Right After Sculptra Injection, Left Side Swelled Much More Than Right Side, Was It Due to More Injection on Left Side? (photo)

 

                       The HISTORY OF SCULPTRA: What happened to integrity at the FDA

 

The accelerated (compassionate) approval process at the FDA has swiftly provided a number of new drugs and devices that have conferred substantial clinical benefit in rapidly evolving therapeutic areas such as HIV/AIDS.  Treatment of HIV was revolutionized by the introduction of highly active antiretroviral therapy (HAART) in 1997. Furthermore, the rapid –track process has provided a number of significant therapeutic advances to treat those individuals with persistent viremia. As HIV therapy has evolved, a number of unexpected side-effects have been observed.  In particular, lipoatrophy and various metabolic abnormalities have been noted which are the result of HARRT therapy, specific antiviral agents or the disease process itself.  Unfortunately, the facial fat loss associated with this lipoatrophy has become tantamount to a visible stigma of HIV.

Recently, SculptraR received accelerated approval as an agent to correct the appearance of these individuals. What follows is the case history of a patient who experienced a significant adverse reaction to Sculptra.  More importantly it shows how the accelerated approval process was utilized to bring to market an agent which was only approved for limited use in patients with HIV.  In spite of this limited approval, Sculptra is now being heavily promoted to physicians for use and treatment in the immunocompetent general public. It is difficult to understand how this occurred, since the FDA advisory panel unanimously advised that this product be limited only to individuals with HIV(reference the fda  minutes)


CASE REPORT

DP is a 45 year old man with HIV who has been maintained on HAART for the last 5 years. His therapeutic regimen included a protease inhibitor. Over the past 2 years he noted significant  “shrinking’ of his cheeks combined with increased abdominal girth. Finally, he noted significant fat accumulation at the superior aspect of his back (dorsocervical fat pads or "buffalo hump”).  The protease inhibitor was replaced in his therapeutic regimen but there was no improvement in HIV-associated lipodystrophy. Seven months prior to the date of examination, he had undergone a series of three monthly injections of SculptraR to the cheeks, nasolabial folds, and periorbital areas.  By the third visit, he had developed severe swelling in the periorbital area and refused further treatment with SculptraR.

When the patient was first examined by me, he had 3 nodules (>10mm) in the inferior periorbital area of his left eye and 2 nodules under his right eye (fig 1).  The original physician attempted to treat these nodules with intralesional steroids but with no response.  Under local anesthesia, these lesions were subsequently incised revealing a white gelatinous material. This material was excised and submitted for histopathologic analysis (fig 2).  Microscopic analysis showed this to be “a foreign body granuloma” (fig 3). The patient was seen a week later and had responded well to this surgery. The patient has been advised against the use of Sculptra in this area and is now being followed every 3 months.

DISCUSSION

There is a critical need for an agent or device that can effectively manage the cosmetic facial changes observed in patients with HIV who develop lipoatrophy. Such agents should be nonallergenic, temporary (so migration is not feasible) and have the ability to provide a large volumetric enhancement at a reasonable cost. In reviewing the information presented at the FDA hearing for SculptraR as well as the manufacturer’s literature, it is suggested that, once implanted, SculptraR increases skin thickness through a process called “neocollagenesis.” In many studies, the efficacy of this agent was determined by utilizing skin calipers to measure skin thickness, even though it is loss of subcutaneous fat which occurs with lipoatrophy and not change in skin thickness. 

