[The Physician and Sportsmedicine]

Aggressive Acne Treatment: As Simple as One, Two, Three?

Ronald C. Savin, MD; Lisa M. Donofrio, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 24 - NO. 9 - SEPTEMBER 96

In Brief: Too often acne treatment focuses on diminishing lesions without considering what an active patient really wants: completely clear skin. In addition to benzoyl peroxide cleansing and topical acne medication, a three-tier approach of oral agents often achieves clear skin regardless of the severity of acne. Tetracycline is the first line of treatment, followed by minocycline if the first drug is not effective. If these two antibiotics fail to clear the acne, isotretinoin can be highly effective--but patients need to know that the drug produces birth defects in almost all women who take the drug while pregnant.

Acne is a common affliction that causes discomfort in almost all age-groups, sparing only the very old and the very young. It occurs any time after puberty, frequently in the teens. Consequently, it can be of special concern to athletes. Those who must expose large areas of skin (like gymnasts, wrestlers, swimmers, and body builders) and have acne on their trunk may refuse to compete. In addition, acne induced by oral anabolic steroids is of real concern and may be highly resistant to treatment. Also, football players wearing shoulder pads and sweating in the hot summer months suffer pain and bursting of cysts where the straps touch the skin.

The treatment of acne should involve both topical and oral acne medications. Though topical therapy alone is beneficial, it will not clear the skin of acne in most patients. People afflicted with acne suffer from an embarrassing, potentially disfiguring disease and, therefore, want and expect not just improved skin, but clear skin.

We advocate an aggressive therapeutic strategy; it incorporates systemic medication from the beginning and increases the therapeutic effort as needed. It is a progressive "1-2-3" approach consisting of

  1. tetracycline hydrochloride,
  2. minocycline, and, if needed,
  3. isotretinoin.

Acne Types

Acne vulgaris can be classified into three basic types, or grades (see also "Acne Variants: Recognition and Treatment," below). Grade 1 or comedonal acne vulgaris consists of inspissated sebum and epithelial cell plugs, commonly called "blackheads," that have a patent lumen. The pathogenesis of this type of acne lies in the formation of the microcomedo. Cells that line the follicular epithelium become excessively "sticky," limiting the pore's ability to clear the oils that accumulate, adding to the plug.

Acne Variants: Recognition and Treatment

Acne rosacea is a variant that typically causes a red nose and is more common in older people than in young people. It is heralded by four types of lesions: telangiectasia, pustules, firm papules, and glandular hyperplasia. The glandular hyperplasia causes an enlargement of the nose in older persons that is called rhinophyma. Treatment of this disfigurement requires surgical "sculpting" measures that employ dermabrasion, cold knife, or laser modalities. The telangiectatic form of acne rosacea can mimic the butterfly rash of lupus erythematosus, but it rarely exists without concomitant papules or pustules. Treatment consists of judicious, short-term use of very low potency, topical cortisones in combination with topical metronidazole and oral tetracycline. The latter two medications are continued until clearing and then tapered. Recalcitrant cases require prolonged and high-dose oral antibiotics and, in rare cases, isotretinoin.

Two common variations of acne rosacea occur. The first is steroid rosacea caused by the continual topical application of medium-to-high-potency corticosteroids to the face; this problem is usually iatrogenic. Treatment of steroid rosacea involves removal of the offending agent, often in combination with the use of cortisones, metronidazole, and tetracycline.

Perioral dermatitis is a bumpy, papular, sometimes pruritic rash localized to the area around the mouth and eyelids. Perioral dermatitis is of unknown cause but may be related to toothpaste irritation; discontinuation of the current brand often yields improvement (authors' own observation). Perioral dermatitis is cleared and well-controlled with tetracycline. In the pediatric population, topical and oral erythromycin should be used to control perioral dermatitis.

Acne cosmetica is acne that occurs as a result of heavy makeup or hair pomatum use (1). It typically occurs in female patients and consists of multiple, small, closed comedones with very little inflammation. When this condition is secondary to pomatum use, primarily the forehead is involved. Therapies as described above that are directed at a loosening of the keratin/sebaceous plug are helpful, but true clearing is achieved by changing cosmetics to noncomedogenic brands.

