Acute Renal Failure Associated with Cosmetic Soft-Tissue Filler Injections --- North Carolina, 2007

Soft-tissue fillers are substances injected to augment or enhance the appearance of lips, breasts, buttocks, or other soft tissues. Previous reports have linked the administration of soft-tissue fillers, usually liquid silicone, by unlicensed practitioners to severe adverse events, including death (1--9). On December 27, 2007, the North Carolina Division of Public Health (NCDPH) was notified of three cases of renal failure occurring among women who had received cosmetic soft-tissue filler injections at a facility in North Carolina (facility A). This report summarizes the clinical findings for these cases and describes the subsequent public health investigation. All injections were administered by a practitioner with no medical training or supervision (practitioner A). Investigators were not able to identify the substances injected. Although records indicated that the injections contained liquid silicone, this substance has not been associated previously with renal failure. These findings underscore the risks posed by cosmetic injections administered by unlicensed practitioners. Public health officials should be alert for adverse events associated with these injections and take all necessary actions to prevent additional injuries.

Case Reports

Case 1. On December 8, 2007, a District of Columbia woman aged 42 years, who was previously healthy except for a history of anemia, received cosmetic soft-tissue filler injections in her buttocks at facility A. Records specifying the substance injected were unavailable. On December 22, the woman received additional injections at facility A. According to facility records, 300 mL of "dermal silicone/saline solution" were injected into each buttock (600 mL total) during the December 22 visit. The woman experienced headache and vomiting within 30 minutes of these injections and noted that her urine looked like purple blood. She went to an emergency department (ED) in Maryland on December 24 with fatigue, vomiting, and headache and was found to be in acute renal failure, with a serum creatinine level of 4.2 mg/dL (normal: 0.8--1.4 mg/dL). Laboratory investigations, including urine testing for heavy metals, did not reveal a specific etiology. Her serum creatine phosphokinase (CPK) level was 411 U/L on the day of admission (normal: 25--200 U/L). She remained hospitalized for 10 days. Hemodialysis was not required, and her serum creatinine level subsequently returned to normal.

Case 2. On December 8, 2007, a previously healthy Illinois woman aged 26 years received cosmetic soft-tissue filler injections in her buttocks at facility A. Records indicated that she received 500 mL of "25% silicone dermal filler and 75% saline solution" in each buttock (1,000 mL total). She received additional injections at facility A on December 22. Records from December 22 indicate that 400 mL of a "50% concentration of silicone oil dermal filler and saline solution" were injected into each buttock (800 mL total). Within 1 hour of these injections, she experienced headache and nausea and noted that her urine had a burgundy color. She went to an Illinois ED on December 23 with nausea, headache, and fatigue and was found to be in acute renal failure, with a serum creatinine level of 4.0 mg/dL. Serum CPK was 517 U/L on the day of admission. The patient's renal function worsened, and hemodialysis was initiated. A renal biopsy on December 27 revealed severe acute tubular necrosis with cast formation. The casts were not myoglobin or hemoglobin; pathologists were unable to determine their composition, despite the use of specialized stains. No heavy metals were identified in urine specimens, and no other specific etiology was identified. The woman remained in the hospital for 13 days. Hemodialysis was discontinued after 5 weeks, and the woman subsequently regained normal kidney function.

Case 3. A previously healthy Maryland woman aged 26 years received soft-tissue filler injections in her buttocks at facility A on December 8, 2007, and again on December 22. No records were available from either date. The woman developed abdominal pain, lightheadedness, and nausea within 1 hour after the second procedure. She went to an ED on December 26 with fatigue and vomiting and was found to have a serum creatinine level of 11 mg/dL. Hemodialysis was initiated. A renal biopsy on January 11, 2008, demonstrated acute interstitial nephritis with substantial numbers of eosinophils, consistent with a toxic or allergic etiology. Eosinophilia was not found on peripheral blood smears. No heavy metals were identified in urine specimens. She remained in the hospital for 14 days; hemodialysis was discontinued within 1 week after discharge, and her serum creatinine level subsequently returned to normal.

Public Health Investigation

On December 27, 2007, NCDPH was notified of these three cases by a District of Columbia nephrologist who had treated one of the patients. This patient was aware of a second ill patient, and the physician learned of the third after contacting practitioner A. Case investigations were conducted, including interviews with the three patients and their physicians and medical record reviews. Facility A was first inspected on December 28 to identify products and materials used in the procedures, evaluate infection-control practices, review records pertaining to facility A patients, and interview practitioner A. Subsequent inspections and interviews were conducted on January 3 and January 10, 2008. Other patients identified from facility records and interviews with practitioner A as having received injections at facility A also were interviewed to identify additional cases.

