Correspondence
Fat Distribution in AIDS
N Engl J Med 1999; 340:969-970March 25, 1999
- Article
To the Editor:
In the descriptions in the Images in Clinical Medicine (Oct. 29 issue)1,2 of two patients with buffalo hump and infection with the human immunodeficiency virus (HIV) who were receiving antiretroviral therapy, the authors suggest a connection between these conditions. The general appearance of the patient described by Aboulafia and Bundow closely resembles that of patients with multiple symmetric lipomatosis. This rare condition affects middle-aged men and women. In this disease, unencapsulated lipomas appear in the subcutaneous and deep-neck fat, infrequently causing syncope or breathing difficulties by compression of neurovascular structures and the trachea. Computed tomography might reveal not only hypertrophy of the subcutaneous and upper mediastinal fat but also hypertrophy of the pericardial and deep abdominal fat.
Multiple symmetric lipomatosis has been described in patients with alcoholism, patients treated with steroids, and patients with mitochondrial myopathic disorders such as myoclonic epilepsy with ragged-red fibers (MERRF syndrome) and has been described as an idiopathic form frequently accompanied by polyneuropathy and myopathy.3 The pathogenesis of multiple symmetric lipomatosis involves decreased responsiveness of lipocytes to adrenergic stimulation,4 probably as a consequence of mitochondrial dysfunction or the action of corticosteroids on adipose tissue. We wonder whether the described patients were alcoholic or whether they had polyneuropathy or myopathy. Whatever the cause, the designation “multiple symmetric lipomatosis” is used for the description of characteristic fat distribution and should also be used in the cases under discussion.
4 ReferencesValery Teplitsky, M.D.
Aaron Halabe, M.D.
Wolfson Medical Center, Holon 58100, Israel1
Carr A ,Cooper DA . Lipodystrophy associated with an HIV-protease inhibitor. N Engl J Med 1998;339:1296-1296
Full Text | Web of Science | Medline2
Aboulafia DM ,Bundow D . Buffalo hump in a patient with the acquired immunodeficiency syndrome. N Engl J Med 1998;339:1297-1297
Full Text | Web of Science | Medline3
Teplitsky V ,Huminer D ,Dux S ,Learman Y ,Zoldan J ,Pitlik SD . Multiple symmetric lipomatosis presenting with polyneuropathy. Isr J Med Sci 1995;31:693-695
Medline4
Enzi G ,Inelmen EM ,Baritussio A ,Dorigo P ,Prosdocimi M ,Mazzoleni F . Multiple symmetric lipomatosis: a defect in adrenergic-stimulated lipolysis. J Clin Invest 1977;60:1221-1229
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We thank Drs. Teplitsky and Halabe for their comments. We agree with them and other clinicians that HIV-associated lipodystrophy syndrome has several striking features in common with the syndrome of multiple symmetric lipomatosis.1 Like patients with multiple symmetric lipomatosis, HIV-infected persons may report changes in body composition, including enlargement of the cervicodorsal fat pad (buffalo hump) or axillary fat pads (bilateral symmetric lipomatosis), breast enlargement, expansion in abdominal girth (“Crix-belly” or “protease paunch”), and thinning of the extremities. In both conditions, in both men and women, an increase in fat content in the visceral compartment or in the cervicodorsal area is accompanied by a loss of subcutaneous fat.2,3
There are, however, differences between the two conditions. Familial occurrence of multiple symmetric lipomatosis has been reported, and an autosomal dominant mode of inheritance has been postulated. The occurrence of multiple symmetric lipomatosis is confined largely to middle-aged adults, but HIV-associated lipodystrophy may affect children.4 Furthermore, a connection among alcohol intake, peripheral neuropathy, and localized accumulations of fat has not yet been observed in those infected with HIV.
