Figure 1. Comedonal acne:
obstructive and noninflammatory.Acne is a disease of the pilosebaceous unit, also called the sebaceous follicle, and occurs predominantly on the face, chest, and back. Acne typically begins during adolescence but can persist into adulthood. In some persons, significant acne may not begin until adulthood. It is not unusual to see adult women present to their primary care physicians with new onset acne. The pilosebaceous unit has large sebaceous glands and a small hair that is not visible on the surface of the skin. The glands produce sebum, a complex lipid mixture that helps to maintain hydration of the skin. Acne stems from the blockage of the sebaceous follicle with sebum and desquamated cells. In addition, there is also an overgrowth of Propionibacterium acnes (P acnes) within the follicle.
Multiple factors can contribute to the formation of acne including genetics, androgens, stress, excessive friction on the skin (as with sweat bands and helmet straps), occupational exposure to oils and grease, comedogenic cosmetics, and medications (anabolic steroids, systemic corticosteroids, lithium, and isoniazid.)
Acne arises from the interaction of the following four factors:
Obstruction of the sebaceous follicle is the primary pathologic event in acne vulgaris, giving rise to the microcomedo, the precursor of all acne lesions. When this obstruction occurs, the continued production of sebum and keratin gives rise to visible noninflammatory lesions, open comedones (blackheads) and closed comedones (whiteheads). When this process results in the disruption of the follicle wall, an extrusion of P acnes, sebum, hair, and cells occurs in the dermis. Leakage or rupture of the contents of comedones into the dermis causes inflammatory acne lesions, including papules, pustules, nodules, and cysts. Although P acnes is a live bacterium in the follicle, it dies when the disruption occurs and acts only to increase the inflammatory process. Therefore, uncomplicated inflammatory acne is a sterile inflammatory condition and not a skin infection.
Correct classification of the types of lesions is essential for choosing the most effective therapy. This can be confusing, because there are a number of different classification systems for acne. Acne can be classified by severity, morphology, and the presence or absence of inflammation. See Table 1 for a classification system based on acne severity created by a consensus conference of the American Academy of Dermatology. [26]
| Severity | Papules/Pustules | Nodules |
|---|---|---|
| Mild | Few to several | None |
| Moderate | Several to many | Few to several |
| Severe | Numerous or extensive | Many |
The closed comedone, or whitehead is a flesh-colored or whitish, slightly palpable lesion that is approximately 1 to 3 mm in diameter. The open comedone, or blackhead, is a flat or slightly raised, brownish or black lesion that measures up to 5 mm in diameter (Fig. 1) .
Figure 1. Comedonal acne:
obstructive and noninflammatory.
Acne papules are pinkish or reddish inflammatory lesions that range in size from 2 to 5 mm in diameter. Pustules are superficial papules containing grossly purulent material. Acne nodules are solid, raised inflammatory lesions that exceed 5 mm in diameter and are situated deeper in the dermis than papules. The acne cyst is actually a large nodule that has suppurated and become fluctuant. Large, deep, inflammatory nodules are referred to as cysts because of the resemblance to inflamed epidermal cysts. [22] Most of these, however, are not true epithelial cysts. True cysts with an epithelial lining do occur occasionally after a deep nodule heals, even though what is termed cystic acne has few true cysts. For that reason the consensus group prefers to use the term nodular acne rather than cystic acne. You will continue to see both terms used in the literature. Acne scars represent possible sequelae of inflammatory acne and may appear as small, deep, punched-out pits (ice-pick scars), atrophic macules, hypertrophic scars, or broad, sloping depressions.
Severe forms of acne include acne conglobata, acne fulminans, gram-negative folliculitis, and pyoderma faciale. Acne conglobata has epithelial-lined sinus tracks. It is the most severe form of acne, with large, deep nodules, cysts, ulcers, abscesses, sinus tracks, scars and many blackheads. Untreated, this causes severe scarring and keloid formation. Acne fulminans is a severely destructive form of acne that has ulcerations along with fever and arthralgia. Gram-negative folliculitis is a rare complication of long-term oral antibiotic use for treating inflammatory acne. Pyoderma faciale affects only adult women and is notable for severe cysts and sinus tracks on the face.
