Management of acne vulgaris

Authors: Hguyen, Quan H.; Kim, Y. Alyssa; Schwartz, Robert A

Citation: American Family Physician, July 1994 v50 n1 p89(10)

Subjects: Acne Care and treatment
Reference #: A15597728

Author's Abstract: COPYRIGHT American Academy of Family Physicians 1994

Acne vulgaris can affect both adolescents and adults. The pathogenesis of acne is multifactorial and involves overproduction of sebum, an abnormal follicular keratinization process, proliferation of Propionibacterium acnes, and hormonal and immunologic factors. Clinical manifestations of acne range from noninflammatory comedones to inflammatory papules, pustules and cysts. Current therapy allows the physician to select a variety of topical and/or systemic antibiotics, retinoids, and hormone agents aimed at specific pathogenic factors. Most treatment regimens require several weeks of consistent use to be effective. Sound patient education, a strong therapeutic alliance and modification of lifestyle factors are powerful adjuncts to medical management.

Full Text COPYRIGHT American Academy of Family Physicians 1994

Acne vulgaris is a common disorder involving the sebaceous follicles. It is usually first noted during the teenage years. Some degree of acne develops in as many as 80 percent of adolescents.[1-3] Acne usually develops at an earlier age in girls than in boys, but the disorder affects boys more frequently and more severely.[4] Acne can persist into mid-adulthood in some persons, and can also present initially in adulthood. It is estimated that 40 to 50 percent of adult women are affected by a low-grade persistent form of acne.[1]

Although acne is usually considered to be self-limited, it should not be ignored. If untreated, acne can leave emotional and physical scars that last a lifetime. The psychosocial impact on teenagers may be devastating. Most patients with acne present to primary care physicians for treatment. Only a small proportion of patients with acne are referred to a dermatologist.[2]

Pathogenesis

A rational approach to the treatment of acne requires a clear understanding of the multifactorial basis of the disorder.[4-6] The normal pilosebaceous unit is composed of large, multilobulated sebaceous glands, a rudimentary hair and a wide follicular canal lined with stratified squamous epithelium. During the regular turnover process of the skin, desquamated cells from the follicular epithelium are carried up the follicular canal by sebum secreted from the sebaceous glands. If the pilosebaceous unit becomes plugged, the trapped sebum causes bacterial proliferation and inflammation, resulting in the development of acne vulgaris (Figure 1).[7,8]

Stimulation of the sebaceous follicle by a surge of androgenic hormones appears to be an important factor in the development of acne. Acne usually does not occur until puberty, when hormone changes begin, androgen-sensitive sebaceous follicles enlarge and sebum production increases.

An abnormal desquamation process is required to produce clinical acne vulgaris. This process consists of increased sloughing of the epithelium, which becomes more cohesive and blocks the follicular orifice with the accumulation of dead cells. Within the blocked follicle, the impacted sebum favors the proliferation of Propionibacterium acnes, an anaerobic diphtheroid organism that normally resides in the pilosebaceous unit. One nutritional requirement of this bacterium is glycerol, obtained through lipolysis of the triglycerides in the sebum, which releases free fatty acids as byproducts. P. acnes also releases various chemotactic products, which attract neutrophils to the area. These neutrophils secrete hydrolytic enzymes that cause secondary damage to the follicular wall. The irritating free fatty acids and other bacterial enzymes can then leak into the dermis, creating intense inflammation.[1-3]

Clinical Manifestations

The hallmark of acne vulgaris is a micro-comedo formed by a sebum-plugged pilosebaceous follicle. Accumulation of sebum results in a visible closed comedo, or whitehead. Continuing distention of the closed comedo causes protrusion from the follicular orifice, forming an opened comedo, or blackhead. The dark color of a blackhead is due to oxidized lipids, melanin and densely packed keratinocytes. It is not dirt, as commonly assumed.

Inflammatory pustules develop when the compacted follicular contents rupture, releasing bacteria and bacterial products, including free fatty acids, into the dermis. When the inflammatory response occurs at a deeper level in the dermis, a papule develops. Unusually intense inflammation can lead to a fluctuant and painful acne cyst, which heals with post-inflammatory pigment changes and scar formation.

