title: Nonimmediate reactions to systemic corticosteroids suggest an immunological mechanism.
abstract: BACKGROUND
  Administration of corticosteroids (CS) by different routes may cause varying types of allergic reactions, thereby hampering their further use in affected patients. In order to verify an immunological involvement we evaluated a group of patients with symptoms compatible with nonimmediate allergic reactions to CS.
  
  
  METHODS
  Studies included patch and intradermal tests, immunohistochemical studies and controlled administration to reproduce the response. The cytokines interleukin (IL)-4, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were quantified in peripheral blood during the response.
  
  
  RESULTS
  Of 32 subjects evaluated presenting nonimmediate urticaria or exanthema, 21 were finally considered positive after re-exposure. The drugs most frequently involved were betamethasone and dexamethasone. Fewer than half the patients responded to prednisolone whilst some responded to three or more CS. Hydrocortisone and deflazacort were well tolerated by all the patients. Subjects with a positive intradermal or patch test had a perivascular mononuclear cell infiltrate with the presence of CD4 and CD8 lymphocytes positive for CD45RO+ (memory) and CD69 (activation marker) cells. Monitoring peripheral blood during the acute response showed expression of IFN-gamma and TNF-alpha, with downregulation of IL-4.
  
  
  CONCLUSIONS
  Adverse systemic responses to different CS are suggestive of a nonimmediate reaction. The symptoms elicited together with the immunlogical studies suggest a T-cell mediated response. The response to closely related CS was especially marked between betamethasone and dexamethasone, whereas hydrocortisone and deflazacort were well tolerated.
authors.affiliation: Servicio de Alergologia, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Padial
authors.forename: S
authors.initials: S
authors.lastname: Posadas
authors.forename: J
authors.initials: J
authors.lastname: Alvarez
authors.forename: M-J
authors.initials: MJ
authors.lastname: Torres
authors.forename: J A
authors.initials: JA
authors.lastname: Alvarez
authors.forename: C
authors.initials: C
authors.lastname: Mayorga
authors.forename: M
authors.initials: M
authors.lastname: Blanca
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D001623:Betamethasone / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D003907:Dexamethasone / Q000009:adverse effects; D004342:Drug Hypersensitivity / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000009:adverse effects; D012882:Skin Tests; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma; D001623:Betamethasone; D011239:Prednisolone