The consensus panel also recommended a classification system that includes an evaluation of lesions and their complications such as drainage, hemorrhage, and pain. It is suggested that the global evaluation take into account the total impact of the disease. Therefore, psychosocial impact, failure to respond to the previous therapies, and occupational disability are three additional factors to be used in grading acne (Fig. 2) . [1]
Figure 2. Young woman with inflammatory acne. She is a good candidate for hormonal
therapy if she wants pregnancy prevention.
The goals of acne treatment are to lessen physical discomfort from inflamed lesions, to improve the patient's appearance, to avoid any potential adverse psychological impact, and to prevent or minimize any scarring that may occur. Treatment is directed both at preventing acne lesions as well as treating those that do occur.
Acne can be painful both physically and psychologically. Inflamed lesions can hurt and acne breakouts can result in low self-esteem, loss of self-confidence, social isolation, and depression. Scarring is an important physical and psychosocial sequela of acne that occurs in a small percentage of patients with severe inflammatory acne. Acne generally is not cured, therefore the patient needs to understand that the goal of acne treatment is to reduce the frequency and severity of exacerbations. Attempts at scar revision are best limited to patients with significant scarring, whose acne is quiescent or well controlled. In addition, revision of scars should be delayed at least one year to permit the scars to evolve to their final appearance.
Medications for Acne Therapy
It is important to understand the role of the vehicle in choosing topical therapeutic agents. The vehicle is the substance in which the active agent is dispersed. The most commonly used vehicles are creams, ointments, gels, solutions, and lotions. The vehicle affects the potency of the active agent, because it determines the rate at which the active agent is absorbed through the skin. The choice of vehicle is influenced by a variety of factors including characteristics of the skin (dry or oily), the site involved, patient preferences, and even the climate and humidity. [16]
Benzoyl PeroxideBenzoyl peroxide is an organic peroxide that works primarily as an antibacterial agent (being bacteriocidal for P acnes), although it also possesses mild comedolytic properties. At a time where there is increasing resistance of P acnes to antibiotics, [18] benzoyl peroxide has the advantage of being a bacteriocidal through a direct toxic effect. It is available in a variety of concentrations (2.5%, 5%, 10%) and formulations, including lotions, creams, and gels. Because benzoyl peroxide is available in a number of over-the-counter medications, many patients have tried them before seeing a physician. There is little evidence that 10% is better than 2.5% or 5%, and it may be more irritating. [23] A thin film of a low-strength (2.5 or 5%) preparation is applied typically once or twice daily. Benzoyl peroxide can initially irritate the skin, resulting in mild redness and scaling, but this typically improves with continued use. Contact allergy occurs in 1% to 2% percent of patients. The water-based preparations are less irritating. Desquam-E comes in an emollient base and may be less irritating. Benzoyl peroxide is more effective when it is combined with erythromycin in a formulation called Benzamycin. [3]
RetinoidsTopical tretinoin (or Retin-A) is a retinoid, a derivative of vitamin A. It is a comedolytic agent that works by normalizing desquamation of the follicular epithelium. Its value in acne therapy stems from its ability to prevent the formation of new comedones and to eliminate those already present. Topical tretinoin can actually produce an acne flare-up with its initial use.
Skin irritation and photosensitivity are the main side-effects of topical tretinoin. Most patients experience some skin irritation. The increase in photosensitivity is controversial. [30] Tretinoin does induce a slight thinning of the stratum corneum layer that provides much of the blockage from ultraviolet ray penetration. Patients treated with topical tretinoin should be advised to avoid excessive sun exposure and to use protective hats, clothing, and sunscreens (sun protection factor (SPF) greater than 15).
Tretinoin is available in creams at concentrations of 0.025%, 0.05%, and 0.1%. Gel formulations of 0.01% and 0.025% are felt to be equivalent to the stronger two cream forms in potency. Tretinoin is also available in a 0.05% liquid. The potential for skin irritation is dose dependent, therefore those with sensitive skin and those first starting the treatment tolerate it better in lower concentrations and in less irritating bases.
It is advisable to initiate treatment for patients with fair or sensitive skin with the lowest strength cream preparation (0.025%) on an every other night or twice weekly basis, because this preparation is the least irritating. The liquid preparation is the most irritating and generally is reserved for patients with recalcitrant lesions. The skin should be washed before bedtime and allowed to dry for 30 minutes before tretinoin is applied. Allowing the skin to dry decreases the depth of tretinoin absorption and serves to reduce skin irritation without diminishing efficacy.
