Eyelid skin cancer

Botulinum toxin injections have become a popular treatment for minimizing or eliminating facial wrinkles and rejuvenating the face aged by years of sun exposure, hyperkinetic (overactive) muscles, and thinning skin (1,2). Known as Botox, its possibilities are being recognized by physicians and those concerned about deepening furrows, creases on the forehead. cords around the neck, and crow's feet. According to the 2000 US Census, there are more than 80 million Americans over age 50 and 42 million Americans between the ages of 40-49. A few small injections of the toxin performed by a skilled dermatologist or plastic surgeon can relax these muscles and make the skin above it appear smooth and refreshed.

In the upper free, major indications for aesthetic use of botulinum toxin are for treatment of glabellar or frown lines of the forehead, horizontal lines, and crow's feet. It has also been utilized to change the contour of the brows and eyelids. In the lower face. Botox injections can diminish and even eliminate smile or "bunny lines," fine wrinkles around the mouth, and horizontal lines around the neck. They can soften creases and folds at the corners of the mouth, and improve facial asymmetry and nasal flare.

Not All Toxins Are Botox

Seven immunologically distinct serotypes or categories of botulinum toxin, designated from A through G, are known to exist. Two are currently available by prescription for cosmetic use. They are antigenically different, but both otter extremely safe, non surgical=treatment for hyperkinetic facial lines (3,4). Botulinum toxin A (Btx-A) is a freeze-dried powder preparation that needs to be reconstituted before using. Botulinum toxin B (Btx-B) is a ready-to-use liquid. Though both agents are referred to interchangeably by the public as Botox, they are pharmacologically distinct in terms of molecular size, cellular mechanisms of action, and species sensitivity. However; both agents produce the same clinical effect: muscle weakening and paralysis (4).

From Poison to Patient Care.

Botulinum toxins, long regarded as among the most potent biologic substances found in nature, are poisonous proteins produced by the anaerobic spore forming bacterium Clostridium botulinum. This is the same bacterium that causes botulism, a deadly form of food poisoning, but it also produces a protein that blocks the release of acetylcholine, a neurotransmitter, and this relaxes muscles.

Botulinum toxin type A has been the subject of scientific investigation for over 100 years. In the 1960's, its muscle-relaxing properties were studied for treating avariety of conditions caused by overactive muscles. In 1989, Botox[R] entered the marketplace, becoming available to physicians for use in treating crossed eyes, excessive blinking, and cervical dystonia, a painful condition caused by hyperactive muscles in the neck.

Balancing Science and Aesthetics

Now in their most recent incarnation, two serotypes, botulinum toxin A (Btx-A) and botulinum toxin B (Btx-B) have won approval from the U.S. Food and Drug Administration (FDA) and are available for aesthetic and cosmetic use. The first, Btx-B (Myobloc[TM]), won FDA approval in December, 2000, for treatment of cervical dystonia. However, it had been used "offlabel" for over a decade before that, to treat facial wrinkles as reported in several open label studies (6,7). "Off-label" or unapproved use is supported by the FDA as long as the practice is grounded in good science.

Btx-A was granted FDA approval in April, 2002 as Botox[R] Cosmetic, specifically "to treat and temporarily improve the appearance of glabellar lines." Another version of Btx-A, now available in Europe, is waiting for FDA approval in the US.

Formulation of A and B

Btx-A comes to the physician as a vacuum-dried, crystalline preparation packaged in vials of one hundred units each. which are stored in the freezer (at 5[degrees] C). (4) Before use. it is reconstituted with one to five cc of 0.9% saline to minimize injection discomfort. Recent studies have shown that once prepared, Btx-A will remain stable under refrigeration for up to six weeks (5,6).

In contrast, Btx-B is a ready-to-use preparation set at pH5-6 for stability. It comes packaged in vials of 2500, 5000, and 10,000 units with a concentration of 5000u/ml. Each vial contains more Btx-B than is specified on the label, which is important to know when working with this agent. Btx-B is stored in the refrigerator (at 2[degrees] to 8[degrees] C) and will remain stable for up to three years. Btx-B, when diluted up to sixfold with preserved saline, remains stable and potent for at least 24 hours at room temperature. Stability is an important issue to consider, if extra product is left over and can be saved for use in another treatment session (7,8).

Differences and Similarities

Although these two towns ultimately exert the same clinical effect--muscle weakness or paralysis--subtle differences in their size, biosynthesis, and cellular mechanism of action may contribute to differences clinically. Cross-reactions between the different serotypes have not been observed and are not expected. Most patients who are resistant to Btx-A respond to Btx-B.

For treatment of facial wrinkles, 125 units of undiluted Btx-B is the approximate equivalent of one unit of Btx-A. For example, treatment of frown lines would generally require five injections of Btx-A, of 20 to 30 units each. Using Btx-B, this same treatment would require three to five injections of 2400-3600 units each. Frontal facial wrinkles generally require four to six injections of Btx-A at 15 to 35 units each. Three to six injections of Btx-B at 1500 to 3600 units each would be the equivalent dosage for this procedure (9).

Clinical data indicate that Btx-A treatments have a longer duration while Btx-B injections have a more rapid onset and greater diffusion (10). Most clinical studies show that Btx-A injections take effect within three to five days after treatment is administered. Benefits last for about 12 to 16 weeks. There are no complications if injections are not repeated then. The effects of Btx-B become evident within three days after treatment.

Duration of results appear to be more dose-dependent with Btx-B treatments than with Btx-A. Preliminary studies show no increase in adverse effects in patients receiving doses of up to 3600 units per treatment with Btx-B for frown lines. The results last from 10 to 12 weeks.

Preliminary results from dosing studies performed by this author have shown that high doses are associated with more rapid and longer lasting results (8,11). More diffuse, uniform muscle paralysis has been documented with the use of Btx-B than with Btx-A.

Btx-A remains the gold standard for treatment of hyperkinetic wrinkling for several reasons. Recent advances have made the drug more stable for a longer period of time, up to six weeks, when reconstituted. There has been no clinical documentation thus far of complete resistance to its effects. Finally, the longevity of results has been established at 12 to 16 weeks (9).

However, Btx-B has a role to play in treating the aging face. Some patients request rapid results. Others are non-responsive to Btx-A. Some patients may benefit from the option of a more diffuse, uniform paralysis of treated areas. Finally, it may be useful in "touch-ups" because Btx-B does not need to be reconstituted (10,11).

Potential Side-Effects

Each of these toxins is an extremely safe, non-surgical approach to diminishing the unwanted signs of photoaging (3,4). When complications occur, they may be related to technique. immunology, or to the toxin itself.

Potential side effects of the two drugs are remarkably similar. Headaches may occur but are transient for most patients. This usually happens during the first 24-48 hours with both toxins, but occasionally can last for several days. Pain and discomfort during treatment seems to be greater with Btx B injections, mainly because of its acid content. Diluting the toxin with a preservativecontaining saline usually minimizes this side-effect (11).

Bruising, particularly when treating the eyes and forehead, is the most common complication from injection with either Botox product. Patients who use aspirin, non-steroidal anti-inflammatory drugs, or anti-coagulants are at higher risk for bruising and should stop taking these medications at least 72 hours prior to treatment, if possible (11).

Dry-mouth can sometimes occur with the use of Btx-B. This has been reported as a side effect in neurologic use but appears to be less of a problem in aesthetic treatments (8).

Skill is Essential