Acne: Blemishes, Pimples, and Zits

Blemishes, Pimples, and Zits. These are all common names for the skin disease called acne. Acne is so common during childhood and teenage years that it is considered a normal rite of passage. However, when the acne becomes so severe that there is either ridicule from friends or actual disfigurement of the face, then medical treatment becomes necessary. First, I will describe all of the different types of skin lesions that may be found in acne. The earliest lesion of acne is the open comedo or blackhead. An open comedo is a hair follicle opening that is blocked by accumulated skin cells. The dark color is caused by oxidation of the protein on exposure to hair. A closed comedo, also called a

Acne vulgaris with blackheads, whiteheads, and inflammatory papules (“pimples”)

whitehead, is the skin lesion which has a thin layer of normal skin overlying it and is not exposed to the air. Both of these lesions may rupture or break open and expose their contents to the surrounding inflammatory cells in the skin. When this happens, the next skin lesion that will be observed is a red raised bump which dermatologists call inflammatory papules and patients call a “pimple” or a “zit.” Sometimes the inflammatory papules develop a collection of pus or white blood cells on the surface and would then be called a pustule. A deeper and more serious type of inflammation may develop below the surface of the skin

and this would become a cyst which is usually very painful to the patient as well as being disfiguring. All of the inflammatory types of acne lesions including papules, pustules, and cysts may heal with scarring, especially if they are squeezed or otherwise manipulated by the patient. That is why mothers and dermatologists frequently advise their charges: do not squeeze your pimples.

What are the causes of Acne? There are several contributory factors to acne, but it is known that it is necessary to have the following five factors in order for acne to develop:

  1. Sebum. Sebum is the name for the mixture of natural oils and waxes that are produced by the sebaceous glands in the skin which are connected to the hair follicles. This oily substance is what provides the normal lubrication and supple feel and texture to the surface of the skin. Whenever the amount of sebum increases or is excessive, then acne is more likely to develop.
  2. Blockage of the hair follicle opening. This may occur as a result of abnormal growth and maturation and exfoliation of the living cells which line the hair follicle opening. When this happens, the result is a comedo which may result in either a blackhead or a whitehead.
  3. Bacteria. It is normal for several different types of bacteria to inhabit our skin without causing disease. However, when the opening of the hair follicle accumulates a large amount of dead and dying skin cells, the amount of the bacteria increases. The type of bacteria which is known to be increased in large numbers in patients with acne is called P.acnes. While we do not consider acne to be primarily a skin infection, these bacteria do contribute to the overall development of the lesion which will be covered in the next section.
  4. Inflammation. When the blackhead or whitehead ruptures into the surrounding living skin which contains the white blood cells of the immune system, an inflammatory reaction ensues. At first neutrophils will come to the area to try to fight the bacteria and also to digest the oils found in the sebum. As this inflammation continues, a collection of the white blood cells or neutrophils will form a pustule. With time if the pustule is not drained or healed by treatment, then a deeper larger cystic nodule may develop. In these cases the inflammation cells are more chronic and are composed of a mixture of neutrophils and lymph cells.
  5. Male Hormone. The male hormone or testosterone is necessary for the development of acne. Naturally, boys have more testosterone than girls, but this hormone is present in both sexes. That is why acne is usually worse in a male. The testosterone stimulates the sebaceous gland to manufacture and secrete sebum into the hair follicle opening. Girls who have above average testosterone levels also have a greater tendency for acquiring acne.

Acne Myths Because acne can be such an emotionally charged issue as well as a devastating skin condition, there are many questions and myths surrounding acne that can be dealt with simply at this time.

