Clinical, histological, and immunophenotypic characteristics of injection site reactions associated with etanercept - A recombinant tumor necrosis factor alpha receptor: Fc fusion protein

Objective: To study injection site reactions (ISRs) associated with etanerc ept therapy. Design: Retrospective chart review, along with prospective analysis of sele cted patients experiencing ISRs associated with etanercept therapy. Setting: Academic rheumatology/immunology unit and dermatology clinic. Subjects: Patients with rheumatoid arthritis,juvenile rheumatoid arthritis, inflammatory seronegative arthritis, psoriatic arthritis, psoriasis, or in flammatory bowel disease. Interventions: Skin biopsy specimens were taken from selected patients expe riencing ISRs. Main Outcome Measures: Incidence of IRSs and histological and immunophenoty pic analysis of ISRs in 3 patients undergoing prospective study. Results: Twenty-one (20%) of 103 of all patients receiving etanercept repor ted ISRs, all within the first 2 months of inception of therapy. The reacti ons occurred 1 to 2 days after the last injection and resolved within a few days. Moreover. eventual waning of reactions was observed, with none provi ng to be dose limiting. Histological examination of all biopsy specimens sh owed an inflammatory infiltrate composed of predominantly lymphoid cells an d some eosinophils, in a perivascular cuffing pattern, without evidence of leukocytoclastic vasculitis. The infiltrating lymphoid cells were predomina ntly activated mature (HLA-DR+/CD3(+)/CD4(-)/CD8(+)) cytotoxic T lymphocyte s, with a small number of CD4(+) cells. A biopsy specimen from a recall ISR showed strong HLA-DR expression by epidermal keratinocytes. Conclusions: Injection site reactions associated with etanercept therapy ar e common, and may be an example of a T-lymphocyte-mediated delayed-type hyp ersensitivity reaction, with waning over time due to eventual induction of tolerance.