A 16 year old male presents for a pre-sports physical. His sole complaint is his acne, which he admits, has made him reluctant to ask female classmates out on dates. As his acne has become worse in recent years, he feels that he is becoming more withdrawn and self-conscious. He has tried Clearasil as an OTC medication, but he usually just "pops" the lesions when they appear. He'd like anything that would improve his complexion.

His exam is unremarkable except for moderately severe facial acne with secondary scarring.

Acne is a common skin condition of adolescent males and females. It is estimated that it affects 40% of teenagers at some point. The lesions take several forms:

Comedones come in two types. Closed comedones, also known as "whiteheads" are dilated plugged follicles that have not yet reached the surface. Often they are difficult to see and are 1-2 mm papules. When these reach the surface, the follicle becomes dilated at the orifice and are more visible as open comedones, or "blackheads

Inflammatory lesions that grow from comedones are of two types as well. Pustules are superficial, raised white lesions that are filled with pus. Pustules usually resolve in a matter of days without scar formation. Papules are deeper, dermal inflammatory lesions that are more erythematous, raised and solid. They take a longer time to heal and often result in scaring.

Cysts or nodules are the most severe form of acne lesions. These are really suppurative abscesses. Scarring is to be expected.

Scars take two forms. Ice pick scars are atrophic, broad-based depressions that reflect scarring of the deeper dermal tissues. Hypertrophic or keloidal scars are raised, thick fibrotic plaques that occur more frequently on the chest or shoulders. African-Americans are particularly prone to this form of scarring.

The pathogenesis of acne involves abnormalities in follicular keratinization with the excessive proliferation of Propionibacterium acnes. The excessive keratin produces a horny impaction or microcomedo. As this extends to the surface a comedone is formed. The sebaceous gland hypertrophies and secretes excess sebum. This process is greatly promoted by androgen hormones, and thus becomes most evident in puberty. Dehydroepiandrosterone (DHEA), from the adrenal glands along with testosterone, which is converted in the sebaceous glands to the more active dihydrotestosterone, are important in comedone formation.

P. acnes, which is an anaerobic diphtheroid, colonizes the impacted gland. Interestingly, the number of P. acnes bacteria on the skin surface do not correlate to the severity of the acne. Staphylococcus epidermidis and Pityrosporum ovale also are sometimes found from culture of the follicular material. P. acnes possesses a lipase that can hydrolyze sebum to free fatty acids. Intrafollicular free fatty acids promote inflammatory responses with chemotaxis of polymorphonuclear leukocytes and monocytes.

Therapy in acne is usually staged and relates to:
. . . . . 1. The type of lesion.
. . . . . 2. The acne severity.
. . . . . 3. The psychological impact of the disease.

Mild acne can usually be handled with a topical preparation antimicrobial such as benzoyl peroxide. This agent is bactericidal for P. acnes and comes in various strengths from 2.5 to 10% preparations. Higher concentrations are often used with truncal involvement.

Topical antibiotics are also useful in relatively mild cases of acne. Options here include erythromycin and clindamycin. Both have been shown to be equally effective although there are increasing reports of resistance to erythromycin. Pseudomembranous colitis secondary to topical clindamycin is almost unheard of.

For patients with more severe or inflammatory lesions, or those who failed to respond to topical therapy, systemic antibiotics are often added. These drugs can also have an anti-inflammatory effect and may decrease the chances of scar formation in patients predisposed to scarring. Options here include tetracycline BID or doxycycline once a day dosing. Of course these drugs should never be given to pregnant women or children under the age of 12 because of skeletal growth inhibition and discoloration of the teeth. Photosensitivity can also occur.

Topical Retin-A (tretinoin) and Differin (adapalene) normalize follicular keratinization by increasing turnover of cells lining the sebaceous gland. This invariably leads to irritation, erythema and desquamation of the skin that many patients find intolerable. The patient must be counseled prior to treatment about these effects and encouraged to give the drug a 3 month trial before deciding against its use.

Since hormones play a role in the pathogenesis of acne, hormonal manipulation is sometimes useful. The goal here is to reduce androgen production or inhibit androgen metabolism at the follicular level. Estrogen can be added to female patients in the form of oral contraceptives. This is unacceptable in male patients, due to the feminizing side effects. In a similar way, this option should not be used in patients younger than 16 years because of its adverse effect on growth in height.

Finally, systemic (oral) isotretinoin (Accutane) approaches the problem of comedone formation by decreasing sebum secretion. This depletes follicular P. acnes concentrations and then neutrophil chemotaxis. Hyperkeratosis is diminished. Accutane is an oral systemic analog of vitamin A and is indicated in patients with the most severe nodular or cystic forms of acne that have the highest propensity towards scar formation. Side effects are similar to hypervitaminosis A syndrome and include mucocutaneous inflammation, cheilitis (inflammation affecting the lips), conjunctivitis, and xerosis (eye dryness). Patients commonly complain of symptoms such as pruritus, chapped lips, and dry eyes. Moisturizing creams my help the cutaneous symptoms. Pseudotumor cerebri can also result which mandates stopping the drug. 25% of patients show an elevation of serum triglycerides, often with a rise in low-density lipoprotein levels. Liver enzymes may be elevated. The best-known side effect however is teratogenicity which has been shown to cause severe malformations in CNS, cardiac and craniofacial development. All female patients administered this drug should have a negative pregnancy test and advised not to become pregnant while taking the drug.

Questions

1. Organisms associated with the inflammatory process of acne include all of the following except:
. . . . . a. Pityrosporum ovale
. . . . . b. Propionibacterium acnes
. . . . . c. Strep pyogenes
. . . . . d. Staphylococcus epidermidis

2. All of the following are true statements are true of isotretinoin except:
. . . . . a. Cheilitis and xerosis necessitate discontinuing the drug
. . . . . b. Pseudotumor cerebri is sometimes irreversible
. . . . . c. The drug can be used in fertile women
. . . . . d. Increased levels of low density lipoproteins are sometimes seen

3. True/False: Comedones can be thought of as small pustules that can eventually develop into cystic acne.

4. True/False: Closed comedones are composed of small pus collections.

5. True/False: Retin-A (tretinoin) and Accutane (isotretinoin) both act to decrease hyperkeratosis.

References

1. Winston MH, Shalita AR. Acne Vulgaris: Pathogenesis and Treatment. Pediatr Clin North Am 1991;38(4):889-904.

2. Cunliff WJ. Pediatric Dermatology, 2nd edition. 1996, New York: Churchill Livingstone, pp. 639-651.

Answers to questions

1.c, 2.a, 3.False, 4.False, 5.True