  1. Is acne caused by stress? Acne is not caused by stress, that is, it is not one of the required factors for the development of acne. Therefore, completely stress-free individuals, if it is possible for that person to exist, may still develop acne. However, the person who already has acne may certainly develop a flare up or aggravation of the disease during times of stress, for example, during final examination time, job interviews, break ups of a romantic relationship, etc.
  2. Is acne an infection or can it be contagious? Acne is not considered to be an infection. Although, as I mentioned above, bacteria are involved with acne, and acne is often treated with antibiotics, it is not contagious to others. It does not require restriction of personal use articles or isolation of the patient from others.
  3. Is my acne caused by anything in my diet? This one is definitely controversial. The question of the role of diet in acne has been considered many times over the years in the research of the causes of acne. Initially, such dietary items as dairy products and chocolate were considered to play a role in aggravating acne and it is recommended that these be reduced or removed. Then research studies showed that there was no evidence to support changing the patient’s diet. More recently, this conclusion has come back into question, and seems more prudent to recommend to patient that if they definitely know this a flare or an increase in the number of their inflammatory acne lesions associated with a particular dietary item, then they reduce or avoid that item in their diet. Therefore, the dietary recommendation is highly individualized, and no statements can be generalized to all patients.
  4. Is acne caused by my face being dirty? We do not believe that acne is caused by having a dirty face. Soiled skin is not one of the five necessary contributing factors for acne. However, if a person has excessive sebum secretion and accumulation on the face, then that would likely cause more blockage of the hair follicle openings which could lead to more inflammation and the development of more acne lesions. Therefore, we do recommend washing the face 2-3 times daily with certain cleansers that are designed for acne-prone skin which will be discussed under the treatment section.
  5. Are there any other medicines or drugs or conditions that can cause or aggravate acne? Yes. There are several prescription medications that can cause acne-like lesions in people who have never had much acne and also aggravate pre-existing acne. The most common medication associated with acne are the oral cortisone drugs such as Prednisone and Decadron, certain anti-epilepsy medications, and Lithium. There is a form of acne caused by repeated pressure or friction on the face such as might be caused by headbands, chin straps, and telephone applied closely to the side of the cheek and ear.

Acne Treatment The earliest and simplest cases of acne probably begin in pre-pubescent children around 10-12 years of age. They can be treated with the few over-the-counter agents that are effective for acne. We recommend the cleansers that contain 2% Salicylic acid (Neutrogena oil-free acne cleanser and generic store brands), astringent or drying agents that contain rubbing alcohol or acetone, and the Benzoyl Peroxide products which are available as cleansers and gels in 5 and 10 percent concentration. These medications are effective for mild cases with oily skin, but if inflammatory papules and pustules persist, then a consultation with a dermatologist is recommended for prescription medications which are much more effective. Medications for acne may be prescribed by the topical or local application route (gels and lotions) or by the systemic or internal dosing route (tablets or capsules). First, I will cover topicals by medication category.
TOPICAL AGENTS
RETINOIDS
Retinoids are synthetic medicines derived from Vitamin A which cause normalization of skin cell growth within hair follicles allowing for the reduction of the obstruction to the opening to the skin surface, thereby preventing blockage, bacterial overgrowth, and rupture.
Tretinoin: Tretinoin is Vitamin A acid. It was first developed as Retin-A and is available in various concentrations of creams and gels. It is very effective for treatment of all forms of acne except for the deep cystic nodules.
Adapalene: Originally called Differin, it is also available in cream and gel form and may be slightly less effective than Tretinoin but is also less irritating to the skin.
Tazarotene: Available in different concentration of creams and gels, it is a synthetic aromatic form of Vitamin A that is slightly more irritating than Tretinoin but probably more effective at normalizing the cell growth within the hair follicles. This drug is also approved for the treatment of psoriasis which is a disease of abnormally rapid skin cell growth recognized by thick red scaling plaques on elbows and knees.
ANTIBIOTICS
Benzoyl Peroxide Products: These are available as creams, gels, and cleansers, both by prescription and over-the-counter in varying concentrations from 2.5%- 10%. Drying of the skin and irritation increases with the concentration of the drug. Benzoyl peroxide is a mild antibiotic for the skin. Some of its benefits may result from the exfoliation of the skin caused by the drying effect.
Erythromycin: This is one of the first antibiotics available in topical form for the treatment of acne. Antibiotics are used for both their antibacterial effect and anti-inflammatory effect on acne. Because Erythromycin has been around so long for the treatment of acne, many of the bacteria have become resistant to it. Therefore, Erythromycin may not be as effective as Clindamycin.
Clindamycin: Clindamycin is available in liquid solution and gel form. It is very effective at helping to clear mild to moderate superficial inflammatory acne lesions.
Dapsone: A new topical drug for acne has been approved for acne called Aczone which is 5% Dapsone gel. It is a new class of acne treatment which has been available as an oral drug for many years but considered to be too toxic for the treatment of acne. The topical formulation is safe and without significant side effects, however, it is only mildly effective for acne. It may be useful in combination with some of the other medications in this list or as a substitute for other medications that have either been ineffective, too irritating, or caused allergies.
Combinations: After decades of use of Erythromycin and Clindamycin topically in the treatment of acne, it became apparent that these medicines were losing some of their effectiveness because the bacteria were becoming resistant to the antibiotic effect of these drugs. They were able to maintain their anti-inflammatory effects, however. With the addition of Benzoyl peroxide to the treatment regimen, antibiotic resistance has been delayed. Therefore, pharmaceutical companies have developed active combinations of two anti-acne drugs in one cream or gel. For example, Clindamycin has been combined with Benzoyl peroxide, Erythromycin has been combined with Benzoyl peroxide and Benzoyl peroxide has been combined with Adapalene. Clindamycin has also been combined with RetinA. Note that the combination drugs are often more expensive than the same two drugs purchased and applied separately, but the combination may be more effective and improve adherence to the treatment regimen.

