title: Fipronil-amitraz-S-methoprene-triggered pemphigus foliaceus in 21 dogs: clinical, histological and immunological characteristics.
abstract: BACKGROUND
  A recently launched topical ectoparasiticide containing fipronil, amitraz and S-methoprene has been associated with the development of an acantholytic pustular dermatitis similar to that of Promeris-triggered pemphigus foliaceus (PF).
  
  
  OBJECTIVE
  Our objectives were to describe the clinical, histological and immunological features of this PF-like cutaneous adverse drug reaction.
  
  
  METHODS
  Twenty-one dogs with a probable or definitive diagnosis of PF-like cutaneous adverse drug reaction were identified between May 2012 and February 2013.
  
  
  METHODS
  Histology, direct and indirect immunofluorescence were employed to address the study objectives.
  
  
  RESULTS
  Most dogs were middle-aged or older (median, 9 years) and of large size (median, 23 kg). In six dogs (29%), the PF-like lesions remained confined to the site of application, while 15 dogs (71%) exhibited lesions at distant sites. One or two applications of the ectoparasiticide were sufficient to trigger PF-like lesions in seven (33%) and six (29%) dogs, respectively. Systemic signs were reported in nine dogs (43%), all with lesions extending to sites distant from application areas. Tissue-bound antikeratinocyte IgG was detected in the lesional epidermis of eight of 19 (42%) cases by direct immunofluorescence, while serum antikeratinocyte IgG was detected in 10 of 14 (71%) cases by indirect immunofluorescence. Autoantibodies were found to target canine desmocollin-1 in 11 of 14 dogs (79%), but not canine desmoglein-1, by indirect immunofluorescence on transfected cells. These immunological findings were similar in cases with localized and distant disease.
  
  
  CONCLUSIONS
  This new topical ectoparasiticide containing fipronil, amitraz and S-methoprene is capable of triggering the development of an acantholytic pustular dermatosis that is a clinical, histological and immunological close match for Promeris-triggered PF and naturally occurring autoimmune PF in dogs.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA; Center for Comparative Medicine and Translational Research, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Bizikova
authors.forename: Keith E
authors.initials: KE
authors.lastname: Linder
authors.forename: Thierry
authors.initials: T
authors.lastname: Olivry
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D004285:Dogs; D004338:Drug Combinations; D005260:Female; D007306:Insecticides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008726:Methoprene / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010392:Pemphigus / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D014052:Toluidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D004338:Drug Combinations; D007306:Insecticides; D011720:Pyrazoles; D014052:Toluidines; C014983:amitraz; D008726:Methoprene; C082360:fipronil