© 2001 by the American Society for Dermatologic Surgery, Inc. • Published by Blackwell Science, Inc.ISSN: 1076-0512/01/$15.00/0 • Dermatol Surg 2001;27:497–500

BRIEF COMMUNICATION /

CASE REPORT

HIV Lipodystrophy: Review of the Syndrome and Report of a Case Treated with Liposuction

Mark A. Chastain, MD, Jennifer Buckley Chastain, MD, MPH, and William P. Coleman, III, MD

Department of Dermatology, Tulane University School of Medicine, New Orleans, Louisiana

background.

A syndrome characterized by loss of fat onthe face and limbs, localized fatty deposits on the trunk, andmetabolic disturbances is becoming increasingly recognizedin the human immunodeficiency virus (HIV) patient popula-tion.

objective.

To increase awareness of this syndrome amongdermatologists and dermatologic surgeons and to review itsvarious treatment options, including liposuction.

methods.

We present a patient with HIV lipodystrophy syn-drome who underwent tumescent liposuction. We also describeour experience with liposuction in the management of this con-

dition and review the treatment options that have been pro-posed in the literature.

results.

In the medical management of HIV lipodystrophy,various agents have been utilized but most have yielded disap-pointing results. Preliminary evidence on the use of tumescentliposuction in these patients suggests that significant improve-ment in the cosmetic disfigurement can be achieved.

conclusion.

This syndrome is common among HIV-infectedpatients and remains difficult to treat. Although medical ther-apy may be preferable in most patients, liposuction represents aviable option in selected individuals.

IN THE LAST few years, there have been many reportsin the literature describing human immunodeficiency vi-rus (HIV)-infected patients who developed subcuta-neous fat redistribution in association with metabolicdisturbances. This so-called HIV-related lipodystrophysyndrome typically manifests as fat wasting on periph-eral areas of the body and localized fat accumulationcentrally. Various metabolic disturbances such as dysli-poproteinemia and glucose intolerance are often associ-ated with this condition. Although medical managementhas been considered first-line therapy, the results re-ported in selected patients are disappointing and con-trolled data on its effectiveness are limited. As a result,many patients and clinicians have opted for surgical in-tervention in order to manage the more severe or resis-tant cases. Experience at our institution with liposuctionin the management of this syndrome has been favorable,as demonstrated in the following case report.

Case Report

The patient is a 44-year-old white man who had a10-year history of HIV disease that had not been com-plicated by an opportunistic infection or acquired im-munodeficiency syndrome (AIDS)-defining illness. He

was being treated with nelfinavir, stavudine, didano-sine, and lisinopril/hydrochlorothiazide. Since startingnelfinavir 3 years earlier, the patient had slowly devel-oped swelling of the subcutaneous tissue on his upperback and anterior neck as well as loss of the buccal fatpads (Figure 1). The patient’s weight of 82 kg had re-mained stable. Laboratory evaluation 3 months priorto presentation revealed the following pertinent data:

absolute CD4 count 416/mm

3

, serum glucose 110 mg/dl(normal 65–109), total cholesterol 261 mg/dl (nor-mal 100–199), triglycerides 142 mg/dl (normal 0–199),HDL (high-density lipoprotein) 44 mg/dl (normal 35–150), LDL (low-density lipoprotein) 188 mg/dl (nor-mal 0–129), and VLDL (very low-density lipoprotein)28 mg/dl (normal 5–40).

He initially underwent tumescent liposuction of hisupper back with blunt cannulas 2–3 mm in diameter.Following infiltration of 1500 cc of tumescent fluid(total lidocaine dosage 10 mg/kg), liposuction was per-formed yielding 600 cc of aspirate. The operation wasterminated earlier than expected because the aspiratebecame largely composed of blood. He had an uncom-plicated postoperative course with a significant reduc-tion in the size of the adiposity (Figure 2). Continuedfollow-up failed to identify signs of recurrence, so thepatient elected to undergo liposuction of the anteriorneck and chin and had similar results. The patient hasremained on continuous therapy for HIV disease withboth a protease inhibitor and nucleoside analog reversetranscriptase inhibitors since the operation.