When prescribing Retin-A (tretinoin), it is important to inform the patient that redness and scaling may occur and that the acne may worsen during the first 2 to 4 weeks. For most patients, it helps to start with the mildest formulation, 0.025% cream. One may then increase to 0.05% to 0.1% cream if needed and tolerated. For oily skin and more severe acne, it may help to switch to the gel.
Tretinoin is partially inactivated by ultraviolet light exposure and is best applied at night. It should not be caked into skin folds around the nose or eyes, because that may produce significant irritation. Because it is oxidized by benzoyl peroxide, these two agents should not be applied at the same time of day.
Although there is no good evidence for teratogenicity of the topical retinoids, there is strong evidence for the teratogenicity of oral retinoids. Even though systemic absorption of topical retinoids is minimal, it is best to avoid them in pregnant women or women trying to become pregnant.
Retin-A Micro and RenovaTretinoin 0.1% gel has become available as Retin-A Micro, a time-release microsponge delivery system that also causes less irritation than previously available formulations. [10] In the microsphere formulation, the drug is entrapped in a microscopic particle (referred to as a microsponge), which localizes to the follicle after topical application and releases the tretinoin. It is theorized that the delivery of higher concentrations of tretinoin more selectively to the follicle reduces the potential for cutaneous irritation [30] permitting its initiation at a higher concentration and eliminating the need for delaying its application after washing. Topical tretinoin also is available in a more moisturizing base as Renova. This formulation, which is approved for the cosmetic treatment of photodamaged skin, may be of value in selected acne patients experiencing significant problems with skin dryness.
Adapalene Gel (Differin)Adapalene gel is a recently introduced naphthoic acid, with potent retinoid activity similar to topical tretinoin. In a meta-analysis of five randomized trials reported by Cunliffe et al, [9] adapalene 0.1% gel was found to be just as efficacious as tretinoin 0.025% gel, with more rapid efficacy and greater tolerability. In two randomized comparative studies reported by Galvin et al, [13] adapalene 0.1% gel produced significantly less skin irritation than six formulations of tretinoin including the 0.025% cream and the 0.1% microsphere gel. In fact, adapalene was no more irritating than petrolatum.
Grosshan and colleagues [15] evaluated the clinical efficacy and safety of adapalene 0.1% gel versus tretinoin 0.025% gel, with particular reference to the onset of action and impact on quality of life. They found that adapalene reduced inflammatory and total lesion counts more rapidly than tretinoin, and this was matched by earlier and greater quality of life improvements. This more rapid onset of action may improve compliance in adolescent patients looking for a speedy resolution of their acne. [15]
Adapalene 0.1% gel also has been shown to have a low skin irritation potential, even when applied immediately after washing. [8] This is a significant improvement over tretinoin, which should be applied only after waiting 20 minutes after washing the face. Adapalene reduces both inflammatory and noninflammatory lesions and may be a good monotherapy in mild forms of acne. [8]
As with tretinoin, adapalene is applied once a day as a thin film at bedtime, avoiding the sensitive areas around the eyes, lips, and mucous membranes. Similar to tretinoin, the patient's acne may worsen the first few weeks of therapy. Because of its direct anti-inflammatory effect, adapalene does show a more rapid rate of improvement in inflamed lesions early on as compared with tretinoin. [8] Adapalene is incorporated into microcrystals ranging in size from 3 to 10 mum to achieve specific follicular targeting. This is similar to the mechanism used in the new tretinoin in microspheres. As for tretinoin, patients should be advised to minimize exposure to either sunlight or artificial ultraviolet irradiation.
TazaroteneBetter known for its use in the treatment of plaque psoriasis, topical tazarotene (Tazorac) is a synthetic retinoid that possesses comedolytic properties and carries FDA approval for the treatment of mild to moderate facial acne. [12] Available commercially as a 0.05% and 0.1% gel applied once daily in the evenings, tazarotene, like all retinoids, is associated with skin irritation. Experience with this agent in acne patients is limited and it appears to offer no advantage over tretinoin or adapalene.