ORAL AGENTS
ANTIBIOTICS
The Tetracycline class of antibiotics was the first oral and topical antibiotic that came into general use. The topical formulation was dropped because it made the skin glow in ultraviolet light, not a pretty sight in the discotheques of the 1980’s. These medicines are very effective as antibiotic and anti-inflammatory drugs because they are concentrated in the oily or lipid layers of the skin including concentrating in the sebum where the P.acnes bacteria grow.
Tetracycline is very safe and inexpensive. Occasionally, people may suffer from mild gastrointestinal side effects and women may develop vaginal yeast infections as with any other broad spectrum antibiotic. There are some minor disadvantages: 1) Tetracycline is best taken on an empty stomach which means one hour before or two hours after a meal. This may be difficult for some of our busy teenage patients that find themselves eating snacks throughout the day. 2) Tetracycline may not be taken with dairy products at the same time as swallowing the capsule because the calcium in milk or cheese prevents the antibiotic from being absorbed well into the bloodstream. Therefore, it is best to take the capsule on an empty stomach with a full glass of water. 3) Tetracycline is slightly sun sensitizing. That means that you may be more likely to get a sunburn even after a shorter exposure to the sun than usual. This can be more of a problem to patients who live in southern or tropical climates where it is sunny even during the winter. Recently, there has been a shortage of Tetracycline, making it difficult to obtain. To overcome some of the shortcomings of Tetracycline, different but related chemical derivatives of Tetracycline were developed.
One of these is Doxycycline. It may be taken with food or dairy products. It has slightly more gastrointestinal side effects than Tetracycline and is definitely more sun sensitizing than Tetracycline. The patient must be willing not to get excessive sun exposure while taking the medication and to diligently use sunscreens which are broad spectrum, that is, blocking both UVB and UVA.
Minocycline is also very effective for all forms of acne including cystic acne. It concentrates in the lipid fractions of skin very well. It is less likely to cause gastrointestinal side effects than Doxycycline and is much less sun sensitizing than Doxycycline. One disadvantage that occasionally occurs is darkening of the skin either generalized after sun exposure or in healing inflammatory lesions or bruises.
None of the Tetracycline antibiotics should be given during pregnancy because the medication accumulates in the teeth and bones of the developing fetus. Tetracycline should not be given to children who are younger than 8 years of age. While it is uncommon, some patients develop rashes or hives while taking Tetracycline antibiotics. If that happens, the antibiotic must be stopped and usually cannot be substituted with another antibiotic in the same category.
Erythromycin Erythromycin is also one of the first medications that was used for acne in both topical and oral form. Most of the bacteria have developed resistance to Erythromycin, and it is considered not to be as effective as the other alternatives listed here. However, because it is cheap and relatively safe, it can be tried as a second line therapy for a patient who cannot tolerate the Tetracycline antibiotics.
Sulfa-containing antibiotics such as Bactrim and Septra which are most often used for urinary tract and other infections, are also very effective for certain forms of acne, especially in older females who have tried many of the other treatments. Naturally, if the patient is known to be allergic to Sulfa-containing antibiotics, they cannot be used. There is also a fairly high incidence of developing rashes from taking Sulfa antibiotics. Again, if this happens, then the medication must be stopped immediately. There is also a slight amount of sun sensitivity associated with Sulfa-containing antibiotics, and the patient must be aware of their tendency to sunburn more easily and to avoid tanning salons and therapeutic ultraviolet light.
Clindamycin Clindamycin is very effective for acne and other acne-like diseases. The main side effect is that it can cause diarrhea which may lead to a more serious condition called colitis. This side effect was once considered to be more common than it is today, thus the drug may have been underutilized. Clindamycin has been making a comeback of sorts, especially for patients who are either resistant or intolerant to the other antibiotics on this list.