Reference

  1. Arnold HL, Odom RB, James WD (eds): Andrews' Diseases of the Skin. Philadelphia, WB Saunders Co, 1990, p 260

The comedo is a noninflammatory lesion, and treatment should be directed at controlling sebum production and loosening the accumulated debris. Keratolytic agents (which dissolve keratin) are most appropriate in this setting. They include topical retinoic acid, salicylic acid, and glycolic acid (1,2). All three of these agents can cause irritation, so the chosen drug should be started at the lowest concentration initially and increased as tolerated. Once the keratin plug is loosened, it will rub out or can be readily removed with a comedo extractor.

Grade 2 or papular acne vulgaris consists of red bumps and pustules with or without clinically evident comedones (figure 1: not shown). The pathogenesis again lies in the microcomedo, but in this situation the follicular contents rupture into the dermis, leading to varying degrees of inflammation (3). The role of bacteria is uncertain. The population of Propionibacterium acnes, a commonly associated pathogen, is not greater on acne-prone skin than on normal skin (4). In fact, when factors such as sebum production and P. acnes population are compared in patients with and without acne, differences are difficult to detect (5).

Grade 2 acne, however, frequently responds to both topical and oral antibiotic medications, apparently because of their ability to moderate inflammatory mediators (6,7). Oral tetracycline and its pharmacologic derivatives are most commonly used to treat this grade of acne. All such medications require 5 months (sometimes less) to produce clinical improvement, and all are contraindicated in pregnancy and early childhood because of their deposition in the teeth and bones of the developing fetus.

Grade 3 or cystic acne vulgaris consists of the above lesions in the presence of fluctuant cysts. This is typically a scarring form of acne that is best treated by a physician trained in administration of aggressive antiacne therapies. Often the inflammatory cysts are loculated and need to be drained in the office. Other employed modalities include intralesional injections of very dilute corticosteroid solutions. Patients with this type of acne need to be started on high doses of antibiotics or eventually, if conventional therapy fails, isotretinoin.

How long a patient will be troubled with acne is nearly impossible to predict. Sometimes, patients believe they have some other disease because the acne persists for so long. In the end, they are disappointed and frustrated to learn that it is only common acne for which they have delayed therapy, and therefore endured embarrassment and increased scarring.

Acne Factors

The importance of diet as a contributing factor in acne has been overemphasized; it is probably unimportant. The danger of consuming chocolate, cola, nuts, milk, and greasy, fried, and spicy foods has been talked about so long and so loudly that it is accepted as a truism, but there are no well-controlled scientific investigations establishing that diet contributes to acne.

As a general rule, if any foods appear to make the acne worse, they should be eliminated from the diet for a while and then tried again. If the acne recurs, the patient should permanently eliminate these foods from the diet.

Poor hygiene is often blamed for causing acne, but acne is not caused by the transmission of dirt to the face via the hands. Neat and clean teenagers and adults suffer from acne to the same degree as those who are sloppy. Nevertheless, frequent cleansing is extremely helpful in removing skin oils--a vital part of acne therapy.

Nervousness and anxiety are often incriminated as the cause of acne, but this is simply not true. Anxiety may, however, increase picking or excoriation because of intolerance and frustration with the acne.

Flare-ups related to the menstrual cycle are common. The frequency and regularity vary, but acne may worsen before, during, or after the menstrual period. In some women, acne will flare during the middle of the cycle. Obviously, this is due to a hormonal influence, but one that is irregular, unpredictable, and scientifically undefined.

Scarring--permanent dents and depressions due to deep acne--can be prevented and minimized by early facial care at home and dermatologic care in the office. Not all acne lesions result in scarring; the reason for the selectivity is unknown. Some large acne cysts leave no residual marks while other tiny acne lesions produce prominent scars. Because the correction of postacne scarring is difficult, early treatment of acne is vital.

One-Two-Three Treatment

The pharmacologic treatment of acne can be separated into three categories: topical agents, systemic antibiotics, and isotretinoin. In common practice, therapy for acne generally involves putting a patient on topical agents (some of which are a little better than others) with little or no follow-up and little or no clearing. Complete clearing is uncommon.