All three of the index patients learned of facility A directly or indirectly through Internet chat rooms and had selected it based on price and a perception that the procedure as described presented a low risk for adverse effects because it was performed in a clinic. All three patients were told by practitioner A that she was under the supervision of a physician, although none had seen a physician during their visits. Two of the patients had traveled to facility A together; the third had no association with the others. None of the patients reported any illicit drug use or common exposures to food or drinks.

Representatives of the Guilford County Health Department and NCDPH interviewed practitioner A and conducted inspections of facility A with assistance from CDC, the Food and Drug Administration, the North Carolina Food and Drug Protection Division, the North Carolina Statewide Program for Infection Control and Epidemiology, and the North Carolina Medical Board. Multiple breaches of standard infection-control practice were noted at the facility. Records pertaining to facility A patients were available on-site. However, these records contained scant information regarding procedure techniques and materials used, and in some cases, conflicted with information obtained through patient interviews. All patients had signed forms labeled "Consent to Treatment." However, these forms did not mention soft-tissue filler procedures or the potential risks associated with these procedures. Although records from the patients in cases 1 and 2 indicated that they had received dermal silicone, investigators were not able to confirm which substances had been injected or how they had been procured. No residual products or materials used in the soft-tissue filler injections were available at the clinic. Practitioner A claimed that she had injected a specific brand of medical-grade silicone oil mixed with saline. However, she provided no invoices, ordering information, or other evidence to support this claim.

Practitioner A had trained as a radiology technician and was administering the soft-tissue filler injections without medical supervision. Signage and promotional materials available on the Internet and in facility A referred to the facility as a family medicine practice and used the name of a family medicine physician licensed in North Carolina. However, this physician had no recent affiliation with facility A and no involvement with the soft-tissue filler procedures. In addition to soft-tissue fillers, practitioner A was administering small volumes of other injectable products purported to produce weight loss.

Investigators were unable to determine how long practitioner A had been administering soft-tissue filler injections or how many patients had received them. Practitioner A initially reported that 50 persons had received these injections at facility A over a 1-year period. However, only five additional recipients were identified through subsequent reviews of facility records and interviews with practitioner A. Investigators were able to contact four of these patients. All were women and had received injections during November 17--December 18, 2007. Three resided outside North Carolina. According to facility records, three had large volumes (540--1,000 mL) of silicone oil and saline injected in the buttocks; the fourth received small-volume facial injections. Practitioner A stated that all four of these women had received silicone oil from the same shipment as the index patients, although she provided no evidence to support this claim. One of the four patients had experienced pink urine transiently after the procedure, which she attributed to menstrual bleeding. None of the other three women reported adverse effects. All four women were encouraged to see their physicians and have their renal function tested; results of these evaluations are not known. Six persons identified from facility records as having received other types of injections during the same period were contacted; three did not report any adverse events associated with these injections, and three reported various symptoms, including nausea, bruising, diarrhea, and weight gain.

On December 28, 2007, notification regarding this cluster was posted on CDC's Epidemic Information Exchange (Epi-X) and distributed to nephrologists and toxicologists throughout the United States. No additional cases have been reported in response to these notifications. On January 16, 2008, NCDPH issued a press release. After reports appeared in the local media, the Guilford County Health Department received calls from five persons reporting adverse events after injections at facility A. Four callers reported injection-site reactions, including knots, inflammation, abscesses, and ulcers. The fifth caller reported being hospitalized for a pulmonary embolism approximately 3 weeks after her last injection. Each of these persons reported receiving small-volume injections of various substances purported to produce weight loss; none reported receiving silicone oil or other soft-tissue fillers.

On December 28, 2007, the Guilford County Health Director issued an abatement order prohibiting any owner or employee at facility A from administering injections containing silicone oil. On January 3, 2008, this order was expanded to prohibit administration of all injections. The findings of this investigation were presented to the local district attorney; practitioner A subsequently was arrested and charged with practicing medicine without a license.

Reported by: M Branton, MD, AD Bivins, MD, District of Columbia. LTR Terrado, MD, Olympia Fields, Illinois. M Green, MPH, Guilford County Health Dept; R Langley, MD, D Campbell, MD, North Carolina Div of Public Health. M Sutter, MD, J Schier, MD, J Lando, MD, National Center for Environmental Health; PR Patel, MD, M Jhung, MD, National Center for Preparedness, Detection, and Control of Infectious Diseases; B Goode, MPH, Coordinating Office for Terrorism Preparedness and Emergency Response; ZS Moore, MD, EIS Officer, CDC.