Azelaic AcidA relatively new agent for the treatment of acne is 20% azelaic acid (Azelex cream). Azelaic acid is a naturally occurring substance found in wheat, rye, and barley. Available outside the United States since 1989, azelaic acid did not receive FDA approval until 1996. Possessing both antimicrobial and comedolytic properties, azelaic acid appears to be as effective as topical tretinoin, benzoyl peroxide, and topical erythromycin. [2] [11]
Azelex is applied either twice daily or applied in the morning, coupled with the application of topical retinoid at night. There is some evidence that a synergistic effect may occur when both Azelex and Retin-A are used within the same day on a daily basis.
When applied in a 20% concentration in a cream, Azelex normalizes the follicular keratinization process and reduces the concentration of P acnes in the pilosebaceous unit. As a result, Azelex has a therapeutic role for both comedonal and inflammatory acne. Unlike the situation with topical antibiotics, resistant strains of P acnes to azelaic acid have not thus far been reported.
Azelex is moisturizing and, unlike retinoid therapy, does not produce photosensitivity. Azelaic acid cream causes mild skin irritation in only 5% to 10% of patients. [11] [28] It is a good choice for acne patients with either dry skin or those with fair skin who are unable (or unwilling) to avoid a significant amount of sun exposure. Itching, burning, and stinging are the most common adverse effects and tend to become diminished after 4 weeks of daily use. Azelex offers the added potential benefit of reducing the postinflammatory hyperpigmentation caused by inflammatory acne (and other conditions) (Fig. 3) . Care must be used in patients with dark skin because it may cause hypopigmentation in normal skin.
Figure 3. Perioral acne in a
26-year-old woman with post-inflammatory hyperpigmentation. The patient is a
good candidate for treatment with azelaic acid.
The value of antibiotics in the treatment of acne rests in their ability to inhibit the growth and activity of P acnes. The development of topical antibiotics was spurred by the discovery of the high degree of effectiveness of oral clindamycin in acne patients coupled with the recognition of pseudomembranous colitis as a complication of systemic clindamycin use. The main two antibiotics used in the topical treatment of acne are clindamycin and erythromycin. Both are available in a variety of gels, creams, lotions, solutions, and pads, and generally are fairly close to oral antibiotics in their effectiveness. Which form, oral or topical, the patient prefers, therefore, may dictate the choice of delivery, because patient compliance usually is better if the patient is more comfortable with the treatment. Although there is no evidence that their concomitant use is therapeutically advantageous directly, topical antibiotics often are prescribed concurrently with an oral antibiotic in the hopes of facilitating the tapering of the oral antibiotic once the desired result is achieved. Pseudomembranous colitis has been reported from use of topical clindamycin, but this appears to be a rare event.
Generic erythromycin preparations are less expensive than clindamycin preparations, which are available only as name brand products. Topical clindamycin and erythromycin are equally effective. Both of these agents are applied twice daily to the affected areas. Resistance of P acnes to erythromycin is encountered frequently after 6 months of therapy.
BenzamycinA useful combination product for the treatment of acne is Benzamycin, a preparation that combines 5% benzoyl peroxide and 3% erythromycin. Studies suggest that this combination is more effective than either of the two ingredients used alone. [3] A study by Eady and colleagues [9] suggests that the combination of 5% benzoyl peroxide and 3% erythromycin has greater in vivo anti-propionibacterial activity than erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin-resistant P acnes pretreatment. The proposed mechanism for the synergy is that the benzoyl peroxide limits the development of resistance of P acnes to the erythromycin, because benzoyl peroxide kills bacteria by direct toxicity. A potential disadvantage of this product (especially while traveling) is the need to keep it refrigerated.
Oral antibiotics act by limiting the proliferation of P acnes and decreasing inflammation. [8] These antibiotics are used to treat inflammatory acne only and have no place in the treatment of pure comedonal acne. Although P acnes strains have become increasingly more resistant over time, the exact clinical significance of this is still uncertain. [4] [5] [7]
Tetracycline is inexpensive but has the tremendous disadvantage of needing to be taken on an empty stomach. Timing the doses to avoid food and milk can be very difficult for teenagers and working adults. It causes photosensitivity in about one person in a thousand. The usual starting dose is 500 mg bid. It needs to be taken on an empty stomach to maximize its absorption. Once or twice daily dosing is deemed adequate, because tetracycline accumulates in the pilosebaceous unit, thus there is no need to maintain a blood level of the antibiotic.
