COLLAGEN

WHAT IS INJECTABLE COLLAGEN?
Collagen is a natural substance found in humans (and all mammals), lending support and structure to skin, bones, ligaments and other parts of the body. Injectable Collagen is a natural protein, similar to our own collagen, derived from purified bovine (cow) collagen. Collagen Corporation produces two types of injectable collagen - Zyderm and Zyplast Collagen - which can be used to replace the collagen your skin loses over time to smooth facial wrinkles. scars and other contour deformities. Your physician will determine which product is appropriate for you.

ARE THERE ANY OTHER PRODUCTS ON THE MARKET THAT CONTAIN BOVINE COLLAGEN?
Bovine collagen has been used for decades in medical and surgical products like absorbable sutures and hemostatic agents (materials used to help control bleeding during surgery) manufactured by major medical and pharmaceutical companies. These products have been used in millions of patients world-wide, with no significant reported health risks.

WHAT IS COLLAGEN REPLACEMENT THERAPY?
Collagen Replacement Therapy is a series of non-surgical treatments in which Zydern and Zyplast Collagen are used to replenish the skin's natural collagen. Zyderm and Zyplast Collagen are injected through a fine gauge needle just below the surface of the skin where they are incorporated into the body's own network of collagen fibers.

FOR WHICH USES IS COLLAGEN REPLACEMENT THERAPY RECOMMENDED?
Collagen Corporation began marketing its Zyderm I Collagen in 1981 for correction of facial contour deformities, including scars and wrinkles. The product line was extended in 1983 to include Zyderm II Collagen and again in 1985 with Zyplast Collagen.

IS INJECTABLE COLLAGEN RECOMMENDED FOR LIP TREATMENTS?
Injectable Collagen is used around the edge of the lips for smoothing vertical lines above the upper lip, often referred to as "smoker's lines." Collagen is also used to replenish the natural border of the lip that gradually wears away with age. Collagen treatments directly into the lip are not a recommended use for injectable collagen.

HOW SAFE IS COLLAGEN REPLACEMENT THERAPY?
Collagen Replacement Therapy has been clinically proven safe for treatment of facial wrinkles, scars and contour deformities. However, it, like all medical procedures, carries risk. Before injectable collagen came on the market in 1981, clinical trials over two years involving more than 5,000 patients were conducted. Since then, more than 750,000 people in 28 countries have been treated with collagen injections, including more than 500,000 in North America. Injectable collagen has been extensively researched by physicians and scientists, with more than 200 scientific papers published concerning product safety, technique, usage and effectiveness.

WHAT ARE THE KNOWN RISKS ASSOCIATED WITH COLLAGEN TREATMENTS?
The known risks associated with Collagen Replacement Therapy can be classified into two categories: those associated with the collagen material itself, and those associated with the injection procedure.

The primary known risk of the collagen material is an allergic reaction. About 3% of the population is allergic to bovine collagen. A skin test is done before treatment to help determine whether you are allergic to the material. Some physicians will perform the skin test more than once. If you are allergic to injectable collagen you should not receive treatments. About 2% of patients treated will experience an allergic reaction, despite a negative skin test or tests.

This allergic reaction can result in prolonged redness, swelling, firmness and itching or, in rare instances, in formation of an abscess (cyst) that may result in hardness or a scar. These reactions are temporary in nature; however, in a few cases, periodic flare-ups have occurred for more than 24 months.

The primary risk from the injection procedure is bruising and swelling at the injection site. In rare cases, necrosis (tissue sloughing, or shedding, and resulting scab or sear formation) at the injection site may occur.

WHAT ARE AUTOIMMUNE DISEASES AND WHY HAVE THEY ALLEGEDLY BEEN LINKED TO COLLAGEN TREATMENTS?
Autoimmune diseases are conditions in which development of an allergic reaction to a part of the body causes the destruction of body tissues. Many diseases are classified as autoimmune, including connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus. Polymyositis/dermatomyositis (PM/DM) are two very rare autoimmune diseases which involve the destruction of muscle tissue. Like many autoimmune diseases, PM/DM are very difficult to diagnose and their cause is unknown. Certain autoimmune diseases are occasionally referred to as "collagen-vascular diseases" because the tissues affected are themselves, in part, composed of collagen. This misnomer led some people to speculate about links between autoimmune disease and injectable collagen.

IS THERE A CAUSAL RELATIONSHIP BETWEEN INJECTABLE COLLAGEN AND AUTOIMMUNE DISEASE?
Some physicians have reported the occurrence of connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis (DM), and polymyositis (PM) subsequent to collagen injections, in patients with no previous history of these disorders. A comparison of the observed number of cases of PM/DM in the collagen treated population with an estimate of the expected number of cases suggests an association between collagen injections and PM/DM; i.e., there appears to be a higher than expected incidence of PM/DM in the collagen treated population. However, a causal relationship between collagen injection and the onset of autoimmune disease or systemic connective tissue disease has not been established.

ARE COLLAGEN TREATMENTS WORTH IT?
Your physician will inform you of the risks and benefits associated with Collagen Replacement Therapy, and determine whether you are a good candidate for treatment. It is up to you and your physician to decide whether collagen treatments are right for you.

