Friday, December 28, 2007

Lipodystrophy

Lipodystrophy is an umbrella term, covering three separate and possibly related changes in the way our bodies handle fat cells. Lipodystrophy includes both gains and losses in the body's stores of fat and changes in the amount of fat circulating in the blood. Scientists haven't yet agreed on the best way to measure or describe these dysfunctions and predicting who is at most risk for them is difficult.

The first two listed here are physical (or body). They are the ones I will spend time discussing as these are the patients I sometimes see. The third is in the blood. The three forms are:

  • Fat wasting, also known as lipoatrophy -- In this form fat is lost from particular areas of the body:
    • face (sunken cheeks, temples, and eyes)
    • arms and legs (veins may become more visible; this is called "roping")
    • buttocks

  • Fat accumulation, also known as lipohypertrophy -- In this form, fat builds up in particular parts of the body :
  1. back of the neck and upper shoulders (often described as "buffalo hump")
  2. abdomen (also called "protease paunch" or "Crixivan potbelly") This abdominal fat gained is underneath the muscle wall (visceral fat) and feels firm to the touch.
  3. breasts (in both men and women)
  4. lipomas (fatty growths in different parts of the body)
  • The third type is known as hyperlipidemia or dyslipidemia. It has been linked to higher rates of heart disease and diabetes-like symptoms. Before the availability and use of anti-HIV drugs, HIV disease progression was associated with decreases in cholesterol levels, particularly "good" cholesterol. An increase in this blood fat is uniquely associated with using certain anti-HIV drugs.

Lipodystrophy in combination with hyperlipidemia and insulin resistance is called lipodystrophy syndrome. For the metabolic discussions, may I suggest you read the 2nd, 3rd, and 4th articles in the reference section.

From the plastic surgeons viewpoint, these patients present wanting to regain a more "normal" face/body.

NONSURGICAL THERAPY

  • Diet and Exercise--Diet and exercise are essential to maintaining muscle mass and lean body mass, but will do nothing to address the substantial atrophy of the face or remove the "buffalo hump".
  • Anabolic Steroids hormones, the synthetic derivatives of testosterone, are thought to prevent catabolism and help preserve lean body mass. At this time, the only approved indications for these drugs are anemia, hereditary angioedema, and metastatic breast cancer, so their use in HIV-related wasting or lipodystrophy is considered “off-label.” Many products are currently available, including nandrolone and oxymetholone. Inherent in the use of anabolic steroids are the risks of hypertension, which may be treated with antihypertensive medications, and liver toxicity. Liver function tests should be monitored closely.
  • Growth Hormone is a naturally occurring product of the anterior pituitary. Growth hormone directly causes lipolysis of adipocytes and has indirect anabolic effects by the action of insulin-like growth factor I. Baseline growth hormone concentrations were found to be decreased in patients with lipodystrophy when compared with concentrations in unaffected HIV patients. There are reports by Torres et al. and Wanke et al. using recombinant growth hormone in HIV patients with truncal obesity and buffalo hump. Improvements in visceral adipose tissue and buffalo hump were noted in all patients. In addition, Torres et al. found that those patients who discontinued treatment experienced a recurrence of their dystrophic fat. Adverse effects of growth hormone included arthralgias, myalgias, carpal tunnel syndrome, and impaired glucose tolerance and hyperglycemia. Although growth hormone therapy is probably the safest and easiest way of increasing lean body mass, its utility is limited because it is prohibitively expensive for these patients, who are already taking a multidrug regimen presumably for the rest of their lives.
  • Metformin is an oral hypoglycemic used in the treatment of type II diabetes. Metformin decreases gluconeogenesis, improves insulin sensitivity, and decreases intestinal absorption of glucose. HIV patients treated with metformin have been shown to have significant decreases in weight and waist circumference, along with greater decreases in visceral adiposity. Although metformin may have minimal effects on HIV lipodystrophy–associated body composition, no study to date has mentioned the effects of metformin on buffalo hump, and it has no effect on the lipoatrophy aspects of the syndrome. Metformin is generally well tolerated in this population. However, lactic acidosis is a persistent and
    serious risk and there has been one fatal case reported in a man being treated with a nucleoside reverse transcriptase inhibitor and metformin.
  • Experimental Medications -- Several newer medications have been investigated in the treatment of HIV-associated lipodystrophy. Studies of the thiazolidinediones, a class of drugs that decrease insulin resistance and gluconeogenesis, have reported conflicting results. Ultimately, no drug therapy exists to fully ameliorate or correct the cosmetic changes of HIVassociated lipodystrophy. Studies of human growth hormone, however, have produced the most substantial results. If it is cost effective, human growth hormone may be the pharmacologic treatment of choice for certain patients with HIV lipodystrophy.

RECONSTRUCTIVE SURGERY

Three problems that can be treated with reconstructive surgery are the abnormal areas of fat deposition in the cervicodorsal fat pad (buffalo hump), gynecomastia, and facial wasting. The options include

  • suction-assisted lipectomy for anatomic areas that show abnormal fat deposition
  • injection of natural substances, such as collagen, as well as synthetic substances, such as New-Fill (Ashford Aesthetics, Inc., Belgium, Germany) and Sculptra (Aventis Pharmaceuticals, Bridgewater, N.J.), to treat facial wasting;
  • surgical injection of autogenous fat
  • a combination of lipoaspiration of the buffalo hump and use of the aspirate as a donor graft
  • fat/dermal grafting
  • alternative tissue grafting, using material from donor sites with concurrent deformities, such as gynecomastia tissue and cystic parotid gland.


