title: Immediate type I hypersensitivity response implicated in worsening injection site reactions to adalimumab.
abstract: BACKGROUND
  Tumor necrosis factor (TNF) inhibitors such as adalimumab, etanercept, and infliximab play an increasingly important role in the management of a variety of chronic inflammatory disorders. With their increasing use, a wide spectrum of dermatological adverse effects, including injection site reactions and the development of dermatitis, have been recognized. Previous studies have implicated the role of the delayed-type hypersensitivity reaction in mediation of injection site reactions to etanercept. To our knowledge, there have been no published studies on immunologic mechanism of injection site reactions to adalimumab to date.
  
  
  METHODS
  We describe 2 patients with a history of worsening injection site reactions to adalimumab. Findings from skin testing in both patients were suggestive of an immediate type I hypersensitivity reaction to adalimumab. A histamine release assay performed on peripheral blood leukocytes from both patients demonstrated significant histamine release on exposure to adalimumab. Furthermore, passive transfer of serum from one of the allergic patients to basophils from a nonatopic, healthy donor sensitized those cells to release significant amounts of histamine with exposure to adalimumab. Conclusion This study demonstrates that an IgE-mediated immediate type I hypersensitivity reaction plays a role in the mediation of worsening injection site reactions in some patients receiving adalimumab.
authors.affiliation: Department of Dermatology, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Paltiel
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gober
authors.forename: April
authors.initials: A
authors.lastname: Deng
authors.forename: Jamal
authors.initials: J
authors.lastname: Mikdashi
authors.forename: Irena
authors.initials: I
authors.lastname: Alexeeva
authors.forename: Sarbjit S
authors.initials: SS
authors.lastname: Saini
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Gaspari
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D005260:Female; D006636:Histamine Release; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D007114:Immunization; D007279:Injections, Subcutaneous / Q000009:adverse effects; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D012720:Severity of Illness Index; D012882:Skin Tests; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab