714 Pathology of Injection Site Reactions with Enfuvirtide R. A. Ball*1, T. Kinchelow2 1Greensboro Pathology Assoc, Greensboro, NC and 2Hoffmann-La Roche, Inc, Nutley, NJ
Background: Enfuvirtide (T-20) is the first of a new class of antiretroviral agents, the fusion inhibitors, under investigation for the treatment of HIV infection. It is administered by subcutaneous (SQ) injection, and the most common adverse event is injection site reactions (ISRs). This study investigated the pathology of enfuvirtide-associated ISRs.
Methods: Seven (7) HIV-infected patients (pts) were recruited and showed a range of ISRs: 4 with nodules, and 1 each with erythema, induration, or no clinical reaction. An excisional biopsy of the injection site (= 1 cm³) was taken. Time from injection to biopsy ranged from 3 h-40 h. Samples were examined dermatopathologically and the degree of inflammation and relative localization to the dermis or SQ tissue was graded. Samples were also examined by immunoperoxidase staining for enfuvirtide and inflammatory cells.
Results: Pathologic changes were seen in all pts, but varied, particularly with regards to the density of the inflammatory response and its localization to the dermis or SQ tissue. The degree or localization of inflammation did not correlate with clinical findings. Inflammatory infiltrate consistent with a hypersensitivity reaction was present in all cases, as was focal pallor and some fragmentation of the connective tissue. The inflammatory cells included histiocytes with some multinucleated forms aggregated around the areas of collagen change, reminiscent of a palisaded granulomatous response, as in granuloma annular. Focal lipophagic fat necrosis and hemorrhage consistent with trauma was also seen. Fibrosis and widening of the SQ septae was seen in a pt with a history of diabetes and SQ insulin injection. All cases were positive for enfuvirtide by immunoperoxidase staining, with increased positivity in areas of greatest inflammatory response. Enfuvirtide deposited in the interstitium and on the surface of collagen fibers in areas of collagen degradation. In one specimen, large aggregates of intense staining both intra- and extra-cellularly were seen, some within foamy macrophages in the SQ tissue. In all but 1 sample, most lymphocytes were T-cells. CD20 and CD68 staining was seen in all cases, confirming the presence of B-cells and macrophages.
Conclusions: This is the first report of the pathological changes associated with enfuvirtide-associated ISRs. Many resemble an interstitial granulomatous drug reaction, a rare entity previously seen only with systemically administered drugs.