Suction Lipectomy

Dense adipose tissue is routinely encountered in these patients, particularly in the cervicodorsal fat pads. Ultrasound-assisted suction lipectomy may make it easier (as compared to traditional liposuction) to do body contouring of fibrous areas. Timing of surgery and antibiotic prophylaxis is important, as the viral load in HIV-positive patients fluctuates during the course of their illness. It is recommended that surgery be postponed (1) during increased viral activity, (2) when preoperative laboratory results reveal an inversion of the normal 2:1 CD4-to-CD8 ratio, or (3) when patients report increased fatigue or weight loss.

Facial Fillers

New-Fill and, more recently, Sculptra, a hydrogel of microspheres of polylactic acid, have been used to correct facial fat atrophy in HIV lipodystrophy. In a large European study, 50 patients with HIV facial wasting were treated with New-Fill. At week 96, 43 percent of patients had increased their subcutaneous facial thickness more than 10 mm. Sculptra is a newer form of polylactic acid recently approved by the U.S. Food and Drug Administration for facial fill in HIV wasting. Treatment, however, is staged, time-limited, and expensive, ranging from $8000 to $10,000 per full course of treatment. Although no large studies have evaluated its efficacy in this population to date, it may serve an adjunctive role in the treatment of facial wasting. However, because severe wasting results from wasting of the buccal fat pad of Bichat, and the hollows of the malar region are also particularly deep, these superficially injected fillers may not adequately address the needs of the patient with severe facial wasting.

Autologous Free Fat

Serra-Renom et al. recently reported a series of HIV lipodystrophy patients with facial atrophy treated with autologous fat injection. Thirty-eight patients underwent augmentation with fat obtained from the infraumbilical region by liposuction. Symmetry and volume were evaluated at 6 months and 1 year, and in 12 cases, a new fat injection was performed to improve symmetry and resorption (often none of the fat will remain at 6 months and the loss may be uneven leaving a lumpy result). Some facilities may have the resources to store extra aspirate (frozen) which can then be injected 2 to 3 months later. This can be useful, as there is usually some resorption of the transplanted fat. Areas of dystrophic fat, such as the buffalo hump and gynecomastia tissue, are good sources for the fat used for augmentation. As the fat needs to be harvested and then injected and may need to be repeated this can be expensive.

Dermal-Fat Grafts

Strauch et al reported the use of dermafat transfers to the malar area for HIV facial wasting in five patients. The aesthetic results were dramatic and stable, lasting throughout the 1- to 2-year follow-up period. Dermafat grafts (dermis and fat in combination) have the ability to vascularize and persist indefinitely which may make them an attractive option in the reconstruction of HIV facial atrophy, either alone or in conjunction with other surgical techniques. The downside is the donor site which may result in an unsightly scar.

Malar Implants

Malar implants possess several substantial risks in the HIV population. The most serious of which are delayed infection and exposure, to which this immunocompromised group is already disposed. There is has been a few cases of the implants eroding through the thin wall of the anterior maxilla. This option may be less risky in non-HIV patients.

 

Algorithm (from the 6th reference below) lists Dr. Stevenson's preferences for surgical correction of HIV lipodystrophy. "Blue boxes indicate the presenting problems of HIV lipodystrophy: buffalo hump, gynecomastia, cystic parotid, and facial wasting, which we further classify as mild, moderate, or severe. Mild or moderate wasting may first be addressed with facial fillers and fat injection of buffalo hump (if available). Buffalo hump, if present, may initially be treated with suction-assisted liposuction (SAL); if it recurs or persists, it may need to be addressed with ultrasound-assisted liposuction (UAL). Gynecomastia may be treated with a subcutaneous mastectomy, and cystic parotid enlargement can be addressed with parotidectomy. Both of these autogenous tissues then may be used for treatment of severe cases of facial wasting, and they are more permanent than fat injection. These treatments may then be supplemented by additional fat injection."

REFERENCES

Lipodystrophy and Women--March 2005 Article at TheBody.com

Update on Lipodystrophy...Or Is It Just Lipoatrophy? by Donald P. Kotler, MD -- MedScape Article, 2002

Lipodystrophy, Generalized by Robert A Gabbay, MD & others --eMedicine Article, July 17, 2007

Lipodystrophy, HIV by Ali Hendi, MD & others -- eMedicine Article, January 18, 2006

Lipodystrophy -- DermNet NZ, updated 12-25-2007

Surgical Algorithm for Management of HIV Lipodystrophy; Plastic & Reconstructive Surgery, Vol 120(7):1843-1858, December 2007; Davison, Steven P. M.D., D.D.S.; Timpone, Joseph Jr M.D.; Hannan, Catherine M. M.D.

Cosmetic Interventions for HIV-Associated Lipoatrophy by Graeme J. Moyle, MD, MBBS -- MedScape Article

4 comments:

Christine-Megan said...

I've always heard of this in reference to why you need to rotate insulin sites, but never knew people could get it otherwise.

drkid34 said...

myself, a pediatrician, aged 42yr,
Could be The Spotter case, Peculair LD - Lipo Atrophy ,
Non Diabedtic, Negative for HIV screening, and primary Infertility.

The LD features, Peculiar with fat Depostion in the abdominal wall, unlike the classic - visceral fat, depositon beneath the abd- musculature.
And the classic features of LD, facial muscle wasting and roping at arms, legs and buttock wasting as well.

Hope to find help to manage with this Distressiing problem- causing - Weak-back -ache, and with droooping abd.fat wt,mechanical affect with urinary disturbance.

Edwin said...

Great Info, thanks.

togoresk said...

woman 36yr,
all the same as drkid34 and getting worse, please help me, it's terrible, don't know what to do