Comedones can occur anywhere on the body, but are usually found on the forehead and upper cheeks in adolescent patients. Comedones may progress to inflammatory lesions on the lower cheeks, chin, chest, upper back and shoulders, where many pilosebaceous follicles are found. Acne conglobata, an atypical and severe form of acne, is characterized by numerous inflamed cystic lesions, sinuses and extensive scarring over the face and upper trunk.[2]

When choosing a treatment regimen and evaluating the response to treatment, it is sometimes helpful to grade acne in a particular patient on the basis of the following severity scale.

Type 1: comedonal, few lesions (fewer than 10) on face only, without scarring.

Type 2: papular, moderate number of lesions (10 to 25) on face and trunk, with mild scarring.

Type 3: pustular, many lesions (more than 25), moderate scarring.

Type 4: nodulocystic, extensive scarring.

Course and Prognosis

While many cases of mild to moderately severe acne resolve over time, most comedones do not usually resolve spontaneously. Larger inflammatory papules and pustules may take several weeks to resolve and the post-inflammatory hyperpigmentation can last for months. Inflammatory cystic lesions can result in acne scars, which may appear as hypotrophic pitted scars or, less commonly, as hypertrophic scars and keloids.

Assessment

A complete history should be obtained and important points about the etiology and treatment of acne should be discussed with the patient prior to the initiation of treatment.[1-4,8] The more the patient knows about acne, the more compliant he or she will be. Important issues to discuss are the following.

ENDOCRINE

Acne may flare up premenstrually because the sebaceous duct orifice may become more obstructed at this time in the cycle. In females, the possibility of androgenic disorders, such as polycystic ovarian disease and Cushing’s syndrome, should be considered; the patient should be asked about menstrual irregularities and evidence of hirsutism should be looked for on physical examination. In young women with acne that does not respond to therapy, hormone testing may reveal an androgen excess, even in the absence of symptoms such as menstrual abnormality, male-pattern hair loss or hirsutism. An endocrinology consultation may be warranted in complicated cases.

DIET

Although clinical studies have not demonstrated any causal relationship between certain foods and acne, patients should be advised to eat a well-balanced diet and avoid those foods which consistently result in acne flare-ups.

CLEANLINESS

The development of acne is not related to dirt. Patients should be advised that excessive scrubbing, especially with abrasive cleaning lotions and facial sponges, may actually worsen the condition. Patients who have oily skin should wash their faces using a mild, unscented soap (i.e., Dial, Ivory, Lever-2000) and water.

ENVIRONMENT

Although sunshine can be beneficial in some patients, very humid environments and heavy sweating can worsen acne in other patients. Exposure to pollution and hydrogenated hydrocarbons may aggravate acne.

MECHANICAL TRAUMA

Constant pressure, rubbing and humidity from tight or occlusive clothing can aggravate acne. In addition, patients should be warned that repeatedly picking the lesions can result in more inflammation, scarring and pigmentary changes.

COSMETICS

Comedogenic agents such as heavy oils, greases or dyes in cosmetic creams and hairsprays can exacerbate acne. Patients who use cosmetics should be advised to use water-based products instead of occlusive, oil-based products.

MEDICATIONS

Certain drugs, including corticosteroids, adrenocorticotropic hormone (ACTH), androgens, phenytoin, barbiturates, lithium, isoniazid, cyclosporine, iodides and bromides, are now known to cause acne. Although some oral contraceptives may provide excellent therapy for acne, those with androgenic and antiestrogenic progesterones may actually promote acne eruptions. Also, gram-negative folliculitis can occur as a complication of chronic broadspectrum antibiotic therapy.

Therapy

Strong rapport between the patient and the physician is necessary in the treatment of acne vulgaris. During the initial visit, sufficient time should be spent explaining the causes of acne, its aggravating factors and the rationale for therapy. The patient should be advised that medication may take weeks to have its full effect and that therapy can only control acne, not cure it. Patients need to understand that therapy may be continued and modified according to response.[9-12]

COMEDONAL ACNE

Mild noninflammatory acne can be treated with topical antibacterial agents such as benzoyl peroxide or comedolytic agents such as tretinoin (Retin-A) and salicylic acid (Table 1). These agents can unplug the blocked follicles with their exfoliative effects. The combination of benzoyl peroxide in the morning and tretinoin at night may be effective when either agent alone has failed. Comedone extraction can accelerate resolution when it is used in addition to topical medications.[4]