Editorial Note:

This report describes three cases of acute renal failure that were identified among patients receiving injections of an unknown substance from an unlicensed and unsupervised practitioner. These cases illustrate the dangers of receiving cosmetic injections from unlicensed practitioners.

The substance injected was reported to be silicone oil, although this could not be verified. The etiology of renal failure also could not be determined. Renal failure has not previously been associated with silicone injections, increasing the likelihood that another substance might have been involved in these cases. The lack of residual product or documentation and inconsistent information from the practitioner complicated efforts to investigate this possibility. Previous reports have indicated that products misidentified as silicone oil might contain other substances, such as mineral oil, linseed oil, or flax oil (2). No liquid silicone products are currently approved or cleared by the Food and Drug Administration for cosmetic injection. However, such products are licensed for other indications, and off-label use within a legitimate practitioner-patient relationship is not generally prohibited by federal law.*

Various adverse events have been reported in association with cosmetic silicone injections, including granuloma formation, infection, pneumonitis, pulmonary embolism, ulceration, product migration, and death (1--7). Most reported adverse events have occurred after injections by unlicensed practitioners using formulations not intended for medical use (2--7). These formulations often are administered in large volumes and might be intentionally adulterated with tissue irritants to increase swelling or unintentionally adulterated with microorganisms or other contaminants (2,3). Practitioners implicated in similar episodes have been convicted of offenses ranging from practicing medicine without a license to third-degree murder (4). Few data are available regarding the incidence of adverse events after administration of silicone oil soft-tissue fillers by licensed medical providers (1). No adverse events were reported among 77 patients in a recent pilot trial of highly purified silicone oil for treatment of human immunodeficiency virus--associated facial lipoatrophy (10).

Soft-tissue filler injections should be administered only by licensed providers with appropriate medical training. Laws governing medical procedures vary by state. In North Carolina, all injections are considered medical procedures and must be performed or supervised by licensed physicians. The cases described in this report and the other adverse events reported among clients of facility A serve to remind consumers and public health officials of the substantial risks associated with cosmetic procedures performed by unlicensed practitioners.

Acknowledgments

The findings in this report are based, in part, on contributions from D Pittman, North Carolina Medical Board; D Weber, MD, Univ of North Carolina School of Medicine; K Carter, RS, Guilford County Health Dept; D Ragan, RPh, J Reardon, North Carolina Dept of Agriculture and Consumer Svcs; D Bergmire-Sweat, MPH, North Carolina Div of Public Health; and T Berry, RPh, Food and Drug Admin.

References

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2. Hage JJ, Kanhai RC, Oen AL, van Diest PJ, Karim RB. The devastating outcome of massive subcutaneous injection of highly viscous fluids in male-to-female transsexuals. Plast Reconstr Surg 2001;107:734--41.
3. Fox LP, Geyer AS, Husain S, Della-Latta P, Grossman ME. Mycobacterium abscessus cellulitis and multifocal abscesses of the breasts in a transsexual from illicit intramammary injections of silicone. J Am Acad Dermatol 2004;50:450--4.
4. Price EA, Schueler H, Perper JA. Massive systemic silicone embolism: a case report and review of the literature. Am J Forensic Med Pathol 2006;27:97--102.
5. Chastre J, Brun P, Soler P, et al. Acute and latent pneumonitis after subcutaneous injections of silicone in transsexual men. Am Rev Respir Dis 1987;135:236--40.
6. Chen YM, Lu CC, Perng RP. Silicone fluid-induced pulmonary embolism. Am Rev Respir Dis 1993;147:1299--302.
7. Duong T, Schonfeld AJ, Yungbluth M, Slotten R. Acute pneumopathy in a nonsurgical transsexual. Chest 1998;113:1127--9.
8. Toy BR, Frank PJ. Outbreak of Mycobacterium abscessus infection after soft tissue augmentation. Dermatol Surg 2003;29:971--3.
9. Rollins CE, Reiber G, Guinee DG, Lie JT. Disseminated lipogranulomas and sudden death from self-administered mineral oil injection. Am J Forensic Med Pathol 1997;18:100--3.
10. Jones DH, Carruthers A, Orentreich D, et al. Highly purified 1000-cSt silicone oil for treatment of human immunodeficiency virus-associated facial lipoatrophy: an open pilot trial. Dermatol Surg 2004; 30:1279--86.

* Food and Drug Administration Modernization Act (FDAMA) of 1997. Public law 105--115, section 214. Available at http://www.fda.gov/cder/guidance/105-115.htm.

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Date last reviewed: 5/1/2008