A portion of the aspirate from both operations wassubmitted for histopathology. Though the specimens

M.A. Chastain, MD, J. Buckley, MD, MPH, and W.P. Coleman III,MD have indicated no significant interest with commercial supporters.

Address correspondence and reprint requests to: Mark A. Chastain, MD, Tu-lane University School of Medicine, Department of Dermatology, 1430 Tu-lane Avenue, TB-36, New Orleans, LA 70112. Email: mchastain@pol.net.

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were not ideal for evaluation due to aspiration-induceddisruption in the tissue architecture, no abnormalitieswere noted from either site. Follow-up laboratoryevaluation has revealed no changes in lipid levels.

Discussion

Although it has been most closely associated with pro-tease inhibitor (PI) therapy, HIV lipodystrophy hasalso been described in PI-naive nucleoside analog re-verse transcriptase inhibitor (NRTI) recipients andin HIV patients who have never taken antiretroviraldrugs.

1–6

In its typical form, the lipodystrophy syn-drome occurs in the first 3–12 months after initiationof PI therapy.

7–10

The incidence in PI-treated patientshas varied greatly from 1.8% to 64%,

2,4,5,7,11,12

withmost reports suggesting that a majority of patients areafflicted. This great disparity may be explained by thelack of uniform criteria for its diagnosis, the heteroge-neity of the syndrome, and the direct correlation be-tween the syndrome’s incidence and duration of PItherapy.

13–16

Patients experience the loss of subcutane-ous fat on their face and extremities, which often leadsto prominence of the underlying veins and muscula-ture. The areas of localized lipohypertrophy have apredilection for the trunk, especially the dorsocervicalregion (the so-called buffalo hump),

3

lower abdomen(the so-called protease paunch),

17

and breasts. Thesyndrome occurs in both sexes, with females usuallymanifesting more pronounced breast enlargement.

15

The metabolic abnormalities increase the patient’s riskof adverse cardiovascular events,

18–20

while the cos-metic disfigurement often leads to significant psycho-social problems.

21,22

In the vast majority of lipodystrophy cases de-scribed in association with PI therapy, the most con-

sistent laboratory finding has been hypertriglyceri-demia, which is present in approximately three-fourthsof patients.

5,8

Other commonly observed lipid distur-bances have included reductions in HDL and elevationsin LDL and VLDL. Insulin resistance with high insulinlevels, hyperglycemia, and elevated C-peptide values aresometimes present, but overt diabetes mellitus is uncom-mon.

8,9

Cases of PI-naive, NRTI-induced lipodystrophyappear to represent a distinct subset characterized bylactic acidemia, liver dysfunction, a lesser degree of lipidelevations, and constitutional symptoms.

1

Findings in skin biopsy specimens from lipoatro-phic areas have included thinning of the subcutaneousfat

23

and variations in the shapes and sizes of individ-ual adipocytes.

8

The presence of small lipocytes, vas-cular proliferation resembling fetal fat, and lympho-histiocytic infiltrates with focal lipogranuloma formationhave also been observed.

8,24

The histopathologic fea-tures of the panniculus in areas of lipohypertrophyhave not been adequately described.

The pathogenesis of this disorder remains some-what speculative. Though indinavir has been the mostfrequently implicated drug, all PIs have been associ-ated with the lipodystrophy syndrome. HIV-1 protease,the target molecule of the PIs, shares 60% homologywith specific regions of two proteins involved in lipidand adipocyte metabolism, lipoprotein receptor-relatedprotein and cytoplasmic retinoic acid-binding proteintype I.

25

Inhibition of these two proteins with PI drugtherapy causes preferential apoptosis and reduced dif-ferentiation of adipocytes located in peripheral ar-eas.

25,26

The result of this peripheral wasting of fat isan elevation of serum lipids and their consequent ac-cumulation centrally. Antiretroviral drug-induced dys-regulation of tumor necrosis factor (TNF)-

a

synthe-sis, a cytokine involved in lipid metabolism, has also

Figure 1. There is a large subcutaneous mass on the upper back ofthis patient with HIV lipodystrophy. Atrophy of the buccal fatpads can also be seen.

Figure 2. Significant improvement 3 months after tumescent lipo-suction.