TABLE 1
Topical Agents for the Treatment of Acne Vulgaris
 
Antibacterial preparations
Benzoyl peroxide gel, cream, lotion, soap
Erythromycin ointment, lotion, swab or gel
Clindamycin solution, lotion or gel (Cleocin T)
Meclocycline cream (Meclan)
 
Keratolytic preparations
Tretinoin cream, gel or liquid (Retin-A)
Salicylic acid
 
Miscellaneous
Astringents, soaps, cleansers

Sulfur

Resorcinol

Benzoyl Peroxide. Benzoyl peroxide is the most commonly used acne medication available without a prescription. It is a potent anti-bacterial oxidizing agent that can decrease the number of P. acnes organisms and, consequently, the amount of free fatty acids. Its mild comedolytic and exfoliant properties can also unplug obstructed follicles.

Benzoyl peroxide is the first-line monotherapy for mild acne, and it may be used in combination with other agents in more severe acne. Benzoyl peroxide is available in over-the-counter preparations of 2.5 percent, 5 percent, and 10 percent gels, creams, lotions or soaps. All concentrations seem to be therapeutically equivalent. The liquid and cream formulations (Benoxyl, Oxy-10) are less irritating and may be useful in patients with dry skin. The gel formulation (Benzagel, Persa-Gel, Desquam-X) is more irritating but more effective for patients with oily skin.

Benzoyl peroxide should be applied once or twice daily Patients should expect mild redness and scaling of the skin during the first week of use. Contact sensitivity is reported in a small percentage of patients.

Tretinoin. This all-trans-retinoic acid is the most effective topical comedolytic agent; it can normalize the desquamation process[7,9,10] Tretinoin decreases the cohesiveness of follicular epithelial cells, thus inhibiting the formation of microcomedones, and increases cell turnover, resulting in the expulsion of existing comedones. The agent also decreases the thickness of the stratum corneum and potentiates the penetration of other topical antibiotic agents.

Tretinoin is available as Retin-A cream (0.025 percent, 0.05 percent, 0.1 percent), Retin-A gel (0.01 percent, 0.025 percent), and Retin-A liquid (0.05 percent). Tretinoin therapy should usually be started with the lower strength cream or gel. If no response occurs after a few weeks of treatment, then the higher-concentration liquid formulation can be used. The lubricating cream is favored in patients with dry skin, and the drying gel is best for patients with oily skin.

Tretinoin is applied once daily before bedtime to the affected areas. Mild redness and peeling are part of the therapeutic effect of the medication but can decrease compliance. Patients should be aware that improvement may take six to 12 weeks, and that flare-ups of acne can occur during the first few weeks of therapy due to surfacing of the lesions onto the skin. It is extremely important that patients avoid excessive sun exposure and use appropriate sunscreens.

Exfoliants. These agents include salicylic acid, glycolic acid, trichloroacetic acid, elemental sulfur and resorcinol. They are not effective in removing deep comedones and can cause irritation of the skin.

PAPULAR ACNE

Mild inflammatory lesions can be treated effectively with topical antibiotics.[7,9,10,14] The main action of topical antibiotics is to eliminate R acnes from the sebaceous follicles and thereby suppress free fatty acid production. Some topical antibiotics have anti-inflammatory effects through the inhibition of chemotactic factors. The effectiveness of topical antibiotics in the treatment of acne is limited by their low lipid solubility and consequent difficulty in penetrating sebum-filled follicles. All topical antibiotics are applied twice daily.

Clindamycin. Clindamycin is available in a 1 percent concentration prepared as a solution, lotion or gel formulation (Cleocin-T). Clindamycin is as effective in the treatment of acne as erythromycin.[15-18] Rare cases of pseudomembranous colitis have been reported with clindamycin use.

Erythromycin. This agent is available in a 2 percent solution (Eryderm, A/T/S), gel (Erygel, Emgel) or pledgets (Erycette, T-Stat). Topical erythromycin is considered to be the safest antibiotic for use during pregnancy. It is also available in a 3 percent gel formulation combined with 5 percent benzoyl peroxide (Benzamycin). This new formulation is probably the most effective current topical antibiotic and may be as effective as systemic antibiotics in some patients. This product has not been fully evaluated in pregnant or lactating women.

Meclocycline. Meclocycline is available in a topical cream (Meclan). It is less drying but may be less effective than other topical agents.

