By Nelson Vergel, www.facialwasting.org

Dr. Lemperle is currently professor of cosmetic surgery at UC- San Diego medical school. He moved to the US three years ago from Germany, where he holds patents with his son on microspheres for facial implants.

Nelson Vergel is director of the Program for Wellness Restoration (PoWeR). Following is the text of his interview with Dr. Lemperle.



Vergel: What criteria are used to evaluate the effectiveness of an implant for facial lipoatrophy?

For facial lipoatrophy, there are solid and injectable implants that are commercially available. The solid ones made from polymerized silicone, Teflon, hydroxyapatite, or polyethylene can be cut to suitable shapes and implanted on the malar bone, maxillary sinus, and the mandibular arch.

The center of the cheek, the atrophied Bichat's fat pad can be augmented with an oval shaped implant from soft silicone (1), which was the first line choice before the era of permanent soft tissue fillers.

The ideal injectable dermal filler substance must be biocompatible and safe, stable at the implantation site, retain its volume and remain soft and pliable, should not dislocated by gravity, and evoke minimal foreign body reaction (2).

Vergel: What risks are associated with the use of implants?

The potential risks of temporary filler substances, such as collagen, hyaluronic acids, polylactic acid or PMA beads, are fast absorption within 3 to 6 months, allergic reactions and - not yet understood - late granuloma formation.

Permanent filler substances, such as silicone fluid or gel, polyacrylamides, silicone particles, or PMMA microspheres, carry the risk of technical mistakes during implantation, allergic reactions, dislocation by muscle movement or gravity, and late granuloma formation.

Vergel: How do you treat side effects such as granuloma and migration?

Dislocated implants or lumps can be diminished and softened effectively by intralesional corticosteroid (Kenalog) injections (3). They inhibit fibroblasts from producing collagen fibers, thereby reducing the volume of the encapsulating host tissue by half.

The rather rare granulomas (1 in 10,000), which are an ongoing foreign body reaction, can also be reduced to its former size by use of corticosteroids. Since every patient reacts differently to these drugs, which may cause temporary atrophy when injected into the subcutaneous fat, these strictly intralesional injections have to be repeated in 3-weeks intervals.

Larger depositions of silicone gel or polyacrylamides can be reduced by suction. Surgical excisions are never indicated!

Vergel: Is there any evidence of a cause and effect relationship between soft tissue augmentation and cancer?

In rats, artificial substances such as solid polymers can cause sarcoma formation on smooth surfaces and edges (Oppenheimer effect). This effect, however, could never be demonstrated with the same substances injected in powder form, e.g. as micro particles or microspheres.

In humans, no malignant tumor formation has been reported on substances, which have been used for more than 50 years, such as paraffin, silicone, or PMMA-bone cement.

Vergel: What do you consider the best options for cosmetic treatment of facial atrophy in HIV patients?

Since 20 years, I have 20 years of personal and professional experience with injectable substances. I have injected all of them into the skin of my left forearm to control persistence and histology. There is no question: the risks of lumpiness and dislocation are less in temporary fillers since both will be absorbed within a few months. On the other hand, the costs of repeating these treatments every 6 months are certainly much higher than one to three treatments with a permanent filler.

Silicone fluid can be effective and durable, however, dislocation by gravity in patients with loose connective tissue, and late granuloma formation in some patients have banned its use in most countries.

What is your opinion of polyacrylamide-based products?

Polyacrylamides have been used extensively in the Ukraine for 20 years. Polyacrylamides appear to be very biocompatible and do not cause the formation of a capsule at all. Therefore, the deposit can dislocate by gravity in certain patients and have to be removed by suction.

For me, tiny microspheres from any non-absorbable polymer are the material of choice for tissue augmentation today. Their smooth surface allows encapsulation instead of rejection, and permanent fixation at the location where they are injected.

Vergel: What is your opinion of use of polylactic acid (New-Fill) for sunken cheeks caused by HIV-related lipoatrophy?

For two years, we have been trying to find a substance that which will have a semi-permanent effect of about 2 years in human tissue. All efforts to change the formulation of polylactic acids have failed, so far. New-Fill® microspheres are absorbed within 3 - 6 months and therefore not the best choice for the treatment of a lasting condition such as facial lipoatrophy.

Vergel: What is your experience with Artecoll?

Artecoll has been used in Europe and other countries for over ten years and in more than 200,000 patients worldwide. Each of the 6 million microspheres is encapsulated with the body's own connective tissue, which makes up 80% of the final implant.

