Eosinophilic Cellulitislike Reaction to Subcutaneous Etanercept Injection

Abstract

Background: Injection site reactions are well recognized in patients treated with etanercept. Previous reports describe histologic findings of a cell-mediated T H 1 reaction, with CD8 ϩ T cells composing the majority of the dermal infiltrate. Observations: A pruritic, erythematous, edematous patch occurred on the right thigh of a 57-year-old white woman treated for rheumatoid arthritis within 12 to 24 hours after her second dose of subcutaneous etanercept. The patient had a similar reaction to adalimumab injection 2 weeks prior to presentation. While benzyl alcohol is present in the etanercept preparation, and mannitol in both drugs, dermal injection revealed no reaction to these additives. Biopsy specimens from the etanercept injection site demonstrated papillary dermal edema accompanied by a brisk polymorphous infiltrate with a predominance of eosinophils and scattered flame figures.

Rapid subcutaneous desensitization for the management of local and systemic hypersensitivity reactions to etanercept and adalimumab in 12 patients

“…[1][2][3][4] ISRs are thought to be T lymphocyte-mediated delayed type IV hypersensitivity reactions, which may preclude subsequent medication administration. 5,6 Rapid drug desensitization protocols have been developed for the delivery of a variety of parenteral chemotherapeutic agents, including monoclonal antibodies, to sensitized patients. 7 However, desensitization protocols have not been standardized for the treatment of ISRs and systemic reactions following subcutaneous medication injections.…”

“…Some authors have suggested that reactions to TNF inhibitors may also have a T-cell inflammatory component. 5,6 Biopsies were not done for this study but are needed to further assess the mechanism of these reactions.…”

Eosinophilic Drug Allergy

“…While mostly of unclear etiology, it has been reported as a side effect of anti-TNF agents including infliximab [90], adalumimab [91], and etanercept [92], with positive delayed intradermal testing to adalimumab and etanercept reported [92].…”

Immune-mediated adverse effects of biologicals used in the treatment of rheumatic diseases

“…Both types of reaction wane over time, which is though to represent a type of desensitization, although this may not be an accurate term in cases of CD8 þ T lymphocyte-mediated DTH responses [34]. Interestingly, there is a report of a patient who exhibited ISRs to adalimumab and subsequently developed an eosinophilic cellulitis-like ISR upon the first injection of etanercept [32]. The patient showed no skin-test reactivity to mannitol, a common constituent of the etanercept and adalimumab preparations.…”