RETINOIDS
The only retinoid or Vitamin A derivative that is approved for the treatment of acne in the U.S. is Isotretinoin. It is better known by its original brand name Accutane although it is

Original promotional material for Accutane showing patient before and after 16 weeks of treatment.

only available now as a generic. This medication is remarkably effective at healing the most severe and resistant forms of acne which are usually cystic and scarring and involve the face as well as the back and chest. It has many minor side effects which relate mostly to dryness of the skin and mucous membranes, but it is notorious for its more serious side effects which include teratogenicity (the ability to cause birth defects in women who are pregnant at the time of taking the medication), causing mood changes that may result in depression and suicidal thoughts, and diarrhea which may lead to inflammatory bowel diseases (ulcerative colitis and Crohn’s disease). Because most of our acne patients are young and therefore of childbearing potential, the Federal Drug Administration and the American Academy of Dermatology have implemented very strict control on the prescribing of this medication by a program called “ iPledge.” This program requires that the patients return for a follow up appointment for every refill of a prescription including a pregnancy test for females and blood tests for males and females. The medication is dosed by the weight of the patient, and the treatment is continued until an effective cumulative dose is reached or the patient’s skin is completely clear. About 80 percent of treated patients will enjoy a nearly complete remission or “cure” of their acne which may only recur as mild superficial lesions that can be treated topically. Of the remaining 20 percent some will require a second or a third treatment course of Accutane in order to obtain a satisfactory response. A minority of patients may still require oral medication after discontinuing the Accutane. A course of Accutane typically lasts between 3 and 6 months.

HORMONES
Because we know that the male hormone is necessary for the appearance and sustaining of acne, it is reasonable to expect that the female hormone counteracts the effect of the male hormone. Therefore, females may benefit from the addition of estrogen to their hormone balance. Certain oral contraceptive pills have been developed which contain a small amount of estrogen and have been shown to be beneficial for the treatment of acne as well as for providing contraception. Examples of brands are Ortho Tri-Cyclen, Yasmin, Yaz, and Estrostep Fe. Some dermatologists are comfortable prescribing birth control pills for their patients for the treatment of acne, but others prefer that these drugs be provided by their gynecologists so that a more thorough evaluation of their female reproductive health may be undertaken to include pap smears, breast exams, and management of the menstrual cycle as appropriate.

COMBINATIONS
In order to get the best response in any given patient, it is common to prescribe a combination of a topical medication and an oral medication. A typical example of a patient with moderate acne might be treated with topical Clindamycin solution in the morning, Tretinoin cream at bedtime and oral Tetracycline or Minocycline during the day. There are also some combinations to be avoided. For example, the Tetracycline antibiotic should not be given at the same time to patients who are also taking Accutane. A rare side effect of swelling of the brain has been reported with the latter combination. On the other hand, for the young females who are taking Accutane, it would it be beneficial for them to take one of the oral contraceptive agents that improve acne and also prevent pregnancy which could result in a birth defect. Most dermatologists would not prescribe a topical Retinoid such as Tretinoin, Adapalene, or Tazarotene if the patient was also taking Accutane because of the excessive dryness and exfoliation such a combination would likely cause.

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