Anterior neck fat deposition in lipodystrophy syndrome; a new variant on a theme?

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In 1998, Carr et al. [1] described a new clinical phenomenon of lipodystrophy in patients infected with HIV. Their original description was of a syndrome characterized by peripheral lipoatrophy, hyperlipidemia and insulin resistance in patients receiving HIV protease inhibitors. Contemporaneously, other body shape changes were described, including central adiposity and the presence of a buffalo hump [2,3]. We describe in detail one patient who presented with a rarely described component of this syndrome: the deposition of excess subcutaneous fat in the anterior neck. This variation in phenotype of the lipodystrophy syndrome may have treatment implications for individual patients, as well as considerations for pathogenesis. Case report A 35-year-old man as diagnosed with HIV infection in 1989. He was treated initially with zidovudine monotherapy, then zidovudine, lamivudine and saquinavir in 1996, with the subsequent substitution of stavudine, didanosine, indinavir and ritonavir in 2000. He developed renal calculi, and indinavir was replaced with lopinavir/ritonavir in 2001. After starting lopinavir/ritonavir, he noticed increased swelling of his neck anteriorly and posteriorly, and hair loss that was most marked on the legs. He complained of marked discomfort relatine to the anterior swelling in his neck, but no dysphagia, dyspnoea or symptoms of obstructive sleep apnoea. Examination revealed a buffalo hump, and evidence of subzygomatic, limb and buttock fat wasting. He was hypertensive, with a blood pressure of 130/100 mmHg. The neck swelling progressed despite the substitution of nevirapine for lopinavir/ritonavir. Cushing's disease and thyroid disease were both excluded by formal testing, including thyroid function tests, the dexamethasone suppression test and a 24 h urinary cortisol measurement. He had a dual-energy X-ray absorptiometry scan, which showed 18% abdominal fat, 30% arm fat and 7% leg fat. A computed tomography scan showed increased subcutaneous fat in the anterior neck region. Lipid testing revealed a fasting cholesterol level of 5.9 mmol/l and triglycerides of 6.7 mmol/l. His CD4 cell count was 350 cells/μl and his HIV viral load was less than 50 copies/ml. He underwent removal of the fat by liposuction and experienced marked relief of the symptoms of neck discomfort and reduced mobility A preoperative clinical photograph (Fig. 1) reveals the substantial swelling in the anterior neck.Fig. 1.: Anterior and lateral views of one patient showing lipodystrophic changes including swelling in the anterior neck.We have seen at least three further individuals exhibiting the same phenotype, one of whom has been referred for surgical removal of anterior neck fat for reasons of both cosmesis and comfort. All patients had a similar appearance, with fat deposition in the anterior and posterior neck and subzygomatic fat wasting. There were differences in antiretroviral exposure: one patient had no exposure to protease inhibitors, but developed lipodystrophy on lamivudine, stavudine and nevirapine. Of the other two patients, one is currently on didanosine, combivir and lopinavir/ritonavir and the other is on lamivudine, stavudine, indinavir, ritonavir and nevirapine. All three have had other evidence of lipodystrophy and have been on other antiretroviral therapy. The significant deposition of subcutaneous fat in the anterior neck has not been reported previously, but demonstrates another phenotype for the syndrome of lipodystrophy in individuals treated for HIV infection with potent antiretroviral therapy. The lipodystrophy syndrome is a relatively recently described phenomenon, and it is not surprising that novel manifestations should continue to become apparent. These patients experienced discomfort with the excess fat deposited around the neck, which was relieved in the first case by surgical removal. Differences in the clinical pattern of presentation may have significance for patient management, in this case the development of a particular surgical approaroach. It may be that they have an unusual distribution of susceptible tissues, i.e. their anterior neck fat contains the same susceptible receptors or enzymes present truncally or in the posterior neck fat alone. A further understanding of the molecular basis of lipodystrophy may be gained by an examination of the differences in protein expression or mitochondrial markers in adipose tissue from different sites and in relation to the phenotype. It seems unlikely that this phenotype is a result of treatment factors alone, and it is probable that host factors play a significant role. Such phenomena warrant further investigation at a clinical and basic science level.