Other antibiotics used in acne treatment include doxycycline, minocycline, erythromycin, and trimethoprim-sulfamethoxazole. Doxycycline and minocycline are derivatives of tetracycline that are effective in the treatment of acne. Doxycycline and minocycline can both be taken with food. Doxycycline's main limitation is a higher incidence of associated photosensitivity. Minocycline has a much lower risk of photosensitivity. Unfortunately, it is considerably more expensive than tetracycline and is associated with dizziness in 6% of users. Antibiotic resistance of P acnes to minocycline remains uncommon and thus minocycline is felt to be of particular value in acne patients with strains of P acnes demonstrating antibiotic resistance.
Minocycline is very lipophilic and is the most potent oral antibiotic for acne. Because P acnes resistance to it remains rare, [19] minocycline is of particular value for patients with treatment-resistant inflammatory acne stemming from antibiotic resistance. Enthusiasm for its use is curbed not only because of its cost but also because of its potential for side-effects, which include central nervous system symptoms (e.g., dizziness, ataxia, vertigo), mucocutaneous pigmentary changes, and possibly an increased risk of drug-induced liver toxicity and systemic lupus erythematosus. [27]
Erythromycin can be taken with food and does not cause photosensitivity, but gastrointestinal intolerance is a common problem. Trimethoprim-sulfamethoxazole is an effective agent, but its potential for serious side-effects generally limits its use. Occasionally, it is used in patients with acne resistant to erythromycin and tetracyclines and patients with gram-negative folliculitis.
Regardless of the antibiotic chosen, when desired acne control is attained, the dosage should be gradually tapered over 2 to 4 months to the lowest maintenance dose required to maintain control. Patients can be instructed to increase their dose at the first sign of a flare-up. Gram-negative folliculitis is a superinfection seen in 1% to 4% of patients on long-term antibiotic therapy. Tetracycline, doxycycline, and minocycline are contraindicated in pregnant patients and in young children, because these antibiotics may stain developing teeth. Tetracyclines may be used in children after the permanent teeth are in place.
There are concerns about the potential of these antibiotics to decrease the efficacy of the oral contraceptive pill. Helms [17] performed a study that showed that women taking antibiotics had oral contraceptive pill failure rates of 1.6% versus 1% without. Although this difference was not statistically different, it is advisable to warn patients about the slight chance that daily antibiotics may interfere with the efficacy of the birth control pill. [17]
Oral Isotretinoin (Accutane)Isotretinoin (Accutane) is the only acne treatment that can alter the natural history of the disease. It is a highly effective acne treatment that often produces prolonged remissions following a successful course of therapy. Up to 90% of patients with severe acne have a complete or almost complete remission with a 12 to 16 week course of Accutane. [28]
Accutane is indicated for patients with acne that is unresponsive to conventional therapy, who have either severe, nodulocystic acne, or who have moderate to severe, noncystic, inflammatory acne that has the potential for scarring (Fig. 4 and Color Plate 1, Fig. 1) . Isotretinoin is capable of reversing all of the pathogenic events responsible for acne, resulting in an involution of sebaceous glands, a lowering of intrafollicular bacterial counts, a reversal of retention hyperkeratosis, and a direct decrease in inflammation (Fig. 5) .
Figure 4. A 14-year-old boy with
moderately severe inflammatory acne. See also Color Plate 1,
Figure 1.
Figure 5. A, A 34-year-old woman with severe nodulocystic acne. A great
candidate for Accutane and reliable birth control.
B, After completion of 20 weeks of Accutane therapy.
A number of groups have published criteria for the use of isotretinoin that go beyond the strict FDA approved indications. [23] [24] [28] These criteria include:
severe nodular (cystic) acne with scarring acne that improves less than 50% after 6 months of
local and systemic antibiotic therapy moderate acne persisting with significant atrophic
scarring or significant psychological distress acne fulminans gram-negative folliculitis pyoderma faciale inflammatory rosacea hidradenitis suppurativaThe usual recommended daily dosage of isotretinoin is 0.5 to 1.0 mg/kg per day. A dose of 2 mg/kg may be required in resistant cases or patients with severe predominantly truncal acne. During treatment, the dose can be modified according to the clinical response or the appearance of side-effects, most of which are dose related (Table 2) . The drug should be taken once or twice daily for 16 to 20 weeks.