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499

been suggested.

27

Glucose intolerance may be causedby PI-induced impairment of insulin-stimulated glucoseuptake in adipocytes by inhibiting the function of intra-cellular glucose transport molecules.

28

The pathogene-sis of the lipodystrophy syndrome in NRTI-associatedcases may be related to the drug’s induction of mito-chondrial toxicity.

29,30

Despite the evidence support-ing a drug-induced process, some investigators havespeculated that lipodystrophy may be a normal, long-term consequence of HIV disease that is being un-masked by the prolonged survival seen in patients tak-ing PIs.

31

The various modalities proposed for the treatmentof this syndrome have yielded inconsistent results.Discontinuation of drug therapy has sometimes re-sulted in complete reversibility of the clinical and lab-oratory findings in both PI- and NRTI-associatedcases.

11,32

But such a decision should be made withgreat caution because of the likelihood of increasedmorbidity and mortality from HIV disease. SwitchingPI therapy to nelfinavir has yielded equivocal bene-fit,

15,33

while dietary modification and exercise maypromote modest improvement.

34,35

Troglitazone, onedrug in a new class of antihyperglycemic agents, hasbeen shown to reverse fat redistribution and to reducelipid and glucose levels in a small number of diabeticpatients with HIV lipodystrophy, but it is no longermanufactured because of reports of serious adverse ef-fects.

36

Low-dose metformin has been similarly shownto decrease insulin resistance and reduce both visceraland subcutaneous abdominal fat.

37

Preliminary resultsutilizing recombinant human growth hormone ther-apy have shown reductions in central lipohypertrophywithout any effect on peripheral wasting or serumlipid disturbances.

38,39

Other therapeutic options haveincluded anabolic steroids,

35,40

naltrexone,

41

and cho-lesterol-lowering drugs.

42

Liposuction has been used to reduce localized adi-posities for 25 years but has gained acceptance in thelast decade for the treatment of lipodystrophies as wellas fatty neoplasms.

43–45

Though there is a paucity ofreports in the literature on the use of liposuction inHIV-related lipodystrophy syndrome,

46,47

there havebeen multiple patients at our institution and at otherswho have undergone liposuction for this condition.Areas of lipohypertrophy in many of these patientshave responded well to surgical intervention, but thelongevity of improvement is unknown and the meta-bolic disturbances are not likely to be affected. Be-cause imaging studies have found that the increasedabdominal girth is associated with fat accumulation inthe perivisceral region, this area may be less amenableto liposuction.

23,48,49

The higher than normal propor-tion of blood in our patient’s aspirate may be ex-plained by the increased vascularity of the panniculus

that has been noted on histopathology in prior re-ports.

8,24

In the cases described by Wolfort et al.

47

theinternal ultrasound-assisted technique was preferreddue to the high density of fibrous septae in the subcu-taneous fat, but we have not found this necessary.

Before undergoing liposuction for HIV-related lipo-dystrophy, the patient must thoroughly understandthe risks and limitations of surgery. In particular, theimmune deficiency in these patients may predispose tothe development of a postoperative infection or im-paired healing. The increased risk of cardiovasculardisease in lipodystrophy patients due to the associatedmetabolic disturbances should also be considered be-fore the decision is made to proceed with elective sur-gery. Another concern with tumescent liposuction forthe treatment of HIV lipodystrophy syndrome is thepossibility of drug interactions, since most of these pa-tients take a multitude of medications. PIs have beenshown to inhibit lidocaine metabolism

50,51

and mayincrease the risk of lidocaine toxicity. Although thecurrently recommended maximum lidocaine dose whenusing the tumescent technique is 55 mg/kg,

52

it is pru-dent to adjust this for patients on PIs, and temporarydiscontinuation of these and similar drugs may be ad-visable.

Our case illustrates the potential role for liposuc-tion in the management of HIV lipodystrophy. Basedon the favorable postoperative results in the few re-ported cases and in many unreported cases, liposuc-tion represents a reasonable treatment option in thesepatients. It is hoped that other liposuction surgeonswill report their experiences in the surgical manage-ment of this condition so that appropriate guidelinescan be established.

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