PUSTULAR ACNE

Patients with moderate or severe inflammatory acne win require oral antibiotics in addition to topical therapy (Table 2). Systemic antibiotics are favored over topical preparations because of the more rapid clinical improvement achieved (two to six weeks). The side effects of oral antibiotics are gastrointestinal distress and vaginal candidiasis.
 

TABLE 2
Oral Agents for the Treatments of Acne Vulgaris
 

Antibiotics

Tetracyline
Minocyline (Minocin)

Erythromycin
Clindamycin (Cleocin)
Trimethorprin-sulfamethoxazole (Bactrim, Spetra)
 
Hormone therapy

Estrogen

Corticosteroids
Spironolactone (Aldatone)
 

Miscellaneous
Isotretinoin (Accutane)

Tetracycline. Due to its effectiveness and low cost, tetracycline is the first-choice oral antibiotic in the treatment of pustular acne.[19] The usual starting dosage is 250 mg four times daily or 500 mg twice daily one hour before or two hours after meals. Metallic ions in antacids or dairy products can interfere with absorption of tetracycline. Because tetracycline can cause enamel hyperplasia and tooth discoloration, it should not be used in pregnant women or in children younger than 12 years of age.

Erythromycin. The usual dosage of erythromycin is the same as that for tetracycline. P. acnes is more resistant to erythromycin than to tetracycline, and the gastrointestinal side effects of erythromycin often limit its use.

Minocycline. This antibiotic is highly effective because of its lipid solubility and ability to penetrate the sebaceous follicle. Minocycline (Minocin) is used in patients with tetracycline-resistant acne. The drug has good absorption with food. A drawback is its cost. Side effects of minocycline include dizziness and, rarely, color changes in the acne scar. The usual starting dose is 50 mg twice daily or 100 mg once daily.

Doxycycline. This drug is less expensive than minocycline and, due to its high lipid solubility, is also very effective. The usual dosage is 100 mg once daily. Photosensitivity and gastrointestinal distress are the most common side effects.

Trimethoprim-Sulfamethoxazole. This drug is used for severe cases of acne that are refractory to other antibiotics and for gram-negative folliculitis. Therapy is initiated with one double-strength tablet of trimethoprim-sulfamethoxazole (Bactrim DS, Cotrim DS, Septra DS) each day. Potential side effects include a severe eruption reaction. NODULOCYSTIC ACNE

Patients with severe inflammatory acne unresponsive to conventional therapy may require referral to a dermatologist. Treatment options include isotretinoin, steroid injections and hormone therapy Isotretinoin. Oral 13-cis-retinoic acid is a derivative of vitamin A. It is the only systemic drug that decreases sebum production and reverses the abnormal epithelial desquamation process.[20,21] It also can decrease the population of P acnes in the sebaceous follicle. These actions make it the treatment of choice for patients with severe nodulocystic acne.
The initial dose of isotretinoin (Accutane) is 0.5 to 1.0 mg per kg, or 40 to 80 mg per day. The usual duration of therapy is four to five months, and the satisfactory response rate can be as high as 90 percent. Transient exacerbation of acne may occur during the initial month of therapy, but most patients will respond well over time.

Side effects of isotretinoin include cheilitis, dry skin, pruritus, epistaxis and photosensitivity. It can also cause decreased night vision, hypertriglyceridemia, abnormal liver function tests, electrolyte imbalance and elevated platelet count. Pseudotumor cerebri can occur if isotretinoin is taken in combination with tetracycline. These side effects are usually reversible once therapy is discontinued.

Women of child-bearing age must receive counseling about the possibility of teratogenicity, the most serious side effect of isotretinoin, before beginning treatment and must have received a written warning as well. They must not be pregnant (determined by a serum pregnancy test) and must use appropriate contraception one month before the initiation of therapy, during the entire course of therapy, and two months after cessation of therapy.

Corticosteroid Injection. Intralesional injection of triamcinolone acetonide (Kenalog), 1.0 to 2.5 mg per mL of solution, will lead to rapid resolution of most cystic lesions in two to three days.[22] Stock solutions should be diluted in normal saline or 1 percent lidocaine (Xylocaine) to appropriate concentrations. The corticosteroid is injected into the cyst with a 27- to 30-gauge needle. It is important to inject a minimal amount and to do so superficially to avoid local steroid atrophy.

