Clinical, histological, and immunophenotypic characteristics of injection site reactions associated with etanercept - A recombinant tumor necrosis factor alpha receptor: Fc fusion protein
R. Zeltser et al., Clinical, histological, and immunophenotypic characteristics of injection site reactions associated with etanercept - A recombinant tumor necrosis factor alpha receptor: Fc fusion protein, ARCH DERMAT, 137(7), 2001, pp. 893-899
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.