No histologic data was presented at the FDA hearing regarding the fate of this material once implanted. In this case as well as other cases reported in the literature, soft tissue augmentation with SculptraR  can result in a foreign body reaction (1, 2).  With other injectable fillers such as Zyplast, at times local allergic reactions may only be palpable and not visible.  Nodules were reportedly visible and/or palpable in many individuals in the pivotal trials of SculptraR \At the FDA hearing 52 percent of treated patients had evidence of these reactions in the VEGA study (3), and 31 percent had similar reactions in the London’s (C&W) Chelsea and Westminster Hospital study (4).  The onset of these reactions averaged 218 days after implantation, with a range from 9 to 748 days. Because patients with HIV, once on HAART, frequently have their immunological levels restored, they can then mount a foreign body reaction. This suggests that a mechanism of correction of lipodystrophy with SculptraR may be a foreign body reaction. Although the immunologic mechanism of a foreign body reaction is not firmly established, the ability to augment such a response is frequently restored in HIV patients who are on HAART.  Nevertheless, the present case could have possibly hae been avoided if proper education had been given to the physician on injection technique and sites amenable to correction.  Of additional concern is that the manufacturer is now sponsoring meetings and publications suggesting the use of this material for injection in immunocompetent women. I, as well as others, have seen large nodules above the lip, in the cheeks, and elsewhere in immunocompetent patients receiving this treatment. The manufacturer promised the FDA to educate physicians on proper patient selection and proper application of this product upon receiving accelerated approval.  On the contrary, they are promoting it for use in all individuals.

Prior to its approval for HIV- associated lipodystrophy in the USA, the potential side effects of this treatment were described in the European literature.  In a series of 100 patients treated with this product, 5 developed infection, 12 had granulomas and 3 had long term allergic reactions (5). As a physician, I believe in compassion, but I also believe in science. I strongly believe that this product should be available to HIV patients with lipoatrophy and administered only on a case by case basis by trained individuals. Indeed, the FDA advisory panel unanimously agreed with this position (6).  However the Agency took no steps to assure compliance such as a patient registry with controlled access limited to HIV+ patients.  Furthermore, the manufacturer stated SculptraR would not be made available to immunocompetent individuals but continues to promote the general use of the product (7) with no action being taken by the FDA.  The manufacturer of this product states that it is immunologically inert yet should be avoided in individuals who may be hypersensitive to it. This makes little scientific sense, as would the FDA allowing the manufacturer to promote this product for use in immunocompetent individuals.

 

 

 

At present Sculptra has been approved for immunocompetent individuals. There is not a day that goes by where I am not called by someone somewhere about reactions to this product. The American Academy of Dermatology and the FDA are now run by Big Pharma whotcould care less what you  look like but rather are far more interested in  how much of their agent(s)sells. Adverse Reactions occur but are rarely reported.   Most injectors these days can barely inject let alone know what happens under the skin after the injection!

 

 


REFERENCES:

1. Farrant P, Higgins E.  A granulomatous response to tribal medicine as a feature of the immune reconstitution syndrome.  Clin Exp Dermatol (2004 Jul) 29(4):366-8
2. Murray CA, DeKoven J, Spaner DE.  Foreign body granuloma: a new manifestation of immune restoration syndrome.  J Cutan Med Surg (2003 Jan-Feb) 7(1):38-42)
3. Valantin MA, Aubron-Olivier C, Ghosn J, Laglenne E, et al.  Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS (2003 Nov 21) 17(17):2471-7
4. Cheonis N. New-Fill to treat facial wasting BETA 2002; 15(2):10-15
5. Saylan Z.  Facial Fillers and Their Complications. Aesth Surg J (May/June 2003) 23(3): 221-4.
6. United States of America, Food and Drug Administration, Center for Devicies and Radiological Health, Medical Devices Advisory Committee.  General and Plastic Surgery Devices Panel.  Gaithersburg, Maryland.  65th Meeting: Thursday, March 25, 2004
7. Fillers to Sculptors: Addressing Volumetric Restoration.  New Treatment Options in Lipoatrophy.  Supplement to Dermatology Times, August 2005, 1-16.

Usually after sculptra injections, there is moderate swelling of the injection sites followed by subtotal resolution in one to two days.  If there is inadvertent trauma to a blood vessel and subsequent bleeding, there can be more swelling on the affected side.  It may take up to three days for the bruising to manifest itself in the neck or even the upper chest wall on the involved side.  If this is the case, you can expect complete resolution in a week or so.

If more sculptra were injected on one side than the other, one would expect them to be fairly symmetrical in a day.

Please call your physician and have her/him evaluate you.  Good luck.