Until 1994, the microspheres had tiny PMMA particles attached, which were the cause of granuloma formation in some patients. These cases are still mentioned on meetings but are history, fortunately. The clinical trials in the US showed its lasting effectiveness without any side effects worth mentioning.

In my 12-year experience with Artecoll, a medium lipoatrophy needs at least 5 cc of filler material on each side to be treated successfully. Therefore, one or even 2 cc injected too deeply will easily give the impression of disappearance to the patient. Especially in an atrophic skin, one has to be very carefully to deposit Artecoll deep dermally and not into the residual subcutaneous fat! Your friend may have got a small amount injected.
However, no statistical data are available. Histologically, it causes almost no reaction or capsule formation (2) and shows similarities to inert fluid silicone.

Since the patent expired recently, at least 7 European companies produce filler substances from this material. A health official in China, however, told me some months ago that polyacrylamides (Interfall®) will be prohibited soon because of a high incidence of enlarged lymph nodes, dislocation by gravity, and granuloma formation in Chinese patients.

Vergel: What is your opinion about polyacrylamide-based products?

Polyacrylamides have been used extensively in Ukraine for 20 years, however, no statistical data are available. Histologically, it causes almost no reaction or capsule formation (2) and shows similarities to inert fluid silicone. Since the patent expired recently, at least 7 European companies produce filler substances from this material. A high health official in China, however, told me some months ago that polyacrylamides (Interfall®) will be prohibited soon because of a high incidence of enlarged lymphnodes, dislocation by gravity, and granuloma formation in Chinese patients.

 Vergel: What are the most promising products in the research pipeline?

For more than 20 years, there is only one product approved for soft tissue augmentation in the US, and that is bovine collagen (Zyderm® and Zyplast®). Hyaluronic acid products (Restylane® and Hylaform®) are in clinical trials and may be approved soon.  Both are, however, not longer lasting than collagen, have similar side effects and can cause late granulomas like collagen.

Polylactic acid microspheres (New-Fill®) are in clinical trials for facial lipoatrophy but are not longer lasting than collagen, too.

Scientifically, Artecoll®, which consists of microspheres sieved from bone cement (polymethylmethacrylate) and suspended in collagen is the best and longest-lasting proven materials in aesthetic surgery, and therefore my first choice for the treatment of wrinkles and facial lipoatrophy.

I would switch tomorrow to a better injectable material, if there were one.

Vergel: What do you think the HIV community can do to gain faster access to these treatment options?

The HIV community should approach the companies of soft tissue fillers and ask for clinical trials enrolling facial lipodystrophy patients. Later on, these companies should provide the material at their lowest price exclusively for HIV patients.

Because side effects of drugs are real diseases, the FDA should categorize these trials as urgent and review under accelerated approval protocols. The HMO's should recognize facial lipoatrophy as a disease and discuss a certain amount for the physician's reimbursement. If this does not work out soon, it's common practice among pharmaceutical companies to reimburse patients for the treatment of side effects caused by their drugs.

Vergel: Are fears about silicone unfounded?

The fears about silicone gel being immunogenic, which have been launched in the early nineties by some focused physicians, lawyers, and breast implant patients, have been proven by many rheumatologists and epidemiologists to be unfounded. Soon, gel-filled breast implants will be on the US market again.

Vergel: Any final thoughts?

I am well aware of the importance the stigma of facial lipoatrophy means to its bearer. There is an easy, applicable and safe way of leveling this deformity in 3 to 5 ambulatory sessions to its former appearance. The price per syringe is rather high and must be reduced effectively to meet the needs of these real patients. Furthermore, HMOs must realize that access to treatment for facial atrophy will strongly impact the quality of life for the HIV community.

See also Promising Results from a Pilot Study of Polylactic Acid Implants (New-Fill)® to Correct Facial Lipoatrophy in HIV Patients

11/19/03

References
1. Hasse FM, Lemperle G: Resection and augmentation of Bichat's fat pad in facial contouring. Europ J Plast Surg 17: 239, 1994.

2. Lemperle G, Romano JJ, Busso M: Soft tissue augmentation with Artecoll: 10-year history, indications, technique, and potential side effects. Dermatol. Surg.28 2002.

3. Lemperle G, Morhenn VB, Pestonjamasp V, Charrier U, Gallo RL.
Histology, persistence, and migration studies of various injectable filler substances for tissue augmentation. Plast Reconstr Surg 112:, 2003