title: Metaflumizone-amitraz (Promeris)-associated pustular acantholytic dermatitis in 22 dogs: evidence suggests contact drug-triggered pemphigus foliaceus.
abstract: Promeris Duo (PD) is a novel topical flea and tick preventative for dogs, which is also licensed for treatment of canine demodicosis. In this article, we present 22 dogs that all developed pemphigus foliaceus (PF)-like cutaneous drug reactions at the site of PD application. In eight dogs, the lesions were restricted to the application site (localized group). Signs of systemic illness were reported in three dogs, and four required immunosuppressive treatment. Direct immunofluorescence for IgG was positive in four dogs, although circulating antikeratinocyte IgG could not be detected in any tested sera. Complete remission was achieved in all dogs, with one patient still remaining on treatment. Fourteen dogs developed skin lesions at the application site as well as other noncontiguous areas (distant group). Systemic signs were reported in 11 dogs, and immunosuppression was required in 10 cases. Direct and indirect immunofluorescence tests were positive for antikeratinocyte autoantibodies in 10 of 13 and six of 10 patients with distant disease, respectively. Complete remission was achieved in 10 of 13 dogs with distant disease; one-third are still on treatment. Histological changes were similar to canine PF. Desmosomal architectural changes, assessed by desmoglein-1 immunostaining, were also similar to those of dogs with spontaneous autoimmune PF. Apoptosis did not appear to contribute to lesion formation, in either autoimmune or PD-associated PF. In conclusion, PD has the potential of triggering a variant of PF that resembles spontaneously occurring autoimmune PF at clinical, morphological, immunological and treatment outcome levels.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Oberkirchner
authors.forename: Keith E
authors.initials: KE
authors.lastname: Linder
authors.forename: Stan
authors.initials: S
authors.lastname: Dunston
authors.forename: Petra
authors.initials: P
authors.lastname: Bizikova
authors.forename: Thierry
authors.initials: T
authors.lastname: Olivry
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D004283:Dog Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004285:Dogs; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007306:Insecticides / Q000008:administration & dosage / Q000009:adverse effects*; D015603:Keratinocytes / Q000201:enzymology; D008297:Male; D010392:Pemphigus / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary*; D012664:Semicarbazones / Q000008:administration & dosage / Q000009:adverse effects*; D012867:Skin / Q000473:pathology; D014052:Toluidines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents; D007306:Insecticides; D012664:Semicarbazones; D014052:Toluidines; C014983:amitraz; C528570:metaflumizone; D053148:Caspase 3