White [31] studied recurrence rates after the first course of isotretinoin in patients seen at Kaiser Permanente. One hundred fifty-four patients received a total dose of at least 100 mg per kilogram. The outcomes were:
39% had no recurrence of acne 16.9% required topical therapy 25.3% required the use of antibiotics plus topical
therapy 18.8% required an additional course of isotretinoin.Higher relapse rates have been found among preteens and young teenagers with nodular acne, patients receiving a total dose of less than 100 mg/kg, patients with personal or family history of sinus tract disease of the skin, and patients with severe truncal acne. [20] [21] [31]
For patients failing to achieve an adequate response, the standard of care is to wait 2 or more months before retreatment. Some physicians, however, will delay retreatment for at least 4 to 5 months after the initial course of therapy, because patients may continue to show improvement during this post-treatment interval.
Adverse reactions to isotretinoin are frequent. Nearly all patients experience some type of mucocutaneous side-effects. These include cheilitis, blepharoconjunctivitis, epistaxis, xerosis, and photosensitivity. These generally are managed by the use of topical emollients, artificial tears, sunscreens, or dose reduction. Less common side-effects include arthralgias and myalgias, headache, hair loss, diminished night vision and, rarely, the development of pseudotumor cerebri. Pseudotumor cerebri may be more common when tetracycline is administered simultaneously. Musculoskeletal symptoms are common in gymnasts, competitive ice skaters, ballet students, and long distance runners. [21]
Laboratory changes associated with isotretinoin include hypertriglyceridemia, elevated total cholesterol, reduced high-density lipoprotein levels, and abnormalities in liver function tests and hematologic parameters. Careful clinical and laboratory monitoring (particularly of lipid levels and liver function) is needed before and during treatment.
Isotretinoin is highly teratogenic and is associated with the development of a number of major fetal malformations that include central nervous system abnormalities (e.g., hydrocephalus, microcephalus, cerebellar malformation, and cranial nerve deficit), facial dysmorphia, external ear and eye abnormalities, and cardiovascular abnormalities. [19] Isotretinoin is absolutely contraindicated before or during pregnancy. It is essential that women of reproductive age observe strict contraceptive precautions during and for at least 1 month following completion of therapy. Women of reproductive age should have a pregnancy test performed before starting therapy and monthly during therapy. This also is true for adolescent girls, who claim they are not sexually active, because this may change during the months while the patient is on isotretinoin.
Estrogen at a sufficient dosage can reduce sebum production and improve acne by increasing sex hormone-binding globulin resulting in reduction of serum free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) levels. Estrogen in combination with a progestin agent with low androgenicity (i.e., ethynodiol diacetate, norgestimate, and desogestrel) in the form of the birth control pill can be of value in the management of acne in women. The triphasic oral contraceptive formulation, which combines ethinyl estradiol with norgestimate was recently approved by the FDA for the treatment of acne vulgaris. Redmond [25] and associates reported this to be 83% effective for patients with moderate acne. Oral contraceptive pills with low androgenicity may be given to women to prevent acne or as an adjunctive treatment in women who have acne and have birth control needs. There is no role for the use of estrogen in male patients.
Acne Therapy by Severity
Tretinoin or adapalene (Retin-A or
Differin) Azelaic acid (Azelex) Benzoyl peroxide bid No oral antibiotics Topical antibiotics and benzoyl
peroxide (Benzamycin) May add oral antibiotics if topical agents are not working Tretinoin or adapalene (Retin-A or Differin) Azelaic acid (Azelex) May start with topical antibiotic,
benzoyl peroxide, and oral antibiotic Oral antibiotics often essential at this stage Tretinoin or adapalene (Retin-A or Differin) Consider stopping oral antibiotics when topical agents are
working well Consider birth control pills in women Consider isotretinoin (Accutane), if other therapies are
not working in 6 months May try all therapies on list
above for moderate grade Isotretinoin (Accutane) Oral steroids and isotretinoinThe treatment of comedonal, or obstructive acne, begins with the use of comedolytic agents that attempt to correct the abnormal follicular keratinization process. Although the primary agent available for the treatment of this type of acne for decades has been tretinoin (Retin-A), adapalene (Differin) may be a less irritating alternative. Other topical agents that may be of benefit include benzoyl peroxide, azelaic acid or alpha-hydroxy acids. It may also help to avoid agents that are comedogenic, such as certain makeup and moisturizers. If required, synergism can be achieved with these agents by coupling the use of a retinoid with benzoyl peroxide or with azelaic acid.
