Recognizing and treating ProMeris-triggered pemphigus foliaceus in dogs
Pemphigus foliaceus is the most common autoimmune skin disease in dogs.1 Canine pemphigus foliaceus typically manifests as bilaterally symmetrical pustules and erosions and crusts on the face and ears. Occasionally, lesions also develop on the footpads, around the claws, or on the trunk.1
People and dogs affected with pemphigus foliaceus produce autoantibodies that target desmosomes, the structures responsible for cell-to-cell adhesion within the epidermis.1 As a result of autoantibody binding, cells of the superficial epidermal layers lose their attachment to neighboring keratinocytes, and they round up and become the so-called acantholytic cells. Superficial epidermal clefting with pustule formation then ensues.
Genetic and environmental factors, as well as drug administration, are suspected to lead to the development of canine pemphigus foliaceus.1 Since the 1990s, various drugs have been reported as a possible cause of canine pemphigus foliaceus,2-4 but in these cases, only rarely was a direct drug-disease relationship proved.Recently, we reported that 22 dogs treated with a novel topical flea and tick preventive that contains metaflumizone and amitraz (ProMeris Duo [Fort Dodge Animal Health, later acquired by Pfizer Animal Health], marketed as ProMeris for dogs in the United States) all subsequently developed pemphigus foliaceus-like skin lesions at the application site.5 In all of these cases, the earliest skin lesions were noticed between the shoulder blades, which is not a predilection site for typical spontaneously arising autoimmune pemphigus foliaceus. Moreover, in two-thirds of these dogs, skin lesions eventually became generalized.5 Most dogs with generalized skin disease have signs of systemic illness, and they require variable immunosuppressive regimens similar to those given to dogs with spontaneous autoimmune pemphigus foliaceus. Generalized ProMeris-triggered pemphigus foliaceus cannot be distinguished from spontaneously occurring autoimmune pemphigus foliaceus clinically or by histopathology or autoantibody detection tests.5
Since some dogs with ProMeris-triggered pemphigus foliaceus develop more severe signs after each subsequent drug application, veterinary practitioners must recognize this unusual form of pemphigus foliaceus as early as possible. Once this drug-disease relationship is established, application of the preventive must be stopped to prevent further disease progression, and anti-inflammatory or immunosuppressive treatment should be initiated.
In this article, we discuss two dogs with ProMeris-triggered pemphigus foliaceus that we successfully treated. In both cases, the lesions initially presented at the preventive application sites and then extended to distant skin areas to become generalized. In addition to these cases, we also provide information on the prognosis and management of this disease in general.
A 7-year-old female spayed Labrador retriever was presented to the North Carolina State University (NCSU) Veterinary Teaching Hospital Dermatology Service for evaluation of skin lesions and lameness of two weeks' duration.
Ten months before the referral, the dog's monthly flea and tick prevention was changed from Frontline (Merial) to ProMeris. The patient had received a total of three ProMeris applications—the first two three months apart and the third five months later.
One month after the third application, the owner noticed extensive crusting on the application site between the shoulder blades and lameness of the left front leg. The dog was examined by its primary-care veterinarian who suspected that a tick-borne disease caused the lameness. Doxycycline and cefazolin were prescribed. Skin biopsy samples were taken from interscapular crusts, and histologic examination revealed an acantholytic dermatosis of unknown origin.
The patient's health worsened dramatically over the following days. The dog appeared to be in pain and showed lameness of the left front paw, and the skin lesions progressed. The veterinarian subsequently administered a single injection of dexamethasone sodium phosphate (0.13 mg/kg) and cefovecin. Additionally, he prescribed prednisone (1 mg/kg twice daily) and tramadol and applied a transdermal fentanyl patch; the doxycycline was continued. Only minimal improvement of the lameness and skin lesions was seen with this regimen, so the dog was referred to NCSU.