The pathogenesis of HIV-associated lipodystrophy syndrome is uncertain, although two hypotheses have most commonly been offered. The changes may represent a side effect of protease inhibitor therapy. Alternatively, the changes are not directly related to drug therapy but are somehow unmasked by an effect of highly active antiretroviral therapy, such as diminishing viral replication or partial immune reconstitution. The two hypotheses are not mutually exclusive. The syndrome may not be a single entity and may represent a spectrum of abnormalities.5
Whereas the loss of subcutaneous fat (as in lipodystrophy) may be a very distinct entity, the combination of obesity, hyperlipidemia, and insulin resistance is probably an interrelated triad, and several conditions may be associated with this anomaly. The patient we photographed did not report distal paresthesias and did not drink alcohol, nor had he previously received steroid therapy. We are impressed with the seemingly unique circumstances by which fat deposits occur in the milieu of HIV infection. Because HIV and its treatments may act in various ways to promote changes in body composition, we suggest caution and the collection of more complete clinical and laboratory data before the spectrum of multiple symmetric lipomatosis is broadened to include HIV-infected patients.
5 ReferencesDavid M. Aboulafia, M.D.
Denise Bundow, A.R.N.P.
Virginia Mason Clinic, Seattle, WA 981111
Hengel RL, Geary JAM, Vuchetich MA, et al. Multiple symmetrical lipomatosis associated with protease inhibitor therapy. Presented at the Fifth Conference on Retroviruses and Opportunistic Infections, Chicago, 1988. abstract.
2
Kotler DP, Rosenbaum KR, Wang J, et al. Altered body fat distribution in HIV-infected men and women. Presented at the 12th World AIDS Conference, Geneva, 1998.
3
Lo JC ,Mulligan K ,Tai VW ,Algren H ,Schambelan M . “Buffalo hump“ in men with HIV-1 infection. Lancet 1998;351:861-8704
Regan AM, Babl FE. Abnormal body fat (ABF) accumulations in HIV-infected children on antiretroviral therapy. Presented at the 38th ICAAC, San Diego, Calif., 1998.
5
Carr A ,Samaras K ,Chisholm DJ ,Cooper DA . Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1988;351:1881-1883
CrossRef | Web of Science
- Citing Articles (10)
Citing Articles
1
Debbie M. Cheng, Howard Libman, Carly Bridden, Richard Saitz, Jeffrey H. Samet. (2009) Alcohol consumption and lipodystrophy in HIV-infected adults with alcohol problems. Alcohol 43:1, 65-71
CrossRef2
Erika Santos Corraliza, Aurelio Fuertes Martín. (2007) Tratamiento antirretroviral y toxicidad mitocondrial. Medicina Clínica 128:8, 311-316
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Parviz Goshtasby, Glen Brooks, L. Peter Fielding. (2006) Lipomatous Disorder of the Peri-Trochanteric Soft Tissue: Case Report and Review. Current Surgery 63:5, 338-344
CrossRef4
Marcello Pinti, Paolo Salomoni, Andrea Cossarizza. (2006) Anti-HIV drugs and the mitochondria. Biochimica et Biophysica Acta (BBA) - Bioenergetics 1757:5-6, 700-707
CrossRef5
Abby Shevitz, Christine Wanke, Julian Falutz, Donald Kotler. (2001) Aids 15:15, 1917-1930
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Rocco Urso, Marco Gentile. (2001) Aids 15:2, 290-291
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??scar Mir??, Montserrat G??mez, Enric Pedrol, Francesc Cardellach, Virginia Nunes, Jordi Casademont. (2000) Respiratory chain dysfunction associated with multiple mitochondrial DNA deletions in antiretroviral therapy-related lipodystrophy. AIDS 14:12, 1855-1857
CrossRef8
Graeme Moyle. (2000) Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clinical Therapeutics 22:8, 911-936
CrossRef9
Thomas N. Kakuda, Richard C. Brundage, Peter L. Anderson, Courtney V. Fletcher. (1999) Nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity as an etiology for lipodystrophy. AIDS 13:16, 2311
CrossRef10
Kees Brinkman, Jan A Smeitink, Johannes A Romijn, Peter Reiss. (1999) Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. The Lancet 354:9184, 1112-1115
CrossRef