Some general physicians and dermatologists use systemic antibiotics, often with little follow-up. Patients who do not clear are often either continued on antibiotics or switched from antibiotic to antibiotic. Personal experience indicates that only a limited number of physicians use isotretinoin without having the patient try one less effective drug after another for years without achieving clearing.

A progressive schedule for clearing acne with oral medication can be called Acne 1-2-3. The three steps involve tetracycline, minocycline, and, if warranted, isotretinoin. Most other acne treatments (eg, topical creams), even if they are vigorously and aggressively applied, are of minimal benefit compared with the ultimate results delivered by Acne 1-2-3.

Topical therapies for acne are useful, and they help to reduce pimple formation, but they do not clear the skin for most patients. A good acne topical medication may produce 70% improvement. But if you started with 40 lesions on your face (not an unusual number), and took away 28 (70%), would you want to go on a date with 12 pimples on your face? Yet, that is said to make it an "effective medication."

The standard for clear skin is, in fact, the pimple-free complexion of every model in fashion magazines. That's the goal that every person who has acne wants to achieve, and most can with Acne 1-2-3.

Topical foundation. Every patient is first put on a topical program consisting of a benzoyl peroxide wash used twice daily followed by a common acne topical medication such as benzoyl peroxide, erythromycin, or clindamycin. Tretinoin is a useful alternative. For very mild cases, topical medication alone is occasionally effective and should be used for at least 3 months. In addition, topical medication is important in conjunction with systemic medication to achieve an additive effect. Therefore, every patient gets concomitant topical therapy, but the principal weapon in all but very mild cases is systemic medication.

Step 1. Systemic medication can be started as soon as topical medication is begun. Tetracycline is taken 1 g daily for 5 months. It is effective and inexpensive, and often takes 5 months or more to achieve clear, smooth skin. Tetracycline needs to be taken without milk. Vaginal candidiasis is a common side effect, but it can be controlled easily with medication. Sun sensitivity is uncommon. Tetracycline and its analogues should not be taken during pregnancy.

Step 2. If the skin does not clear with tetracycline therapy, minocycline 100 mg twice a day is taken, also for 5 months. It is more effective and easier to administer than tetracycline, and it has fewer side effects (possible ones include vaginitis and, rarely, sun sensitivity). Minocycline is very effective and can be taken with milk, but it costs about $60 per month. Vertigo occurs initially in some patients, but it usually wears off within a few days.

Another second-stage medication is doxycycline. This agent is probably as effective as minocycline, but it produces sun sensitivity in a relatively high percentage of patients. Doxycycline is taken in a dose of 100 mg twice a day and is reasonable in price, but sun sensitivity is a nuisance in warm weather.

Step 3. If none of the antibiotics clears the patient's skin in 5 or 10 months (or more if the physician wants to extend the trial period), the next step is isotretinoin. We realize that isotretinoin is controversial and needs to be dispensed by an experienced and careful physician. Nevertheless, if the acne is more than mild, offensive to the patient, and requires long-term therapy, then isotretinoin will not only clear the skin but will usually cure the patient. It is a wonderful medicine, but--like a sharp knife--must be used carefully.

Isotretinoin, an oral retinoid, decreases the size of the sebaceous glands and moderates production of sebum (8). It also possesses anti-inflammatory effects and decreases follicular keratin plugging (9,10). The treatment period is 20 weeks at an effective dose of 1 mg/kg/day. This translates to a dose of 60 to 80 mg/day for most patients.

Unfortunately, the side effects of isotretinoin are many. Most patients complain of excessively dry skin and eyes, frequent nosebleeds, and muscle aches. Our experience shows that in about 10% of patients, these symptoms are severe but can be managed by such steps as using emollients for dry skin and dry lips. Clinical experience also indicates that significant muscle aches occur in 1 out of 12 patients, but aches that are severe or require discontinuation of the drug occur in very few (1 in 50). Muscle aches are usually not a problem for active patients, but very competitive athletes may want to postpone isotretinoin treatment until after the season. Elevated triglycerides are a potentially serious complication, but not in young people. Blood tests need to be taken monthly during medication usage.

