ePathoPlusPage

	Synopsis of Scene	Patho Foci
"Stuck on You"	Nurse Hathaway is treating an adolescent girl for acne. She wants to give the girl a prescription for Accutane but insists that the girl must also take oral contraceptives at the same time. The girl doesn’t want to do this. Nurse Hathaway insists. She says she will even talk to the girl’s mother to explain. The girl remains dubious.	· The patho of acne: how acne arises. · The rationale for pharmacological approaches to treatment. · The reason why Accutane and oral contraceptives are given together

Explanation:

Acne (precisely we are talking about acne vulgaris) affects 80 –90% of the population with the peak incidence being in the mid to late teens. The pathophysiology of the "pimple" so to speak is actually pretty complicated. It involves the sebaceous follicle, which contains a small vellus (i.e. a very fine) hair and a multilobulated sebaceous gland. Sebaceous glands secrete oil (sebum) and are distributed throughout he skin but have a very high concentration on the face, chest and shoulders.

Exactly which of the following events comes first is hard to say, but basically the formation of a comedone, i.e. the name given to the typical skin lesion found in acne vulgaris, involves the trapping of skin cells, excess sebum and bacteria. The steps are loosely outlined as follows:

a. Abnormal keratinization in the sebaceous follicle occurs. Keratin is a tough protein found in hair and nails and special cells in the skin called keratinocytes produce it. Keratinization is the process by which these special cells progress upward towards the surface of the skin. In a comedone, these cells prevent other epithelial cells from being swept out of the sebaceous follicle by the normal flow of sebum. In other words, abnormal keratinization results in the trapping of epithelial cells inside the follicle.

b. Increased sebum production typically occurs. The problem is that increased sebum allows for bacterial growth.

c. Two bacteria are involved: Proprionobacterium acnes and Proprionobacterium granulosum. Both of these bacteria are anaerobes The bacteria produce fatty acids that contribute to abnormal keratinization and are also pro- inflammatory in themselves. In addition, the bacteria also produce chemotactic factors, i.e. in this case peptides that attract neutrophils which then enter the follicle and initiate a full blown inflammatory response. Excess sebum then is a real problem. Sebum production is normally regulated by androgens (male sex hormones). If androgen levels are high, then sebum production is high. (remember, both men and woman produce androgens)

To summarize, a comedone is a sebaceous follicle in which there is trapped keratin, epithelial cells, sebum and bacteria. In acne vulgaris the comedone becomes inflamed. Given what we know about the pathophysiology behind its formation, three pharmaceutical strategies for treatment of acne emerge.

· First, the use of comedolytic agents, i.e. agents that can dissolve a comedone. These include topical salicylic acid and topical tretinoin (Retin A).

· Second, a strategy aimed at decreasing sebum production. This can be either through

a. hormonal therapy (decreasing androgen in those instances in which androgen production is thought to be excessive) .Estrogen in the form of oral contraceptives can be used to decrease androgen in females, or through

b.administration of isotretinion (Accutane ). Accutane is reserved for severe nodular acne, i.e. inflammatory lesions with a diameter greater then 5 mm..

· Third, a strategy to administer agents that can be anti- inflammatory. These agents would include benzoyl peroxide and topical and systemic antibiotics..

In the scenario above, Accutane is proposed, but only if the client is willing to take oral contraceptives. The reason for this is that Accutane is teratogenic, i.e. it can produce birth defects. The warning on the Accutane label states in unequivocal terms "Accutane must not be used by females who are pregnant or who may become pregnant while undergoing treatment". In addition, before starting a woman on Accutane she has to have had a negative serum pregnancy test with a sensitivity of at least 50mIU/ml within one week prior to beginning therapy and therapy should begin only on the second or third day of the next normal menstrual period. It is also recommended that pregnancy testing and contraception counseling be repeated on a monthly basis. To encourage compliance with this recommendation, the health care provider should prescribe no more than a one-month supply of the drug. In the scenario above, Nurse Hathaway was right!
                                                                                             ©Kenneth Zwolski, RN, EdD, CS