychosocial ramifications of acne.
  • May be compounded and perpetuated by permanent scars
• Scars are easier to prevent than to treat.
  • The emphasis in acne is on early, aggressive medical therapy.
• Established scars are difficult to treat.
  
  • Acne scars are best treated when inflammatory lesions are quiescent.
  • Many patients have been disappointed with the results of dermabrasion.
    
    • Patients treated with isotretinoin should wait for at least 1 year before having dermabrasion.
  • Bovine collagen injections have produced short-term improvement.
    • Repeated injections are often necessary.
    • Long-term results are not yet known.
  • Laser resurfacing by experienced operators has produced some promising results.

• With proper treatment, the prognosis for acne is good, if not excellent.
• Patients should understand that most therapy controls rather than cures acne.
• Cystic acne has been the most difficult to treat, but isotretinoin has become a powerful tool for its treatment.
  • Potential exists for prolonged remissions, sometimes lasting for years after a single course of therapy.
  • Because of serious side effects, its use is usually reserved for patients who have severe cystic or scarring acne (or both) that does not respond to standard treatment.

• Pediatric Dermatology: Acne--PediaLink Learning Center (online course), American Academy of Pediatrics
• Pediatric Dermatology: A Quick Reference Guide (book), American Academy of Pediatrics