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

ase Reports

Case 1. On December 8, 2007, a District of Columbia man aged 42 years, who was previously healthy except r a history of anemia, received cosmetic soft-tissue filler jections in her buttocks at facility A. Records specifying e substance injected were unavailable. On December 22, e woman received additional injections at facility A. cording to facility records, 300 mL of "dermal silicone/ ine solution" were injected into each buttock (600 mL tal) during the December 22 visit. The woman experi

enced 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

William L. Roper, MD, MPH, Chapel Hill, NC, Chairman Virginia A. Caine, MD, Indianapolis, IN

David W. Fleming, MD, Seattle, WA

William E. Halperin, MD, DrPH, MPH, Newark, NJ
Margaret A. Hamburg, MD, Washington, DC
King K. Holmes, MD, PhD, Seattle, WA
Deborah Holtzman, PhD, Atlanta, GA

John K. Iglehart, Bethesda, MD
Dennis G. Maki, MD, Madison, WI
Sue Mallonee, MPH, Oklahoma City, OK
Stanley A. Plotkin, MD, Doylestown, PA
Patricia Quinlisk, MD, MPH, Des Moines, IA
Patrick L. Remington, MD, MPH, Madison, WI
Barbara K. Rimer, DrPH, Chapel Hill, NC
John V. Rullan, MD, MPH, San Juan, PR
Anne Schuchat, MD, Atlanta, GA
Dixie E. Snider, MD, MPH, Atlanta, GA
John W. Ward, MD, Atlanta, GA

(800 mL total). Within 1 hour of these injections, experienced headache and nausea and noted that her un had a burgundy color. She went to an Illinois ED December 23 with nausea, headache, and fatigue and w found to be in acute renal failure, with a serum creatin level of 4.0 mg/dL. Serum CPK was 517 U/L on the day admission. The patient's renal function worsened, an hemodialysis was initiated. A renal biopsy on Decemb 27 revealed severe acute tubular necrosis with cast form tion. The casts were not myoglobin or hemoglobi pathologists were unable to determine their composition despite the use of specialized stains. No heavy metals we identified in urine specimens, and no other specific et ogy was identified. The woman remained in the hospi for 13 days. Hemodialysis was discontinued after 5 week and the woman subsequently regained normal kidne function.

Case 3. A previously healthy Maryland woman aged 1 years received soft-tissue filler injections in her buttocks facility A on December 8, 2007, and again on Decemb 22. No records were available from either date. The woma developed abdominal pain, lightheadedness, and nause within 1 hour after the second procedure. She went to a ED on December 26 with fatigue and vomiting and w found to have a serum creatinine level of 11 mg/d Hemodialysis was initiated. A renal biopsy on January 1 2008, demonstrated acute interstitial nephritis with sub stantial numbers of eosinophils, consistent with a toxic allergic etiology. Eosinophilia was not found on peripher blood smears. No heavy metals were identified in un specimens. She remained in the hospital for 14 day hemodialysis was discontinued within 1 week after di charge, and her serum creatinine level subsequently returne to normal.

Public Health Investigation

On December 27, 2007, NCDPH was notified of the three cases by a District of Columbia nephrologist wh had treated one of the patients. This patient was aware of second ill patient, and the physician learned of the th after contacting practitioner A. Case investigations we conducted, including interviews with the three patients an their physicians and medical record reviews. Facility A w first inspected on December 28 to identify products an materials used in the procedures, evaluate infection control practices, review records pertaining to facility patients, and interview practitioner A. Subsequent inspec tions and interviews were conducted on January 3 and January 10, 2008. Other patients identified from facili

cords and interviews with practitioner A as having eived injections at facility A also were interviewed to iden✓ additional cases.

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

Representatives of the Guilford County Health Departent and NCDPH interviewed practitioner A and concted inspections of facility A with assistance from CDC, e Food and Drug Administration, the North Carolina od and Drug Protection Division, the North Carolina atewide Program for Infection Control and Epidemioly, and the North Carolina Medical Board. Multiple eaches of standard infection-control practice were noted the facility. Records pertaining to facility A patients were ailable on-site. However, these records contained scant formation regarding procedure techniques and materials ed, and in some cases, conflicted with information obned through patient interviews. All patients had signed rms labeled "Consent to Treatment." However, these rms did not mention soft-tissue filler procedures or the tential risks associated with these procedures. Although cords from the patients in cases 1 and 2 indicated that ey had received dermal silicone, investigators were not le to confirm which substances had been injected or how ey had been procured. No residual products or materials ed in the soft-tissue filler injections were available at the nic. Practitioner A claimed that she had injected a speic brand of medical-grade silicone oil mixed with saline. owever, she provided no invoices, ordering information, other evidence to support this claim.

Practitioner A had trained as a radiology technician and as administering the soft-tissue filler injections without edical supervision. Signage and promotional materials ailable on the Internet and in facility A referred to the cility as a family medicine practice and used the name of family medicine physician licensed in North Carolina. owever, this physician had no recent affiliation with cility A and no involvement with the soft-tissue filler produres. 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.