Note: The most serious risk of isotretinoin therapy pertains to pregnant women. Isotretinoin produces birth defects in almost all women who take the drug while pregnant. Thus, it is absolutely contraindicated in pregnant or nursing patients. Also, female patients must adhere to a strict pregnancy prevention program. This includes informed consent, counseling on contraception, and monthly serum pregnancy tests.

The female patient on isotretinoin must practice scrupulous birth control and may need to consider abortion if birth control fails. The details of contraceptive counseling during therapy are beyond the scope of this paper, but the physician's responsibility is great. The patient must be counseled so that she completely understands the possible consequences, and she must be followed carefully. The manufacturer provides useful support material and even funds for contraceptive counseling. After the medication has been eliminated from the body, in about 2 months, there are no further problems.

Why should a physician bother with isotretinoin? It is remarkably effective. Despite its serious side effects, isotretinoin is the only true "cure" for acne and should be made available to patients who qualify and understand the risks and their responsibilities. We have found that when isotretinoin is dosed correctly, it will cure (clear for at least 2 years without therapy) close to 70% of patients.

Undertreatment of acne may result in facial disfigurement and scarring with consequent embarrassment, low self-esteem, and frustration. Nevertheless, physicians tend to withhold aggressive therapy even after a 1- to 2-year trial of a weaker treatment. We argue for a more aggressive therapeutic approach designed to completely clear, not merely improve, the skin.

In Summary

Our program for acne therapy 1-2-3 is progressive but far from simple:

  • Initiate for every patient a program of drying agents, acne soaps, and antibiotic lotions.
  • Prescribe either tetracycline or minocycline for at least 5 months. Because it is more effective, minocycline may be tried if tetracycline fails.
  • If nothing else works well, use isotretinoin. Inform patients of the benefits and side effects, obtain their consent and cooperation, and be careful. It is worth it.

References

  1. Kligman AM, Fulton JE Jr, Plewig O: Topical vitamin A acid in acne vulgaris. Arch Dermatol 1969;99 (4):469-476
  2. Murad H, Shambam AT, Moy LS, et al: Study shows that acne improves with glycolic acid regimen. Cosmet Dermatol 1992;5(11):32-35
  3. Kligman AM: An overview of acne. J Invest Dermatol 1974;62(3):268-287
  4. Leyden JJ, Mcginley KJ, Mills OH et al: Proprionibacterium levels in patients with and without acne vulgaris. J Invest Dermatol 1975;65(4):382-384
  5. Ebling FJG: Hormones, in Frank SB (ed): Acne. Chicago, Year Book Medical Publishers, 1979, pp 53-66
  6. Esterly NB, Furey NL, Flanagan LE: The effect of antimicrobial agents on leukocyte chemotaxis. J Invest Dermatol 1978;70(1):51-55
  7. Webster GF: Inflammation in acne vulgaris. J Am Acad Dermatol 1995;33(2 pt 1):247-253
  8. Goldstein JA, Comite H, Mescon H, et al: Isotretinoin in the treatment of acne: histologic changes, sebum production, and clinical observations. Arch Dermatol 120212;118(8):555-558
  9. Lavker RM, Leyden JJ, Kligman AM: Isotretinoin suppresses the inflammatory infiltrate of acne conglobata, in: Reichart U, Shroot B (eds): Pharmacology of Retinoids in the Skin. New York City, Karger, 120219, pp 227-234
  10. Melnik B, Kinner T, Plewig O: Influences of oral isotretinoin treatment on the composition of comedonal lipids: implications for comedogenesis in acne vulgaris. Arch Dermatol Res 120218;280(2):97-102

Dr Savin is a dermatologist in private practice in New Haven, Connecticut, and a clinical professor of dermatology at Yale University School of Medicine in New Haven. Dr Donofrio is in private practice with Dr Savin and is a clinical instructor at Yale University School of Medicine. Both are members of the American Academy of Dermatology and are active clinical investigators for new dermatologic drugs. Address correspondence to Ronald C. Savin, MD, 134 Park St, New Haven, CT 06511.


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