As part of this decision-making, process, you must weigh the benefits and the risks. The benefits of Collagen Replacement Therapy are psychological as well as physical. Many patients report a sense of heightened self-esteem and self-confidence after their treatments. Others believe the cosmetic benefits help them to be more successful in their jobs and in social situations. Some patients incorporate injectable collagen treatments as part of their ongoing beauty and health routine, while others get treatments for special occasions or holidays. Patients also appreciate the fact that collagen treatments take very little time and provide prompt results.

There are adverse treatment events that occur in a small percentage (2% of treated patients, and are usually limited to temporary, local allergic reactions which do not pose any known threat to one's health. A more detailed discussion is included in the section, "How Safe Is Collagen Replacement Therapy?" of this brochure and in the Safety Summary.

It is important to fully understand the issues surrounding collagen treatments. Your physician is your most important source of medical information about collagen treatments and the associated risks. With this in mind, you should make your decision based on the advice of your physician and your understanding of the risks and benefits of treatment.

SAFETY SUMMARY
Additional Information on Collagen Replacement Therapy for Discussion with Your Physician.

AlI medical procedures are subject to certain risks. Although thousands of men and women have found Zyderm and Zyplast¨ Collagen treatments to be a safe, non-surgical option, for many skin contour problems you should be aware of the safety issues and restrictions associated with their use. Although you should review these points at the time of your consultation with a physician trained in the use of collagen, we have summarized them for you as follows:

• If you have a reaction to the required skin test or previous allergic reaction to injectable collagen products or lidocaine, or have a history of serious allergic (anaphylactic) reactions, Zyderm or Zyplast Collagen must not be used. Also if you are undergoing or planning to undergo desensitization injections to meat products you cannot receive injectable collagen.
  
• The onset of connective tissue diseases has been reported after treatment with collagen injections in patients with no previous history of these disorders. A statistics analysis comparing the number of collagen treated patients who were diagnosed with two rare connective tissue diseases (Polymyositis/Dermatomyositis) with the expected number of these diseases, suggests that the rate of occurrence of these two rare diseases appears to be higher than expected in the collagen treated population. However, a causal relationship between collagen injections and the onset of the diseases has not been established.
  
• Also, patients with connective tissue disease may have an increased susceptibility to hypersensitivity responses and/or accelerated clearance of their implants. Therefore injectable collagen should be used with caution in such patients with consideration given to multiple skin tests.
  
• Since studies have shown that injected collagen may stimulate the deposition of your own collagen at injection sites there is a possibility that part or all of the correction may last two years or more
  
• The risk of injection is always present with any injection and it is possible to experience a reaction to the process itself such as mild bruising or a slight blush at the injection site. This does not mean it is necessary to discontinue treatment. Previous facial herpes simplex at the site of injection may recur if provoked by the injection.
  
• Though unlikely it is possible for the needle to be accidentally placed through a blood vessel during injection, which could result in temporary discoloration of the treated area or in tissue death leading to a scab and/or scar formation. Injectable collagen Iike other substances that are injected (particularly local anesthetics and steroids injected into the head or neck area or the extremities), could be accidentally injected into a blood vessel. A though this possibility is remote, it could result in a blockage of the blood flow and loss of circulation to nearby sites. Blood flow blockage resulting in permanent loss of vision in one eye has been reported once since product introduction in 1981.
  
• Occasionally injected collagen has been reported as visible in the skin, in the form of a small raised or white area at the treatment site, which may persist from a few weeks to several months. Some areas (such as compressed scars) resist precise placement of the material resulting in a slight elevation beside the defect. People with histories of atopic or allergic reactions to other substances require extra care when treated with injectable bovine products. Cautious use of Zyderm and Zyplast ColIagen is recommend and in such cases. In addition, caution is advised with people who are receiving immunosuppressive therapy. (Patients on long-term prednisone or other steroid therapy should consult their doctor before beginning Collagen Replacement Therapy.)
  
• More than one skin test is recommended prior to injectable bovine collagen treatment if you have a history of dietary beef allergy. It a possible that the collagen component of the beef may be causing the allergy
  
• If you are using drugs that reduce coagulation, such as aspirin and non-steroidal anti-inflammatory drugs, you may as with any injection, experience increased bruising or bleeding at injection sites.
  
• Active inflammatory skin conditions (eruptions such as cysts pimples rashes or hives) or infections require that treatment be postponed, untiI the condition has been controlled.
  
• The safety of treatment during pregnancy or in infants or children has not been established.
  
• With more than 500,000 people treated since 1976, injectable collagen has proven to be safe. However, a small number (one to two percent) have developed an allergic reaction after one or more injections, which has consisted of prolonged redness, swelling, itching, and/or firmness at some or alI of the sites. On rare occasions, these reactions can proceed to a cyst-Iike reaction that can drain, and may form a scar. Between one and nine months is the usual duration, but a few cases have involved intermittent flare-ups, which have exceeded 24 months.
  
• Importantly many people who developed an allergic reaction after treatment did not report or recognize a response to the skin test. (With proper monitoring of the skin test, many of these later reactions could have been prevented.)
  
• Systemic complaints have been reported in fewer than two per one thousand people treated and included flu-like symptoms (nausea, dizziness, headache, joint aches), rash, visual disturbances, anaphylactoid reactions (severe allergic reactions) invoIving difficulty in breathing , and various systemic diseases including immune-mediated diseases.
  
• Since every patient's expectations and physical make-up are different and every physician's technique is unique, there have been cases reported where collagen injections have not achieved the desired result.
  
• We encourage you to discuss this information with your doctor. He or she can best evaluate whether treatment is appropriate for you and can answer any questions you may have.