The main factor in the development of inflammatory acne is the bacterial growth and activity of P acnes in the pilosebaceous unit. Prevention and treatment of inflammatory acne is directed primarily at reducing P acnes. This can be accomplished with the use of antibiotics (topical or oral), benzoyl peroxide, or azelaic acid.
Oral tetracycline has been the mainstay in the treatment of inflammatory acne for over three decades, although it has never been approved by the FDA for this purpose. Alternative oral antibiotics that are used in the treatment of inflammatory acne are erythromycin, doxycycline, and minocycline.
Patients with severe nodulocystic acne refractory to standard therapy and those patients with severe acne variants generally are best managed by a dermatologist or a primary care physician experienced in the treatment of acne. Full combination therapy for acne consists of a systemic antibiotic, Retin-A or Differin, and benzoyl peroxide or Azelex. If this fails, oral isotretinoin (Accutane), the most effective of all acne treatments, should be considered.
Accutane is the only agent that significantly alters the course of the disease in those who have severe inflammatory acne. It is capable of providing long-term remission of the disease and may even cure it. The severity and frequency of its side-effects, however, limit its use.
Acne fulminans may be treated with oral steroids and oral antibiotics before isotretinoin. [1] In fact acne fulminans can be precipitated by isotretinoin, so it helps to treat the acute inflammation and infection before starting isotretinoin to deal with the underlying pathologic mechanisms.
Manual extraction of comedones is a simple office procedure that relieves the obstruction of acne lesions. The open or closed comedone is opened first with the tip of a #11 scalpel blade or a 25-gauge needle. Local anesthesia is not needed. Then a comedone extractor is used to apply gentle pressure evenly around the peripheral margins of the comedone expressing the contents of the blocked sebaceous follicle. Both open and closed comedones can be extracted manually by applying gentle pressure with a comedo extractor, the opening of an eyedropper, or a paper clip bent into a small circle.
Intralesional steroid injection is an important adjunct in the management of painful nodulocystic acne lesions. It offers the potential for a rapid reduction in pain and swelling and may reduce the likelihood of scarring. A 30-gauge needle is used to inject a solution containing 1 to 2 mg/mL of triamcinolone acetonide. This solution is made up by diluting 3 mg/mL or 10 mg/mL triamcinolone acetonide with either normal saline or lidocaine. It is important to dilute the steroid to reduce the risk of steroid-induced skin changes (e.g., atrophy, telangiectasia, and hypopigmentation). Approximately 0.05 to 0.3 mL is injected into the cavity of the acne lesion until it is slightly distended (Fig. 6) . One injection site per acne cyst should be adequate. Injections can be repeated after 3 weeks.
Figure 6. Intralesional steroid
injection of a painful acne nodule.
Using the dilute solution and injecting the minimum amount required reduces the risk of steroid-induced skin changes (atrophy, telangiectasia, and pigmentary changes). Adrenal suppression can be avoided by administering no more than 20 mg at a time.
Various options exist for the management of postinflammatory acne scarring. The type of scar determines the choice of treatment. Patients may be referred to dermatologists for chemical peels, collagen injections or dermabrasion.
Successful acne management has its roots in patient education and promotion of compliance. Sufficient time should be allotted at the initial visit to explain the pathogenesis of acne and the rationale behind its treatment. It is important that the patient is made to feel like an active participant in his or her own care and that the physician be viewed as a caring and interested ally. Follow-up visits should be routinely scheduled at regular intervals to monitor therapy and to respond to questions or concerns that may arise.
Important points of information that is important to convey to the patient include:
In the current health care system, it is not unusual for health insurance to not cover the newest topical agents for acne. Because a tube of Azelex or Differin can cost over $40, it is important to discuss the cost issue with patients. Some patients may then prefer other covered medications to avoid the cost of uncovered treatments. Adherence to acne therapy can be maximized when insurance coverage and cost of medications are taken into account when prescribing long-term medications.
Acne is a very common condition seen daily in primary care. The primary care physician can have a large impact on patients with acne by properly classifying the type of acne and successfully treating the acne based on its severity. Reduction of acne lesions provides great psychological and physical benefits to these patients. By understanding how acne develops, its many manifestations and treatment options, the primary care physician can become an expert in acne diagnosis and treatment.
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