Since the inception of protease inhibitors, unusual side effects resulting in body habitus changes have been seen with the use of indinavir (breast hypertrophy) [1] and ritonavir (abdominal girth) [2]. We recently cared for three patients who presented with the rapid onset of increasing cervicodorsal tissue ("buffalo humps") while receiving protease inhibitors.

Table 1 shows the characteristics of these patients. The average size of the cervicodorsal enlargement was 14 x 14 cm. None of the patients had signs of hypercortisolism or a history of steroid use. Findings on evaluation for Cushing disease were negative. Deep punch biopsies revealed increased collagen deposition replacing the periadnexal loose connective tissue in the dermal region, suggesting a scleroderma-like reaction.

Recently, Ruane [3] reported on three similar patients who developed atypical accumulation of presumptive fatty tissue in the posterior neck region while receiving protease inhibitors. However, the histopathologic findings of biopsy performed in our patients suggest that the accumulation of tissue is consistent with a scleroderma-like reaction, not the fatty tissue that is seen with the traditional buffalo hump of Cushing disease. It has been postulated that some medications, such as bleomycin [4], may induce a localized scleroderma-like reaction by forming free radicals that stimulate fibroblasts to proliferate, leading to increased collagen deposition.

The U.S. Food and Drug Administration has reviewed the cases of nine patients with changes in body habitus that mimic those of the Cushing syndrome, including descriptions of buffalo humps associated with each of the four protease inhibitors [5]. The cause of the fat redistribution in these cases remains unclear.

Given the absence of laboratory abnormalities in these cases, an aggressive evaluation of this unusual side effect is probably not warranted unless other clinical features suggest an endocrinopathy. According to our observations, the appearance of buffalo humps should not dissuade practitioners from continuing protease inhibitor therapy.