Systemic Hormones. Hormone therapy should be limited to female patients with severe acne that is unresponsive to medications.[8] Oral contraceptives are useful sources of low-dose estrogen (0.035 to 0.1 mg per day), which can suppress ovarian androgen production. Acne improvement may take three to four months. Combination oral contraceptives that contain androgenic progesterone-like norgestrel should be avoided since these can actually exacerbate acne.

Other less commonly used hormones include prednisone (5 mg per day), which suppresses adrenal overproduction of androgen, and spironolactone (150 to 200 mg per day), which reduces sebum production by sebaceous follicles.[23] These hormones should be administered with caution because of their potential effects.

References:

[1.] Shalita AR, Pochi PE, Leyden JJ. Symposium: acne therapy in the 90's. J Int Postgrad Med 1991;4S:3-16.
[2.] Quan M, Strick RA. Management of acne vulgaris. Am Fam Physician 1988;38(2):207-18.
[3.] Pochi PE, Quan M, eds. Acne vulgaris. Kansas City, Mo.: American Academy of Family Physicians, 1991:1-20.
[4.] Arndt KA. Manual of dermatologic therapeutics. Boston: Little, Brown, 1989:3-11. [5.] Lynch PJ. Dermatology for the house officer. 2d ed. Baltimore: William & Wilkins, 1987:108-14.
[6.] Berger TG, Elias PM, Wintroub BU. Manual of therapy for skin diseases. New York: Churchill Livingstone, 1990:2-7
[7.] Leyden JJ, Shalita AR. Rational therapy for acne vulgaris: an update on topical treatment. J Am Acad Dermatol 1986;15(4 pt 2):907-15.
[8.] American Academy of Dermatology. Guidelines of care for acne vulgaris. J Am Acad Dermatol 1990; 22:676-80.
[9.] Winston MH, Shalita AR. Acne vulgaris. Pathogenesis and treatment. Pediatr Clin North Am 1991;38:889-903.
[10.] Taylor MB. Treatment of acne vulgaris. Guidelines for primary care physicians. Postgrad Med 1991; 89(8):40-2,45-7
[11.] Olsen TG. Therapy of acne. Med Clin North Am 1982;66:851-71.
[12.] Reisner RM. The rational therapy of acne. Cutis 1976;17:527-30.
[13.] Swinyer LJ, Baker MD, Swinyer TA, Mills OH Jr. A comparative study of benzoyl peroxide and clindamycin phosphate for treating acne vulgaris. Br J Dermatol 1988;119:615-22.
[14.] Knutson DD, Swinyer LJ, Smoot WH. Meclocychne sulfosahcylate. Topical antibiotic agent for the treatment of acne vulgaris. Cutis 1981;27:203-4,208-10.
[15.] Schachner L, Pestana A, Kittles C. A clinical trial comparing the safety and efficacy of a topical erythromycin-zinc formulation with a topical clindamycin formulation. J Am Acad Dermatol 1990; 22:489-95.
[16.] Shabta AR, Smith EB, Bauer E. Topical erythromycin v clindamycin therapy for acne. A multicenter, double-blind comparison. Arch Dermatol 1984; 120:351-5.
[17.] Melski JW, Arndt KA. Current concepts: topical therapy for acne. N Engl J Med 1980;302:503-6.
[18.] Stern RS, Pass TM, Komaroff AL. Topical v systemic agent treatment for papulopustular acne. A cost-effectiveness analysis. Arch Dermatol 1984;120:1571-8.
[19.] Eady EA, Cove JH, Holland KT, Cunliffe WJ. Superior antibacterial action and reduced incidence of bacterial resistance in minocycline compared to tetracycline-treated acne patients. Br j Dermatol 1990;122:233-44.
[20.] Strauss JS, Rapini RP, Shafita AR, Konecky E, Pochi PE, Comite H, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol 1984;10:490-6.
[21.] Farrell LN, Strauss JS, Stranieri AM. The treatment of severe cystic acne with 13-cis-retinoic acid. Evaluation of sebum production and the clinical response in a multiple-dose trial. J Am Acad Dermatol 1980;3:602-11.
[22.] Levine RM, Rasmussen JE. Intralesional corticosteroids in the treatment of nodulocystic acne. Arch Dermatol 1983;119:480-1.
[23.] Muhlemann MF, Carter GD, Cream JJ, Wise P. Oral spironolactone: an effective treatment for acne vulgaris in women. Br J Dermatol 1986;115:227-32.